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Neuroscience Publications Archive - May 2016

May 26, 2016

1) 

Martin, N.D., Nguyen, K., McDaniel, M.A.
Structure building differences influence learning from educational text: Effects on encoding, retention, and metacognitive control
(2016) Contemporary Educational Psychology, 46, pp. 52-60. 

DOI: 10.1016/j.cedpsych.2016.03.005


Washington University in St. Louis, One Brookings Drive, St. Louis, MO, United States


Abstract
Structure building describes the process by which people mentally organize information while reading to comprehend and later recall text. We investigated how individual differences in structure building ability affect students' learning of complex, educational texts. College students studied a complex text with a mechanical theme, engaged in retrieval practice, made metamemory judgments, and then were given another study opportunity. Following a short delay, memory and comprehension of the text were assessed with a range of dependent measures, including performance on free recall, multiple-choice questions, and problem-solving questions. Participants with high structure building ability outperformed those with low structure building ability on information recalled, factual and inference multiple-choice questions, and problem solving questions. Although high and low structure builders demonstrated equivalent metamemory accuracy, high structure builders appear to better regulate their restudy time according to a discrepancy reduction strategy, which allowed them to acquire more new information that they were unable to retrieve initially during recitation. Our findings suggest that low structure builders may suffer from deficiencies at many levels of text representations as well as deficiencies in metacognitive control during restudy. Our study highlights structure building ability as an important individual difference for learning educational texts and furthers our understanding of exactly what aspects of learning are related to these differences. © 2016 Elsevier Inc.


Author Keywords
Educational text;  Individual differences;  Learning;  Metacomprehension;  Structure building


Document Type: Article
Source: Scopus




2) 

Jurczyszyn, A.a , Grzasko, N.b c , Gozzetti, A.d , Czepiel, J.a , Cerase, A.d , Hungria, V.e , Crusoe, E.e , Silva Dias, A.L.M.e , Vij, R.f , Fiala, M.A.f , Caers, J.g , Rasche, L.h , Nooka, A.K.i , Lonial, S.i , Vesole, D.H.j , Philip, S.j , Gangatharan, S.k , Druzd-Sitek, A.l , Walewski, J.l , Corso, A.m , Cocito, F.m , Vekemans, M.-C.M.n , Atilla, E.o , Beksac, M.o , Leleu, X.p , Davila, J.q , Badros, A.r , Aneja, E.s , Abildgaard, N.t , Kastritis, E.u , Fantl, D.v , Schutz, N.v , Pika, T.w , Butrym, A.x , Olszewska-Szopa, M.x , Usnarska-Zubkiewicz, L.x , Usmani, S.Z.y , Nahi, H.z , Chim, C.S.aa , Shustik, C.ab , Madry, K.ac , Lentzsch, S.ad , Swiderska, A.ae , Helbig, G.af , Guzicka-Kazimierczak, R.ag , Lendvai, N.ah , Waage, A.ai , Andersen, K.T.aj , Murakami, H.ak , Zweegman, S.al , Castillo, J.J.am
Central nervous system involvement by multiple myeloma: A multi-institutional retrospective study of 172 patients in daily clinical practice
(2016) American Journal of Hematology, 91 (6), pp. 575-580. 

DOI: 10.1002/ajh.24351


a Jagiellonian University Medical College, Cracow, Poland
b Department of Hematooncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland
c Department of Hematology, St. John's Cancer Center, Lublin, Poland
d Azienda Ospedaliera Universitaria Senese, Siena, Italy
e Santa Casa Medical School, Sao Paulo, Brazil
f Washington University School of Medicine, St. Louis, MO, United States
g Centre Hospitalier Universitaire de Liege, Liege, Belgium
h University Hospital Wuerzburg, Wuerzburg, Germany
i Winship Cancer Institute, Emory University, Atlanta, GA, United States
j John Theurer Cancer Center at Hackensack UMC, New Jersey and Georgetown University, Washington, DC, United States
k Fremantle Hospital, Fremantle, Australia
l Maria Sklodowska-Curie Institute, Oncology Center, Warsaw, Poland
m Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
n Cliniques Universitaires Saint-Luc, Brussels, Belgium
o Ankara University Medical School, Ankara, Turkey
p Hopital La Miletrie, CHU Poitiers, France
q Hospital Universitario de Salamanca, Salamanca, Spain
r University of Maryland Medical Center, Baltimore, MD, United States
s Weill Cornell Medical College, New York, NY, United States
t Odense University Hospital, Odense, Denmark
u National and Kapodistrian University of Athens, Athens, Greece
v Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
w University Hospital Olomouc, Olomouc, Czech Republic
x Wroclaw Medical University, Wroclaw, Poland
y Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC, United States
z Karolinska University Hospital, Stockholm, Sweden
aa Queen Mary Hospital, University of Hong Kong, Hong Kong
ab Royal Victoria Hospital, McGill University, Montreal, Canada
ac Medical University, Warsaw, Poland
ad Columbia University Medical Center, New York, NY, United States
ae Provincial Hospital, Zielona Gora, Poland
af Silesian Medical University, Katowice, Poland
ag Pomeranian Medical University, Szczecin, Poland
ah Memorial Sloan-Kettering Cancer Center, New York, NY, United States
ai Norwegian University of Science and Technology, Trondheim, Norway
aj Vejle Hospital, Vejle, Denmark
ak Gunma University Graduate School of Health Sciences, Gunma, Japan
al VU University Medical Center, Amsterdam, Netherlands
am Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States


Abstract
The multicenter retrospective study conducted in 38 centers from 20 countries including 172 adult patients with CNS MM aimed to describe the clinical and pathological characteristics and outcomes of patients with multiple myeloma (MM) involving the central nervous system (CNS). Univariate and multivariate analyses were performed to identify prognostic factors for survival. The median time from MM diagnosis to CNS MM diagnosis was 3 years. Thirty-eight patients (22%) were diagnosed with CNS involvement at the time of initial MM diagnosis and 134 (78%) at relapse/progression. Upon diagnosis of CNS MM, 97% patients received initial therapy for CNS disease, of which 76% received systemic therapy, 36% radiotherapy and 32% intrathecal therapy. After a median follow-up of 3.5 years, the median overall survival (OS) from the onset of CNS involvement for the entire group was 7 months. Untreated and treated patients had median OS of 2 and 8 months, respectively (P<0.001). At least one previous line of therapy for MM before the diagnosis of CNS disease and >1 cytogenetic abnormality detected by FISH were independently associated with worse OS. The median OS for patients with 0, 1 and 2 of these risk factors were 25 months, 5.5 months and 2 months, respectively (P<0.001). Neurological manifestations, not considered chemotherapy-related, observed at any time after initial diagnosis of MM should raise a suspicion of CNS involvement. Although prognosis is generally poor, the survival of previously untreated patients and patients with favorable cytogenetic profile might be prolonged due to systemic treatment and/or radiotherapy. © 2016 Wiley Periodicals, Inc.


Document Type: Article
Source: Scopus




3) 

Mejía-Cruz, D.a , Green, L.b , Myerson, J.b , Morales-Chainé, S.a , Nieto, J.a
Delay and probability discounting by drug-dependent cocaine and marijuana users
(2016) Psychopharmacology, pp. 1-10. Article in Press. 

DOI: 10.1007/s00213-016-4316-8


a National Autonomous University of México, México City, Mexico
b Washington University in St. Louis, St. Louis, MO, United States


Abstract
Rationale: Steep discounting of delayed monetary rewards by substance-dependent individuals is well-established. Less is known, however, about discounting other kinds of outcomes, and very little is known about discounting by marijuana-dependent individuals. Objectives: To determine how cocaine-dependent individuals and marijuana-dependent individuals discount various delayed and probabilistic outcomes, both positive and negative. Methods: Marijuana-dependent individuals, cocaine-dependent individuals, and controls performed delay and probability discounting tasks with various hypothetical outcomes. Results: The cocaine-dependent (but not the marijuana-dependent) group discounted delayed liquid rewards and monetary gains, but not delayed losses, more steeply than the control group. In contrast, the marijuana-dependent group (but not the cocaine-dependent group) discounted delayed monetary losses more steeply than controls. There were no group differences in discounting for any of the probabilistic outcomes. Factor analysis revealed a delayed gain factor, a probabilistic gain factor, and a delayed/probabilistic loss factor. The delayed gain factor scores for the cocaine-dependent group, but not the marijuana-dependent group, differed significantly from those of the control group. The groups did not differ in their probabilistic gain factor scores, and the marijuana-dependent group did not differ from the controls with respect to their loss factor scores. Conclusions: These results are inconsistent with the idea that steep discounting of both gains and losses and both delayed and probabilistic outcomes reflects a general impulsivity trait, as well as with the idea that all drug-dependent individuals are steep discounters. Rather, differences in discounting appear to be related to both the type of outcome and the specific drug on which individuals are dependent. © 2016 Springer-Verlag Berlin Heidelberg


Author Keywords
Cocaine;  Delayed gains;  Delayed losses;  Discounting;  Marijuana;  Polydrug dependence;  Probabilistic outcomes


Document Type: Article in Press
Source: Scopus




4) 

Little, J.L.a b c , Bjork, E.L.c
Multiple-choice pretesting potentiates learning of related information
(2016) Memory and Cognition, pp. 1-17. Article in Press. 

DOI: 10.3758/s13421-016-0621-z


a Department of Psychology, Washington University in St. Louis, St. Louis, MI, United States
b Department of Psychology, Hillsdale College, 33 E. College St., Hillsdale, MI, United States
c Department of Psychology, University of California, Los Angeles, CA, United States


Abstract
Although the testing effect has received a substantial amount of empirical attention, such research has largely focused on the effects of tests given after study. The present research examines the effect of using tests prior to study (i.e., as pretests), focusing particularly on how pretesting influences the subsequent learning of information that is not itself pretested but that is related to the pretested information. In Experiment 1, we found that multiple-choice pretesting was better for the learning of such related information than was cued-recall pretesting or a pre-fact-study control condition. In Experiment 2, we found that the increased learning of non-pretested related information following multiple-choice testing could not be attributed to increased time allocated to that information during subsequent study. Last, in Experiment 3, we showed that the benefits of multiple-choice pretesting over cued-recall pretesting for the learning of related information persist over 48 hours, thus demonstrating the promise of multiple-choice pretesting to potentiate learning in educational contexts. A possible explanation for the observed benefits of multiple-choice pretesting for enhancing the effectiveness with which related nontested information is learned during subsequent study is discussed. © 2016 Psychonomic Society, Inc.


Author Keywords
Learning;  Multiple choice;  Pretesting;  Test-potentiated learning;  Testing effects


Document Type: Article in Press
Source: Scopus




5) 

Xie, J., Padoa-Schioppa, C.
Neuronal remapping and circuit persistence in economic decisions
(2016) Nature Neuroscience, . Article in Press. 

DOI: 10.1038/nn.4300


Department of Neuroscience, Washington University in St. Louis, St. Louis, Missouri, USA.


Abstract
The orbitofrontal cortex plays a central role in good-based economic decisions. When subjects make choices, neurons in this region represent the identities and values of offered and chosen goods. Notably, choices in different behavioral contexts may involve a potentially infinite variety of goods. Thus a fundamental question concerns the stability versus flexibility of the decision circuit. Here we show in rhesus monkeys that neurons encoding the identity or the subjective value of particular goods in a given context 'remap' and become associated with different goods when the context changes. At the same time, the overall organization of the decision circuit and the function of individual cells remain stable across contexts. In particular, two neurons supporting the same decision in one context also support the same decision in different contexts. These results demonstrate how the same neural circuit can underlie economic decisions involving a large variety of goods. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.


Document Type: Article in Press
Source: Scopus




6) 

Miner, J.J.a , Diamond, M.S.a b c d
Understanding how zika virus enters and infects neural target cells
(2016) Cell Stem Cell, 18 (5), pp. 559-560. 

DOI: 10.1016/j.stem.2016.04.009


a Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States
b Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
c Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, United States
d Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Zika virus is a mosquito-transmitted flavivirus that has become a public health concern because of its ability to cause microcephaly. In this issue of Cell Stem Cell, Tang et al. (2016) and Nowakowski et al. (2016) use human neural stem cell models and single-cell RNA sequencing to investigate Zika virus tropism and potential entry receptors. © 2016 Elsevier Inc.


Document Type: Review
Source: Scopus




7) 

Tang, R.a , Razi, A.b c , Friston, K.J.b , Tang, Y.-Y.d
Mapping smoking addiction using effective connectivity analysis
(2016) Frontiers in Human Neuroscience, 10 (MAY2016), art. no. 195, . 

DOI: 10.3389/fnhum.2016.00195


a Department of Psychology, Washington University in St. Louis, St. Louis, MO, United States
b The Wellcome Trust Centre for Neuroimaging, University College London, London, United Kingdom
c Department of Electronic Engineering, NED University of Engineering and Technology, Karachi, Pakistan
d Department of Psychological Sciences, Texas Tech University, Lubbock, TX, United States


Abstract
Prefrontal and parietal cortex, including the default mode network (DMN; medial prefrontal cortex (mPFC), and posterior cingulate cortex, PCC), have been implicated in addiction. Nonetheless, it remains unclear which brain regions play a crucial role in smoking addiction and the relationship among these regions. Since functional connectivity only measures correlations, addiction-related changes in effective connectivity (directed information flow) among these distributed brain regions remain largely unknown. Here we applied spectral dynamic causal modeling (spDCM) to resting state fMRI to characterize changes in effective connectivity among core regions in smoking addiction. Compared to nonsmokers, smokers had reduced effective connectivity from PCC to mPFC and from RIPL to mPFC, a higher self-inhibition within PCC and a reduction in the amplitude of endogenous neuronal fluctuations driving the mPFC. These results indicate that spDCM can differentiate the functional architectures between the two groups, and may provide insight into the brain mechanisms underlying smoking addiction. Our results also suggest that future brain-based prevention and intervention in addiction should consider the amelioration of mPFC-PCC-IPL circuits. © 2016 Tang, Razi, Friston and Tang.


Author Keywords
Dynamic causal modeling (DCM);  Effective connectivity analysis;  Medial prefrontal cortex (mPFC);  Posterior cingulate cortex (PCC);  Smoking addiction


Document Type: Article
Source: Scopus




8) 

Tarawneh, R.a b c d , D'Angelo, G.c e , Crimmins, D.f , Herries, E.f , Griest, T.f , Fagan, A.M.a b c , Zipfel, G.J.b g , Ladenson, J.H.f , Morris, J.C.a b c f , Holtzman, D.M.a b c h
Diagnostic and prognostic utility of the synaptic marker neurogranin in Alzheimer disease
(2016) JAMA Neurology, 73 (5), pp. 561-571. Cited 1 time.

DOI: 10.1001/jamaneurol.2016.0086


a Department of Neurology, Washington University School of Medicine, 660 S Euclid Ave, Campus Box 8111, St Louis, MO, United States
b Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO, United States
c Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, St Louis, MO, United States
d Cleveland Clinic Lou Ruvo Center for Brain Health, Department of Neurology, Neurological Institute, Cleveland Clinic, Cleveland, OH, United States
e Division of Biostatistics, Washington University School of Medicine, St Louis, MO, United States
f Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, United States
g Department of Neurosurgery, Washington University School of Medicine, St Louis, MO, United States
h Department of Developmental Biology, Washington University School of Medicine, St Louis, MO, United States


Abstract
Importance: Synaptic loss is an early pathologic substrate of Alzheimer disease (AD). Neurogranin is a postsynaptic neuronal protein that has demonstrated utility as a cerebrospinal fluid (CSF) marker of synaptic loss in AD. Objective: To investigate the diagnostic and prognostic utility of CSF neurogranin levels in a large, well-characterized cohort of individuals with symptomatic AD and cognitively normal controls. Design, Setting, and Participants: A cross-sectional and longitudinal observational study of cognitive decline in patients with symptomatic AD and cognitively normal controls was performed. Participants were individuals with a clinical diagnosis of early symptomatic AD and cognitively normal controls who were enrolled in longitudinal studies of aging and dementia at the Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, from January 21, 2000, through March 21, 2011. Data analysis was performed from November 1, 2013, to March 31, 2015. Main Outcomes and Measures: Correlations between baseline CSF biomarker levels and future cognitive decline in patients with symptomatic AD and cognitively normal controls over time. Results: A total of 302 individuals (mean [SE] age, 73.1 [0.4] years) were included in this study (95 patients [52 women and 43 men] with AD and 207 controls [125 women and 82 men]). The CSF neurogranin levels differentiated patients with early symptomatic AD from controls with comparable diagnostic utility (mean [SE] area under the receiver operating characteristic curve, 0.71 [0.03]; 95%CI, 0.64-0.77) to the other CSF biomarkers. The CSF neurogranin levels correlated with brain atrophy (normalized whole-brain volumes: adjusted r = -0.38, P = .02; hippocampal volumes: adjusted r = -0.36, P = .03; entorhinal volumes: adjusted r = -0.46, P = .006; and parahippocampal volumes: adjusted r = -0.47, P = .005, n = 38) in AD and with amyloid load (r=0.39, P = .02, n = 36) in preclinical AD. The CSF neurogranin levels predicted future cognitive impairment (adjusted hazard ratio, 1.89; 95% CI, 1.29-2.78; P = .001 as a continuous measure, and adjusted hazard ratio, 2.78; 95%CI, 1.13-5.99; P = .02 as a categorical measure using the 85th percentile cutoff value) in controls and rates of cognitive decline (Clinical Dementia Rating sum of boxes score: β estimate, 0.29; P = .001; global composite scores: β estimate, -0.11; P = .001; episodic memory scores: β estimate, -0.18; P < .001; and semantic memory scores: β estimate, -0.06; P = .04, n = 57) in patients with symptomatic AD over time, similarly to the CSF proteins VILIP-1, tau, and p-tau181. Conclusions and Relevance: The CSF levels of the synaptic marker neurogranin offer diagnostic and prognostic utility for early symptomatic AD that is comparable to other CSF markers of AD. Importantly, CSF neurogranin complements the collective ability of these markers to predict future cognitive decline in cognitively normal individuals and, therefore, will be a useful addition to the current panel of AD biomarkers. © Copyright 2016 American Medical Association. All rights reserved.


Document Type: Article
Source: Scopus




9) 

Papa, L.a , Brophy, G.M.b c , Welch, R.D.d , Lewis, L.M.e , Braga, C.F.a , Tan, C.N.a , Ameli, N.J.a , Lopez, M.A.a , Haeussler, C.A.a , Mendez Giordano, D.I.a , Silvestri, S.a , Giordano, P.a , Weber, K.D.a , Hill-Pryor, C.f , Hack, D.C.g
Time course and diagnostic accuracy of glial and neuronal blood biomarkers GFAP and UCH-L1 in a large cohort of trauma patients with and without mild traumatic brain injury
(2016) JAMA Neurology, 73 (5), pp. 551-560. Cited 1 time.

DOI: 10.1001/jamaneurol.2016.0039


a Department of Emergency Medicine, Orlando Regional Medical Center, 86W Underwood, Ste S-200, Orlando, FL, United States
b Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond, VA, United States
c Department of Neurosurgery, Virginia Commonwealth University, Richmond, VA, United States
d Division of Emergency Medicine, Department of Medicine, Wayne State University School of Medicine, Detroit, MI, United States
e Division of Emergency Medicine, Washington University School of Medicine, St Louis, MO, United States
f US Department of Defense, Silver Springs, MD, United States
g Brain Health, Harpers Ferry, WV, United States


Abstract
Importance: Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) have been widely studied and show promise for clinical usefulness in suspected traumatic brain injury (TBI) and concussion. Understanding their diagnostic accuracy over time will help translate them into clinical practice. Objectives: To evaluate the temporal profiles of GFAP and UCH-L1 in a large cohort of trauma patients seen at the emergency department and to assess their diagnostic accuracy over time, both individually and in combination, for detecting mild to moderate TBI (MMTBI), traumatic intracranial lesions on head computed tomography (CT), and neurosurgical intervention. Design, Setting, and Participants: This prospective cohort study enrolled adult trauma patients seen at a level I trauma center from March 1, 2010, to March 5, 2014. All patients underwent rigorous screening to determine whether they had experienced an MMTBI (blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale score of 9-15). Of 3025 trauma patients assessed, 1030 met eligibility criteria for enrollment, and 446 declined participation. Initial blood samples were obtained in 584 patients enrolled within 4 hours of injury. Repeated blood sampling was conducted at 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 hours after injury. Main Outcomes and Measures: Diagnosis of MMTBI, presence of traumatic intracranial lesions on head CT scan, and neurosurgical intervention. Results: A total of 1831 blood samples were drawn from 584 patients (mean [SD] age, 40 [16] years; 62.0%[362 of 584] male) over 7 days. Both GFAP and UCH-L1 were detectible within 1 hour of injury. GFAP peaked at 20 hours after injury and slowly declined over 72 hours. UCH-L1 rose rapidly and peaked at 8 hours after injury and declined rapidly over 48 hours. Over the course of 1 week, GFAP demonstrated a diagnostic range of areas under the curve for detecting MMTBI of 0.73 (95%CI, 0.69-0.77) to 0.94 (95%CI, 0.78-1.00), and UCH-L1 demonstrated a diagnostic range of 0.30 (95%CI, 0.02-0.50) to 0.67 (95%CI, 0.53-0.81). For detecting intracranial lesions on CT, the diagnostic ranges of areas under the curve were 0.80 (95%CI, 0.67-0.92) to 0.97 (95%CI, 0.93-1.00)for GFAP and 0.31 (95%CI, 0-0.63) to 0.77 (95%CI, 0.68-0.85) for UCH-L1. For distinguishing patients with and without a neurosurgical intervention, the range for GFAP was 0.91 (95%CI, 0.79-1.00) to 1.00 (95% CI, 1.00-1.00), and the range for UCH-L1 was 0.50 (95%CI, 0-1.00) to 0.92 (95%CI, 0.83-1.00). Conclusions and Relevance: GFAP performed consistently in detecting MMTBI, CT lesions, and neurosurgical intervention across 7 days. UCH-L1 performed best in the early postinjury period. © Copyright 2016 American Medical Association. All rights reserved.


Document Type: Article
Source: Scopus




10) 

Bhattacharya, M.R.C.a , Geisler, S.b , Pittman, S.K.b , Doan, R.A.b , Weihl, C.C.b , Milbrandt, J.c , DiAntonio, A.d
TMEM184b promotes axon degeneration and neuromuscular junction maintenance
(2016) Journal of Neuroscience, 36 (17), pp. 4681-4689. 

DOI: 10.1523/JNEUROSCI.2893-15.2016


a Department of Basic Sciences, St. Louis College of Pharmacy, St. Louis, MO, United States
b Department of Neurology, St. Louis, MO, United States
c Department of Genetics, Washington University in St. Louis, St. Louis, MO, United States
d Department of Developmental Biology, Washington University in St. Louis, St. Louis, MO, United States


Abstract
Complex nervous systems achieve proper connectivity during development and must maintain these connections throughout life. The processes of axon and synaptic maintenance and axon degeneration after injury are jointly controlled by a number of proteins within neurons, including ubiquitin ligases and mitogen activated protein kinases. However, our understanding of these molecular cascades is incomplete. Here we describe the phenotype resulting from mutation of TMEM184b, a protein identified in a screen for axon degeneration mediators. TMEM184b is highly expressed in the mouse nervous system and is found in recycling endosomes in neuronal cell bodies and axons. Disruption of TMEM184b expression results in prolonged maintenance of peripheral axons following nerve injury, demonstrating a role for TMEM184b in axon degeneration. In contrast to this protective phenotype in axons, uninjured mutant mice have anatomical and functional impairments in the peripheral nervous system. Loss of TMEM184b causes swellings at neuromuscular junctions that become more numerous with age, demonstrating that TMEM184b is critical for the maintenance of synaptic architecture. These swellings contain abnormal multivesicular structures similar to those seen in patients with neurodegenerative disorders. Mutant animals also show abnormal sensory terminal morphology. TMEM184b mutant animals are deficient on the inverted screen test, illustrating a role for TMEM184b in sensory-motor function. Overall, we have identified an important function for TMEM184b in peripheral nerve terminal structure, function, and the axon degeneration pathway. © 2016 the authors.


Author Keywords
Autophagy;  Axon degeneration;  Intraepidermal nerve fibers;  Mouse;  Neuromuscular junction


Document Type: Article
Source: Scopus




11) 

Chen, Y-H.a , Cimino, P.J.b , Luo, J.c , Dahiya, S.b , Gutmann, D.H.a
ABCG1 maintains high-grade glioma survival in vitro and in vivo
(2016) Oncotarget, 7 (17), pp. 23416-23424. 

DOI: 10.18632/oncotarget.8030


a Departments of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b Departments of Pathology, Washington University School of Medicine, St. Louis, MO, United States
c Departments of Surgery, Washington University School of Medicine, St. Louis, MO, United States


Abstract
The overall survival for adults with malignant glioma (glioblastoma) remains poor despite advances in radiation and chemotherapy. One of the mechanisms by which cancer cells develop relative resistance to treatment is through de-regulation of endoplasmic reticulum (ER) homeostasis. We have recently shown that ABCG1, an ATP-binding cassette transporter, maintains ER homeostasis and suppresses ER stress-induced apoptosis in low-grade glioma. Herein, we demonstrate that ABCG1 expression is increased in human adult glioblastoma, where it correlates with poor survival in individuals with the mesenchymal subtype. Leveraging a mouse model of mesenchymal glioblastoma (NPcis), shRNA-mediated Abcg1 knockdown (KD) increased CHOP ER stress protein expression and resulted in greater NPcis glioma cell death in vitro. Moreover, Abcg1 KD reduced NPcis glioma growth and increased mouse survival in vivo. Collectively, these results demonstrate that ABCG1 is critical for malignant glioma cell survival, and might serve as a future therapeutic target for these deadly brain cancers.


Author Keywords
Apoptosis;  Brain tumor;  ER stress;  Glioblastoma;  Glioma stem cell


Document Type: Article
Source: Scopus




12) 

Tang, Y.-Y.a , Tang, R.b
Cultural Neuroscience of Moral Reasoning and Decision-Making
(2016) Neuroimaging Personality, Social Cognition, and Character, pp. 281-287. 

DOI: 10.1016/B978-0-12-800935-2.00014-2


a Department of Psychological Sciences, Texas Tech University, Lubbock, TX, United States
b Department of Psychology, Washington University, St. Louis, MO, United States


Abstract
Reasoning and decision-making, as an important aspect of a person's high-level cognition, may be influenced by cultural differences. For example, Asians tend to frame the decision to help as a matter of moral responsibility, whereas Americans are more likely to frame it as one's personal choice. In this chapter, we will discuss the cultural differences in high-level cognition, in regards to moral reasoning and decision-making, especially between the Chinese and American cultures. We will also explore the associated brain networks of cultural variation involved in this reasoning and decision process. © 2016 Elsevier Inc. All rights reserved.


Author Keywords
Brain mechanism;  Cultural differences;  Decision-making;  Dilemma;  Moral


Document Type: Book Chapter
Source: Scopus




13) 

Pagliaccio, D.a , Barch, D.M.a b c d
Early Life Adversity and Risk for Depression: Alterations in Cortisol and Brain Structure and Function as Mediating Mechanisms
(2016) Systems Neuroscience in Depression, pp. 29-77. 

DOI: 10.1016/B978-0-12-802456-0.00002-9


a Washington University, St. Louis, MO, United States
b Department of Psychiatry, Washington University, St. Louis, MO, United States
c Department of Psychology, Washington University, St. Louis, MO, United States
d Department of Radiology, Washington University, St. Louis, MO, United States


Abstract
Early life stress (ELS) is one of the largest environmental risk factors for depression, yet the mechanisms underlying this relationship are still being investigated. Much literature has implicated alterations in cortisol and brain structure/function as potential mediating factors. Here, we review evidence associating ELS with later depression, including effects of sexual abuse, poverty, and parental psychopathology. While depression has shown relatively consistent relationships with elevated cortisol, blunted cortisol levels are often associated with ELS, though this varies by a variety of factors, such as methodology and age. Further, there is growing evidence that ELS and depression relate to similar alterations in brain structure/function, particularly in the hippocampus, amygdala, medial prefrontal cortex, and regions of the anterior cingulate cortex. While this potentially suggests that ELS contributes to neural alterations associated with depression, only a small, though growing, body of human studies explicitly test how cortisol and the brain may mediate the effects of ELS. © 2016 Elsevier Inc. All rights reserved.


Author Keywords
Amygdala;  Cortisol;  Depression;  Hippocampus;  Stress


Document Type: Book Chapter
Source: Scopus




14) 

Anokhin, A.P.
Genetics, Brain, and Personality: Searching for Intermediate Phenotypes
(2016) Neuroimaging Personality, Social Cognition, and Character, pp. 71-90. 

DOI: 10.1016/B978-0-12-800935-2.00004-X


Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States


Abstract
Recent theoretical and methodological advances in human genetics and neuroscience offer novel opportunities for understanding biological bases of personality. Building a unifying, biologically based theory of personality will require the elucidation of complex links between genes, brain, and personality traits. Accordingly, in this chapter we review, summarize, and critically evaluate three related lines of research: genetic research on personality, investigation of the relationships between individual variability in the brain and personality traits, and genetic studies of brain structure and function. We also demonstrate how these research directions can be integrated using genetically informative designs in order to determine how genetic influences on personality are mediated by variability in brain structure and function. In conclusion, we identify critical issues that should be addressed in future studies. © 2016 Elsevier Inc. All rights reserved.


Author Keywords
Brain;  Endophenotype;  Genetics;  Personality;  Temperament


Document Type: Book Chapter
Source: Scopus




15) 

Roediger, H.L., III, DeSoto, K.A.
Recognizing the Presidents: Was Alexander Hamilton President?
(2016) Psychological Science, 27 (5), pp. 644-650. 

DOI: 10.1177/0956797616631113


Department of Psychological & Brain Sciences, Washington University in St. Louis, United States


Abstract
Studies over the past 40 years have shown that Americans can recall about half the U.S. presidents. Do people know the presidents even though they are unable to access them for recall? We investigated this question using the powerful cues of a recognition test. Specifically, we tested the ability of 326 online subjects to recognize U.S. presidents when presented with their full names among various types of lures. The hit rate for presidential recognition was.88, well above the proportion produced in free recall but far from perfect. Presidents Franklin Pierce and Chester Arthur were recognized less than 60% of the time. Interestingly, four nonpresidents were falsely recognized at relatively high rates, and Alexander Hamilton was more frequently identified as president than were several actual presidents. Even on a recognition test, knowledge of American presidents is imperfect and prone to error. The false alarm data support the theory that false fame can arise from contextual familiarity. © 2016, © The Author(s) 2016.


Author Keywords
collective memory;  false fame;  familiarity;  open data;  open materials;  presidents;  recognition


Document Type: Article
Source: Scopus




16) 

Cristancho, P.a , O'Connor, B.a , Lenze, E.J.a , Blumberger, D.M.b , Reynolds, C.F.c , Dixon, D.a , Mulsant, B.H.b
Treatment Emergent Suicidal Ideation in depressed older adults
(2016) International Journal of Geriatric Psychiatry, . Article in Press. 

DOI: 10.1002/gps.4498


a Department of Psychiatry, Healthy Mind Lab, School of Medicine Washington University in St. Louis St. Louis, MO USA
b Centre for Addiction and Mental Health University of Toronto Toronto, CA
c Department of Psychiatry University of Pittsburgh PA USA


Abstract
Background: Treatment-Emergent Suicidal Ideation (TESI) in older adults is poorly understood. We characterized TESI in older depressed adults during treatment with venlafaxine and explored whether TESI is related to antidepressant exposure versus dimensions of the psychiatric illness. We examined the relationship among medication exposure, onset of TESI, and clinical characteristics. Methods: We analyzed data on 233 clinical trial participants with major depression and no baseline suicidal ideation who were treated for up to 12weeks with venlafaxine XR (target dose: 150-300mg/day). Suicidal ideation was assessed weekly with the Scale for Suicide Ideation. A Kaplan-Meier curve displayed the time course of TESI. Differences in baseline demographic and clinical variables between the TESI and Non-TESI groups were assessed with analyses of covariance or logistic regression. A final multivariate logistic regression model indicated baseline predictors of TESI. Depression treatment outcomes in subjects developing TESI versus those who did not were examined with a mixed effects model. Results: TESI occurred in 10% of participants, typically with onset within 4weeks of the start of treatment. Anxiety, and depression severity at baseline were predictors of TESI. Most TESI was mild and transient, with 6/233 participants having TESI considered clinically meaningful. TESI was not associated with venlafaxine blood levels or side effects. Conclusions: In older depressed adults, TESI is relatively uncommon and it is likely related to the underlying illness rather than to a medication adverse effect. This suggests that TESI requires continuing rather than discontinuing antidepressant treatment. © 2016 John Wiley & Sons, Ltd.


Author Keywords
Antidepressants;  Depression;  Older adults;  Suicidal ideation;  Suicide;  Treatment


Document Type: Article in Press
Source: Scopus




17) 

Carr, D.B.a , Hunt, L.b c
Driving and transportation: Dementia as a model for evaluation, decision making, and planning
(2015) Occupational Therapy with Aging Adults: Promoting Quality of Life through Collaborative Practice, pp. 331-349. 

DOI: 10.1016/B978-0-323-06776-8.00029-3


a Division of Geriatrics and Nutritional Science, Washington University School of Medicine, St. Louis, MO, United States
b School of Occupational Therapy, Pacific University, Hillsboro, OR, United States
c College of Health Professions, Pacific University, Hillsboro, OR, United States


Document Type: Book Chapter
Source: Scopus




18) 

Hudson, D.L.a , Neighbors, H.W.b , Geronimus, A.T.b , Jackson, J.S.b
Racial Discrimination, John Henryism, and Depression Among African Americans
(2015) Journal of Black Psychology, 42 (3), pp. 221-243. 

DOI: 10.1177/0095798414567757


a Washington University, St. Louis, MO, United States
b University of Michigan, Ann Arbor, MI, United States


Abstract
Evidence from previous studies indicates that racial discrimination is significantly associated with depression and that African Americans with higher levels of socioeconomic status (SES) report greater exposure to racial discrimination compared to those with lower SES levels. Coping strategies could alter the relationship between racial discrimination and depression among African Americans. This study first examined whether greater levels of SES were associated with increased reports of racial discrimination and ratings of John Henryism, a measure of high-effort coping, among African Americans. Second, we examined whether high-effort coping moderated the relationship between racial discrimination and depression. Data were drawn from the National Survey of American Life Reinterview (n = 2,137). Analyses indicated that greater levels of education were positively associated with racial discrimination (p <.001) and increased levels of racial discrimination were positively related to depression (p <.001), controlling for all sociodemographic factors. Greater levels of John Henryism were associated with increased odds of depression but there was no evidence to suggest that the relationship between discrimination and depression was altered by the effects of John Henryism. © The Author(s) 2015.


Author Keywords
African Americans;  coping;  depression;  racial discrimination;  socioeconomic status


Document Type: Article
Source: Scopus

 

May 23, 2016

1) 
Thompson, A.B.a , Goodman, M.S.b , Kwate, N.O.A.c 
Does learning about race prevent substance abuse? Racial discrimination, racial socialization and substance use among African Americans
(2016) Addictive Behaviors, 61, pp. 1-7. 

DOI: 10.1016/j.addbeh.2016.04.010

a National Center on Addiction and Substance Abuse at Columbia University, 633 3rd Ave, New York, NY, United States
b Division of Public Health Sciences, Department of Surgery, Washington University in St. Louis School of Medicine, 660 S. Euclid Avenue, Campus Box 8100, St. Louis, MO, United States
c Rutgers, The State University of New Jersey, 55 Dudley Rd, Cook Office Building, New Brunswick, NJ, United States
 

Author Keywords
African American/Black;  Alcohol use;  Health disparities;  Racial discrimination;  Substance use;  Tobacco use


Document Type: Article
Source: Scopus

 


 

2) 
Smith, J.S.a o , Klineberg, E.b , Shaffrey, C.I.a , Lafage, V.c , Schwab, F.J.c , Protopsaltis, T.d , Scheer, J.K.e , Ailon, T.a , Ramachandran, S.a , Daniels, A.f , Mundis, G.g , Gupta, M.h , Hostin, R.i , Deviren, V.j , Eastlack, R.g , Passias, P.d , Hamilton, D.K.l , Hart, R.m , Burton, D.C.n , Bess, S.d , Ames, C.P.k 
Assessment of Surgical Treatment Strategies for Moderate to Severe Cervical Spinal Deformity Reveals Marked Variation in Approaches, Osteotomies, and Fusion Levels
(2016) World Neurosurgery, 91, pp. 228-237. 

DOI: 10.1016/j.wneu.2016.04.020

a Department of Neurosurgery, University of Virginia, Charlottesville, VA, United States
b Department of Orthopaedic Surgery, University of California, Davis, Sacramento, CA, United States
c Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, NY, United States
d Department of Orthopaedic Surgery, NYU Hospital for Joint Diseases, New York, NY, United States
e University of California San Diego, School of Medicine, San Diego, CA, United States
f Department of Orthopedic Surgery, Warren Alpert School of Medicine, Brown University, Providence, RI, United States
g Department of Orthopaedic Surgery, San Diego Center for Spinal Disorders, San Diego, CA, United States
h Department of Orthopedic Surgery, Washington University, St. Louis, MO, United States
i Department of Orthopaedic Surgery, Baylor Scoliosis Center, Plano, TX, United States
j Department of Orthopedic Surgery, University of California, San Francisco, San Francisco, CA, United States
k Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, United States
l Department of Neurosurgery, University of Pittsburgh, Pittsburgh, PA, United States
m Department of Orthopaedic Surgery, Oregon Health and Science University, Portland, OR, United States
n Department of Orthopaedic Surgery, University of Kansas Medical Center, Kansas City, KS, United States

Abstract
Objective Although previous reports suggest that surgery can improve the pain and disability of cervical spinal deformity (CSD), techniques are not standardized. Our objective was to assess for consensus on recommended surgical plans for CSD treatment. Methods Eighteen CSD cases were assembled, including a clinical vignette, cervical imaging (radiography, computed tomography/magnetic resonance imaging), and full-length standing radiography. Fourteen deformity surgeons (10 orthopedic, 4 neurosurgery) were queried regarding recommended surgical plans. Results There was marked variation in treatment plans across all deformity types. Even for the least complex deformities (moderate midcervical apex kyphosis), there was lack of agreement on approach (50% combined anterior-posterior, 25% anterior only, 25% posterior only), number of anterior (range, 2-6) and posterior (range, 4-16) fusion levels, and types of osteotomies. As the kyphosis apex moved caudally (cervical-thoracic junction/upper thoracic spine) and for cases with chin-on-chest kyphosis, >80% of surgeons agreed on a posterior-only approach and >70% recommended a pedicle subtraction osteotomy or vertebral column resection, but the range in number of anterior (4-8) and posterior (4-27) fusion levels was exceptionally broad. Cases of cervical/cervical-thoracic scoliosis had the least agreement for approach (48% posterior only, 33% combined anterior-posterior, 17% anterior-posterior-anterior or posterior-anterior-posterior, 2% anterior only) and had broad variation in the number of anterior (2-5) and posterior (6-19) fusion levels, and recommended osteotomies (41% pedicle subtraction osteotomy/vertebral column resection). Conclusions Among a panel of deformity surgeons, there was marked lack of consensus on recommended surgical approach, osteotomies, and fusion levels for CSD. Further study is warranted to assess whether specific surgical treatment approaches are associated with better outcomes. © 2016 Elsevier Inc. All rights reserved.

Author Keywords
Deformity;  Fusion;  Key words Cervical;  Kyphosis;  Osteotomy;  Spine;  Surgery


Document Type: Article
Source: Scopus

 


 

3) 
Ostendorf, A.P., Hartman, M.E., Friess, S.H.
Early Electroencephalographic Findings Correlate With Neurologic Outcome in Children Following Cardiac Arrest
(2016) Pediatric Critical Care Medicine, . Article in Press. 

DOI: 10.1097/PCC.0000000000000791

1Department of Neurology, Washington University School of Medicine, St. Louis, MO. 2Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.

Abstract
OBJECTIVES:: To determine the clinical and electroencephalographic findings associated with prognosis in nonneonate children following cardiac arrest. DESIGN:: Retrospective observational study. SETTING:: PICU and cardiac ICU. PATIENTS:: Nonneonate children with a history of cardiac arrest more than 2 minutes. INTERVENTIONS:: Electroencephalographic monitoring within 72 hours of return of spontaneous circulation. MEASUREMENTS AND MAIN RESULTS:: Clinical and features, neurophysiologic data, and Pediatric Cerebral Performance Category scores were collected. Electroencephalographic traces were reviewed in a blinded manner, all seizures and electroencephalographic findings noted, and the electroencephalography was scored at 1 hour, 24 hours, and continuous electroencephalographic end. Discrete data regarding specific characteristics of the electroencephalographic background and seizures were studied. Univariate and multivariate analyses were performed to identify associations between clinical variables, electroencephalographic findings, and Pediatric Cerebral Performance Category score at hospital discharge. Multivariate analysis of 73 children revealed duration of cardiac arrest less than 20 minutes or continuous electroencephalographic background activity within 12 hours postreturn of spontaneous circulation were associated with good short term neurologic outcome. Change in electroencephalographic background score over time and electroencephalographic data collected after the initial hour were not associated with outcome. CONCLUSIONS:: Following pediatric cardiac arrest, an initially normal electroencephalography or generalized slowing of the electroencephalographic background was associated with good neurologic outcome at hospital discharge. ©2016The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies
 


Document Type: Article in Press
Source: Scopus

 


 

4) 
Sheffield, J.M.a , Repovs, G.b , Harms, M.P.c , Carter, C.S.d , Gold, J.M.e , Macdonald, A.W.f , Ragland, J.D.d , Silverstein, S.M.g h , Godwin, D.i , Barch, D.M.a c j 
Evidence for accelerated decline of functional brain network efficiency in schizophrenia
(2016) Schizophrenia Bulletin, 42 (3), pp. 753-761. 

DOI: 10.1093/schbul/sbv148

a Department of Psychology, Washington University in St Louis, 1 Brookings Drive, St Louis, MO, United States
b Department of Psychiatry and Behavioral Science, University of Ljubljana, Ljubljana, Slovenia
c Department of Psychiatry, Washington University in St Louis, St Louis, MO, United States
d Department of Psychiatry and Behavioral Sciences, University of California at Davis, Davis, CA, United States
e Department of Psychiatry, Maryland Psychiatric Research Center, Baltimore, MD, United States
f Department of Psychology, University of Minnesota, Minneapolis, MN, United States
g Rutgers, The State University of New Jersey, University Behavioral Health Care, Piscataway, NJ, United States
h Department of Psychiatry, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, United States
i Department of Psychology, Vanderbilt University, Nashville, TN, United States
j Department of Radiology, Washington University in St Louis, St Louis, MO, United States

Abstract
Previous work suggests that individuals with schizophrenia display accelerated aging of white matter integrity, however, it is still unknown whether functional brain networks also decline at an elevated rate in schizophrenia. Given the known degradation of functional connectivity and the normal decline in cognitive functioning throughout healthy aging, we aimed to test the hypothesis that efficiency of large-scale functional brain networks supporting overall cognition, as well as integrity of hub nodes within those networks, show evidence of accelerated aging in schizophrenia. Using pseudo-resting state data in 54 healthy controls and 46 schizophrenia patients, in which task-dependent signal from 3 tasks was regressed out to approximate resting-state data, we observed a significant diagnosis by age interaction in the prediction of both global and local efficiency of the cingulo-opercular network, and of the local efficiency of the fronto-parietal network, but no interaction when predicting both default mode network and whole brain efficiency. We also observed a significant diagnosis by age interaction for the node degree of the right anterior insula, left dorsolateral prefrontal cortex, and dorsal anterior cingulate cortex. All interactions were driven by stronger negative associations between age and network metrics in the schizophrenia group than the healthy controls. These data provide evidence that is consistent with accelerated aging of large-scale functional brain networks in schizophrenia that support higher-order cognitive ability. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

Author Keywords
accelerated aging;  central executive networks;  cognition;  functional connectivity;  graph theory


Document Type: Article
Source: Scopus

 


 

5) 
Bouhlel, A.a b , Alyami, W.c , Li, A.a , Yuan, L.d , Rich, K.d , McConathy, J.a e 
Effect of α-Methyl versus α-Hydrogen Substitution on Brain Availability and Tumor Imaging Properties of Heptanoic [F-18]Fluoroalkyl Amino Acids for Positron Emission Tomography (PET)
(2016) Journal of Medicinal Chemistry, 59 (7), pp. 3515-3531. 

DOI: 10.1021/acs.jmedchem.6b00189

a Department of Radiology, School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
b Inserm, Vascular Center of Marseille, UMR-S1076, CERIMED, Aix-Marseille University, Marseille, France
c Doisy College of Health Sciences, Saint Louis University, St. Louis, MO, United States
d Department of Neurosurgery, School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
e Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, United States

Abstract
Two [18F]fluoroalkyl substituted amino acids differing only by the presence or absence of a methyl group on the α-carbon, (S)-2-amino-7-[18F]fluoro-2-methylheptanoic acid ((S)-[18F]FAMHep, (S)-[18F]14) and (S)-2-amino-7-[18F]fluoroheptanoic acid ((S)-[18F]FAHep, (S)-[18F]15), were developed for brain tumor imaging and compared to the well-established system L amino acid tracer, O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET), in the delayed brain tumor (DBT) mouse model of high-grade glioma. Cell uptake, biodistribution, and PET/CT imaging studies showed differences in amino acid transport of these tracer by DBT cells. Recognition of (S)-[18F]15 but not (S)-[18F]14 by system L amino acid transporters led to approximately 8-10-fold higher uptake of the α-hydrogen substituted analogue (S)-[18F]15 in normal brain. (S)-[18F]15 had imaging properties similar to those of (S)-[18F]FET in the DBT tumor model while (S)-[18F]14 afforded higher tumor to brain ratios due to much lower uptake by normal brain. These results have important implications for the future development of α-alkyl and α,α-dialkyl substituted amino acids for brain tumor imaging. © 2016 American Chemical Society.
 


Document Type: Article
Source: Scopus

 


 

6) 
Durrant, D.M.a , Ghosh, S.b , Klein, R.S.b c d 
The Olfactory Bulb: An Immunosensory Effector Organ during Neurotropic Viral Infections
(2016) ACS Chemical Neuroscience, 7 (4), pp. 464-469. 

DOI: 10.1021/acschemneuro.6b00043

a Biological Sciences Department, California State Polytechnic University, 3801 West Temple Ave., Pomona, CA, United States
b Department of Medicine, Washington University, School of Medicine, 660 S. Euclid Ave., St Louis, MO, United States
c Department of Pathology and Immunology, Washington University, School of Medicine, 660 S. Euclid Ave., St Louis, MO, United States
d Department of Neuroscience, Washington University, School of Medicine, 660 S. Euclid Ave., St Louis, MO, United States

Abstract
In 1935, the olfactory route was hypothesized to be a portal for virus entry into the central nervous system (CNS). This hypothesis was based on experiments in which nasophayngeal infection with poliovirus in monkeys was prevented from spreading to their CNS via transection of olfactory tracts between the olfactory neuroepithelium (ONE) of the nasal cavity and the olfactory bulb (OB). Since then, numerous neurotropic viruses have been observed to enter the CNS via retrograde transport along axons of olfactory sensory neurons whose cell bodies reside in the ONE. Importantly, this route of infection can occur even after subcutaneous inoculation of arboviruses that can cause encephalitis in humans. While the olfactory route is now accepted as an important pathway for viral entry into the CNS, it is unclear whether it provides a way for infection to spread to other brain regions. More recently, studies of antiviral innate and adaptive immune responses within the olfactory bulb suggest it provides early virologic control. Here we will review the data demonstrating that neurotropic viruses gain access to the CNS initially via the olfactory route with emphasis on findings that suggest the OB is a critical immunosensory effector organ that effectively clears virus. © 2016 American Chemical Society.

Author Keywords
encephalitis;  neuroinvasion;  Olfactory bulb;  olfactory sensory neurons;  virus


Document Type: Review
Source: Scopus

 


 

7) 
Ulrich, J.D., Holtzman, D.M.
TREM2 Function in Alzheimer's Disease and Neurodegeneration
(2016) ACS Chemical Neuroscience, 7 (4), pp. 420-427. 

DOI: 10.1021/acschemneuro.5b00313

Department of Neurology, Knight Alzheimer's Disease Research Center, Hope Center for Neurological Disorders, Washington University School of Medicine, 660 S. Euclid Ave., Box 8111, St. Louis, MO, United States

Abstract
Alzheimer's disease (AD), the most common cause of dementia in the elderly, is a complex neurodegenerative disease marked by the appearance of amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles. Alzheimer's disease has a strong genetic component, and recent advances in genome technology have unearthed novel variants in several genes, which could provide insight into the pathogenic mechanisms that contribute to AD. Particularly interesting are variants in the microglial-expressed receptor TREM2 which are associated with a 2-4-fold increased risk of developing AD. Since the discovery of a link between TREM2 and AD, multiple studies have emerged testing whether partial or complete loss of TREM2 function contributed to Aβ deposition or Aβ-associated microgliosis. Although some confounding conflicting data have emerged from these studies regarding the role of TREM2 in regulating Aβ deposition within the hippocampus, the most consistent and striking observation is a strong decrease in microgliosis surrounding Aβ plaques in TREM2 haploinsufficient and TREM2 deficient mice. Interestingly, a similar impairment in microgliosis has been reported in mouse models of prion disease, stroke, and multiple sclerosis, suggesting a critical role for TREM2 in supporting microgliosis in response to pathology in the central nervous system. In this Review, we summarize recent reports on the role of TREM2 in AD pathology and hypothesized mechanisms by which TREM2 function could influence AD-induced microgliosis. © 2016 American Chemical Society.

Author Keywords
Alzheimer's disease;  amyloid-β;  apolipoprotein E;  microglia;  neurodegeneration;  TREM2


Document Type: Review
Source: Scopus

 


 

8) 
Benitez, B.A.a , Davis, A.A.b , Jin, S.C.c , Ibanez, L.c , Ortega-Cubero, S.d e f , Pastor, P.e g , Choi, J.c , Cooper, B.c , Perlmutter, J.S.b h i , Cruchaga, C.c i 
Resequencing analysis of five Mendelian genes and the top genes from genome-wide association studies in Parkinson's Disease
(2016) Molecular Neurodegeneration, 11 (1), art. no. 97, . 

DOI: 10.1186/s13024-016-0097-0

a Department of Internal Medicine, School of Medicine, Washington University, 8007660 South Euclid Avenue, St. Louis, MO, United States
b Department of Neurology, School of Medicine, Washington University, St. Louis, MO, United States
c Department of Psychiatry, School of Medicine, Washington University, St. Louis, MO, United States
d Department of Neurology, Complejo Asistencial Universitario de Palencia, Palencia, Spain
e Center for Applied Medical Research, CIMA, University of Navarra, School of Medicine, Pamplona, Spain
f Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
g Movement Disorders Unit, Department of Neurology, University Hospital Mutua de Terrassa, University of Barcelona, Terrassa, Barcelona, Spain
h Department of Radiology, Anatomy and Neurobiology, Program in Occupational Therapy, Program in Physical Therapy, Washington University, St. Louis, MO, United States
i Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University, St. Louis, MO, United States

Abstract
Background: Most sequencing studies in Parkinson's disease (PD) have focused on either a particular gene, primarily in familial and early onset PD samples, or on screening single variants in sporadic PD cases. To date, there is no systematic study that sequences the most common PD causing genes with Mendelian inheritance [α-synuclein (SNCA), leucine-rich repeat kinase 2 (LRRK2), PARKIN, PTEN-induced putative kinase 1 (PINK1) and DJ-1 (Daisuke-Junko-1)] and susceptibility genes [glucocerebrosidase beta acid (GBA) and microtubule-associated protein tau (MAPT)] identified through genome-wide association studies (GWAS) in a European-American case-control sample (n=815). Results: Disease-causing variants in the SNCA, LRRK2 and PARK2 genes were found in 2 % of PD patients. The LRRK2, p.G2019S mutation was found in 0.6 % of sporadic PD and 4.8 % of familial PD cases. Gene-based analysis suggests that additional variants in the LRRK2 gene also contribute to PD risk. The SNCA duplication was found in 0.8 % of familial PD patients. Novel variants were found in 0.8 % of PD cases and 0.6 % of controls. Heterozygous Gaucher disease-causing mutations in the GBA gene were found in 7.1 % of PD patients. Here, we established that the GBA variant (p.T408M) is associated with PD risk and age at onset. Additionally, gene-based and single-variant analyses demostrated that GBA gene variants (p.L483P, p.R83C, p.N409S, p.H294Q and p.E365K) increase PD risk. Conclusions: Our data suggest that the impact of additional untested coding variants in the GBA and LRRK2 genes is higher than previously estimated. Our data also provide compelling evidence of the existence of additional untested variants in the primary Mendelian and PD GWAS genes that contribute to the genetic etiology of sporadic PD. © 2016 Benitez et al.

Author Keywords
Association study;  DJ-1;  GBA rare variants;  gene-based analysis;  LRRK2;  MAPT;  PARKIN;  Parkinson's;  PINK1;  SNCA


Document Type: Article
Source: Scopus

 


 

9) 
Kanuri, N.a , Cassell, B.a , Bruce, S.E.b , White, K.S.b , Gott, B.M.c , Gyawali, C.P.a , Sayuk, G.S.a c d 
The impact of abuse and mood on bowel symptoms and health-related quality of life in irritable bowel syndrome (IBS)
(2016) Neurogastroenterology and Motility, . Article in Press. 

DOI: 10.1111/nmo.12848

a Division of Gastroenterology Washington University School of Medicine St. Louis, MO USA
b Center for Trauma Recovery University of Missouri-St. Louis St. Louis, MO USA
c Department of Psychiatry Washington University School of Medicine St. Louis, MO USA
d Gastroenterology Section John Cochran Veterans Affairs Medical Center St. Louis, MO USA

Abstract
Background: Irritable bowel syndrome (IBS) is a common abdominal pain disorder without an organic explanation. Abuse histories (physical, sexual, emotional) are prevalent in IBS. While abuse relates to mood disorders (depression and anxiety) also common in IBS, the influence of abuse on gastrointestinal (GI) symptoms and health-related quality of life (HRQOL) and its independence from psychological symptom comorbidity has not been studied. Methods: Consecutive GI outpatients completed the ROME III Research Diagnostic Questionnaire and questionnaires on trauma (Life-Stress Questionnaire), mood (Beck Depression/Anxiety Inventories), somatic symptoms (PHQ-12), and HRQOL (SF-36). Current GI symptom severity and bother were assessed using 10-cm Visual Analog Scales. Key Results: 272 ROME-defined IBS (47.6 ± 0.9 years, 81% female) and 246 non-FGID (51.6 ± 1.0 years, 65% female) subjects participated. IBS patients reported greater rates of physical, sexual, and emotional abuse (p < 0.006 each), and higher depression, anxiety, and somatic symptoms (p < 0.001). Greater bowel symptom bother (7.4 ± 0.2 vs 6.7 ± 0.2, p = 0.040), severity (7.7 ± 0.2 vs 6.5 ± 0.2, p < 0.001), recent symptomatic days (9.8 ± 0.4 vs 8.5 ± 0.3, p = 0.02), and poorer HRQOL (40.9 ± 2.3 vs 55.5 ± 1.7, p < 0.001) were noted in IBS with abuse. Abuse effects were additive, with greater IBS symptom severity and poorer HRQOL noted in cases with multiple forms of abuse. Mediation analyses suggested that abuse effects on GI symptoms and HRQOL were partially mediated by mood. Conclusions & Inferences: Abuse experiences common among IBS sufferers are associated with reports of greater GI symptoms and poorer HRQOL, particularly in those with multiple forms of abuse; this relationship may be partially mediated by concomitant mood disturbances. © 2016 John Wiley & Sons Ltd.

Author Keywords
Abuse;  Depression;  Health-related quality of life;  Irritable bowel syndrome


Document Type: Article in Press
Source: Scopus

 


 

10) 
Wells, A.a , Kopp, N.a b , Xu, X.c , O'Brien, D.R.a b , Yang, W.a , Nehorai, A.c , Adair-Kirk, T.L.d , Kopan, R.e , Dougherty, J.D.a b 
The anatomical distribution of genetic associations
(2015) Nucleic Acids Research, 43 (22), pp. 10804-10820. 

DOI: 10.1093/nar/gkv1262

a Department of Genetics, Washington University, School of Medicine, St. Louis, MO, United States
b Department of Psychiatry, Washington University, School of Medicine, St. Louis, MO, United States
c Preston M. Green Department of Electrical and Systems Engineering, Washington University, St. Louis, MO, United States
d Department of Medicine, Washington University, School of Medicine, St. Louis, MO, United States
e Division of Developmental Biology, Cincinnati Childrens Hospital, Medical Center, Cincinnati, OH, United States

Abstract
Deeper understanding of the anatomical intermediaries for disease and other complex genetic traits is essential to understanding mechanisms and developing new interventions. Existing ontology tools provide functional, curated annotations for many genes and can be used to develop mechanistic hypotheses; yet information about the spatial expression of genes may be equally useful in interpreting results and forming novel hypotheses for a trait. Therefore, we developed an approach for statistically testing the relationship between gene expression across the body and sets of candidate genes from across the genome. We validated this tool and tested its utility on three applications. First, we show that the expression of genes in associated loci from GWA studies implicates specific tissues for 57 out of 98 traits. Second, we tested the ability of the tool to identify novel relationships between gene expression and phenotypes. Specifically, we experimentally confirmed an underappreciated prediction highlighted by our tool: that white blood cell count - a quantitative trait of the immune system - is genetically modulated by genes expressed in the skin. Finally, using gene lists derived from exome sequencing data, we show that human genes under selective constraint are disproportionately expressed in nervous system tissues. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.
 


Document Type: Article
Source: Scopus

 


 

11) 
Cheuy, V.A.a , Hastings, M.K.b , Commean, P.K.c , Mueller, M.J.b 
Muscle and Joint Factors Associated with Forefoot Deformity in the Diabetic Neuropathic Foot
(2015) Foot and Ankle International, 37 (5), pp. 514-521. 

DOI: 10.1177/1071100715621544

a Physical Therapy Program, University of Colorado, Mail Stop C244, 13121 East 17th Ave, Aurora, CO, United States
b Program in Physical Therapy, Washington University, School of Medicine, St. Louis, MO, United States
c Mallinckrodt Institute of Radiology, Washington University, School of Medicine, St. Louis, MO, United States

Abstract
Background: Diabetic forefoot joint deformities are a known risk factor for skin breakdown and amputation, but the causes of deformity are not well understood. The purposes of this study were to determine the effects of intrinsic foot muscle deterioration and limited ankle joint mobility on the severity of metatarsophalangeal joint (MTPJ) deformity, and determine the relationships between these potential contributing factors and indicators of diabetic complications (peripheral neuropathy and advanced glycation end products). Methods: A total of 34 participants with diabetic neuropathy (average age, 59 years; range 41-73) were studied. MTPJ angle and intrinsic foot muscle deterioration were measured with computed tomography and magnetic resonance imaging, respectively. Maximum ankle dorsiflexion was measured using kinematics. Skin intrinsic fluorescence served as a proxy measure for advanced glycation end product accumulation. Results: Total forefoot lean muscle volume (r = â'0.52, P <.01) and maximum ankle dorsiflexion (r = â'0.42, P <.05) were correlated with severity of MTPJ deformity. Together they explained 35% of the variance of MTPJ angle. Neuropathy was correlated with forefoot muscle deterioration (Ï = 0.53, P <.01). Skin intrinsic fluorescence was correlated to severity of neuropathy (r = 0.50, P <.01) but not maximum ankle dorsiflexion, or forefoot deterioration when controlling for neuropathy. Conclusion: These results suggest that the interplay of intrinsic foot muscle deterioration and limited ankle mobility may be the primary contributor to the development of MTPJ deformity. Identifying these muscle and ankle motion impairments as risk factors for MTPJ deformity supports the need for targeted interventions early in the disease process to slow, or possibly stop the progression of deformity over time and reduce the risk of amputation. Level of Evidence: Level IV, case series. © 2016 The Author(s).

Author Keywords
advanced glycation end products;  hammertoe;  intermuscular adipose tissue;  muscle;  neuropathy


Document Type: Article
Source: Scopus

 

May 13, 2016

1) 
Ottati, V.a c , Wilson, C.a c , Lambert, A.b d 
Accessibility, priming, and political judgment
(2016) Current Opinion in Psychology, 12, pp. 1-5. 

DOI: 10.1016/j.copsyc.2016.04.010

a Loyola University Chicago, United States
b Washington University, United States
c Department of Psychology, Loyola University of Chicago, 1032 W. Sheridan Rd., Chicago, IL, United States
d Psychological and Brain Sciences, Washington University, One Brookings Drive, St. Louis, MO, United States

Abstract
Classic and contemporary approaches to understanding political judgment implicitly acknowledged the role of chronic accessibility. Contemporary models also emphasize that situationally primed knowledge structures influence citizens' political attitudes and opinions. Priming effects are evident when specific concepts are primed (e.g., an issue, the American Flag, terrorism), and when media frames activate narratives that prime specific aspects of a political event. Metaphoric media frames (e.g., the presidential campaign is a horserace) can prime or highlight specific aspects of a political event (e.g., candidate electability) and thereby influence the public's attitudes and opinion (e.g., attitudes toward a political candidate). The immediate context in which political judgments are reported also produces priming effects on political judgment. © 2016 Elsevier Ltd.
 


Document Type: Review
Source: Scopus

 


 

2) 
Sartor, C.E.a b , Grant, J.D.b , Duncan, A.E.b c , McCutcheon, V.V.b , Nelson, E.C.b , Calvert, W.J.d , Madden, P.A.F.b , Heath, A.C.b , Bucholz, K.K.b 
Childhood sexual abuse and two stages of cigarette smoking in African-American and European-American young women
(2016) Addictive Behaviors, 60, pp. 131-136. 

DOI: 10.1016/j.addbeh.2016.03.039

a Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States
b Midwest Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
c George Warren Brown School of Social Work, Washington University, St. Louis, MO, United States
d University of Missouri, St. Louis College of Nursing, St. Louis, MO, United States

Abstract
Objective: The aim of the current study was to determine whether the higher rates of childhood sexual abuse (CSA) but lower rates of cigarette smoking in African-American vs. European-American women can be explained in part by a lower magnitude of association between CSA and smoking in African-American women. Methods: Data were drawn from a same-sex female twin study of substance use (n = 3521; 14.3% African-American). Cox proportional hazards regression analyses using CSA to predict smoking initiation and progression to regular smoking were conducted separately by race/ethnicity. Co-twin status on the smoking outcome was used to adjust for familial influences on smoking (which may overlap with family-level influences on CSA exposure). Results: After adjusting for co-twin status, CSA was associated with smoking initiation in European Americans (hazard ratio (HR) = 1.43, 95% confidence intervals (CI): 1.26-1.62) and with smoking initiation ≤. 16 in African Americans (HR = 1.70, CI: 1.26-2.29). CSA was associated with regular smoking onset ≤. 15 in European Americans (HR = 1.63, CI: 1.21-2.18), with no change in HR after adjusting for co-twin status. In the African-American subsample, the HR for CSA was reduced to non-significance after adjusting for co-twin status (from HR = 3.30, CI: 1.23-8.89 to HR = 1.16, CI: 0.71-1.92 for regular smoking ≤. 15). Conclusions: CSA is associated with moderate elevation in risk for initiating smoking among African-American and European-American women. By contrast, CSA is associated with elevated risk for (adolescent onset) regular smoking only in European-American women. Furthermore, there is significant overlap between risk conferred by CSA and familial influences on regular smoking in African-American but not European-American women. © 2016 Elsevier Ltd.

Author Keywords
African Americans;  Sexual abuse;  Smoking;  Women


Document Type: Article
Source: Scopus

 


 

3) 
Carney, R.M.a , Freedland, K.E.a , Steinmeyer, B.C.a , Rubin, E.H.a , Stein, P.K.b , Rich, M.W.b 
Nighttime heart rate predicts response to depression treatment in patients with coronary heart disease
(2016) Journal of Affective Disorders, 200, pp. 165-171. 

DOI: 10.1016/j.jad.2016.04.051

a Departments of Psychiatry, Washington University, School of Medicine, St. Louis, MO, United States
b Departments of Medicine, Washington University, School of Medicine, St. Louis, MO, United States

Abstract
Background: Previous studies suggest that patients with coronary heart disease (CHD) who do not respond to treatment for depression are at higher risk of mortality than are treatment responders. The purpose of this study was to determine whether elevated nighttime heart rate (HR) and low heart rate variability (HRV), both of which have been associated with depression and with cardiac events in patients with CHD, predict poor response to depression treatment in patients with CHD. Methods: Patients with stable CHD and a current major depressive episode completed 24 h ambulatory ECG monitoring and were then treated for up to 16 weeks with cognitive behavior therapy (CBT), either alone or in combination with an antidepressant. Pre-treatment HR and HRV were calculated for 124 patients who had continuous ECG from early evening to mid-morning. Results: Following treatment, 64 of the 124 patients (52%) met study criteria for remission (Hamilton Rating Scale for Depression score≤7). Prior to treatment, non-remitters had higher nighttime HR (p=0.03) and lower nighttime HRV (p=0.01) than did the remitters, even after adjusting for potential confounds. Limitations: Polysomnography would have provided information about objective sleep characteristics and sleep disorders. More CBT sessions and higher doses of antidepressants may have resulted in more participants in remission. Conclusions: High nighttime HR and low nighttime HRV predict a poor response to treatment of major depression in patients with stable CHD. These findings may help explain why patients with CHD who do not respond to treatment are at higher risk for mortality. © 2016 Elsevier B.V. All rights reserved.

Author Keywords
Coronary heart disease;  Depression treatment;  Nighttime heart rate


Document Type: Article
Source: Scopus

 


 

4) 
Kim, S.H.a b t , Lyu, I.c , Fonov, V.S.d , Vachet, C.e , Hazlett, H.C.a , Smith, R.G.a , Piven, J.a , Dager, S.R.f , Mckinstry, R.C.g , Pruett, J.R., Jr.h , Evans, A.C.d , Collins, D.L.d , Botteron, K.N.h , Schultz, R.T.i , Gerig, G.j , Styner, M.A.a b c , Piven, J.k , Hazlett, H.C.k , Chappell, C.k , Dager, S.l , Estes, A.l , Shaw, D.m , Botteron, K.m , McKinstry, R.m , Constantino, J.m , Pruett, J.m , Schultz, R.n , Paterson, S.n , Zwaigenbaum, L.o , Ellison, J.p , Evans, A.C.q , Collins, D.L.q , Pike, G.B.q , Fonov, V.q , Kostopoulos, P.q , Das, S.q , Gerig, G.r , Styner, M.k , Gu, H.s 
Development of cortical shape in the human brain from 6 to 24months of age via a novel measure of shape complexity
(2016) NeuroImage, 135, pp. 163-176. 

DOI: 10.1016/j.neuroimage.2016.04.053

a Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, United States
b Department of Psychiatry, University of North Carolina at Chapel HillNC, United States
c Department of Computer Science, University of North Carolina at Chapel HillNC, United States
d McConnell Brain Imaging Center, Montreal Neurological Institute, Montreal, QC, Canada
e Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, UT, United States
f Department of Radiology, University of Washington, Seattle, United States
g Department of Neuroradiology, Washington University, St. Louis, United States
h Department of Psychiatry, Washington University School of Medicine, St. Louis, United States
i Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
j Tandon School of Engineering, Department of Computer Science and Engineering, NYUNY, United States
k University of North Carolina, United States
l University of Washington, United States
m Washington University, United States
n Children's Hospital of Philadelphia, United States
o University of Alberta, Canada
p University of Minnesota, United States
q Data Coordinating Center, Montreal Neurological Institute, Canada
r Image Processing Core, University of Utah, United States
s Statistical Analysis Core, University of North Carolina, United States

Abstract
The quantification of local surface morphology in the human cortex is important for examining population differences as well as developmental changes in neurodegenerative or neurodevelopmental disorders. We propose a novel cortical shape measure, referred to as the 'shape complexity index' (SCI), that represents localized shape complexity as the difference between the observed distributions of local surface topology, as quantified by the shape index (SI) measure, to its best fitting simple topological model within a given neighborhood. We apply a relatively small, adaptive geodesic kernel to calculate the SCI. Due to the small size of the kernel, the proposed SCI measure captures fine differences of cortical shape. With this novel cortical feature, we aim to capture comparatively small local surface changes that capture a) the widening versus deepening of sulcal and gyral regions, as well as b) the emergence and development of secondary and tertiary sulci. Current cortical shape measures, such as the gyrification index (GI) or intrinsic curvature measures, investigate the cortical surface at a different scale and are less well suited to capture these particular cortical surface changes. In our experiments, the proposed SCI demonstrates higher complexity in the gyral/sulcal wall regions, lower complexity in wider gyral ridges and lowest complexity in wider sulcal fundus regions. In early postnatal brain development, our experiments show that SCI reveals a pattern of increased cortical shape complexity with age, as well as sexual dimorphisms in the insula, middle cingulate, parieto-occipital sulcal and Broca's regions. Overall, sex differences were greatest at 6 months of age and were reduced at 24 months, with the difference pattern switching from higher complexity in males at 6 months to higher complexity in females at 24 months. This is the first study of longitudinal, cortical complexity maturation and sex differences, in the early postnatal period from 6 to 24. months of age with fine scale, cortical shape measures. These results provide information that complement previous studies of gyrification index in early brain development. © 2016.

Author Keywords
Age effect;  And sexual dimorphism;  Earth mover distance;  Shape complexity index;  Shape index


Document Type: Article
Source: Scopus

 


 

5) 
Werner, K.B.a , Griffin, M.G.b , Galovski, T.E.c 
Objective and subjective measurement of sleep disturbance in female trauma survivors with posttraumatic stress disorder
(2016) Psychiatry Research, 240, pp. 234-240. 

DOI: 10.1016/j.psychres.2016.04.039

a George Warren Brown School of Social Work, Washington University in St. Louis, Saint Louis, MO, United States
b Department of Psychology, Center for Trauma Recovery, University of Missouri - Saint Louis, Saint Louis, MO, United States
c Women's Health Sciences Division, National Center for PTSD, VA Boston Healthcare System, Boston, MA, United States

Abstract
Sleep disturbance may be the most often endorsed symptom of posttraumatic stress disorder (PTSD). Much of this research is based on subjective reports from trauma survivors; however, objective measures of sleep-related impairment have yielded findings inconsistent with self-report data. More studies investigating subjective and objective assessments concordantly are needed to understand sleep impairment in PTSD. The current study examined PTSD-related sleep disturbance in a female interpersonal violence cohort with full PTSD diagnoses (N=51) assessing subjective (global and daily diary measures) and objective (actigraphy) sleep measures concurrently. PTSD severity was positively associated with global, subjective reports of sleep impairment and insomnia. Subjective measures of sleep (including global sleep impairment, insomnia, and daily sleep diary reports of total sleep time, sleep efficiency, and sleep onset latency) were moderately to strongly correlated. However, no significant correlations between subjective and objective reports of sleep impairment were found in this cohort. Analyses demonstrated an overall elevation in subjectively reported sleep impairment when compared to objective measurement assessed concurrently. Findings demonstrate a lack of agreement between subjective and objective measurements of sleep in a PTSD-positive female cohort, suggesting objective and subjective sleep impairments are distinct sleep parameters that do not necessarily directly co-vary. © 2016 Elsevier Ireland Ltd.

Author Keywords
Actigraphy;  Posttraumatic stress disorder;  Sleep;  Women


Document Type: Article
Source: Scopus

 


 

6) 
Winterheld, H.A.
Calibrating Use of Emotion Regulation Strategies to the Relationship Context: An Attachment Perspective
(2016) Journal of Personality, 84 (3), pp. 369-380. 

DOI: 10.1111/jopy.12165

Department of Psychology, Washington University in St. Louis, Campus Box 1125, St. Louis, MO, United States

Abstract
This research tested whether adult attachment orientations predict use of emotion regulation strategies in theoretically consistent ways, and whether associations among attachment orientations and emotion regulatory strategies are moderated by critical features of the relationship context. Ninety-six couples (192 individuals) reported on their attachment orientations, habitual use of emotion regulation strategies (cognitive reappraisal, expressive suppression, negative emotion expressivity), and perceptions of relationship closeness and negative partner behaviors. Highly secure individuals reported greater use of cognitive reappraisal, especially when they felt closer to their partners, and engaged in less suppression when their partners behaved more negatively toward them. Highly avoidant individuals reported greater use of suppression, especially when they perceived more negative partner behaviors, and when their partners were more avoidant. Highly anxious individuals also used more suppression when their partners were more avoidant, but they expressed more negative emotions when they were paired with less avoidant partners. Fearful-avoidant individuals' emotion regulation patterns resembled those of both highly secure and dismissive-avoidant individuals. This study illustrates how attending to moderating effects within specific relationships and testing joint effects of both partners' personality characteristics can help identify contextual boundaries of emotion regulation strategies and clarify emotional response patterns in couples. © 2016 Wiley Periodicals, Inc.
 


Document Type: Article
Source: Scopus

 


 

7) 
Few, L.R., Agrawal, A.
Commentary on Verweij et al. (2016): Conduct problems and substance use-genetic and environmental perspectives on sex differences
(2016) Addiction, 111 (6), pp. 1046-1047. 

DOI: 10.1111/add.13371

Washington University School of Medicine, Department of Psychiatry, St Louis, MO, United States
 

Author Keywords
Adolescence;  Cannabis;  Conduct;  Correlation;  Finntwin;  Tobacco;  Twin


Document Type: Note
Source: Scopus

 


 

8) 
Jou, J.a , Flores, S.b , Cortes, H.M.a , Leka, B.G.a 
The effects of weak versus strong relational judgments on response bias in Two-Alternative-Forced-Choice recognition: Is the test criterion-free?
(2016) Acta Psychologica, 167, pp. 30-44. 

DOI: 10.1016/j.actpsy.2016.03.014

a University of Texas - Rio Grande Valley, United States
b Washington University in St. Louis, United States

Abstract
It is widely believed that a Two-Alternative-Forced-Choice (2AFC) in an old/new recognition memory test is made by comparing the two items and choosing the item with the higher strength. For this reason, it is considered to be criterion-free by some researchers. We found evidence that subjects probabilistically compromised the comparison by choosing the left item when they recognized it as old. Using both normal test pairs (comprised of one new and one old item) and two types of null pairs (comprised of both-new or both-old items), we found that a left-biased choice was coupled with higher hit and false alarm rates and a shorter left than right-choice RT for the normal pairs, consistent with the hypothesis of a bias for making a choice on the basis of a left individual-item recognition. For the null pairs, RT was much longer for the both-new than for the both-old pairs, providing additional evidence for basing decision on an individual-item's absolute, rather than a relative, familiarity. Additionally, subjects gave higher confidence ratings to choices for the both-old than the normal and both-new pairs, again suggesting that their decision was based on absolute familiarity of the items. The results were found to be not due to a fast-response instruction. A comparative judgment experiment in which subjects chose the item higher or lower in an attribute magnitude did not show the response side bias and RT asymmetry. The presence of bias in the former, and the absence of it in the latter can be explained by a weak versus strong relational judgment in the former and the latter type of 2AFC, respectively. We discuss the implications these findings have for the use of the 2AFC as a method for testing recognition memory. © 2016 Elsevier B.V.

Author Keywords
2AFC recognition;  Criterion in recognition memory;  Null test items in 2AFC;  Old/new 2AFC versus comparative judgment;  Two-alternative-forced-choice


Document Type: Article
Source: Scopus

 


 

9) 
Baum, C.M.a , Wolf, T.J.a , Wong, A. W. K.a , Chen, C.H.b , Walker, K.a , Young, A.C.a , Carlozzi, N. E.c , Tulsky, D.S.d , Heaton, R.K.e , Heinemann, A.W.f 
Validation and clinical utility of the executive function performance test in persons with traumatic brain injury
(2016) Neuropsychological Rehabilitation, pp. 1-15. Article in Press. 

DOI: 10.1080/09602011.2016.1176934

a Occupational Therapy, Washington University School of Medicine, St. Louis, MO, USA
b Saw Swee Hock School of Public Health, National University of Singapore, Singapore
c Department of Physical Medicine & Rehabilitation, University of Michigan, Ann Arbor, MI, USA
d Department of Physical Therapy, University of Delaware, College of Health Sciences, Newark, DE, USA
e Department of Psychiatry, UC San Diego, La Jolla, CA, USA
f Department of Physical Medicine & Rehabilitation, Northwestern University, Chicago, IL, USA

Abstract
This study examined the relationships between the Executive Function Performance Test (EFPT), the NIH Toolbox Cognitive Function tests, and neuropsychological executive function measures in 182 persons with traumatic brain injury (TBI) and 46 controls to evaluate construct, discriminant, and predictive validity. Construct validity: There were moderate correlations between the EFPT and the NIH Toolbox Crystallized (r = −.479), Fluid Tests (r = −.420), and Total Composite Scores (r = −.496). Discriminant validity: Significant differences were found in the EFPT total and sequence scores across control, complicated mild/moderate, and severe TBI groups. We found differences in the organisation score between control and severe, and between mild and severe TBI groups. Both TBI groups had significantly lower scores in safety and judgement than controls. Compared to the controls, the severe TBI group demonstrated significantly lower performance on all instrumental activities of daily living (IADL) tasks. Compared to the mild TBI group, the controls performed better on the medication task, the severe TBI group performed worse in the cooking and telephone tasks. Predictive validity: The EFPT predicted the self-perception of independence measured by the TBI-QOL (beta = −0.49, p < .001) for the severe TBI group. Overall, these data support the validity of the EFPT for use in individuals with TBI. © 2016 Informa UK Limited, trading as Taylor & Francis Group

Author Keywords
Executive function;  NIH Toolbox;  performance-based testing;  traumatic brain injury


Document Type: Article in Press
Source: Scopus

 


 

10) 
Shutov, L.P.a , Warwick, C.A.a , Shi, X.b , Gnanasekaran, A.a , Shepherd, A.J.a c , Mohapatra, D.P.a c , Woodruff, T.M.d , David Clark, J.b , Usachev, Y.M.a 
The complement system component C5a produces thermal hyperalgesia via macrophage-to-nociceptor signaling that requires NGF and TRPV1
(2016) Journal of Neuroscience, 36 (18), pp. 5055-5070. 

DOI: 10.1523/JNEUROSCI.3249-15.2016

a Department of Pharmacology, University of Iowa, Iowa City, IA, United States
b Department of Anesthesia, Veterans Administration Palo Alto Healthcare System and Stanford University, Palo Alto, CA, United States
c Department of Anesthesiology, Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, United States
d School of Biomedical Sciences, University of Queensland, St. Lucia, QLD, Australia

Abstract
The complement cascade is a principal component of innate immunity. Recent studies have underscored the importance of C5a and other components of the complement system in inflammatory and neuropathic pain, although the underlying mechanisms are largely unknown. In particular, it is unclear how the complement system communicates with nociceptors and which ion channels and receptors are involved. Here we demonstrate that inflammatory thermal and mechanical hyperalgesia induced by complete Freund’s adjuvant was accompanied by C5a upregulation and was markedly reduced by C5a receptor (C5aR1) knock-out or treatment with the C5aR1 antagonist PMX53. Direct administration of C5a into the mouse hindpaw produced strong thermal hyperalgesia, an effect that was absent in TRPV1 knock-out mice, and was blocked by the TRPV1 antagonist AMG9810. Immunohistochemistry of mouse plantar skin showed prominent expression of C5aR1 in macrophages. Additionally, C5a evoked strong Ca2+ mobilization in macrophages. Macrophage depletion in transgenic macrophage Fas-induced apoptosis mice abolished C5a-dependent thermal hyperalgesia. Examination of inflammatory mediators following C5a injection revealed a rapid upregulation of NGF, a mediator known to sensitize TRPV1. Preinjection of an NGFneutralizing antibody or Trk inhibitor GNF-5837 prevented C5a-induced thermal hyperalgesia. Notably, NGF-induced thermal hyperalgesia was unaffected by macrophage depletion. Collectively, these results suggest that complement fragment C5a induces thermal hyperalgesia by triggering macrophage-dependent signaling that involves mobilization of NGF and NGF-dependent sensitization of TRPV1. Our findings highlight the importance of macrophage-to-neuron signaling in pain processing and identify C5a, NGF, and TRPV1 as key players in this cross-cellular communication. © 2016 the authors.

Author Keywords
C5a;  C5aR1;  Complement;  Macrophage;  NGF;  TRPV1


Document Type: Article
Source: Scopus

 


 

11) 
Luby, J.L.a , Belden, A.C.a , Whalen, D.a , Harms, M.P.a , Barch, D.M.a b 
Breastfeeding and Childhood IQ: The Mediating Role of Gray Matter Volume
(2016) Journal of the American Academy of Child and Adolescent Psychiatry, 55 (5), pp. 367-375. 

DOI: 10.1016/j.jaac.2016.02.009

a Washington University, School of Medicine, Department of Psychiatry, Box 8511, 660 S. Euclid, St. Louis, MO, United States
b Program in Neuroscience, Washington University, St. Louis, United States

Abstract
Objective A substantial body of literature has established the positive effect of breastfeeding on child developmental outcomes. There is increasing consensus that breastfed children have higher IQs after accounting for key variables, including maternal education, IQ, and socioeconomic status. Cross-sectional investigations of the effects of breastfeeding on structural brain development suggest that breastfed infants have larger whole brain, cortical, and white matter volumes. To date, few studies have related these measures of brain structure to IQ in breastfed versus nonbreastfed children in a longitudinal sample. Method Data were derived from the Preschool Depression Study (PDS), a prospective longitudinal study in which children and caregivers were assessed annually for 8 waves over 11 years. A subset completed neuroimaging between the ages of 9.5 and 14.11 years. A total of 148 individuals had breastfeeding data at baseline and complete data on all variables of interest, including IQ and structural neuroimaging. General linear models and process mediation models were used. Results Breastfed children had significantly higher IQ scores and larger whole brain, total gray matter, total cortical gray matter, and subcortical gray matter volumes compared with the nonbreastfed group in models that covaried for key variables. Subcortical gray matter volume significantly mediated the association between breastfeeding and children's IQ scores. Conclusion The study findings suggest that the effects of breastfeeding on child IQ are mediated through subcortical gray volume. This effect and putative mechanism is of public health significance and further supports the importance of breastfeeding in mental health promotion. © 2016 American Academy of Child and Adolescent Psychiatry.

Author Keywords
brain development;  breastfeeding;  IQ


Document Type: Article
Source: Scopus

 


 

12) 
Barch, D.M.a , Carter, C.S.b c 
Functional and Structural Brain Connectivity in Psychopathology
(2016) Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 1 (3), pp. 196-198. 

DOI: 10.1016/j.bpsc.2016.03.006

a Departments of Psychological and Brain Sciences, Psychiatry, and Radiology, Washington University in St. Louis, Box 1125, One Brookings Drive, St. Louis, MO, United States
b Departments of Psychiatry and Psychology, University of California Davis, Davis, CA, United States
c Center for Neuroscience, University of California Davis, Davis, CA, United States
 
 


Document Type: Short Survey
Source: Scopus

 


 

13) 
Scherrer, J.F.a b , Salas, J.a b , Bucholz, K.K.c , Schneider, F.D.a , Burroughs, T.d , Copeland, L.A.e f g , Sullivan, M.D.h , Lustman, P.J.c i 
New depression diagnosis following prescription of codeine, hydrocodone or oxycodone
(2016) Pharmacoepidemiology and Drug Safety, 25 (5), pp. 560-568. 

DOI: 10.1002/pds.3999

a Department of Family and Community Medicine, Saint Louis University School of Medicine, St. Louis, MO, United States
b Harry S. Truman Veterans Administration Medical Center, Columbia, MO, United States
c Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States
d Saint Louis University Center for Outcomes Research, St. Louis, MO, United States
e Center for Applied Health Research, Baylor Scott and White Health, and Central Texas Veterans Health Care System, United States
f Texas A and M Health Science Center, Bryan, TX, United States
g UT Health Science Center, San Antonio, TX, United States
h Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, United States
i The Bell Street Clinic, VA St. Louis Health Care System-John Cochran Division, St. Louis, MO, United States

Abstract
Purpose: Longer duration of prescription opioid use is associated with risk of major depression after controlling for daily morphine equivalent dose and pain. It is not known if risk of depression varies as a function of the type of opioid prescribed. Methods: A retrospective cohort design was used to model onset of new depression diagnosis among 11462 Veterans Health Administration (VA) patients who were prescribed only codeine, only hydrocodone or only oxycodone for >30days. Patients were free of prevalent opioid use and depression at baseline (2000-2001). Follow-up was 2002-2012. Propensity scores and weighting were used to balance covariates across opioid type. Cox-proportional hazard models were computed, using weighted data and additional adjustment for morphine equivalent dose (MED), duration of use, and pain after opioid initiation, to estimate the risk of new depression diagnosis among patients prescribed only codeine, only oxycodone vs. those prescribed only hydrocodone. Results: After controlling for confounding, we observed that patients prescribed codeine, compared to hydrocodone, were significantly more likely to have a new depression diagnosis (HR=1.27; 95%CI: 1.12-1.43). Oxycodone was significantly associated with onset of new depression diagnosis when exposure was modeled as total days exposed in post-hoc analysis, but not when exposure was duration of incident period of use. Conclusions: Although codeine is a less potent opioid, after controlling for MED, chronic use of this agent is associated with nearly a 30% greater risk of depression compared to hydrocodone. Additional research is needed to determine the mechanisms for this association. © 2016 John Wiley & Sons, Ltd.

Author Keywords
Depression;  Epidemiology;  Opioids;  Pharmacoepidemiology;  Retrospective cohort


Document Type: Article
Source: Scopus

 


 

14) 
Haroutounian, S.
Somatosensory phenotyping for better translation in neuropathic pain?
(2016) Pain, 157 (5), pp. 995-996. 

DOI: 10.1097/j.pain.0000000000000505

Division of Clinical and Translational Research, Department of Anesthesiology, Washington University, St Louis, MO, United States
 
 


Document Type: Note
Source: Scopus

 


 

15) 
Scahill, L.a , Jeon, S.b , Boorin, S.J.b , McDougle, C.J.c , Aman, M.G.d , Dziura, J.e , McCracken, J.T.f , Caprio, S.e , Arnold, L.E.d , Nicol, G.g , Deng, Y.h , Challa, S.A.i , Vitiello, B.j 
Weight Gain and Metabolic Consequences of Risperidone in Young Children with Autism Spectrum Disorder
(2016) Journal of the American Academy of Child and Adolescent Psychiatry, 55 (5), pp. 415-423. 

DOI: 10.1016/j.jaac.2016.02.016

a Emory University, School of Medicine, Marcus Autism Center, Atlanta, United States
b Yale University School of Nursing, West Haven, CT, United States
c Harvard Medical School, Massachusetts General Hospital, Lurie Center for Autism, Boston, United States
d Nisonger Center, Ohio State University, Columbus, United States
e Yale School of Medicine, New Haven, CT, United States
f Division of Child Psychiatry, University of California, Los Angeles, United States
g Washington University, St. Louis, United States
h Yale University, United States
i Emory University School of Medicine, United States
j National Institute of Mental Health (NIMH), Bethesda, MD, United States

Abstract
Objective We examine weight gain and metabolic consequences of risperidone monotherapy in children with autism spectrum disorder (ASD). Method This was a 24-week, multisite, randomized trial of risperidone only versus risperidone plus parent training in 124 children (mean age 6.9 ± 2.35 years; 105 boys and 19 girls) with ASD and serious behavioral problems. We monitored height, weight, waist circumference, and adverse effects during the trial. Fasting blood samples were obtained before treatment and at week 16. Results In 97 children with a mean of 22.9 ± 2.8 weeks of risperidone exposure, there was a 5.4 ± 3.4 kg weight gain over 24 weeks (p <.0001); waist circumference increased from 60.7 ± 10.4 cm to 66.8 ± 11.3 cm (p <.0001). At baseline, 59 of 97 children (60.8%) were classified as having normal weight; by week 24, only 25 of 85 (29.4%) remained in that group. Growth curve analysis showed a significant change in body mass index (BMI) z scores from pretreatment to week 24 (p <.0001). This effect was significantly greater for children with reported increased appetite in the first 8 weeks. From before treatment to week 16, there were significant increases in glucose (p =.02), hemoglobin A1c (p =.01), insulin (p <.0001), homeostatic model assessment-insulin resistance (HOMA-IR; p <.001), alanine aminotransferase (p =.01), and leptin (p <.0001). Adiponectin declined (p =.003). At baseline, 7 children met conventional criteria for metabolic syndrome; by week 16, 12 additional children were so classified. Conclusion Rapid weight gain with risperidone treatment may promote the cascade of biochemical indices associated with insulin resistance and metabolic syndrome. Appetite, weight, waist circumference, liver function tests, blood lipids, and glucose warrant monitoring. Clinical trial registration information - Drug and Behavioral Therapy for Children With Pervasive Developmental Disorders; http://clinicaltrials.gov/; NCT00080145.

Author Keywords
autism spectrum disorder;  insulin resistance;  metabolic syndrome;  risperidone;  weight gain


Document Type: Article
Source: Scopus

 


 

16) 
Roe, C.M., Barco, P.P., Head, D.M., Ghoshal, N., Selsor, N., Babulal, G.M., Fierberg, R., Vernon, E.K., Shulman, N., Johnson, A., Fague, S., Xiong, C., Grant, E.A., Campbell, A., Ott, B.R., Holtzman, D.M., Benzinger, T.L.S., Fagan, A.M., Carr, D.B., Morris, J.C.
Amyloid Imaging, Cerebrospinal Fluid Biomarkers Predict Driving Performance Among Cognitively Normal Individuals
(2016) Alzheimer Disease and Associated Disorders, . Article in Press. 

DOI: 10.1097/WAD.0000000000000154

*Charles F. and Joanne Knight Alzheimer’s Disease Research Center Departments of †Neurology ‡Occupational Therapy ?Psychology ¶¶Pathology and Immunology ##Physical Therapy **Radiology §§Neurosurgery ??Medicine ¶Center for Clinical Studies #Division of Biostatistics, Washington University School of Medicine, St. Louis, MO §The Rehabilitation Institute of St. Louis ††The Alzheimer’s Disease & Memory Disorders Center, Alpert Medical School of Brown University ‡‡Rhode Island Hospital, Providence, Rhode Island

Abstract
Postmortem brain studies of older drivers killed in car accidents indicate that many had Alzheimer disease (AD) neuropathologic changes. We examined whether AD biomarkers are related to driving performance among cognitively normal older adults. Individuals with normal cognition, aged 65+ years, and driving at least once per week, were recruited. Participants (N=129) took part in clinical assessments, a driving test, and positron emission tomography imaging with Pittsburgh compound B (PIB) and/or cerebrospinal fluid (CSF) collection. General linear models tested whether the number of driving errors differed as a function of each of the biomarker variables (mean cortical binding potential for PIB, and CSF Aβ42, tau, ptau181, tau/Aβ42, ptau181/Aβ42). Higher ratios of CSF tau/Aβ42, ptau181/Aβ42, and PIB mean cortical binding potential, were associated with more driving errors (P<0.05). Preclinical AD may have subtle cognitive and functional effects, which alone may go unnoticed. However, when combined, these changes may impact complex behaviors such as driving. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved
 


Document Type: Article in Press
Source: Scopus

 


 

17) 
Kubanek, J.a b , Shi, J.b , Marsh, J.d , Chen, D.c , Deng, C.c , Cui, J.b 
Ultrasound modulates ion channel currents
(2016) Scientific Reports, 6, art. no. 24170, . 

DOI: 10.1038/srep24170

a Department of Molecular and Cellular Physiology, Stanford University, 279 Campus Drive, Stanford, CA, United States
b Department of Biomedical Engineering, Washington University in St. Louis, One Brookings Dr., St. Louis, MO, United States
c Department of Biomedical Engineering, University of Michigan, 2200 Bonisteel Blvd., Ann Arbor, MI, United States
d Department of Internal Medicine, Washington University, 4320 Forest Park Ave, St. Louis, MO, United States

Abstract
Transcranial focused ultrasound (US) has been demonstrated to stimulate neurons in animals and humans, but the mechanism of this effect is unknown. It has been hypothesized that US, a mechanical stimulus, may mediate cellular discharge by activating mechanosensitive ion channels embedded within cellular membranes. To test this hypothesis, we expressed potassium and sodium mechanosensitive ion channels (channels of the two-pore-domain potassium family (K2P) including TREK-1, TREK-2, TRAAK; Na V 1.5) in the Xenopus oocyte system. Focused US (10 MHz, 0.3-4.9 W/cm2) modulated the currents flowing through the ion channels on average by up to 23%, depending on channel and stimulus intensity. The effects were reversible upon repeated stimulation and were abolished when a channel blocker (ranolazine to block Na V 1.5, BaCl 2 to block K2P channels) was applied to the solution. These data reveal at the single cell level that focused US modulates the activity of specific ion channels to mediate transmembrane currents. These findings open doors to investigations of the effects ofUS on ion channels expressed in neurons, retinal cells, or cardiac cells, which may lead to important medical applications. The findings may also pave the way to the development of sonogenetics: A non-invasive, US-based analogue of optogenetics.
 


Document Type: Article
Source: Scopus

 


 

18) 
Ong, C.J., Dhand, A., Diringer, M.N.
Early Withdrawal Decision-Making in Patients with Coma After Cardiac Arrest: A Qualitative Study of Intensive Care Clinicians
(2016) Neurocritical Care, pp. 1-8. Article in Press. 

DOI: 10.1007/s12028-016-0275-5

Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8111, St. Louis, MO, United States

Abstract
Introduction: Neurologists are often asked to define prognosis in comatose patients. However, comatose patients following cardiac arrest are usually cared for by cardiologists or intensivists, and it is their approach that will influence decisions regarding withdrawal of life-sustaining interventions (WLSI). We observed that factors leading to these decisions vary across specialties and considered whether they could result in self-fulfilling prophecies and early WLSI. We conducted a hypothesis-generating qualitative study to identify factors used by non-neurologists to define prognosis in these patients and construct an explanatory model for how early WLSI might occur. Methods: This was a single-center qualitative study of intensivists caring for cardiac arrest patients with hypoxic-ischemic coma. Thirty attending physicians (n = 16) and fellows (n = 14) from cardiac (n = 8), medical (n = 6), surgical (n = 10), and neuro (n = 6) intensive care units underwent semi-structured interviews. Interview transcripts were analyzed using grounded theory techniques. Results: We found three components of early WLSI among non-neurointensivists: (1) development of fixed negative opinions; (2) early framing of poor clinical pictures to families; and (3) shortened windows for judging recovery potential. In contrast to neurointensivists, non-neurointensivists’ negative opinions were frequently driven by patients’ lack of consciousness and cardiopulmonary resuscitation circumstances. Both groups were influenced by age and comorbidities. Conclusions: The results demonstrate that factors influencing prognostication differ across specialties. Some differ from those recommended by published guidelines and may lead to self-fulfilling prophecies and early WLSI. Better understanding of this framework would facilitate educational interventions to mitigate this phenomenon and its implications on patient care. © 2016 Springer Science+Business Media New York

Author Keywords
Cardiac arrest;  Coma;  Decision-making;  Hypoxic-ischemic injury;  Prognostication;  Withholding treatment


Document Type: Article in Press
Source: Scopus

 


 

19) 
Bidwell, L.C.a b c , Palmer, R.H.C.b , Brick, L.b , Madden, P.A.F.d , Heath, A.C.d , Knopik, V.S.b 
A Propensity Scoring Approach to Characterizing the Effects of Maternal Smoking During Pregnancy on Offspring’s Initial Responses to Cigarettes and Alcohol
(2016) Behavior Genetics, pp. 1-15. Article in Press. 

DOI: 10.1007/s10519-016-9791-5

a Institute of Cognitive Science, University of Colorado, UCB 344, Boulder, CO, United States
b Division of Behavioral Genetics, Rhode Island Hospital; Department of Psychiatry and Human Behavior, The Warren Alpert Medical School of Brown University, Providence, RI, United States
c Center for Alcohol and Addiction Studies, Department of Psychiatry and Human Behavior, Brown University, Providence, RI, United States
d Midwest Alcoholism Research Center, Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States

Abstract
When examining the effects of prenatal exposure to maternal smoking during pregnancy (MSDP) on later offspring substance use, it is critical to consider familial environments confounded with MSDP. The purpose of this study was to examine the effect of MSDP on offspring’s initial reactions to cigarettes and alcohol, which are indicators of future substance-use related problems. We tested these effects using two propensity score approaches (1) by controlling for confounding using the MSDP propensity score and (2) examining effects of MSDP across the MSDP risk distribution by grouping individuals into quantiles based on their MSDP propensity score. This study used data from 829 unrelated mothers with a reported lifetime history of smoking to determine the propensity for smoking only during their first trimester (MSDP-E) or throughout their entire pregnancy (MSDP-T). Propensity score analyses focused on the offspring (N = 1616 female twins) of a large subset of these mothers. We examined the effects of levels of MSDP-E/T on offspring initial reactions to their first experiences with alcohol and cigarettes, across the distribution of liability for MSDP-E/T. MSDP-E/T emerged as significant predictors of offspring reactions to alcohol and cigarettes, but the effects were confounded by the familial liability for MSDP. Further, the unique MSDP effects that emerged were not uniform across the MSDP familial risk distribution. Our findings underscore the importance of properly accounting for correlated familial risk factors when examining the effects of MSDP on substance related outcomes. © 2016 Springer Science+Business Media New York

Author Keywords
Genetic;  Nicotine;  Prenatal exposure;  Subjective drug responses;  Substance use;  Tobacco


Document Type: Article in Press
Source: Scopus

 


 

20) 
Weiss, M.D.a , Macklin, E.A.b , Simmons, Z.c , Knox, A.S.d , Greenblatt, D.J.e , Atassi, N.d , Graves, M.f , Parziale, N.f , Salameh, J.S.g , Quinn, C.g , Brown, R.H.g , Distad, J.B.a , Trivedi, J.h , Shefner, J.M.i , Barohn, R.J.j , Pestronk, A.k , Swenson, A.l , Cudkowicz, M.E.d 
A randomized trial of mexiletine in ALS
(2016) Neurology, 86 (16), pp. 1474-1481. Cited 1 time.

DOI: 10.1212/WNL.0000000000002507

a Department of Neurology, University of Washington Medical Center, Seattle, WA, United States
b Biostatistics Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
c Department of Neurology, Penn State Hershey Medical Center, Hershey, PA, United States
d Department of Neurology, Neurological Clinical Research Institute, Massachusetts General Hospital, Boston, MA, United States
e Program in Pharmacology and Experimental Therapeutics, Tufts University, School of Medicine, Boston, MA, United States
f Department of Neurology, UCLA Medical Center, Los Angeles, CA, United States
g Department of Neurology, University of Massachusetts, Memorial Medical Center, Worcester, MA, United States
h Department of Neurology, University of Texas, Southwestern Medical Center, Dallas, TX, United States
i Department of Neurology, Barrow Neurological Institute, Phoenix, AZ, United States
j Department of Neurology, University of Kansas Medical Center, Kansas City, KS, United States
k Department of Neurology, Washington University Medical Center, St. Louis, MO, United States
l Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, IA, United States

Abstract
Objective: To determine the safety and tolerability of mexiletine in a phase II double-blind randomized controlled trial of sporadic amyotrophic lateral sclerosis (SALS). Methods: Sixty participants with SALS from 10 centers were randomized 1:1:1 to placebo, mexiletine 300 mg/d, or mexiletine 900 mg/d and followed for 12 weeks. The primary endpoints were safety and tolerability. Secondary endpoints were pharmacokinetic study from plasma and CSF, ALS Functional Rating Scale-Revised (ALSFRS-R) score, slow vital capacity (SVC), and muscle cramp frequency and severity. Results: The only serious adverse event among active arm participants was one episode of imbalance. Thirty-two percent of participants receiving 900 mg of mexiletine discontinued study drug vs 5% on placebo (p 0.026). Pharmacokinetic study demonstrated a peak plasma concentration 2 hours postdose and strong correlation between plasma and CSF (p < 0.001). Rates of decline of ALSFRS-R and SVC did not differ from placebo. Analysis of all randomized patients demonstrated significant reductions of muscle cramp frequency (300 mg: rate 31% of placebo, p 0.047; 900 mg: 16% of placebo, p 0.002) and cramp intensity (300 mg: mean 45% of placebo, p 0.08; 900 mg: 25% of placebo, p 0.005). Conclusions: Mexiletine was safe at both doses and well-tolerated at 300 mg/d but adverse effects at 900 mg/d led to a high rate of discontinuation. Mexiletine treatment resulted in large dose-dependent reductions in muscle cramp frequency and severity. No effect on rate of progression was detected, but clinically important differences could not be excluded in this small and short-duration study. Classification of evidence: This study provides Class I evidence that mexiletine is safe when given daily to patients with amyotrophic lateral sclerosis at 300 and 900 mg and well-tolerated at the lower dose. © 2016 American Academy of Neurology.
 


Document Type: Article
Source: Scopus

 


 

21) 
Beck, D.B.a , Cho, M.T.b , Millan, F.b , Yates, C.b , Hannibal, M.c , O’Connor, B.c , Shinawi, M.d , Connolly, A.M.e , Waggoner, D.f , Halbach, S.f , Angle, B.g , Sanders, V.g , Shen, Y.h , Retterer, K.b , Begtrup, A.b , Bai, R.b , Chung, W.K.a 
A recurrent de novo CTBP1 mutation is associated with developmental delay, hypotonia, ataxia, and tooth enamel defects
(2016) Neurogenetics, pp. 1-6. Article in Press. 

DOI: 10.1007/s10048-016-0482-4

a Departments of Pediatrics and Medicine, Columbia University Medical Center, New York, NY, United States
b GeneDx, Gaithersburg, MD, United States
c Department of Pediatrics and Communicable Diseases, Division of Pediatric Genetics, Metabolism & Genomic Medicine, University of Michigan Medical School, Ann Arbor, MI, United States
d Department of Pediatrics, Division of Genetics and Genomic Medicine, Washington University School of Medicine, St. Louis, MO, United States
e Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
f Department of Pediatrics, University of Chicago, Chicago, IL, United States
g Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
h Departments of Systems Biology and Biomedical Informatics, Columbia University Medical Center, New York, NY, United States

Abstract
Exome sequencing is an effective way to identify genetic causes of etiologically heterogeneous conditions such as developmental delay and intellectual disabilities. Using exome sequencing, we have identified four patients with similar phenotypes of developmental delay, intellectual disability, failure to thrive, hypotonia, ataxia, and tooth enamel defects who all have the same de novo R331W missense variant in C-terminal binding protein 1 (CTBP1). CTBP1 is a transcriptional regulator critical for development by coordinating different regulatory pathways. The R331W variant found in these patients is within the C-terminal portion of the PLDLS (Pro-Leu-Asp-Leu-Ser) binding cleft, which is the domain through which CTBP1, interacts with chromatin-modifying enzymes and mediates chromatin-dependent gene repression pathways. This is the first report of mutations within CTBP1 in association with any human disease. © 2016 Springer-Verlag Berlin Heidelberg

Author Keywords
Ataxia;  Chromatin;  CTBP1;  Developmental delay;  Enamel defects;  Hypotonia;  Whole exome sequencing


Document Type: Article in Press
Source: Scopus

 


 

22) 
Abel, J.H.a b , Meeker, K.c , Granados-Fuentes, D.d , John, P.C.S.a e , Wang, T.J.d , Bales, B.B.c , Doyle, F.J., IIIa f , Herzog, E.D.d , Petzold, L.R.c 
Functional network inference of the suprachiasmatic nucleus
(2016) Proceedings of the National Academy of Sciences of the United States of America, 113 (16), pp. 4512-4517. 

DOI: 10.1073/pnas.1521178113

a Department of Chemical Engineering, University of California, Santa Barbara, CA, United States
b Systems Biology Program, Harvard University, Cambridge, MA, United States
c Department of Computer Science, University of California, Santa Barbara, CA, United States
d Department of Biology, Washington University in St. Louis, St. Louis, MO, United States
e Biosciences Center, National Renewable Energy Laboratory, Golden, CO, United States
f Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, United States

Abstract
In the mammalian suprachiasmatic nucleus (SCN), noisy cellular oscillators communicate within a neuronal network to generate precise system-wide circadian rhythms. Although the intracellular genetic oscillator and intercellular biochemical coupling mechanisms have been examined previously, the network topology driving synchronization of the SCN has not been elucidated. This network has been particularly challenging to probe, due to its oscillatory components and slow coupling timescale. In this work, we investigated the SCN network at a single-cell resolution through a chemically induced desynchronization. We then inferred functional connections in the SCN by applying the maximal information coefficient statistic to bioluminescence reporter data from individual neurons while they resynchronized their circadian cycling. Our results demonstrate that the functional network of circadian cells associated with resynchronization has small-world characteristics, with a node degree distribution that is exponential. We show that hubs of this small-world network are preferentially located in the central SCN, with sparsely connected shells surrounding these cores. Finally, we used two computational models of circadian neurons to validate our predictions of network structure.

Author Keywords
Biological clock;  Circadian oscillator;  Mathematical model;  Synchronization;  Systems biology


Document Type: Article
Source: Scopus

 


 

23) 
Xiong, C.a f , Jasielec, M.S.a f , Weng, H.a f , Fagan, A.M.a b , Benzinger, T.L.S.a h i , Head, D.a g h , Hassenstab, J.a b g , Grant, E.a f , Sutphen, C.L.a b , Buckles, V.a b , Moulder, K.L.a b , Morris, J.C.a b c d e 
Longitudinal relationships among biomarkers for Alzheimer disease in the Adult Children Study
(2016) Neurology, 86 (16), pp. 1499-1506. 

DOI: 10.1212/WNL.0000000000002593

a Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University, School of Medicine, St. Louis, MO, United States
b Departments of Neurology, Washington University, School of Medicine, St. Louis, MO, United States
c Departments of Pathology and Immunology, Washington University, School of Medicine, St. Louis, MO, United States
d Departments of Physical Therapy, Washington University, School of Medicine, St. Louis, MO, United States
e Departments of Occupational Therapy, Washington University, School of Medicine, St. Louis, MO, United States
f Division of Biostatistics, Washington University, School of Medicine, St. Louis, MO, United States
g Departments of Psychology, Washington University, School of Medicine, St. Louis, MO, United States
h Departments of Radiology, Washington University, School of Medicine, St. Louis, MO, United States
i Departments of Neurological Surgery, Washington University, School of Medicine, St. Louis, MO, United States

Abstract
Objective: To determine whether and how longitudinal rates of change in MRI volumetrics, CSF concentrations of Alzheimer-related proteins, molecular imaging of cerebral fibrillar amyloid with PET using the [ 11 C] benzothiazole tracer, Pittsburgh compound B (PiB), and cognition were associated among asymptomatic middle-aged to older individuals. Methods: Multivariate mixed models for repeated measures were used to assess the correlations on the rates of changes across markers. Results: Among 209 asymptomatic middle-aged to older individuals longitudinally followed for up to 11 years (mean 6.7 years), a faster intraindividual decrease in CSF Aβ 42 was associated with a faster increase in PiB mean cortical standardized uptake value ratio (MCSUVR, p 0.04), but not others. The rate of change in CSF tau (and Ptau 181) was correlated with the rate of change in PiB MCSUVR (p 0.002), hippocampal volume (p 0.04), and global cognition (p 0.008). The rate of change in hippocampal volume was correlated with the rate of change in global cognition (p 0.04). Only 3 significant correlations were observed at baseline: CSF Aβ 42 and PiB MCSUVR (p < 0.001), CSF tau and PiB MCSUVR (p < 0.001), and CSF Aβ 42 and global cognition (p 0.01). Conclusions: CSF tau (Ptau 181), PiB MCSUVR, and hippocampal volume were all longitudinally correlated with each other, whereas CSF Aβ 42 was correlated only with PiB binding. Unlike the baseline values, the longitudinal change in CSF tau (Ptau 181) and hippocampal volume were correlated with the longitudinal change in global cognition, validating the role of these biomarkers in Alzheimer disease prevention trials. © 2016 American Academy of Neurology.
 


Document Type: Article
Source: Scopus

 


 

24) 
Ding, X.-Q.a , Thapa, A.a g , Ma, H.a , Xu, J.a h , Elliott, M.H.b d , Rodgers, K.K.c , Smith, M.L.e , Wang, J.-S.f , Pittler, S.J.e , Kefalov, V.J.f 
The B3 subunit of the cone cyclic nucleotide-gated channel regulates the light responses of cones and contributes to the channel structural flexibility
(2016) Journal of Biological Chemistry, 291 (16), pp. 8721-8734. 

DOI: 10.1074/jbc.M115.696138

a Department of Cell Biology, University of Oklahoma Health Sciences Center, 940 Stanton L Young Blvd., BMSB 553, Oklahoma City, OK, United States
b Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
c Department of Biochemistry, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
d McGee Eye Institute, Oklahoma City, OK, United States
e Department of Vision Sciences, University of Alabama, Birmingham, AL, United States
f Department of Ophthalmology and Visual Sciences, Washington University, School of Medicine, Saint Louis, MO, United States
g Dept. of Chemical and Nuclear Engineering, Center for Biomedical Engineering, University of New Mexico, Albuquerque, NM, United States
h Inst. of Reproduction and Development, Insts. of Biomedical Sciences, Fudan University, 2140 Xietu Rd., Shanghai, China

Abstract
Cone photoreceptor cyclic nucleotide-gated (CNG) channels play a pivotal role in cone phototransduction, which is a process essential for daylight vision, color vision, and visual acuity. Mutations in the cone channel subunits CNGA3 and CNGB3 are associated with human cone diseases, including achromatopsia, cone dystrophies, and early onset macular degeneration. Mutations in CNGB3 alone account for 50% of reported cases of achromatopsia. This work investigated the role of CNGB3 in cone light response and cone channel structural stability. As cones comprise only 2-3% of the total photoreceptor population in the wild-type mouse retina, we used Cngb3-/-/Nrl-/- mice with CNGB3 deficiency on a cone-dominant background in our study. We found that, in the absence of CNGB3, CNGA3 was able to travel to the outer segments, co-localize with cone opsin, and form tetrameric complexes. Electroretinogram analyses revealed reduced cone light response amplitude/sensitivity and slower response recovery in Cngb3-/-/Nrl-/- mice compared with Nrl-/- mice. Absence of CNGB3 expression altered the adaptation capacity of cones and severely compromised function in bright light. Biochemical analysis demonstrated that CNGA3 channels lacking CNGB3 were more resilient to proteolysis than CNGA3/CNGB3 channels, suggesting a hindered structural flexibility. Thus, CNGB3 regulates cone light response kinetics and the channel structural flexibility. This work advances our understanding of the biochemical and functional role of CNGB3 in cone photoreceptors. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
 


Document Type: Article
Source: Scopus

 


 

25) 
Cicero, T.J.a , Ellis, M.S.b 
Nonmedical Prescription-Opioid Use and Heroin Use
(2016) The New England journal of medicine, 374 (13), pp. 1295-1296. 

DOI: 10.1056/NEJMc1601875#SA1

a Washington University School of Medicine in St. Louis, St. Louis, MO cicerot@wustl.edu
b Washington University School of Medicine in St. Louis, St. Louis, MO cicerot@wustl.edu
 
 


Document Type: Letter
Source: Scopus

 


 

26) 
Bartus, R.T.a , Johnson, E.M.b 
Clinical tests of neurotrophic factors for human neurodegenerative diseases, part 2: Where do we stand and where must we go next?
(2016) Neurobiology of Disease, . Article in Press. 

DOI: 10.1016/j.nbd.2016.03.026

a RTBioconsultants, Inc., San Diego, CA, USA
b Departments of Neurology and Developmental Biology, Washington University Medical School, St. Louis, MO, USA

Abstract
The therapeutic potential of neurotrophic factors has been recognized for decades, with clinical trials in human neurodegenerative diseases extending back at least 25. years. While improvements in clinical dosing paradigms have reduced the side effects commonly seen in the earlier trials, efficacy has remained a serious disappointment (reviewed in Bartus and Johnson, 2016). This lengthy clinical effort stands in contrast to robust effects consistently achieved from different neurotrophic factors in a variety of animal models of neurodegeneration. This review discusses the prevailing assumption and supporting data that the major reason for the disappointing efficacy of past clinical trials is related to suboptimal dosing methods. It is concluded that while further improvements in dosing parameters might be useful, a much greater problem centers around a number of specific morphologic and functional changes in neurons in human neurodegenerative disease that mitigate the ability of neurotrophic factors to exert their effects. Moreover, the biological substrate which neurotrophic factors depend upon to exert their effects continues to erode as time progresses, due to the progressive nature of these diseases. For this reason, most of the empirically-supported reasons contributing to the weak neurotrophic responses in human patients can be mitigated by enrolling less severely advanced cases. It is further concluded that recent clinical trials of neurotrophic factors have generated important evidence that shifts risk: benefit assessments to support enrolling earlier-stage patients. While the Alzheimer's field has begun to shift attention toward much earlier-stage (even prodromal) patients in trials intended to modify disease progression, other neurodegenerative diseases (e.g., Parkinson's, ALS and possibly HD) must now consider similar changes in approach. © 2016 Elsevier Inc.

Author Keywords
ALS;  Alzheimer's;  Clinical trials;  Disease progression;  Gene therapy;  Huntington's;  Neurodegeneration;  Neuron repair;  Neuroprotection;  Neurorestoration;  Parkinson's;  Peripheral neuropathies;  Stage-of-disease;  Treatment approaches


Document Type: Article in Press
Source: Scopus

 


 

27) 
Bosch, M.K.a , Nerbonne, J.M.a b , Townsend, R.R.b c , Miyazaki, H.d , Nukina, N.d , Ornitz, D.M.a , Marionneau, C.e 
Proteomic analysis of native cerebellar iFGF14 complexes
(2016) Channels, pp. 1-16. Article in Press. 

DOI: 10.1080/19336950.2016.1153203

a Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA
b Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA
c Cell Biology & Physiology, Washington University School of Medicine, St. Louis, MO, USA
d Laboratory of Structural Pathology, Doshisha University, Kyotanabe-shi, Kyoto, Japan
e L'Institut du Thorax, INSERM UMR1087, CNRS UMR6291, Université de Nantes, Nantes, France

Abstract
Intracellular Fibroblast Growth Factor 14 (iFGF14) and the other intracellular FGFs (iFGF11-13) regulate the properties and densities of voltage-gated neuronal and cardiac Na+ (Nav) channels. Recent studies have demonstrated that the iFGFs can also regulate native voltage-gated Ca2+ (Cav) channels. In the present study, a mass spectrometry (MS)-based proteomic approach was used to identify the components of native cerebellar iFGF14 complexes. Using an anti-iFGF14 antibody, native iFGF14 complexes were immunoprecipitated from wild type adult mouse cerebellum. Parallel control experiments were performed on cerebellar proteins isolated from mice (Fgf14−/−) harboring a targeted disruption of the Fgf14 locus. MS analyses of immunoprecipitated proteins demonstrated that the vast majority of proteins identified in native cerebellar iFGF14 complexes are Nav channel pore-forming (α) subunits or proteins previously reported to interact with Nav α subunits. In contrast, no Cav channel α or accessory subunits were revealed in cerebellar iFGF14 immunoprecipitates. Additional experiments were completed using an anti-PanNav antibody to immunoprecipitate Nav channel complexes from wild type and Fgf14−/− mouse cerebellum. Western blot and MS analyses revealed that the loss of iFGF14 does not measurably affect the protein composition or the relative abundance of Nav channel interacting proteins in native adult mouse cerebellar Nav channel complexes. © 2016 Taylor & Francis

Author Keywords
cerebellum;  intracellular fibroblast growth factors;  native interactomes;  proteomics;  voltage-gated Na+ channels


Document Type: Article in Press
Source: Scopus

 


 

28) 
Tien, N.-W.a b , Kim, T.a b , Kerschensteiner, D.a c d e 
Target-Specific Glycinergic Transmission from VGluT3-Expressing Amacrine Cells Shapes Suppressive Contrast Responses in the Retina
(2016) Cell Reports, . Article in Press. 

DOI: 10.1016/j.celrep.2016.04.025

a Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint Louis, MO 63110, USA
b Graduate Program in Neuroscience, Washington University School of Medicine, Saint Louis, MO 63110, USA
c Department of Neuroscience, Washington University School of Medicine, Saint Louis, MO 63110, USA
d Department of Biomedical Engineering, Washington University School of Medicine, Saint Louis, MO 63110, USA
e Hope Center for Neurological Disorders, Washington University School of Medicine, Saint Louis, MO 63110, USA

Abstract
Neurons that release more than one transmitter exist throughout the CNS. Yet, how these neurons deploy multiple transmitters and shape the function of specific circuits is not well understood. VGluT3-expressing amacrine cells (VG3-ACs) provide glutamatergic input to ganglion cells activated by contrast and motion. Using optogenetics, we find that VG3-ACs provide selective glycinergic input to a retinal ganglion cell type suppressed by contrast and motion (SbC-RGCs). Firing of SbC-RGCs is suppressed at light ON and OFF over a broad range of stimulus sizes. Anatomical circuit reconstructions reveal that VG3-ACs form inhibitory synapses preferentially on processes that link ON and OFF arbors of SbC-RGC dendrites. Removal of VG3-ACs from mature circuits reduces inhibition and attenuates spike suppression of SbC-RGCs in a contrast- and size-selective manner, illustrating the modularity of retinal circuits. VG3-ACs thus use dual transmitters in a target-specific manner and shape suppressive contrast responses in the retina by glycinergic transmission. Tien et al. show that VG3-ACs deploy dual transmitters (glycine and glutamate) in a target-specific manner and form glycinergic synapses on the link processes connecting ON and OFF arbors of SbC-RGC dendrites. Cell-type-specific deletion in mature circuits reveals contrast- and size-selective influences of VG3-ACs on SbC-RGC responses. © 2016 The Authors.
 


Document Type: Article in Press
Source: Scopus

 


 

29) 
Amin-Hanjani, S.a , Pandey, D.K.b , Rose-Finnell, L.a , Du, X.a , Richardson, D.J.b c , Thulborn, K.R.d , Elkind, M.S.V.e , Zipfel, G.J.f , Liebeskind, D.S.g , Silver, F.L.h , Kasner, S.E.i , Aletich, V.A.a , Caplan, L.R.j , Derdeyn, C.P.f k , Gorelick, P.B.l m , Charbel, F.T.a 
Effect of hemodynamics on stroke risk in symptomatic atherosclerotic vertebrobasilar occlusive disease
(2016) JAMA Neurology, 73 (2), pp. 178-185. 

DOI: 10.1001/jamaneurol.2015.3772

a Department of Neurosurgery, University of Illinois at Chicago, Neuropsychiatric Institute, 912 SWood St (MC 799), Chicago, IL, United States
b Department of Neurology and Rehabilitation, University of Illinois at Chicago, United States
c Department of Mathematics and Computer Science, Lake Forest College, Lake Forest, IL, United States
d Center for Magnetic Resonance Research, University of Illinois at Chicago, United States
e Departments of Neurology and Epidemiology, Columbia University, New York, NY, United States
f Department of Neurosurgery and Neurology, Washington University in St Louis, St Louis, MO, United States
g Department of Neurology, UCLA (University of California, Los Angeles), United States
h Department of Medicine, Division of Neurology, University of Toronto, Toronto, ON, Canada
i Department of Neurology, University of Pennsylvania, Philadelphia, United States
j Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, United States
k Mallinkrodt Institute of Radiology, Washington University in St Louis, St Louis, MO, United States
l Department of Translational Science and Molecular Medicine, Michigan State University, College of Human Medicine, Grand Rapids, MI, United States
m Mercy Health Hauenstein Neurosciences, Grand Rapids, MI, United States

Abstract
Importance Atherosclerotic vertebrobasilar (VB) occlusive disease is a significant etiology of posterior circulation stroke, with regional hypoperfusion as an important potential contributor to stroke risk. Objective To test the hypothesis that, among patients with symptomatic VB stenosis or occlusion, those with distal blood flow compromise as measured by large-vessel quantitative magnetic resonance angiography (QMRA) are at higher risk of subsequent posterior circulation stroke. Design, Setting, and Participants A prospective, blinded, longitudinal cohort studywas conducted at 5 academic hospital-based centers in the United States and Canada; 82 patients from inpatient and outpatient settings were enrolled. Participants with recent VB transient ischemic attack or stroke and 50% or more atherosclerotic stenosis or occlusion in vertebral and/or basilar arteries underwent large-vessel flow measurement in the VB territory using QMRA. Physicians performing follow-up assessments were blinded to QMRA flow status. Follow-up included monthly telephone calls for 12 months and biannual clinical visits (for a minimum of 12 months, and up to 24 months or the final visit). Enrollment took place from July 1, 2008, to July 31, 2013, with study completion on June 30, 2014; data analysis was performed from October 1, 2014, to April 10, 2015. EXPOSURE Standard medical management of stroke risk factors. Main Outcomes and Measures The primary outcomewas VB-territory stroke. Results Of the 82 enrolled patients, 72 remained eligible after central review of their angiograms. Sixty-nine of 72 patients completed the minimum 12-month follow-up; median follow-up was 23 (interquartile range, 14-25) months. Distal flow status was low in 18 of the 72 participants (25%) included in the analysis and was significantly associated with risk for a subsequent VB stroke (P =.04), with 12-and 24-month event-free survival rates of 78%and 70%, respectively, in the low-flow group vs 96%and 87%, respectively, in the normal-flow group. The hazard ratio, adjusted for age and stroke risk factors, in the low distal flow status group was 11.55 (95%CI, 1.88-71.00; P =.008). Medical risk factor management at 6-month intervals was similar between patients with low and normal distal flow. Distal flow status remained significantly associated with risk even when controlling for the degree of stenosis and location. Conclusions and Relevance Distal flow status determined using a noninvasive and practical imaging tool is robustly associated with risk for subsequent stroke in patients with symptomatic atherosclerotic VB occlusive disease. Identification of high-risk patients has important implications for future investigation of more aggressive interventional or medical therapies. © 2016 American Medical Association. All rights reserved.
 


Document Type: Article
Source: Scopus

 


 

30) 
Longbrake, E.E., Cross, A.H.
Effect of multiple sclerosis disease-modifying therapies on b cells and humoral immunity
(2016) JAMA Neurology, 73 (2), pp. 219-225. 

DOI: 10.1001/jamaneurol.2015.3977

Department of Neurology, Washington University, Campus-Box 8111, 660 S Euclid Ave, St Louis, MO, United States

Abstract
The unequivocal success of B-cell-depleting agents in reducingmagnetic resonance imaging and clinical activity in therapeutic trials indicates that B cells play a vital role in mediating the clinical course of relapsing multiple sclerosis (MS). Although no agent that specifically targets B cells has yet been approved for clinical use, all existing disease-modifying therapies (DMTs) forMS modulate B-cell immunity to some degree. This review examines the effects of MS DMTs on B-cell immunity. MostMS DMTs induced a relative decrease in circulating memory B cells with concomitant expansion of circulating B-cell precursors and/or naive B cells. B-cell function was also altered; most DMTs induced B-cell production of the anti-inflammatory cytokine interleukin 10 while inhibiting B-cell expression of proinflammatory cytokines. The commonalities in the effects of approved DMTs on B-cell phenotype and function among treated patients with MS are striking and suggest that effects on B cells underlie part of their efficacy. More complete understanding of how the existing DMTs modulate B-cell immunity may identify future targets for therapeutic intervention. © 2016 American Medical Association. All rights reserved.
 


Document Type: Review
Source: Scopus

 


 

31) 
Hendrix, J.A.a , Bateman, R.J.b , Brashear, H.R.c , Duggan, C.b , Carrillo, M.C.a , Bain, L.J.d , DeMattos, R.e , Katz, R.G.f , Ostrowitzki, S.g , Siemers, E.e , Sperling, R.h , Vitolo, O.V.i 
Challenges, solutions, and recommendations for Alzheimer's disease combination therapy
(2016) Alzheimer's and Dementia, . Article in Press. 

DOI: 10.1016/j.jalz.2016.02.007

a Medical and Scientific Relations, Alzheimer's Association, Chicago, IL, USA
b Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
c Janssen Research and Development, South San Francisco, CA, USA
d Independent Science Writer, Elverson, PA, USA
e Eli Lilly and Company, Indianapolis, IN, USA
f Independent Consultant, San Diego, CA, USA
g F. Hoffmann-La Roche Ltd, Neuroscience, Basel, Switzerland
h Memory Disorders Unit, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States
i Pfizer, Inc., Neuroscience Research Unit, Cambridge, MA

Abstract
Given the complex neuropathology Alzheimer's disease (AD), combination therapy may be necessary for effective treatment. However, scientific, pragmatic, regulatory, and business challenges need to be addressed before combination therapy for AD can become a reality. Leaders from academia and industry, along with a former member of the Food and Drug Administration and the Alzheimer's Association, have explored these challenges and here propose a strategy to facilitate proof-of-concept combination therapy trials in the near future. First, a more integrated understanding of the complex pathophysiology and progression of AD is needed to identify the appropriate pathways and the disease stage to target. Once drug candidates are identified, novel clinical trial designs and selection of appropriate outcome assessments will be needed to enable definition and evaluation of the appropriate dose and dosing regimen and determination of efficacy. Success in addressing this urgent problem will only be achieved through collaboration among multiple stakeholders. © 2016 The Alzheimer's Association.
 


Document Type: Article in Press
Source: Scopus

 


 

32) 
Grucza, R.A.a , Agrawal, A.a , Krauss, M.J.a , Bongu, J.a , Plunk, A.D.b , Cavazos-Rehg, P.A.a , Bierut, L.J.a 
Declining Prevalence of Marijuana Use Disorders Among Adolescents in the United States, 2002 to 2013
(2016) Journal of the American Academy of Child and Adolescent Psychiatry, . Article in Press. 

DOI: 10.1016/j.jaac.2016.04.002

a Washington University School of Medicine, St. Louis
b Eastern Virginia Medical School, Norfolk, VA

Abstract
Objective: Little is known about recent trends in marijuana use disorders among adolescents in the United States. We analyzed trends in the past-year prevalence of . DSM-IV marijuana use disorders among adolescents, both overall and conditioned on past-year marijuana use. Potential explanatory factors for trends in prevalence were explored. Method: We assembled data from the adolescent samples of the 2002 to 2013 administrations of the National Survey on Drug Use and Health (N = 216,852; aged 12-17 years). The main outcome measures were odds ratios describing the average annual change in prevalence and conditional prevalence of marijuana use disorders, estimated from models of marijuana use disorder as a function of year. Post hoc analyses incorporated measures of potentially explanatory risk and protective factors into the trend analyses. Results: A decline in the past-year prevalence of marijuana use disorders was observed (odds ratio = 0.976 per year; 95% CI = 0.968, 0.984; . p < .001). This was due to both a net decline in past-year prevalence of use and a decline in the conditional prevalence of marijuana use disorders. The trend in marijuana use disorders was accounted for by a decrease in the rate of conduct problems among adolescents (e.g., fighting, stealing). Conclusion: Past-year prevalence of marijuana use disorders among US adolescents declined by an estimated 24% over the 2002 to 2013 period. The decline may be related to trends toward lower rates of conduct problems. Identification of factors responsible for the reduction in conduct problems could inform interventions targeting both conduct problems and marijuana use disorders. © 2016 American Academy of Child and Adolescent Psychiatry.

Author Keywords
Addiction;  Adolescence;  Epidemiology;  Externalizing;  Marijuana


Document Type: Article in Press
Source: Scopus

 


 

33) 
Culbreth, A.J.a , Gold, J.M.b , Cools, R.c d , Barch, D.M.a e 
Impaired activation in cognitive control regions predicts reversal learning in schizophrenia
(2016) Schizophrenia Bulletin, 42 (2), pp. 484-493. 

DOI: 10.1093/schbul/sbv075

a Department of Psychology, Washington University in St Louis, One Brookings Drive, St Louis, MO, United States
b Department of Psychiatry and Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, United States
c Department of Psychiatry, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
d Centre for Cognitive Neuroimaging, Donders Institute for Brain Cognition and Behaviour, Nijmegen, Netherlands
e Department of Psychiatry and Radiology, Washington University in St Louis, St Louis, MO, United States

Abstract
Reinforcement learning deficits have been associated with schizophrenia (SZ). However, the pathophysiology that gives rise to these abnormalities remains unclear. To address this question, SZ patients (N = 58) and controls (CN; N = 36) completed a probabilistic reversal-learning paradigm during functional magnetic resonance imaging scanning. During the task, participants choose between 2 stimuli. Initially, 1 stimulus was frequently rewarded (80%); the other was infrequently rewarded (20%). The reward contingencies reversed periodically because the participant learned the more rewarded stimulus. The results indicated that SZ patients achieved fewer reversals than CN, and demonstrated decreased winstayloseshift decision-making behavior. On loseshift compared to winstay trials, SZ patients showed reduced Blood Oxygen Level Dependent activation compared to CN in a network of brain regions widely associated with cognitive control, and striatal regions. Importantly, relationships between group membership and behavior were mediated by alterations in the activity of cognitive control regions, but not striatum. These findings indicate an important role for the cognitive control network in mediating the use and updating of value representations in SZ. Such results provide biological targets for further inquiry because researchers attempt to better characterize decision-making neural circuitry in SZ as a means to discover new pathways for interventions.

Author Keywords
Cognitive control;  FMRI;  Negative symptoms;  Reinforcement learning;  Reversal learning;  Reward processing;  Schizophrenia


Document Type: Article
Source: Scopus

 


 

34) 
Luking, K.R.a , Pagliaccio, D.b , Luby, J.L.c , Barch, D.M.c d e f 
Reward Processing and Risk for Depression Across Development
(2016) Trends in Cognitive Sciences, . Article in Press. 

DOI: 10.1016/j.tics.2016.04.002

a Department of Psychology, Stony Brook University, Stony Brook, NY 11794, USA
b Emotion and Development Branch, National Institute of Mental Health (NIMH), Bethesda, MD 20892, USA
c Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63130, USA
d Department of Psychology, Washington University in St. Louis, St. Louis, MO 63130, USA
e Department of Radiology, Washington University in St. Louis, St. Louis, MO 63130, USA
f Neuroscience Program, Washington University in St. Louis, St. Louis, MO 63130, USA

Abstract
Striatal response to reward has been of great interest in the typical development and psychopathology literatures. These parallel lines of inquiry demonstrate that although typically developing adolescents show robust striatal response to reward, adolescents with major depressive disorder (MDD) and those at high risk for MDD show a blunted response to reward. Understanding how these findings intersect is crucial for the development and application of early preventative interventions in at-risk children, ideally before the sharp increase in the rate of MDD onset that occurs in adolescence. Robust findings relating blunted striatal response to reward and MDD risk are reviewed and situated within a normative developmental context. We highlight the need for future studies investigating longitudinal development, specificity to MDD, and roles of potential moderators and mediators. Offspring of depressed mothers are at increased risk for developing depression and show blunted responses to reward, relative to low-risk peers, within the dorsal and ventral striatum.The strongest evidence for the relationship between depression risk and blunted striatal response to reward has been found during mid-adolescence, a time in development when healthy low-risk groups show maximal striatal response to reward.Blunted striatal response to reward is not simply a consequence of experiencing depression because both never-depressed high-risk adolescents and currently depressed adolescents show a similarly blunted striatal response to reward relative to low-risk controls.Blunted striatal response to reward may specifically relate to maternal depression, and not to maternal anxiety.Blunted striatal response to reward may co-occur with enhanced responses to loss of reward or punishment in high-risk groups. © 2016 Elsevier Ltd.

Author Keywords
Depression;  Development;  Reward


Document Type: Article in Press
Source: Scopus

 


 

35) 
Siddiqi, S.H., Chockalingam, R., Cloninger, C.R., Lenze, E.J., Cristancho, P.
Use of the temperament and character inventory to predict response to repetitive transcranial magnetic stimulation for major depression
(2016) Journal of Psychiatric Practice, 22 (3), pp. 193-202. 

DOI: 10.1097/PRA.0000000000000150

Department of Psychiatry, Washington University, School of Medicine in St Louis, P.O. Box 8134, 660 S Euclid Ave., St Louis, MO, United States

Abstract
Objective: The goal of this study was to investigate the utility of the Temperament and Character Inventory (TCI) in predicting antidepressant response to repetitive transcranial magnetic stimulation (rTMS). Background: Although rTMS of the dorsolateral prefrontal cortex is an established antidepressant treatment, little is known about predictors of response. The TCI measures multiple personality dimensions (harm avoidance, novelty seeking, reward dependence, persistence, self-directedness, self-transcendence, and cooperativeness), some of which have predicted response to pharmacotherapy and cognitive-behavioral therapy. A previous study suggested a possible association between self-directedness and response to rTMS in melancholic depression, although this was limited by the fact that melancholic depression is associated with a limited range of TCI profiles. Methods: Nineteen patients with a major depressive episode completed the TCI before a clinical course of rTMS over the dorsolateral prefrontal cortex. Treatment response was defined as ≥50% decrease in scores on the Hamilton Rating Scale for Depression (Ham-D). Baseline scores on each TCI dimension were compared between responders and nonresponders through analysis of variance. Pearson correlations were also calculated for temperament/character scores in comparison with percentage improvement in Ham-D scores. Results: Eleven of the 19 patients responded to rTMS. T-scores for persistence were significantly higher in responders than in nonresponders (P=0.022). Linear regression revealed a correlation between persistence scores and percentage improvement in Ham-D scores. Conclusions: Higher persistence scores predicted antidepressant response to rTMS. This may be explained by rTMS-induced enhancement of cortical excitability, which has been found to be decreased in patients with high persistence. Personality assessment that includes measurement of TCI persistence may be a useful component of precision medicine initiatives in rTMS for depression. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Author Keywords
Character;  Depression;  Dorsolateral prefrontal cortex;  Major depressive disorder;  Repetitive TMS (rTMS);  Temperament;  Temperament and Character Inventory (TCI);  Transcranial magnetic stimulation (TMS)


Document Type: Article
Source: Scopus

 


 

36) 
Sen, S.a , An, H.b , Menezes, P.c , Oakes, J.c , Eron, J.c , Lin, W.d , Robertson, K.e , Powers, W.e 
Increased Cortical Cerebral Blood Flow in Asymptomatic Human Immunodeficiency Virus-Infected Subjects
(2016) Journal of Stroke and Cerebrovascular Diseases, . Article in Press. 

DOI: 10.1016/j.jstrokecerebrovasdis.2016.03.045

a Department of Neurology, University of South Carolina, Columbia, South Carolina
b Mallinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, Missouri
c Division of Infectious Disease, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina
d Department of Radiology, University of North Carolina, Chapel Hill, North Carolina
e Department of Neurology, University of North Carolina, Chapel Hill, North Carolina

Abstract
Background: Human immunodeficiency virus (HIV)-infected individuals are at high risk for ischemic stroke. To investigate the physiological basis for this risk, we used magnetic resonance imaging (MRI) to measure oxygen extraction fraction (OEF) and cerebral blood flow (CBF) in treatment-naive asymptomatic HIV-infected subjects and controls. Methods: In treatment-naive asymptomatic HIV-infected subjects and age-, gender-, and race-matched controls, OEF was measured by MRI asymmetric spin-echo echo-planar imaging sequences and CBF was measured by MRI pseudocontinuous arterial spin labeling. Results: Twenty-six treatment-naive HIV-infected subjects and 27 age-, gender-, race-matched controls participated. Whole-brain, gray matter (GM), and white matter OEF were not different between the groups (all P > .70). Unexpectedly, HIV-infected subjects had significantly higher CBF in cortical GM (72.9 ± 16.2 mL/100 g/min versus 63.9 ± 9.9 mL/100 g/min; P = .01) but not in subcortical GM (P = .25). Conclusions: The observed increase in cortical GM CBF in treatment-naive HIV-infected subjects is unexpected, contrary to CBF decreases reported in HIV-infected subjects on treatment, and may represent an initial increase in metabolic activity due to an HIV-mediated inflammation. © 2016 National Stroke Association.

Author Keywords
Cerebral blood flow measurement;  Cerebrovascular disease;  Infectious disease;  Inflammation;  MRI


Document Type: Article in Press
Source: Scopus

 


 

37) 
Van Essen, D.C., Smith, J., Glasser, M.F., Elam, J., Donahue, C.J., Dierker, D.L., Reid, E.K., Coalson, T., Harwell, J.
The Brain Analysis Library of Spatial maps and Atlases (BALSA) database
(2016) NeuroImage, . Article in Press. 

DOI: 10.1016/j.neuroimage.2016.04.002

Neuroscience Department, Washington University School of Medicine, St. Louis, MO, United States

Abstract
We report on a new neuroimaging database, BALSA, that is a repository for extensively analyzed neuroimaging datasets from humans and nonhuman primates. BALSA is organized into two distinct sections. BALSA Reference is a curated repository of reference data accurately mapped to brain atlas surfaces and volumes, including various types of anatomically and functionally derived spatial maps as well as brain connectivity. BALSA Studies is a repository of extensively analyzed neuroimaging and neuroanatomical datasets associated with specific published studies, as voluntarily submitted by authors. It is particularly well suited for sharing of neuroimaging data as displayed in published figures. Uploading and downloading of data to BALSA involves 'scene' files that replicate how datasets appear in Connectome Workbench visualization software. Altogether, BALSA offers efficient access to richly informative datasets that are related to but transcend the images available in scientific publications. © 2016.

Author Keywords
Connectivity;  Human;  Neuroanatomy;  Neuroimaging;  Nonhuman primate


Document Type: Article in Press
Source: Scopus

 


 

38) 
Bartus, R.T.a , Johnson, E.M.b 
Clinical tests of neurotrophic factors for human neurodegenerative diseases, part 1: Where have we been and what have we learned?
(2016) Neurobiology of Disease, . Article in Press. 

DOI: 10.1016/j.nbd.2016.03.027

a RTBioconsultants, Inc., San Diego, CA, USA
b Departments of Neurology and Developmental Biology, Washington University Medical School, St. Louis, MO, USA

Abstract
Over the past 25. years, about 3 dozen clinical reports have been published regarding the safety and possible efficacy of neurotrophic factors in patients with various neurodegenerative diseases. This effort involved a half dozen different neurotrophic factors, using at least 5 different general delivery approaches for ALS (amyolateral sclerosis), peripheral neuropathies, PD (Parkinson's disease) and AD (Alzheimer's disease). While none of these efforts have yet produced efficacy data sufficiently robust or reliable to establish neurotrophic factors as treatments for any human disease, the obstacles encountered and novel information reported, when viewed collectively, provide important insight to help future efforts. Three consistent themes emerge from these publications: (1) unexpected and undesirable side effects, at times serious, have plagued many efforts to deliver neurotrophic factors to humans; (2) the magnitude and consistency of clinical benefit has been disappointing; (3) by far that most consistently proposed reason for the side effects and poor efficacy has been inadequate dosing and delivery.This paper reviews and attempts to synthesize the available data derived from clinical tests of neurotrophic factors for neurodegenerative diseases. The obstacles encountered, the solutions attempted, and the lessons learned are discussed. The vast majority of solutions have involved changes in dosing paradigms and dose levels, which has primarily led to improved safety outcomes. However, lack of adequate efficacy remains a significant issue. While current efforts continue to focus exclusively on still-further changes in dosing parameters, a review of available data argues that it may now be the time to ask whether other, non-dose-related variables should be given more serious consideration as being responsible for the great divide that exists between the robust effects seen in animal models and the relatively weak effects seen in human neurodegenerative patients. Foremost among these appears to be the severe degeneration seen in the majority of patients enrolled in past and current trials testing neurotrophic factors in humans. A companion paper (Bartus and Johnson, 2016), reviews the contemporary data and concludes that compelling empirical evidence already exists for enrolling earlier-stage subjects as likely essential to achieving more robust and reliable benefit. © 2016 Elsevier Inc.

Author Keywords
ALS;  Alzheimer's;  Clinical trials;  Disease progression;  Gene therapy;  Huntington's;  Neurodegeneration;  Neuron repair;  Neuroprotection;  Neurorestoration;  Parkinson's;  Peripheral neuropathies;  Stage-of-disease;  Treatment approaches


Document Type: Article in Press
Source: Scopus

 


 

39) 
Reddy, A.S.a , O'Brien, D.a b , Pisat, N.a b , Weichselbaum, C.T.a b , Sakers, K.a b , Lisci, M.a b , Dalal, J.S.a b , Dougherty, J.D.a b 
A Comprehensive Analysis of Cell Type-Specific Nuclear RNA From Neurons and Glia of the Brain
(2016) Biological Psychiatry, . Article in Press. 

DOI: 10.1016/j.biopsych.2016.02.021

a Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri
b Department of Genetics, Washington University School of Medicine, St. Louis, Missouri

Abstract
Background: Studies in psychiatric genetics have identified >100 loci associated with disease risk, yet many of these loci are distant from protein coding genes. Recent characterization of the transcriptional landscape of cell lines and whole tissues has suggested widespread transcription in both coding and noncoding regions of the genome, including differential expression from loci that produce regulatory noncoding RNAs that function within the nucleus; however, the nuclear transcriptome of specific cell types in the brain has not been previously investigated. Methods: We defined the nuclear transcriptional landscape of the three major cellular divisions of the nervous system using flow sorting of genetically labeled nuclei from bacTRAP mouse lines. Next, we characterized the unique expression of coding, noncoding, and intergenic RNAs in the mature mouse brain with RNA-Seq and validation with independent methods. Results: We found diverse expression across the cell types of all classes of RNAs, including long noncoding RNAs, several of which were confirmed as highly enriched in the nuclei of specific cell types using anatomic methods. We also discovered several examples of cell type-specific expression of tandem gene fusions, and we report the first cell type-specific expression of circular RNAs-a neuron-specific and nuclear-enriched RNA arising from the gene Hnrnpu. Conclusions: These data provide an important resource for studies evaluating the function of various noncoding RNAs in the brain, including noncoding RNAs that may play a role in psychiatric disease. © 2016 Society of Biological Psychiatry.

Author Keywords
Circular RNA;  Hnrnpu;  LincRNA;  Mirg1;  NcRNA;  Nuclear


Document Type: Article in Press
Source: Scopus

 


 

40) 
Kelly, M.P.a , Anderson, P.A.b , Sasso, R.C.c , Riew, K.D.d 
Preoperative opioid strength may not affect outcomes of anterior cervical procedures: a post hoc analysis of 2 prospective, randomized trials
(2015) Journal of neurosurgery. Spine, 23 (4), pp. 484-489. 

DOI: 10.3171/2015.1.SPINE14985

a Department of Orthopedic Surgery, Washington University School of Medicine, Saint Louis, Missouri;
b Department of Orthopedics & Rehabilitation, University of Wisconsin, Madison, Wisconsin; and
c Department of Orthopedic Surgery, Indiana Spine Group, Indianapolis, Indiana
d Department of Orthopedic Surgery, Washington University School of Medicine, Saint Louis, Missouri;

Abstract
OBJECT: The aim of this study is to evaluate the relationship between preoperative opioid strength and outcomes of anterior cervical decompressive surgery.

METHODS: A retrospective cohort of 1004 patients enrolled in 1 of 2 investigational device exemption studies comparing cervical total disc arthroplasty (TDA) and anterior cervical discectomy and fusion (ACDF) for single-level cervical disease causing radiculopathy or myelopathy was selected. At a preoperative visit, opioid use data, Neck Disability Index (NDI) scores, 36-Item Short-Form Health Survey (SF-36) scores, and numeric rating scale scores for neck and arm pain were collected. Patients were divided into strong (oxycodone/morphine/meperidine), weak (codeine/propoxyphene/hydrocodone), and opioid-naïve groups. Preoperative and postoperative (24 months) outcomes scores were compared within and between groups using the paired t-test and ANCOVA, respectively.

RESULTS: Patients were categorized as follows: 226 strong, 762 weak, and 16 opioid naïve. The strong and weak groups were similar with respect to age, sex, race, marital status, education level, Worker's Compensation status, litigation status, and alcohol use. At 24-month follow-up, no differences in change in arm or neck pain scores (arm: strong -52.3, weak -50.6, naïve -54.0, p = 0.244; neck: strong -52.7, weak -50.8, naïve -44.6, p = 0.355); NDI scores (strong -36.0, weak -33.3, naïve -32.3, p = 0.181); or SF-36 Physical Component Summary scores (strong: 14.1, weak 13.3, naïve 21.7, p = 0.317) were present. Using a 15-point improvement in NDI to determine success, the authors found no between-groups difference in success rates (strong 80.6%, weak 82.7%, naïve 73.3%, p = 0.134). No difference existed between treatment arms (TDA vs ACDF) for any outcome at any time point.

CONCLUSIONS: Preoperative opioid strength did not adversely affect outcomes in this analysis. Careful patient selection can yield good results in this patient population.

Author Keywords
ACDF = anterior cervical discectomy and fusion;  cervical arthroplasty;  cervical fusion;  IDE = investigational device exemption;  MCS = Mental Component Summary;  narcotic;  NDI = Neck Disability Index;  opioid;  pain;  PCS = Physical Component Summary;  SF-36 = 36-Item Short-Form Health Survey;  TDA = total disc arthroplasty


Document Type: Article
Source: Scopus

 


 

41) 
Golosheykin, S., Grant, J.D., Novak, O.V., Heath, A.C., Anokhin, A.P.
Genetic influences on heart rate variability
(2016) International Journal of Psychophysiology, . Article in Press. 

DOI: 10.1016/j.ijpsycho.2016.04.008

Washington University School of Medicine, St. Louis, MO, USA

Abstract
Heart rate variability (HRV) is the variation of cardiac inter-beat intervals over time resulting largely from the interplay between the sympathetic and parasympathetic branches of the autonomic nervous system. Individual differences in HRV are associated with emotion regulation, personality, psychopathology, cardiovascular health, and mortality. Previous studies have shown significant heritability of HRV measures. Here we extend genetic research on HRV by investigating sex differences in genetic underpinnings of HRV, the degree of genetic overlap among different measurement domains of HRV, and phenotypic and genetic relationships between HRV and the resting heart rate (HR). We performed electrocardiogram (ECG) recordings in a large population-representative sample of young adult twins (n = 1060 individuals) and computed HRV measures from three domains: time, frequency, and nonlinear dynamics. Genetic and environmental influences on HRV measures were estimated using linear structural equation modeling of twin data. The results showed that variability of HRV and HR measures can be accounted for by additive genetic and non-shared environmental influences (AE model), with no evidence for significant shared environmental effects. Heritability estimates ranged from 47 to 64%, with little difference across HRV measurement domains. Genetic influences did not differ between genders for most variables except the square root of the mean squared differences between successive R-R intervals (RMSSD, higher heritability in males) and the ratio of low to high frequency power (LF/HF, distinct genetic factors operating in males and females). The results indicate high phenotypic and especially genetic correlations between HRV measures from different domains, suggesting that >. 90% of genetic influences are shared across measures. Finally, about 40% of genetic variance in HRV was shared with HR. In conclusion, both HR and HRV measures are highly heritable traits in the general population of young adults, with high degree of genetic overlap across different measurement domains. © 2016 Elsevier B.V.

Author Keywords
Autonomic balance;  Genetics;  Heart rate variability;  Heritability;  Twins


Document Type: Article in Press
Source: Scopus

 


 

42) 
Lipson, S.K.a b , Jones, J.M.c d , Taylor, C.B.e f , Wilfley, D.E.g , Eichen, D.M.h , Fitzsimmons-Craft, E.E.g , Eisenberg, D.a i 
Understanding and promoting treatment-seeking for eating disorders and body image concerns on college campuses through online screening, prevention and intervention
(2016) Eating Behaviors, . Article in Press. 

DOI: 10.1016/j.eatbeh.2016.03.020

a University of Michigan School of Public Health, Department of Health Management and Policy, 1415 Washington Heights M3517, SPH II, Ann Arbor, MI 48109, USA
b University of Michigan School of Education, Center for the Study of Higher and Postsecondary Education, 610 East University Avenue, Ann Arbor, MI 48109, USA
c Lantern, 589 Howard Street, San Francisco, CA 94105, USA
d Medical University of Vienna, Spitalgasse 23, 1090, Wien, Austria
e Department of Psychiatry, Stanford University, 401 Quarry Road, Stanford, CA 94305, USA
f Palo Alto University, 1791 Arastradero Road, Palo Alto, CA 94304, USA
g Washington University School of Medicine, Department of Psychiatry, Campus Box 8134, 660 S. Euclid Avenue, St. Louis, MO 6311, USA
h University of California, San Diego, Department of Pediatrics, 9500 Gilman Drive, MC 0874, La Jolla, CA 92093, USA
i University of Michigan, Population Studies Center, Institute for Social Research, 426 Thompson Street, Ann Arbor, MI 48104, USA

Abstract
While there have been important recent advances in the development of effective universal prevention and intervention programs, it is not yet clear how to engage large numbers of students in these programs. In this paper, we report findings from a two-phase pilot study. In the first phase, we used a population-level, online survey to assess eating disorder symptom level and habits/attitudes related to service utilization (N = 2180). Using validated screening tools, we found that roughly one in three students has significant symptoms of eating disorders or elevated weight concerns, the vast majority of whom (86.5%) have not received treatment. In the second phase, we referred students to online prevention and selective/indicated intervention programs based on symptom classification (N = 1916). We find that program enrollment is highest for students in the indicated intervention (18.1%) and lowest for students in the universal prevention (4.1%). We find that traditionally-emphasized barriers such as stigma, misinformation, and financial limitations do not appear to be the most important factors preventing treatment-seeking. Rather students report not seeking help for reasons such as lack of time, lack of perceived need, and a desire to deal with the issue "on my own." Findings offer insight into the treatment-seeking habits and attitudes of college students, including those barriers that may be overcome by offering online programs and those that persist despite increased access to and convenience of relevant resources. © 2016 Elsevier Ltd.

Author Keywords
College students;  Eating disorders;  Prevention;  Treatment-seeking


Document Type: Article in Press
Source: Scopus

 


 

43) 
Catterson, A.D.a , Eldesouky, L.b , John, O.P.c 
An experience sampling approach to emotion regulation: Situational suppression use and social hierarchy
(2016) Journal of Research in Personality, . Article in Press. 

DOI: 10.1016/j.jrp.2016.04.004

a Institute of Personality and Social Research, Berkeley, CA, United States
b Department of Psychological and Brain Sciences, Washington University in St. Louis, United States
c Department of Psychology, University of California, Berkeley, United States

Abstract
Whereas past research has examined the use of emotion regulation strategies in terms of individual differences or responses to experimental manipulations, this research takes a naturalistic and repeated-measures approach to examine suppression use in specific situations. Using an experience sampling design, we find evidence across two samples (total N = 215) that (1) there was substantial within-person variation in suppression use, (2) the situational use of suppression was explained by situational differences in extraversion and social hierarchy, and (3) when used in contexts in which people felt they were low in social hierarchy, the negative relationship between suppression and well-being was attenuated. These findings suggest there are contexts in which suppression use may not be maladaptive, and demonstrate the benefits of studying emotion processes in real-life. © 2016.

Author Keywords
Emotion regulation;  Experience sampling;  Social hierarchy;  Suppression


Document Type: Article in Press
Source: Scopus

 


 

44) 
Mickle, A.D.a b , Shepherd, A.J.a b , Loo, L.a d , Mohapatra, D.P.a b c 
Induction of thermal and mechanical hypersensitivity by parathyroid hormone-related peptide through upregulation of TRPV1 function and trafficking
(2015) Pain, 156 (9), pp. 1620-1636. Cited 1 time.

DOI: 10.1097/j.pain.0000000000000224

a Department of Pharmacology, University of Iowa, Roy J. and Lucile A. Carver College of Medicine, Iowa City, IA, United States
b Department of Anesthesiology, Washington University Pain Center, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO, United States
c Department of Anesthesia, University of Iowa, Roy J. and Lucile A. Carver College of Medicine, Iowa City, IA, United States
d Department of Cell Biology and Physiology, UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC, United States

Abstract
The neurobiological mechanisms underlying chronic pain associated with cancers are not well understood. It has been hypothesized that factors specifically elevated in the tumor microenvironment sensitize adjacent nociceptive afferents. We show that parathyroid hormone-related peptide (PTHrP), which is found at elevated levels in the tumor microenvironment of advanced breast and prostate cancers, is a critical modulator of sensory neurons. Intraplantar injection of PTHrP led to the development of thermal and mechanical hypersensitivity in both male and female mice, which were absent in mice lacking functional transient receptor potential vanilloid-1 (TRPV1). The PTHrP treatment of cultured mouse sensory neurons enhanced action potential firing, and increased TRPV1 activation, which was dependent on protein kinase C (PKC) activity. Parathyroid hormone-related peptide induced robust potentiation of TRPV1 activation and enhancement of neuronal firing at mild acidic pH that is relevant to acidic tumor microenvironment. We also observed an increase in plasma membrane TRPV1 protein levels after exposure to PTHrP, leading to upregulation in the proportion of TRPV1-responsive neurons, which was dependent on the activity of PKC and Src kinases. Furthermore, co-injection of PKC or Src inhibitors attenuated PTHrP-induced thermal but not mechanical hypersensitivity. Altogether, our results suggest that PTHrP and mild acidic conditions could induce constitutive pathological activation of sensory neurons through upregulation of TRPV1 function and trafficking, which could serve as a mechanism for peripheral sensitization of nociceptive afferents in the tumor microenvironment. © 2015 International Association for the Study of Pain.

Author Keywords
Mechanical hypersensitivity;  Nociceptor sensitization;  Parathyroid hormone-related peptide;  Peripheral sensitization;  Thermal hypersensitivity;  TRPV1;  TRPV1 phosphorylation


Document Type: Article
Source: Scopus

 


 

45) 
Ji, W.a , Gamanut, R.b , Bista, P.c , D'Souza, R.D.d , Wang, Q.e , Burkhalter, A.f 
Modularity in the Organization of Mouse Primary Visual Cortex
(2015) Neuron, 87 (3), pp. 632-643. 

DOI: 10.1016/j.neuron.2015.07.004

a Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA
b Stem Cell and Brain Research Institute, INSERM U846, 69500 Bron, France; Université Claude Bernard Lyon, 69003 Lyon, France
c Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA
d Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA
e Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA; Allen Institute for Brain Science, Seattle, WA 98103, USA
f Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. Electronic address: burkhala@pcg.wustl.edu

Abstract
Layer 1 (L1) of primary visual cortex (V1) is the target of projections from many brain regions outside of V1. We found that inputs to the non-columnar mouse V1 from the dorsal lateral geniculate nucleus and feedback projections from multiple higher cortical areas to L1 are patchy. The patches are matched to a pattern of M2 muscarinic acetylcholine receptor expression at fixed locations of mouse, rat, and monkey V1. Neurons in L2/3 aligned with M2-rich patches have high spatial acuity, whereas cells in M2-poor zones exhibited high temporal acuity. Together M2+ and M2- zones form constant-size domains that are repeated across V1. Domains map subregions of the receptive field, such that multiple copies are contained within the point image. The results suggest that the modular network in mouse V1 selects spatiotemporally distinct clusters of neurons within the point image for top-down control and differential routing of inputs to cortical streams. Copyright © 2015 Elsevier Inc. All rights reserved.
 


Document Type: Article
Source: Scopus

 


 

46) 
Beaumont, T.L.a , Godzik, J.b , Dahiya, S.c , Smyth, M.D.d e 
Subependymal giant cell astrocytoma in the absence of tuberous sclerosis complex: case report
(2015) Journal of neurosurgery. Pediatrics, 16 (2), pp. 134-137. 

DOI: 10.3171/2015.1.PEDS13146

a Departments of 1 Neurosurgery and
b Departments of 1 Neurosurgery and
c Neuropathology, Washington University School of Medicine, and
d Departments of 1 Neurosurgery and
e St. Louis Children's Hospital, St. Louis, Missouri

Abstract
The authors report the case of a 14-year-old male with a subependymal giant cell astrocytoma (SEGA) that occurred in the absence of tuberous sclerosis complex (TSC). The patient presented with progressive headache and the sudden onset of nausea and vomiting. Neuroimaging revealed an enhancing left ventricular mass located in the region of the foramen of Monro with significant mass effect and midline shift. The lesion had radiographic characteristics of SEGA; however, the diagnosis remained unclear given the absence of clinical features of TSC. The patient underwent gross-total resection of the tumor with resolution of his symptoms. Although tumor histology was consistent with SEGA, genetic analysis of both germline and tumor DNA revealed no TSC1/2 mutations. Similarly, a comprehensive clinical evaluation failed to reveal any clinical features characteristic of TSC. Few cases of SEGA without clinical or genetic evidence of TSC have been reported. The histogenesis, genetics, and clinical approach to this rare lesion are briefly reviewed.

Author Keywords
GFAP = glial fibrillary acidic protein;  mosaicism;  oncology;  SEGA;  SEGA = subependymal giant cell astrocytoma;  subependymal giant cell astrocytoma;  TSC;  TSC = tuberous sclerosis complex;  tuberous sclerosis complex


Document Type: Article
Source: Scopus

 


 

47) 
Klose, M.a , Duvall, L.a c , Li, W.a , Liang, X.a , Ren, C.a d , Steinbach, J.b , Taghert, P.a 
Functional PDF Signaling in the Drosophila Circadian Neural Circuit Is Gated by Ral A-Dependent Modulation
(2016) Neuron, . Article in Press. 

DOI: 10.1016/j.neuron.2016.04.002

a Department of Neuroscience, Washington University Medical School, 660 South Euclid Avenue, St. Louis, MO 63110, USA
b Department of Anesthesiology, Washington University Medical School, 660 South Euclid Avenue, St. Louis, MO 63110, USA
c Laboratory of Neurogenetics and Behavior, The Rockefeller University, 1230 York Avenue, Box 63, New York, NY 10065, USA
d Center for Neural Circuits and Behavior, University of California, San Diego, La Jolla, CA 92092, USA

Abstract
The neuropeptide PDF promotes the normal sequencing of circadian behavioral rhythms in Drosophila, but its signaling mechanisms are not well understood. We report daily rhythmicity in responsiveness to PDF in critical pacemakers called small LNvs. There is a daily change in potency, as great as 10-fold higher, around dawn. The rhythm persists in constant darkness and does not require endogenous ligand (PDF) signaling or rhythmic receptor gene transcription. Furthermore, rhythmic responsiveness reflects the properties of the pacemaker cell type, not the receptor. Dopamine responsiveness also cycles, in phase with that of PDF, in the same pacemakers, but does not cycle in large LNv. The activity of RalA GTPase in s-LNv regulates PDF responsiveness and behavioral locomotor rhythms. Additionally, cell-autonomous PDF signaling reversed the circadian behavioral effects of lowered RalA activity. Thus, RalA activity confers high PDF responsiveness, providing a daily gate around the dawn hours to promote functional PDF signaling. Klose et al. demonstrate daily rhythmic sensitivity to neuropeptide PDF in the Drosophila circadian neural circuit: this rhythm gates PDF modulation of behavior to the period around dawn. The rhythm is cell type specific, ligand independent, and regulated by the RalA GTPase. © 2016 Elsevier Inc.

Author Keywords
Circadian rhythms;  Dopamine;  Drosophila;  GPCR;  PDF;  RalA


Document Type: Article in Press
Source: Scopus

 


 

48) 
Mauras, N.a , Mazaika, P.b , Buckingham, B.c , Weinzimer, S.d , White, N.H.e , Tsalikian, E.f , Hershey, T.g , Cato, A.h , Cheng, P.i , Kollman, C.j , Beck, R.W.k , Ruedy, K.l , Aye, T.m , Fox, L.n , Arbelaez, A.M.o , Wilson, D.p , Tansey, M.q , Tamborlane, W.r , Peng, D.s , Marzelli, M.t , Winer, K.K.u , Reiss, A.L.v , Diabetes Research in Children Network (DirecNet)w 
Longitudinal assessment of neuroanatomical and cognitive differences in young children with type 1 diabetes: association with hyperglycemia
(2015) Diabetes, 64 (5), pp. 1770-1779. 

DOI: 10.2337/db14-1445

a Division of Endocrinology, Diabetes & Metabolism, Nemours Children's Clinic, Jacksonville, FL nmauras@nemours.org
b Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA
c Department of Pediatrics, Stanford University School of Medicine, Stanford, CA
d Department of Pediatrics, Yale University School of Medicine, New Haven, CT
e Department of Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, MO
f Pediatric Endocrinology, University of Iowa, Iowa City, IA
g Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, MO Department of Radiology, Washington University School of Medicine in St. Louis, St. Louis, MO Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, MO
h Division of Neurology, Nemours Children's Clinic, Jacksonville, FL
i Jaeb Center for Health Research, Tampa, FL
j Jaeb Center for Health Research, Tampa, FL
k Jaeb Center for Health Research, Tampa, FL
l Jaeb Center for Health Research, Tampa, FL
m Department of Pediatrics, Stanford University School of Medicine, Stanford, CA
n Division of Endocrinology, Diabetes & Metabolism, Nemours Children's Clinic, Jacksonville, FL
o Department of Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, MO
p Department of Pediatrics, Stanford University School of Medicine, Stanford, CA
q Pediatric Endocrinology, University of Iowa, Iowa City, IA
r Department of Pediatrics, Yale University School of Medicine, New Haven, CT
s Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA
t Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA Department of Bioengineering, Stanford University School of Medicine, Stanford, CA
u Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD
v Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA Department of Pediatrics, Stanford University School of Medicine, Stanford, CA Department of Radiology, Stanford University School of Medicine, Stanford, CA

Abstract
Significant regional differences in gray and white matter volume and subtle cognitive differences between young diabetic and nondiabetic children have been observed. Here, we assessed whether these differences change over time and the relation with dysglycemia. Children ages 4 to <10 years with (n = 144) and without (n = 72) type 1 diabetes (T1D) had high-resolution structural MRI and comprehensive neurocognitive tests at baseline and 18 months and continuous glucose monitoring and HbA1c performed quarterly for 18 months. There were no differences in cognitive and executive function scores between groups at 18 months. However, children with diabetes had slower total gray and white matter growth than control subjects. Gray matter regions (left precuneus, right temporal, frontal, and parietal lobes and right medial-frontal cortex) showed lesser growth in diabetes, as did white matter areas (splenium of the corpus callosum, bilateral superior-parietal lobe, bilateral anterior forceps, and inferior-frontal fasciculus). These changes were associated with higher cumulative hyperglycemia and glucose variability but not with hypoglycemia. Young children with T1D have significant differences in total and regional gray and white matter growth in brain regions involved in complex sensorimotor processing and cognition compared with age-matched control subjects over 18 months, suggesting that chronic hyperglycemia may be detrimental to the developing brain. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
 


Document Type: Article
Source: Scopus

 


 

49) 
Hung, C.-F.a b , Breen, G.c d , Czamara, D.e , Corre, T.f g , Wolf, C.h , Kloiber, S.i , Bergmann, S.j k , Craddock, N.l , Gill, M.m , Holsboer, F.n , Jones, L.o , Jones, I.p , Korszun, A.q , Kutalik, Z.r s , Lucae, S.t , Maier, W.u , Mors, O.v , Owen, M.J.w , Rice, J.x, Rietschel, M.y , Uher, R.z aa , Vollenweider, P.ab , Waeber, G.ac , Craig, I.W.ad , Farmer, A.E.ae , Lewis, C.M.af ag , Müller-Myhsok, B.ah , Preisig, M.ai , McGuffin, P.aj , Rivera, M.ak al am an 
A genetic risk score combining 32 SNPs is associated with body mass index and improves obesity prediction in people with major depressive disorder
(2015) BMC medicine, 13, p. 86. 

DOI: 10.1186/s12916-015-0334-3

a MRC SGDP Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, Box PO82, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK. chifa.hung@gmail.com
b Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan. chifa.hung@gmail.com
c MRC SGDP Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, Box PO82, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK. 
d National Institute for Health Research Biomedical Research Centre for Mental Health at the Maudsley and Institute of Psychiatry, King's College London, London, UK. 
e Max-Planck-Institute of Psychiatry, Kraepelinstraße 2, 80804, Munich, Germany. darina@mpipsykl.mpg.de
f Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier, Universitaire Vaudois (CHUV), 1010, Lausanne, Switzerland. 
g Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland. 
h Max-Planck-Institute of Psychiatry, Kraepelinstraße 2, 80804, Munich, Germany. cwolf@mpipsykl.mpg.de
i Max-Planck-Institute of Psychiatry, Kraepelinstraße 2, 80804, Munich, Germany. stkloiber@mpipsykl.mpg.de
j Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier, Universitaire Vaudois (CHUV), 1010, Lausanne, Switzerland. 
k Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland. 
l MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ, UK. craddockn@Cardiff.ac.uk
m Department of Psychiatry, Trinity Centre for Health Sciences, Dublin 8, Ireland. mgill@tcd.ie
n Max-Planck-Institute of Psychiatry, Kraepelinstraße 2, 80804, Munich, Germany. holsboer@mpipsykl.mpg.de
o Department of Psychiatry, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, B15 2TT, UK. l.a.jones@bham.ac.uk
p MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ, UK. jonesir1@cf.ac.uk
q Barts and The London School of Medicine and Dentistry, Queen Mary's University of London, London, E1 2AD, UK. a.korszun@qmul.ac.uk
r Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier, Universitaire Vaudois (CHUV), 1010, Lausanne, Switzerland. 
s Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland. 
t Max-Planck-Institute of Psychiatry, Kraepelinstraße 2, 80804, Munich, Germany. lucae@mpipsykl.mpg.de
u Department of Psychiatry, University of Bonn, 53127, Bonn, Germany. 
v Research Department P, Aarhus University Hospital, Skovagervej 2, DK-8240, Risskov, Denmark. nielmors@rm.dk
w MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Henry Wellcome Building, Heath Park, Cardiff, CF14 4XN, UK. owenmj@cardiff.ac.uk
x Department of Psychiatry, Washington University School of Medicine, St Louis, MO, 63130, USA. jrice@wustl.edu
y Central Institute of Mental Health, 68159, Mannheim, Germany. 
z MRC SGDP Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, Box PO82, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK. 
aa Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, NS, B3H 3J5, Canada. 
ab Division of Internal Medicine, CHUV, Rue du Bugnon 21, 1011, Lausanne, Switzerland. 
ac Division of Internal Medicine, CHUV, Rue du Bugnon 21, 1011, Lausanne, Switzerland. 
ad MRC SGDP Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, Box PO82, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK. ian.craig@kcl.ac.uk
ae MRC SGDP Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, Box PO82, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK. anne.farmer@kcl.ac.uk
af MRC SGDP Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, Box PO82, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK. cathryn.lewis@kcl.ac.uk
ag Department of Medical and Molecular Genetics, School of Medicine, King's College London, 8th Floor, Tower Wing, Guys Hospital, London, SE1 9RT, UK. cathryn.lewis@kcl.ac.uk
ah Max-Planck-Institute of Psychiatry, Kraepelinstraße 2, 80804, Munich, Germany. bmm@mpipsykl.mpg.de
ai Department of Psychiatry, Lausanne University Hospital, 1008, Prilly-Lausanne, Switzerland. 
aj MRC SGDP Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, Box PO82, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK. 
ak MRC SGDP Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, Box PO82, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK. 
al National Institute for Health Research Biomedical Research Centre for Mental Health at the Maudsley and Institute of Psychiatry, King's College London, London, UK. 
am CIBERSAM-University of Granada and Institute of Neurosciences Federico Olóriz, Centro de Investigación Biomédica, University of Granada, Avda del Conocimiento s/n, 18100 Armilla, Granada, Spain. 
an Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, 18012, C/ Dr. Azpitarte, 4, 18012, Granada, Spain. 

Abstract
BACKGROUND: Obesity is strongly associated with major depressive disorder (MDD) and various other diseases. Genome-wide association studies have identified multiple risk loci robustly associated with body mass index (BMI). In this study, we aimed to investigate whether a genetic risk score (GRS) combining multiple BMI risk loci might have utility in prediction of obesity in patients with MDD.

METHODS: Linear and logistic regression models were conducted to predict BMI and obesity, respectively, in three independent large case-control studies of major depression (Radiant, GSK-Munich, PsyCoLaus). The analyses were first performed in the whole sample and then separately in depressed cases and controls. An unweighted GRS was calculated by summation of the number of risk alleles. A weighted GRS was calculated as the sum of risk alleles at each locus multiplied by their effect sizes. Receiver operating characteristic (ROC) analysis was used to compare the discriminatory ability of predictors of obesity.

RESULTS: In the discovery phase, a total of 2,521 participants (1,895 depressed patients and 626 controls) were included from the Radiant study. Both unweighted and weighted GRS were highly associated with BMI (P < 0.001) but explained only a modest amount of variance. Adding 'traditional' risk factors to GRS significantly improved the predictive ability with the area under the curve (AUC) in the ROC analysis, increasing from 0.58 to 0.66 (95% CI, 0.62-0.68; χ(2) = 27.68; P < 0.0001). Although there was no formal evidence of interaction between depression status and GRS, there was further improvement in AUC in the ROC analysis when depression status was added to the model (AUC = 0.71; 95% CI, 0.68-0.73; χ(2) = 28.64; P <0.0001). We further found that the GRS accounted for more variance of BMI in depressed patients than in healthy controls. Again, GRS discriminated obesity better in depressed patients compared to healthy controls. We later replicated these analyses in two independent samples (GSK-Munich and PsyCoLaus) and found similar results.

CONCLUSIONS: A GRS proved to be a highly significant predictor of obesity in people with MDD but accounted for only modest amount of variance. Nevertheless, as more risk loci are identified, combining a GRS approach with information on non-genetic risk factors could become a useful strategy in identifying MDD patients at higher risk of developing obesity.
 


Document Type: Article
Source: Scopus

 


 

50) 
Sunkara, A.a , DeAngelis, G.C.b , Angelaki, D.E.c 
Role of visual and non-visual cues in constructing a rotation-invariant representation of heading in parietal cortex
(2015) eLife, 4, . 

DOI: 10.7554/eLife.04693

a Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, United States
b Department of Brain and Cognitive Sciences, University of Rochester, Rochester, United States
c Department of Neuroscience, Baylor College of Medicine, Houston, United States

Abstract
As we navigate through the world, eye and head movements add rotational velocity patterns to the retinal image. When such rotations accompany observer translation, the rotational velocity patterns must be discounted to accurately perceive heading. The conventional view holds that this computation requires efference copies of self-generated eye/head movements. Here we demonstrate that the brain implements an alternative solution in which retinal velocity patterns are themselves used to dissociate translations from rotations. These results reveal a novel role for visual cues in achieving a rotation-invariant representation of heading in the macaque ventral intraparietal area. Specifically, we show that the visual system utilizes both local motion parallax cues and global perspective distortions to estimate heading in the presence of rotations. These findings further suggest that the brain is capable of performing complex computations to infer eye movements and discount their sensory consequences based solely on visual cues.

Author Keywords
dynamic perspective;  macaca mulatta;  neuroscience;  optic flow;  pursuit eye movements;  rhesus macaque;  self motion;  ventral intraparietal area


Document Type: Article
Source: Scopus

 

May 5, 2016

Hassenstab, J.a b c , Chasse, R.a b , Grabow, P.a d , Benzinger, T.L.S.a e f , Fagan, A.M.a b g , Xiong, C.a h , Jasielec, M.h , Grant, E.a h , Morris, J.C.a b i j k 
Certified normal: Alzheimer's disease biomarkers and normative estimates of cognitive functioning
(2016) Neurobiology of Aging, 43, pp. 23-33. 

DOI: 10.1016/j.neurobiolaging.2016.03.014

a Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
c Department of Psychological and Brian Sciences, Washington University in St. Louis, St. Louis, MO, United States
d Department of Psychology, University of Missouri-St. Louis, St. Louis, MO, United States
e Department of Radiology, Washington University School of Medicine, St. Louis, MO, United States
f Department of Neurological Surgery, University of Missouri-St. Louis, St. Louis, MO, United States
g Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States
h Department of Biostatistics, Washington University School of Medicine, St. Louis, MO, United States
i Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
j Department of Physical Therapy, Washington University School of Medicine, St. Louis, MO, United States
k Department of Occupational Therapy, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Normative samples drawn from older populations may unintentionally include individuals with preclinical Alzheimer's disease (AD) pathology, resulting in reduced means, increased variability, and overestimation of age effects on cognitive performance. A total of 264 cognitively normal (Clinical Dementia Rating = 0) older adults were classified as biomarker negative ("Robust Normal," n = 177) or biomarker positive ("Preclinical Alzheimer's Disease" [PCAD], n = 87) based on amyloid imaging, cerebrospinal fluid biomarkers, and hippocampal volumes. PCAD participants performed worse than robust normals on nearly all cognitive measures. Removing PCAD participants from the normative sample yielded higher means and less variability on episodic memory, visuospatial ability, and executive functioning measures. These results were more pronounced in participants aged 75 years and older. Notably, removing PCAD participants from the sample significantly reduced age effects across all cognitive domains. Applying norms from the robust normal sample to a separate cohort did not improve Clinical Dementia Rating classification when using standard deviation cutoff scores. Overall, removing individuals with biomarker evidence of preclinical AD improves normative sample quality and substantially reduces age effects on cognitive performance but provides no substantive benefit for diagnostic classifications. © 2016 Elsevier Inc.

Author Keywords
Alzheimer's disease;  Biomarkers;  Cognition;  Memory;  Normative data;  Preclinical disease


Document Type: Article
Source: Scopus

 


 

2) 
Pisetsky, E.M.a , Crosby, R.D.b c , Cao, L.b , Fitzsimmons-Craft, E.E.d , Mitchell, J.E.b c , Engel, S.G.b c , Wonderlich, S.A.b c , Peterson, C.B.a 
An examination of affect prior to and following episodes of getting drunk in women with bulimia nervosa
(2016) Psychiatry Research, 240, pp. 202-208. 

DOI: 10.1016/j.psychres.2016.04.044

a Department of Psychiatry, University of Minnesota, F282/2A West, 2450 Riverside Ave., Minneapolis, MN, United States
b Department of Psychiatry and Behavioral Science, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, United States
c Department of Clinical Research, Neuropsychiatric Research Institute, 120 8th Street S., Fargo, ND, United States
d Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States

Abstract
The current study examined the association between affect and self-reported alcohol intoxication in women with bulimia nervosa (BN; N=133). Participants completed a two-week ecological momentary assessment protocol. Momentary global positive affect (PA) and negative affect (NA), as well as the facets of NA (fear, guilt, hostility and sadness), were measured. Forty-five participants endorsed that they "got drunk" during the study period. Daily mean and variability of global PA and NA were compared between days with self-reported alcohol intoxication and days without self-reported alcohol intoxication. Trajectories of affect were modeled prior to and following episodes of self-reported alcohol intoxication. There were no differences in the mean or variability of PA or NA on days characterized by self-reported alcohol intoxication compared to days with no self-reported alcohol intoxication (ps>0.05). PA decreased significantly prior to self-reported alcohol intoxication and remained stable afterwards. There were no changes in global NA before or after self-reported alcohol intoxication, but an examination of the facets of NA showed that sadness increased following episodes of self-reported alcohol intoxication. These findings showed only partial support for a negative reinforcement model of alcohol use in women with BN. © 2016 .

Author Keywords
Alcohol use;  Bulimia nervosa;  Ecological momentary assessment


Document Type: Article
Source: Scopus

 


 

3) 
Wesonga, E.a , Shimony, J.S.b , Rutlin, J.c , Grange, D.K.d , White, D.A.a d 
Relationship between age and white matter integrity in children with phenylketonuria
(2016) Molecular Genetics and Metabolism Reports, 7, pp. 45-49. 

DOI: 10.1016/j.ymgmr.2016.03.003

a Department of Psychological and Brain Sciences, Washington University, One Brookings Drive, Campus Box 1125, St. Louis, MO, United States
b Mallinckrodt Institute of Radiology, Washington University, Campus Box 8131, St. Louis, MO, United States
c Department of Psychiatry, Washington University, Campus Box 8134, St. Louis, MO, United States
d Department of Pediatrics, Washington University, St. Louis, MO, United States

Abstract
Diffusion tensor imaging (DTI) has shown poorer microstructural white matter integrity in children with phenylketonuria (PKU), specifically decreases in mean diffusivity (MD), in comparison with healthy children. However, little research has been conducted to investigate the relationship between age and white matter integrity in this population. The present study examined group differences in the relationship between age and MD across a range of brain regions in 31 children with early- and continuously-treated PKU and 51 healthy control children. Relationships among MD, age, and group were explored using hierarchical linear regression and Pearson correlation. Results indicated a stronger age-related decrease in MD for children with PKU in comparison with healthy children in 4 of the 10 brain regions examined, suggesting that the trajectory of white matter development is abnormal in children with PKU. Further research using longitudinal methodology is needed to fully elucidate our understanding of white matter development in children with PKU. © 2016 The Authors. Published by Elsevier Inc.

Author Keywords
Brain;  Children;  Diffusion tensor imaging;  Phenylketonuria;  White matter


Document Type: Article
Source: Scopus

 


 

4) 
Guan, F.a b , Zhang, T.c , Liu, X.b d , Han, W.a b , Lin, H.e , Li, L.b , Chen, G.b , Li, T.b d 
Evaluation of voltage-dependent calcium channel γ gene families identified several novel potential susceptible genes to schizophrenia
(2016) Scientific Reports, 6, art. no. 24914, . 

DOI: 10.1038/srep24914

a Department of Forensic Psychiatry, School of Medicine and Forensics, Xi'An Jiaotong University, Xi'an, China
b Key Laboratory of National Ministry of Health for Forensic Sciences, School of Medicine and Forensics, Xi'An Jiaotong University, Xi'an, China
c Department of Psychiatry, School of Medicine, Washington University, Saint Louis, MO, United States
d Department of Forensic Medicine, School of Medicine and Forensics, Xi'An Jiaotong University, Xi'an, China
e Xi'An Mental Health Center, Xi'an, China

Abstract
Voltage-gated L-type calcium channels (VLCC) are distributed widely throughout the brain. Among the genes involved in schizophrenia (SCZ), genes encoding VLCC subunits have attracted widespread attention. Among the four subunits comprising the VLCC (α - 1, α -2/δ, β, and γ), the γ subunit that comprises an eight-member protein family is the least well understood. In our study, to further investigate the risk susceptibility by the γ subunit gene family to SCZ, we conducted a largescale association study in Han Chinese individuals. The SNP rs17645023 located in the intergenic region of CACNG4 and CACNG5 was identified to be significantly associated with SCZ (OR = 0.856, P = 5.43 × 10-5). Similar results were obtained in the meta-analysis with the current SCZ PGC data (OR = 0.8853). We also identified a two-SNP haplotype (rs10420331-rs11084307, P = 1.4 × 10-6) covering the intronic region of CACNG8 to be significantly associated with SCZ. Epistasis analyses were conducted, and significant statistical interaction (OR = 0.622, P = 2.93 × 10-6, Pperm &lt; 0.001) was observed between rs192808 (CACNG6) and rs2048137 (CACNG5). Our results indicate that CACNG4, CACNG5, CACNG6 and CACNG8 may contribute to the risk of SCZ. The statistical epistasis identified between CACNG5 and CACNG6 suggests that there may be an underlying biological interaction between the two genes.
 


Document Type: Article
Source: Scopus

 


 

5) 
Go, V.F.a , Morales, G.J.a , Mai, N.T.a , Brownson, R.C.b c , Ha, T.V.a , Miller, W.C.d e f 
Finding what works: Identification of implementation strategies for the integration of methadone maintenance therapy and HIV services in Vietnam
(2016) Implementation Science, 11 (1), art. no. 54, . 

DOI: 10.1186/s13012-016-0420-8

a University of North Carolina Gillings School of Global Public Health, Department of Health Behavior, Chapel Hill, NC, United States
b Washington University, Prevention Research Center in St. Louis, Brown School, St. Louis, MO, United States
c Washington University, Division of Public Health Sciences and Alvin J. Siteman Cancer Center, School of Medicine, St. Louis, MO, United States
d University of North Carolina Gillings School of Global Public Health, Department of Epidemiology, Chapel Hill, NC, United States
e University of North Carolina at Chapel Hill, Department of Medicine, School of Medicine, Chapel Hill, NC, United States
f The Ohio State University, Division of Epidemiology, College of Public Health, Columbus, OH, United States

Abstract
Background: Integration of methadone maintenance therapy (MMT) and HIV services is an evidence-based intervention (EBI) that benefits HIV care and reduces costs. While MMT/HIV integration is recommended by the World Health Organization and the Centers for Disease Control and Prevention, it is not widely implemented, due to organizational and operational barriers. Our study applied an innovative process to identify implementation strategies to address these barriers. Methods: Our process was adapted from the Expert Recommendations for Implementing Change (ERIC) protocol and consisted of two main phases. In Phase 1, we conducted 16 in-depth interviews with stakeholders and developed matrices to display barriers to integration. In Phase 2, we selected implementation strategies that addressed the barriers identified in Phase 1 and conducted a poll to vote on the most important and feasible strategies among a panel with expertise in cultural context and implementation science. Results: Barriers fell into two broad categories: policy and programmatic. At the policy level, barriers included lack of a national mandate, different structures (MMT vs. HIV clinic) for cost reimbursement and staff salaries, and resistance on the part of staff to take on additional tasks without compensation. Programmatic barriers included the need for cross-training in MMT and HIV tasks, staff accountability, and commitment from local leaders. In Phase 2, we focused on programmatic challenges. Based on voting results and iterative dialogue with our expert panel, we selected several implementation strategies in the domains of technical assistance, staff accountability, and local commitment that targeted these barriers. Conclusions: Key programmatic barriers to MMT/HIV integration in Vietnam may be addressed through implementation strategies that focus on technical assistance, staff accountability, and local commitment. Our process of identifying implementation strategies was simple, low cost, and potentially replicable to other settings. © 2016 Go et al.

Author Keywords
Implementation research;  Implementation science;  Implementation strategies;  MMT/HIV integration;  People who inject drugs;  Vietnam


Document Type: Article
Source: Scopus

 


 

6) 
Bucelli, R.C., Lee, M.S., McClelland, C.M.
Chronic Progressive External Ophthalmoplegia in the Absence of Ptosis
(2016) Journal of Neuro-Ophthalmology, . Article in Press. 

DOI: 10.1097/WNO.0000000000000384

Department of Neurology (RB), Washington University School of Medicine, St. Louis, Missouri; and Departments of Ophthalmology and Visual Neurosciences (ML, CMM), Neurology (ML), and Neurosurgery (ML), University of Minnesota, Minneapolis, Minnesota.

Abstract
ABSTRACT:: Classically defined as bilateral, symmetric, and progressive ophthalmoparesis with myopathic ptosis, chronic progressive external ophthalmoplegia (CPEO) rarely has been reported in the absence of ptosis. We describe 2 patients with CPEO and without ptosis who presented with binocular diplopia related to small-angle esodeviations, poor fusional amplitudes, and slow saccades. In both cases, hematological studies and neuroimaging ruled out alternative etiologies, whereas muscle biopsy showed findings of mitochondrial myopathy. © 2016 by North American Neuro-Ophthalmology Society
 


Document Type: Article in Press
Source: Scopus

 


 

7) 
Zhang, Y.a , Shi, P.b c d , Agarwal, R.K.e , Shi, Y.f 
Dissipativity Analysis for Discrete Time-Delay Fuzzy Neural Networks With Markovian Jumps
(2016) IEEE Transactions on Fuzzy Systems, 24 (2), art. no. 7164316, pp. 432-443. 

DOI: 10.1109/TFUZZ.2015.2459759

a College of Science, Henan University of Technology, Zhengzhou, China
b School of Electrical and Electronic Engineering, University of Adelaide, Adelaide, SA, Australia
c College of Engineering and Science, Victoria University, Melbourne, VIC, Australia
d College of Automation, Harbin Engineering University, Harbin, China
e Department of Mechanical Engineering, Washington University, St. Louis, MO, United States
f Graduate School of Science and Technology, Tokai University, Toroku, Kumamoto, Japan

Abstract
This paper is concerned with the dissipativity analysis and design of discrete Markovian jumping neural networks with sector-bounded nonlinear activation functions and time-varying delays represented by Takagi-Sugeno fuzzy model. The augmented fuzzy neural networks with Markovian jumps are first constructed based on estimator of Luenberger observer type. Then, applying piecewise Lyapunov-Krasovskii functional approach and stochastic analysis technique, a sufficient condition is provided to guarantee that the augmented fuzzy jump neural networks are stochastically dissipative. Moreover, a less conservative criterion is established to solve the dissipative state estimation problem by using matrix decomposition approach. Furthermore, to reduce the computational complexity of the algorithm, a dissipative estimator is designed to ensure stochastic dissipativity of the error fuzzy jump neural networks. As a special case, we have also considered the mixed H∞ and passive analysis of fuzzy jump neural networks. All criteria can be formulated in terms of linear matrix inequalities. Finally, two examples are given to show the effectiveness and potential of the new design techniques. © 2015 IEEE.

Author Keywords
dissipativity;  Fuzzy neural networks;  stochastic state estimation


Document Type: Article
Source: Scopus

 


 

8) 
Chung, Y.S., Barch, D.M.
Frontal-Striatum dysfunction during reward processing: Relationships to amotivation in schizophrenia
(2016) Journal of Abnormal Psychology, 125 (3), pp. 1-17. 

DOI: 10.1037/abn0000137

Washington University in St. Louis, United States

Abstract
Schizophrenia is characterized by deficits of context processing, thought to be related to dorsolateral prefrontal cortex (DLPFC) impairment. Despite emerging evidence suggesting a crucial role of the DLPFC in integrating reward and goal information, we do not know whether individuals with schizophrenia can represent and integrate Reward-Related context information to modulate cognitive control. To address this question, 36 individuals with schizophrenia (n=29) or schizoaffective disorder (n=7) and 27 healthy controls performed a variant of a response conflict task (Padmala & Pessoa, 2011) during fMRI scanning, in both baseline and reward conditions, with monetary incentives on some reward trials. We used a mixed State-Item design that allowed us to examine both sustained and transient reward effects on cognitive control. Different from predictions about impaired DLPFC function in schizophrenia, we found an intact pattern of increased sustained DLPFC activity during reward versus baseline blocks in individuals with schizophrenia at a group level but blunted sustained activations in the putamen. Contrary to our predictions, individuals with schizophrenia showed blunted Cue-Related activations in several regions of the basal ganglia responding to Reward-Predicting cues. Importantly, as predicted, individual differences in anhedonia/amotivation symptoms severity were significantly associated with reduced sustained DLPFC activation in the same region that showed overall increased activity as a function of reward. These results suggest that individual differences in motivational impairments in schizophrenia may be related to dysfunction of the DLPFC and striatum in motivationally salient situations. General Scientific Summary: This study found that individual differences in anhedonia and/or amotivation symptoms in schizophrenia were related to sustained brain activity in the dorsolateral prefrontal cortex during reward context. These findings suggest one of the potential neural mechanisms that may lead to motivational impairments in individuals with schizophrenia. © 2016 American Psychological Association.

Author Keywords
Dorsolateral prefrontal cortex;  Mixed fMRI design;  Negative symptoms;  Reward;  Schizophrenia


Document Type: Article
Source: Scopus

 


 

9) 
Ferradal, S.L.a b , Liao, S.M.c , Eggebrecht, A.T.b , Shimony, J.S.b , Inder, T.E.e , Culver, J.P.a b , Smyser, C.D.c d 
Functional Imaging of the Developing Brain at the Bedside Using Diffuse Optical Tomography
(2016) Cerebral Cortex, 26 (4), pp. 1558-1568. 

DOI: 10.1093/cercor/bhu320

a Department of Biomedical Engineering, Washington University, St Louis, MO, United States
b Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO, United States
c Department of Pediatrics, Washington University School of Medicine, St Louis, MO, United States
d Department of Neurology, Washington University School of Medicine, 660 South Euclid, St Louis, MO, United States
e Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Boston, MA, United States

Abstract
While histological studies and conventional magnetic resonance imaging (MRI) investigations have elucidated the trajectory of structural changes in the developing brain, less is known regarding early functional cerebral development. Recent investigations have demonstrated that resting-state functional connectivity MRI (fcMRI) can identify networks of functional cerebral connections in infants. However, technical and logistical challenges frequently limit the ability to perform MRI scans early or repeatedly in neonates, particularly in those at greatest risk for adverse neurodevelopmental outcomes. High-density diffuse optical tomography (HD-DOT), a portable imaging modality, potentially enables early continuous and quantitative monitoring of brain function in infants. We introduce an HD-DOT imaging system that combines advancements in cap design, ergonomics, and data analysis methods to allow bedside mapping of functional brain development in infants. In a cohort of healthy, full-term neonates scanned within the first days of life, HD-DOT results demonstrate strong congruence with those obtained using co-registered, subject-matched fcMRI and reflect patterns of typical brain development. These findings represent a transformative advance in functional neuroimaging in infants, and introduce HD-DOT as a powerful and practical method for quantitative mapping of early functional brain development in normal and high-risk neonates. © 2015 The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Author Keywords
developmental neuroimaging;  diffuse optical tomography;  functional magnetic resonance imaging;  infant;  neurodevelopment


Document Type: Article
Source: Scopus

 


 

10) 
Wallace, A.N.a , Tomasian, A.a , Vaswani, D.a , Vyhmeister, R.b , Chang, R.O.b , Jennings, J.W.a 
Radiographic local control of spinal metastases with percutaneous radiofrequency ablation and vertebral augmentation
(2016) American Journal of Neuroradiology, 37 (4), pp. 759-765. 

DOI: 10.3174/ajnr.A4595

a Mallinckrodt Institute of Radiology, Siteman Cancer Center, Washington University, School of Medicine, 510 S Kingshighway Blvd., St. Louis, MO, United States
b Washington University, School of Medicine, St. Louis, MO, United States

Abstract
BACKGROUND AND PURPOSE: Combination radiofrequency ablation and vertebral augmentation is an emerging minimally invasive therapy for patients with metastatic spine disease who have not responded to or have contraindications to radiation therapy. The purpose of this study was to evaluate the rate of radiographic local control of spinal metastases treated with combination radiofrequency ablation and vertebral augmentation. MATERIALS AND METHODS: We retrospectively reviewed our tumor ablation database for all patients who underwent radiofrequency ablation and vertebral augmentation of spinal metastases between April 2012 and July 2014. Tumors treated in conjunction with radiation therapy were excluded. Tumor characteristics, procedural details, and complications were recorded. Posttreatment imaging was reviewed for radiographic evidence of tumor progression. RESULTS: Fifty-five tumors met study inclusion criteria. Radiographic local tumor control rates were 89% (41/46) at 3 months, 74% (26/35) at 6 months, and 70% (21/30) at 1 year after treatment. Clinical follow-up was available in 93% (51/55) of cases. The median duration of clinical follow-up was 34 weeks (interquartile range, 15-89 weeks), during which no complications were reported and no patients had clinical evidence of metastatic spinal cord compression at the treated levels. CONCLUSIONS: Combination radiofrequency ablation and vertebral augmentation appears to be an effective treatment for achieving local control of spinal metastases. A prospective clinical trial is now needed to replicate these results.
 


Document Type: Article
Source: Scopus

 


 

11) 
Etzel, J.A.a , Cole, M.W.a b , Zacks, J.M.a , Kay, K.N.a , Braver, T.S.a 
Reward Motivation Enhances Task Coding in Frontoparietal Cortex
(2016) Cerebral Cortex, 26 (4), pp. 1647-1659. 

DOI: 10.1093/cercor/bhu327

a Washington University in St Louis, 1 Brookings Drive, St Louis, MO, United States
b Rutgers University, Newark, NJ, United States

Abstract
Reward motivation often enhances task performance, but the neural mechanisms underlying such cognitive enhancement remain unclear. Here, we used a multivariate pattern analysis (MVPA) approach to test the hypothesis that motivation-related enhancement of cognitive control results from improved encoding and representation of task set information. Participants underwent two fMRI sessions of cued task switching, the first under baseline conditions, and the second with randomly intermixed reward incentive and no-incentive trials. Information about the upcoming task could be successfully decoded from cue-related activation patterns in a set of frontoparietal regions typically associated with task control. More critically, MVPA classifiers trained on the baseline session had significantly higher decoding accuracy on incentive than non-incentive trials, with decoding improvement mediating reward-related enhancement of behavioral performance. These results strongly support the hypothesis that reward motivation enhances cognitive control, by improving the discriminability of task-relevant information coded and maintained in frontoparietal brain regions. © 2015 The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Author Keywords
cognitive control;  fMRI;  motivation;  MVPA;  prefrontal


Document Type: Article
Source: Scopus

 


 

12) 
McAvoy, M.a , Mitra, A.a , Coalson, R.S.a b , D'Avossa, G.c , Keidel, J.L.c , Petersen, S.E.a b d e f g , Raichle, M.E.a b d g 
Unmasking Language Lateralization in Human Brain Intrinsic Activity
(2016) Cerebral Cortex, 26 (4), pp. 1733-1746. 

DOI: 10.1093/cercor/bhv007

a Department of Radiology, Washington University, 4525 Scott Avenue, Saint Louis, MO, United States
b Department of Neurology, Washington University, Saint Louis, MO, United States
c School of Psychology, Bangor University, Bangor, United Kingdom
d Department of Anatomy and Neurobiology, Washington University, Saint Louis, MO, United States
e Department of Neurosurgery, Washington University, Saint Louis, MO, United States
f Department of Psychology, Washington University, Saint Louis, MO, United States
g Department of Biomedical Engineering, Washington University, Saint Louis, MO, United States

Abstract
Lateralization of function is a fundamental feature of the human brain as exemplified by the left hemisphere dominance of language. Despite the prominence of lateralization in the lesion, split-brain and task-based fMRI literature, surprisingly little asymmetry has been revealed in the increasingly popular functional imaging studies of spontaneous fluctuations in the fMRI BOLD signal (so-called resting-state fMRI). Here, we show the global signal, an often discarded component of the BOLD signal in resting-state studies, reveals a leftward asymmetry that maps onto regions preferential for semantic processing in left frontal and temporal cortex and the right cerebellum and a rightward asymmetry that maps onto putative attention-related regions in right frontal, temporoparietal, and parietal cortex. Hemispheric asymmetries in the global signal resulted from amplitude modulation of the spontaneous fluctuations. To confirm these findings obtained from normal, healthy, right-handed subjects in the resting-state, we had them perform 2 semantic processing tasks: synonym and numerical magnitude judgment and sentence comprehension. In addition to establishing a new technique for studying lateralization through functional imaging of the resting-state, our findings shed new light on the physiology of the global brain signal. © 2015 The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Author Keywords
attention network;  global signal;  hemispheric asymmetry;  resting-state;  semantic network


Document Type: Article
Source: Scopus

 


 

13) 
Agrawal, A.a , Grant, J.D.a , Lynskey, M.T.b , Madden, P.A.F.a , Heath, A.C.a , Bucholz, K.K.a , Sartor, C.E.c 
The genetic relationship between cannabis and tobacco cigarette use in European- and African-American female twins and siblings
(2016) Drug and Alcohol Dependence, . Article in Press. 

DOI: 10.1016/j.drugalcdep.2016.04.011

a Washington University School of Medicine, Department of Psychiatry, 660 S. Euclid, CB 8134, Saint Louis, MO 63110, USA
b King's College, Department of Addictions, London, UK
c Yale University School of Medicine, Department of Psychiatry, New Haven, CT, USA

Abstract
Background: Use of cigarettes and cannabis frequently co-occurs. We examine the role of genetic and environmental influences on variation in and covariation between tobacco cigarette and cannabis use across European-American (EA) and African-American (AA) women. Methods: Data on lifetime cannabis and cigarette use were drawn from interviews of 956 AA and 3557 EA young adult female twins and non-twin same sex female full siblings. Twin modeling was used to decompose variance in and covariance between cigarette and cannabis use into additive genetic, shared, special twin and non-shared environmental sources. Results: Cigarette use was more common in EAs (75.3%, 95% C.I. 73.8-76.7%) than AAs (64.2%, 95% C.I. 61.2-67.2%) while cannabis use was marginally more commonly reported by AAs (55.5%, 95% C.I. 52.5-58.8%) than EAs (52.4%, 95% C.I. 50.7-54.0%). Additive genetic factors were responsible for 43-66% of the variance in cigarette and cannabis use. Broad shared environmental factors (shared + special twin) played a more significant role in EA (23-29%) than AA (2-15%) women. In AA women, the influence of non-shared environment was more pronounced (42-45% vs. 11-19% in EA women). There was strong evidence for the same familial influences underlying use of both substances (rA = 0.82-0.89; rC+T = 0.70-0.75). Non-shared environmental factors were also correlated but less so (rE = 0.48-0.66). No racial/ethnic differences were apparent in these sources of covariation. Conclusion: Heritability of cigarette and cannabis use is comparable across racial/ethnic groups. Differences in the contribution of shared and non-shared environmental influences indicate that different factors may shape substance use in EA and AA women. © 2016.

Author Keywords
Cannabis;  Cigarette;  Heritability;  Initiation;  Tobacco;  Twin


Document Type: Article in Press
Source: Scopus

 


 

14) 
Kawadler, J.M.a , Clark, C.A.a , Mckinstry, R.C.b , Kirkham, F.J.a 
Brain atrophy in paediatric sickle cell anaemia: Findings from the silent infarct transfusion (SIT) trial
(2016) British Journal of Haematology, . Article in Press. 

DOI: 10.1111/bjh.14039

a Developmental Neurosciences UCL Institute of Child Health London UK
b Mallinckrodt Institute of Radiology Washington University School of Medicine St. Louis, MO USA
 

Author Keywords
Magnetic resonance imaging;  Paediatric haematology;  Sickle cell anaemia


Document Type: Article in Press
Source: Scopus

 


 

15) 
Atabaki, S.M.a , Hoyle, J.D.b c , Schunk, J.E.d , Monroe, D.J.e , Alpern, E.R.f g , Quayle, K.S.h , Glass, T.F.i j , Badawy, M.K.k l , Miskin, M.d , Schalick, W.O.m , Dayan, P.S.n , Holmes, J.F.o , Kuppermann, N.o p 
Comparison of Prediction Rules and Clinician Suspicion for Identifying Children With Clinically Important Brain Injuries After Blunt Head Trauma
(2016) Academic Emergency Medicine, . Article in Press. 

DOI: 10.1111/acem.12923

a Department of Pediatrics and Emergency Medicine George Washington University School of Medicine Washington, DC
b Department of Emergency Medicine Michigan State University School of Medicine Grand Rapids, MI
c Departments of Emergency Medicine and Pediatrics Western Michigan University Homer Stryker School of Medicine Kalamazoo, MI
d Department of Pediatrics University of Utah School of Medicine Salt Lake City, UT
e Department of Emergency Medicine Howard County General Hospital Columbia, MD
f Department of Pediatrics University of Pennsylvania School of Medicine Philadelphia, PA
g Department of Pediatrics Feinberg School of Medicine Northwestern University Chicago, IL
h Department of Pediatrics Washington University School of Medicine St. Louis, MO
i Department of Pediatrics University of Cincinnati College of Medicine Cincinnati, OH
j Department of Pediatrics Nemours Children's Hospital Orlando, FL
k Departments of Emergency Medicine and Pediatrics University of Rochester School of Medicine and Dentistry Rochester, NY
l Department of Emergency Medicine University of Texas Southwestern Medical Center Dallas, TX
m Departments of Orthopedics Rehabilitation University of Wisconsin School of Medicine Madison, WI
n Department of Pediatrics Columbia University College of Physicians and Surgeons New York, NY
o Department of Emergency Medicine University of California Davis School of Medicine Sacramento, CA
p Department of Pediatrics University of California Davis School of Medicine Sacramento, CA

Abstract
Objective: Children with minor head trauma frequently present to emergency departments (EDs). Identifying those with traumatic brain injuries (TBIs) can be difficult, and it is unknown whether clinical prediction rules outperform clinician suspicion. Our primary objective was to compare the test characteristics of the Pediatric Emergency Care Applied Research Network (PECARN) TBI prediction rules to clinician suspicion for identifying children with clinically important TBIs (ciTBIs) after minor blunt head trauma. Our secondary objective was to determine the reasons for obtaining computed tomography (CT) scans when clinical suspicion of ciTBI was low. Methods: This was a planned secondary analysis of a previously conducted observational cohort study conducted in PECARN to derive and validate clinical prediction rules for ciTBI among children with minor blunt head trauma in 25 PECARN EDs. Clinicians recorded their suspicion of ciTBI before CT as <1, 1-5, 6-10, 11-50, or >50%. We defined ciTBI as 1) death from TBI, 2) neurosurgery, 3) intubation for more than 24 hours for TBI, or 4) hospital admission of 2 nights or more associated with TBI on CT. To avoid overfitting of the prediction rules, we performed comparisons of the prediction rules and clinician suspicion on the validation group only. On the validation group, we compared the test accuracies of clinician suspicion > 1% versus having at least one predictor in the PECARN TBI age-specific prediction rules for identifying children with ciTBIs (one rule for children <2 years [preverbal], the other rule for children >2 years [verbal]). Results: In the parent study, we enrolled 8,627 children to validate the prediction rules, after enrolling 33,785 children to derive the prediction rules. In the validation group, clinician suspicion of ciTBI was recorded in 8,496/8,627 (98.5%) patients, and 87 (1.0%) had ciTBIs. CT scans were obtained in 2,857 (33.6%) patients in the validation group for whom clinician suspicion of ciTBI was recorded, including 2,099/7,688 (27.3%) of those with clinician suspicion of ciTBI of <1% and 758/808 (93.8%) of those with clinician suspicion >1%. The PECARN prediction rules were significantly more sensitive than clinician suspicion >1% of ciTBI for preverbal (100% [95% confidence interval (CI) = 86.3% to 100%] vs. 60.0% [95% CI = 38.7% to 78.9%]) and verbal children (96.8% [95% CI = 88.8% to 99.6%] vs. 64.5% [95% CI = 51.3% to 76.3%]). Prediction rule specificity, however, was lower than clinician suspicion >1% for preverbal children (53.6% [95% CI = 51.5% to 55.7%] vs. 92.4% [95% CI = 91.2% to 93.5%]) and verbal children (58.2% [95% CI = 56.9% to 59.4%] vs. 90.6% [95% CI = 89.8% to 91.3%]). Of the 7,688 patients in the validation group with clinician suspicion recorded as <1%, CTs were nevertheless obtained in 2,099 (27.3%). Three of 16 (18.8%) patients undergoing neurosurgery had clinician suspicion of ciTBI <1%. Conclusions: The PECARN TBI prediction rules had substantially greater sensitivity, but lower specificity, than clinician suspicion of ciTBI for children with minor blunt head trauma. Because CT ordering did not follow clinician suspicion of <1%, these prediction rules can augment clinician judgment and help obviate CT ordering for children at very low risk of ciTBI. © 2016 Society for Academic Emergency Medicine.
 


Document Type: Article in Press
Source: Scopus

 


 

16) 
Lemasson, B.a , Wang, H.b , Galbán, S.c , Li, Y.f g , Zhu, Y.f g , Heist, K.A.b , Tsein, C.d , Chenevert, T.L.b , Rehemtulla, A.d , Galbán, C.J.b , Holland, E.C.e , Ross, B.D.b 
Evaluation of Concurrent Radiation, Temozolomide and ABT-888 Treatment Followed by Maintenance Therapy with Temozolomide and ABT-888 in a Genetically Engineered Glioblastoma Mouse Model
(2016) Neoplasia (United States), 18 (2), pp. 82-89. 

DOI: 10.1016/j.neo.2015.11.014

a University Joseph Fourier, Grenoble Institut des Neurosciences, Grenoble, France
b Department of Radiology, University of Michigan, Ann Arbor, MI, United States
c Department of Pathology, University of Michigan, Ann Arbor, MI, United States
d Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, United States
e Department of Neurological Surgery, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, United States
f Children's Research Institute, NW Washington, DC, United States
g Department of Radiation Oncology, Washington University, St. Louis, MO, United States

Abstract
Despite the use of ionizing radiation (IR) and temozolomide (TMZ), outcome for glioblastoma (GBM) patients remains dismal. Poly (ADP-ribose) polymerase (PARP) is important in repair pathways for IR-induced DNA damage and TMZ-induced alkylation at N7-methylguanine and N3-methyldenine. However, optimized protocols for administration of PARP inhibitors have not been delineated. In this study, the PARP inhibitor ABT-888 was evaluated in combination with and compared to current standard-of-care in a genetically engineered mouse GBM model. Results demonstrated that concomitant TMZ/IR/ABT-888 with adjuvant TMZ/ABT-888 was more effective in inducing apoptosis and reducing proliferation with significant tumor growth delay and improved overall survival over concomitant TMZ/IR with adjuvant TMZ. Diffusion-weighted MRI, an early translatable response biomarker detected changes in tumors reflecting response at 1 day post TMZ/IR/ABT-888 treatment. This study provides strong scientific rationale for the development of an optimized dosing regimen for a PARP inhibitor with TMZ/IR for upfront treatment of GBM. © 2015 The Authors.
 


Document Type: Article
Source: Scopus

 


 

17) 
Giakoumaki, S.G.a , Karagiannopoulou, L.a , Rózsa, S.b , Zouraraki, C.a , Karamaouna, P.a , Cloninger, C.R.b 
Psychometric properties of the Greek TCI-R and its clinical correlates: Schizotypy and the self-regulation of affective and cognitive functioning
(2016) PeerJ, 2016 (3), art. no. 1830, . 

DOI: 10.7717/peerj.1830

a Department of Psychology, University of Crete, Rethymno, Greece
b Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Background. The revised Temperament and Character Inventory (TCI-R) measures Cloninger's psychobiological model of personality. The average effects of individual temperament and character traits have been associated with schizotypy and with impaired regulation of affect and cognition. We extended prior research by testing predictions about the association of specific multidimensional configurations of temperament and character traits on schizotypy, affect balance, and self-perceived cognitive functioning. Method. A well-educated sample of native Greeks (N = 483), completed a new Greek translation of the TCI-R, as well as the Schizotypal Personality Questionnaire (SPQ), the Positive/Negative Affect Schedule (PANAS) and the Cognitive Failures Questionnaire (CFQ). The factor structure of the TCI-R was examined with exploratory and confirmatory tests. Associations between reported measures were examined with correlational and regression analyses. Results. The TCI-R had good psychometric properties as expected from studies in other countries. As predicted, specific configurations of temperament and character were associated with schizotypy, negative affect balance, and cognitive lapses. The "Borderline/Explosive temperament" (high Novelty Seeking, high Harm Avoidance, low Reward Dependence), "Schizotypal/Disorganized character" (low Self-directedness, low Cooperativeness, high Self-transcendence), and "Low Ego Strength/Fragile" profile (high Harm Avoidance, low Persistence, low Self-Directedness) were each strongly associated with higher stereotypy, negative affect balance (low positive affect and high negative affect), and subjective cognitive lapses compared to their contrast groups. Discussion. Multidimensional TCI profiles are strongly related to individual differences in schizotypy and self-reported regulation of affect and cognition. The Greek translation of the TCI-R is psychometrically sound and useful for clinical assessment and research. © 2016 Giakoumaki et al.

Author Keywords
Affect balance;  Character;  Cognition;  Resilience;  Schizotypy;  Temperament;  Temperament character inventory-revised


Document Type: Article
Source: Scopus

 


 

18) 
Poretti, A.a b , Denecke, J.c , Miller, D.C.d , Schiffmann, H.e , Buhk, J.H.f , Grange, D.K.g , Doherty, D.h , Boltshauser, E.b 
Brainstem disconnection: Two additional patients and expansion of the phenotype
(2015) Neuropediatrics, 46 (2), pp. 139-144. 

DOI: 10.1055/s-0034-1544127

a Russell H. Morgan Department of Radiology and Radiological Science, Section of Pediatric Neuroradiology, Johns Hopkins University School of Medicine, 1800 Orleans Street, Baltimore, MD, United States
b Department of Pediatric Neurology, University Children's Hospital, Zurich, Switzerland
c Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
d Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, Columbia, MO, United States
e Department of Pediatrics, Paracelsus Medical University, Nuremberg, Germany
f Department of Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
g Division of Medical Genetics, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States
h Department of Pediatrics, University of Washington, Seattle Children's Hospital, Seattle, WA, United States

Abstract
Brainstem disconnection (BD) is a rare posterior fossa abnormality defined by the nearly complete absence of a brainstem segment with the rostral and caudal brainstem portions connected only by a thin cord of tissue. The outcome is poor and the majority of children die within the first 2 months of life without achieving developmental milestones. We report on the cases of two children with BD and a prolonged spontaneous survival. Neither patient required intubation or mechanical ventilation and each survived longer than 2 months (one child died at the age of 8 months, the other is alive at the age of 4.5 years). In addition, patient 1 is the only child with BD reported so far who achieved some developmental milestones. Although the long-term neurodevelopmental outcome of BD remains unfavorable, the expansion of the phenotypic spectrum may be important in terms of counseling. © 2015 Georg Thieme Verlag KG Stuttgart New York.

Author Keywords
brainstem;  brainstem disconnection;  brainstem malformation;  neonates;  neuroimaging;  outcome


Document Type: Article
Source: Scopus

 


 

19) 
Mattingly, G.a , Culpepper, L.b , Babcock, T.c , Arnold, V.d 
Aiming for remission in adults with attention-deficit/hyperactivity disorder: The primary care goal
(2015) Postgraduate Medicine, 127 (3), pp. 323-329. 

DOI: 10.1080/00325481.2015.1012481

a Washington University School of Medicine, St. Charles, MO, United States
b Boston University School of Medicine, Boston, MA, United States
c Shire, Wayne, PA, United States
d CNS Healthcare, University of Tennessee, Memphis, TN, United States

Abstract
Attention-deficit/hyperactivity disorder (ADHD) is often undiagnosed and undertreated in adults, resulting in wide-ranging problems and functional deficits in patients’ lives. In addition, psychiatric comorbidities unrelated to symptom severity may be present. However, effective treatment that can alleviate symptoms and bring about meaningful improvements in functionality is available. Primary care providers can play a crucial role in recognizing and diagnosing ADHD, initiating and monitoring treatment, and obtaining consultations or arranging referrals when necessary, all with the goal of achieving and maintaining remission. Fulfillment of this role requires a practical understanding of the diverse clinical manifestations of ADHD in patients stratified by age and sex, and familiarity with current treatment guidelines. Although there is no absolute consensus on the criteria by which remission is defined, treatment response may be guided by objective ratings of global symptom severity and patients’ self-reports of changes in their ability to cope with routine daily tasks, academic and vocational responsibilities, and social relationships. Although there has been much research into the genetic and neurophysiologic basis of ADHD, it is more important for primary care providers to appreciate that ADHD is a chronic condition requiring lifelong follow-up and that clinical presentation and response to treatment can vary widely among patients and over time in the same patients. Such variability makes the management of ADHD challenging, but the opportunity to bring about dramatic improvement in patients’ lives makes it imperative for primary care providers to be competent in this area. This review provides primary care clinicians with a practical definition of remission in adults with ADHD, to emphasize that symptom reduction does not necessarily mean intact functionality, and to suggest a multidisciplinary approach aimed at achieving the greatest possible reduction of symptoms and normalization of functionality. © 2015 Informa UK Ltd.

Author Keywords
Adults;  Attention-deficit/hyperactivity disorder;  Primary care;  Remission


Document Type: Review
Source: Scopus

 


 

20) 
Botvinick, M.a , Braver, T.b 
Motivation and cognitive control: From behavior to neural mechanism
(2015) Annual Review of Psychology, 66, pp. 83-113. 

DOI: 10.1146/annurev-psych-010814-015044

a Princeton Neuroscience Institute, Department of Psychology, Princeton University, Princeton, NJ, United States
b Department of Psychology, Washington University in St. Louis, St. Louis, MO, United States

Abstract
Research on cognitive control and executive function has long recognized the relevance of motivational factors. Recently, however, the topic has come increasingly to center stage, with a surge of new studies examining the interface of motivation and cognitive control. In the present article we survey research situated at this interface, considering work from cognitive and social psychology and behavioral economics, but with a particular focus on neuroscience research. We organize existing findings into three core areas, considering them in the light of currently vying theoretical perspectives. Based on the accumulated evidence, we advocate for a view of control function that treats it as a domain of reward-based decision making. More broadly, we argue that neuroscientific evidence plays a critical role in understanding the mechanisms by which motivation and cognitive control interact. Opportunities for further cross-fertilization between behavioral and neuroscientific research are highlighted. © 2015 by Annual Reviews. All rights reserved.

Author Keywords
Cognitive control;  Effort;  Motivation;  Prefrontal cortex;  Reward


Document Type: Article
Source: Scopus

 


 

21) 
Solga, A.C.a , Pong, W.W.a , Kim, K.-Y.b , Cimino, P.J.c , Toonen, J.A.a , Walker, J.d , Wylie, T.d , Magrini, V.d , Griffith, M.d , Griffith, O.L.d , Ly, A.d , Ellisman, M.H.b , Mardis, E.R.d , Gutmann, D.H.a 
RNA Sequencing of Tumor-Associated Microglia Reveals Ccl5 as a Stromal Chemokine Critical for Neurofibromatosis-1 Glioma Growth
(2015) Neoplasia (United States), 17 (10), pp. 776-788. 

DOI: 10.1016/j.neo.2015.10.002

a Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
b National Center for Microscopy and Imaging Research, University of California, San Diego, CA, United States
c Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
d The Genome Institute, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Solid cancers develop within a supportive microenvironment that promotes tumor formation and growth through the elaboration of mitogens and chemokines. Within these tumors, monocytes (macrophages and microglia) represent rich sources of these stromal factors. Leveraging a genetically engineered mouse model of neurofibromatosis type 1 (NF1) low-grade brain tumor (optic glioma), we have previously demonstrated that microglia are essential for glioma formation and maintenance. To identify potential tumor-associated microglial factors that support glioma growth (gliomagens), we initiated a comprehensive large-scale discovery effort using optimized RNA-sequencing methods focused specifically on glioma-associated microglia. Candidate microglial gliomagens were prioritized to identify potential secreted or membrane-bound proteins, which were next validated by quantitative real-time polymerase chain reaction as well as by RNA fluorescence in situ hybridization following minocycline-mediated microglial inactivation in vivo. Using these selection criteria, chemokine (C-C motif) ligand 5 (Ccl5) was identified as a chemokine highly expressed in genetically engineered Nf1 mouse optic gliomas relative to nonneoplastic optic nerves. As a candidate gliomagen, recombinant Ccl5 increased Nf1-deficient optic nerve astrocyte growth in vitro. Importantly, consistent with its critical role in maintaining tumor growth, treatment with Ccl5 neutralizing antibodies reduced Nf1 mouse optic glioma growth and improved retinal dysfunction in vivo. Collectively, these findings establish Ccl5 as an important microglial growth factor for low-grade glioma maintenance relevant to the development of future stroma-targeted brain tumor therapies. © 2015 The Authors.
 


Document Type: Article
Source: Scopus

 


 

22) 
Snyder-Warwick, A.K.a , Fattah, A.Y.a , Zive, L.a , Halliday, W.a , Borschel, G.H.b , Zuker, R.M.a 
The degree of facial movement following microvascular muscle transfer in pediatric facial reanimation depends on donor motor nerve axonal density
(2015) Plastic and Reconstructive Surgery, 135 (2), pp. 370e-381e. 

DOI: 10.1097/PRS.0000000000000860

a Facial Nerve Institute, Department of Surgery, Division of Plastic and Reconstructive Surgery, Washington University School of Medicine; the Facial Nerve Program, Regional Pediatric Burns and Plastic Surgery Service, Alder Hey Children's NHS Foundation Trust; Department of Surgery, , Division of Pathology, The Hospital for Sick Children; Division of Plastic and Reconstructive Surgery, University of Toronto
b Division of Plastic Surgery, Department of Pediatric Laboratory Medicine, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada

Abstract
Background: Free functional muscle transfer to the face is a standard of facial animation. The contralateral facial nerve, via a cross-face nerve graft, provides spontaneous innervation for the transferred muscle, but is not universally available and has additional shortcomings. The motor nerve to the masseter provides an alternative innervation source. In this study, the authors compared donor nerve histomorphometry and clinical outcomes in a single patient population undergoing free muscle transfer to the face. Methods: Pediatric patients undergoing dynamic facial (re-)animation with intraoperative nerve biopsies and gracilis transfer to the face powered by either the contralateral facial nerve via a cross-face nerve graft or the motor nerve to the masseter were reviewed over a 7-year period. Myelinated nerve counts were assessed histomorphometrically, and functional outcomes were evaluated with the Scaled Measurement of Improvement in Lip Excursion software. Results: From 2004 to 2011, 91 facial (re-)animation procedures satisfied study inclusion criteria. Average myelinated fiber counts were 6757 per mm2 in the donor facial nerve branch, 1647 per mm2 in the downstream cross-face nerve graft at the second stage, and 5289 per mm2 in the masseteric nerve. Reconstructions with either innervation source resulted in improvements in oral commissure excursion and smile symmetry, with the greatest amounts of oral commissure excursion noted in the masseteric nerve group. Conclusions: Facial (re-)animation procedures with use of the cross-face nerve graft or masseteric nerve are effective and result in symmetric smiles. The masseteric nerve provides a more robust innervation source and results in greater commissure excursion. Copyright © 2015 by the American Society of Plastic Surgeons.
 


Document Type: Conference Paper
Source: Scopus