Arts & Sciences Brown School McKelvey School Medicine Weekly Publications

WashU weekly Neuroscience publications

“Automatic labeling of cortical sulci for the human fetal brain based on spatio-temporal information of gyrification” (2019) NeuroImage

Automatic labeling of cortical sulci for the human fetal brain based on spatio-temporal information of gyrification
(2019) NeuroImage, 188, pp. 473-482. 

Yun, H.J.a b , Chung, A.W.a b , Vasung, L.a b , Yang, E.c , Tarui, T.a b d e , Rollins, C.K.f , Ortinau, C.M.g , Grant, P.E.a b c , Im, K.a b

a Fetal Neonatal Neuroimaging and Developmental Science Center, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, United States
b Division of Newborn Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, United States
c Department of Radiology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, United States
d Mother Infant Research Institute, Tufts Medical Center, Tufts University School of Medicine, Boston, MA 02111, United States
e Department of Pediatrics, Tufts Medical Center, Tufts University School of Medicine, Boston, MA 02111, United States
f Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, United States
g Department of Pediatrics, Washington University in St. Louis, St. Louis, MO 63110, United States

Abstract
Accurate parcellation and labeling of primary cortical sulci in the human fetal brain is useful for regional analysis of brain development. However, human fetal brains show large spatio-temporal changes in brain size, cortical folding patterns, and relative position/size of cortical regions, making accurate automatic sulcal labeling challenging. Here, we introduce a novel sulcal labeling method for the fetal brain using spatio-temporal gyrification information from multiple fetal templates. First, spatial probability maps of primary sulci are generated on the templates from 23 to 33 gestational weeks and registered to an individual brain. Second, temporal weights, which determine the level of contribution to the labeling for each template, are defined by similarity of gyrification between the individual and the template brains. We combine the weighted sulcal probability maps from the multiple templates and adopt sulcal basin-wise approach to assign sulcal labels to each basin. Our labeling method was applied to 25 fetuses (22.9–29.6 gestational weeks), and the labeling accuracy was compared to manually assigned sulcal labels using the Dice coefficient. Moreover, our multi-template basin-wise approach was compared to a single-template approach, which does not consider the temporal dynamics of gyrification, and a fully-vertex-wise approach. The mean accuracy of our approach was 0.958 across subjects, significantly higher than the accuracies of the other approaches. This novel approach shows highly accurate sulcal labeling and provides a reliable means to examine characteristics of cortical regions in the fetal brain. © 2018 Elsevier Inc.

Author Keywords
Cortical surface;  Fetal brain;  Multi-template labeling;  Parcellation;  Primary sulci

Document Type: Article
Publication Stage: Final
Source: Scopus

“Life engagement is associated with higher GDP among societies” (2019) Journal of Research in Personality

Life engagement is associated with higher GDP among societies
(2019) Journal of Research in Personality, 78, pp. 210-214. 

Hill, P.L.a , Cheung, F.b , Kube, A.a , Burrow, A.L.c

a Department of Psychological and Brain Sciences, Washington University in St. Louis, United States
b School of Public Health, University of Hong Kong, Hong Kong
c Department of Human Development, Cornell University, United States

Abstract
Research suggests that individuals who report a greater sense of purpose in life tend to fare better economically, which may be expected to extend to the societal-level, in terms of higher GDP. However, previous work has demonstrated a negative association between citizens’ reports of purpose and GDP. The current study reconciles these differences by specifically considering an important component of sense of purpose missing in the past societal work, namely life engagement. Using data representative of 99% of the world’s adult population from 2013 to 2015 Gallup World Poll, results demonstrate a clear positive association between life engagement and countries’ GDP. Moreover, results demonstrate the distinctive importance of assessing life engagement relative to alternative metrics for related constructs. © 2018 Elsevier Inc.

Author Keywords
GDP;  Life engagement;  Purpose in life;  Society-level outcomes

Document Type: Article
Publication Stage: Final
Source: Scopus

“Clinical challenges and future therapeutic approaches for neuronal ceroid lipofuscinosis” (2019) The Lancet. Neurology

Clinical challenges and future therapeutic approaches for neuronal ceroid lipofuscinosis
(2019) The Lancet. Neurology, 18 (1), pp. 107-116. 

Mole, S.E.a , Anderson, G.b , Band, H.A.c , Berkovic, S.F.d , Cooper, J.D.e , Kleine Holthaus, S.-M.f , McKay, T.R.g , Medina, D.L.h , Rahim, A.A.i , Schulz, A.j , Smith, A.J.f

a University College London, Medical Research Council Laboratory for Molecular Cell Biology and UCL Great Ormond Street Institute of Child Health, London, United Kingdom
b Department of Histopathology, Great Ormond Street Hospital, London, United Kingdom
c Batten Disease Family Association, Farnborough, United Kingdom
d Epilepsy Research Centre, Department of Medicine, Austin Health & Northern Health, University of Melbourne, Melbourne, VIC, Australia
e Department of Pediatrics, Washington University School of Medicine, St Louis, MO, United States
f UCL Institute of Ophthalmology, University College London, London, United Kingdom
g Centre for Bioscience, Manchester Metropolitan University, Manchester, United Kingdom
h Telethon Institute of Genetics and Medicine, Naples, Italy
i UCL School of Pharmacy, University College London, London, United Kingdom
j Department of Pediatrics, University Medical Center Hamburg-EppendorfHamburg, Germany

Abstract
Treatment of the neuronal ceroid lipofuscinoses, also known as Batten disease, is at the start of a new era because of diagnostic and therapeutic advances relevant to this group of inherited neurodegenerative and life-limiting disorders that affect children. Diagnosis has improved with the use of comprehensive DNA-based tests that simultaneously screen for many genes. The identification of disease-causing mutations in 13 genes provides a basis for understanding the molecular mechanisms underlying neuronal ceroid lipofuscinoses, and for the development of targeted therapies. These targeted therapies include enzyme replacement therapies, gene therapies targeting the brain and the eye, cell therapies, and pharmacological drugs that could modulate defective molecular pathways. Such therapeutic developments have the potential to enable earlier diagnosis and better targeted therapeutic management. The first approved treatment is an intracerebroventricularly administered enzyme for neuronal ceroid lipofuscinosis type 2 disease that delays symptom progression. Efforts are underway to make similar progress for other forms of the disorder. Copyright © 2019 Elsevier Ltd. All rights reserved.

Document Type: Review
Publication Stage: Final
Source: Scopus

“Misdiagnosis of multiple sclerosis: Impact of the 2017 McDonald criteria on clinical practice” (2019) Neurology

Misdiagnosis of multiple sclerosis: Impact of the 2017 McDonald criteria on clinical practice
(2019) Neurology, 92 (1), pp. 26-33. 

Solomon, A.J., Naismith, R.T., Cross, A.H.

From the Department of Neurological Sciences (A.J.S.), Larner College of Medicine at The University of Vermont, University Health Center, Burlington; and Department of Neurology (R.T.N., A.H.C.), Washington University in St. Louis, MO

Abstract
Misdiagnosis of multiple sclerosis (MS) (the incorrect assignment of a diagnosis of MS) remains a problem in contemporary clinical practice. Studies indicate that misdiagnosed patients are often exposed to prolonged unnecessary health care risks and morbidity. The recently published 2017 revision of the McDonald criteria for the diagnosis of MS provides an opportunity to consider the effect of these revisions on the problem of MS misdiagnosis. The 2017 McDonald criteria include several new recommendations to reduce potential for misdiagnoses. The criteria should be used for the types of patients in which validation studies were performed, specifically those patients who present with typical demyelinating syndromes. MRI lesion characteristics were defined for which McDonald criteria would be expected to perform with accuracy. However, 2017 revisions, which now include assessment for cortical lesions, and the inclusion of symptomatic lesions and positive oligoclonal bands for the fulfillment of diagnostic criteria, may have the potential to lead to misdiagnosis of MS if not applied appropriately. While the 2017 McDonald criteria integrate issues relating to MS misdiagnosis and incorporate specific recommendations for its prevention more prominently than prior criteria, the interpretation of clinical and radiologic assessments upon which these criteria depend will continue to allow misdiagnoses. In patients with atypical clinical presentations, the revised McDonald criteria may not be readily applied. In those situations, further evaluation or monitoring rather than immediate diagnosis of MS is prudent. © 2018 American Academy of Neurology.

Document Type: Review
Publication Stage: Final
Source: Scopus

“New insights into the role of TREM2 in Alzheimer’s disease” (2018) Molecular Neurodegeneration

New insights into the role of TREM2 in Alzheimer’s disease
(2018) Molecular Neurodegeneration, 13 (1), art. no. 66, . 

Gratuze, M.a b c , Leyns, C.E.G.a b c , Holtzman, D.M.a b c

a Department of Neurology, St. Louis, United States
b Hope Center for Neurological Disorders, St. Louis, United States
c Knight Alzheimer’s Disease Research Center, Washington University, School of Medicine, St. Louis, MO 63110, United States

Abstract
Alzheimer’s disease (AD) is the leading cause of dementia. The two histopathological markers of AD are amyloid plaques composed of the amyloid-β (Aβ) peptide, and neurofibrillary tangles of aggregated, abnormally hyperphosphorylated tau protein. The majority of AD cases are late-onset, after the age of 65, where a clear cause is still unknown. However, there are likely different multifactorial contributors including age, enviornment, biology and genetics which can increase risk for the disease. Genetic predisposition is considerable, with heritability estimates of 60-80%. Genetic factors such as rare variants of TREM2 (triggering receptor expressed on myeloid cells-2) strongly increase the risk of developing AD, confirming the role of microglia in AD pathogenesis. In the last 5 years, several studies have dissected the mechanisms by which TREM2, as well as its rare variants affect amyloid and tau pathologies and their consequences in both animal models and in human studies. In this review, we summarize increases in our understanding of the involvement of TREM2 and microglia in AD development that may open new therapeutic strategies targeting the immune system to influence AD pathogenesis. © 2018 The Author(s).

Author Keywords
Alzheimer’s disease;  ApoE;  Gliosis;  Microglia;  Neurodegeneration;  TREM2

Document Type: Review
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“The Itch–Scratch Cycle: A Neuroimmune Perspective” (2018) Trends in Immunology

The Itch–Scratch Cycle: A Neuroimmune Perspective
(2018) Trends in Immunology, 39 (12), pp. 980-991. 

Mack, M.R.a b , Kim, B.S.a b c d

a Center for the Study of Itch, Washington University School of Medicine, St. Louis, MO 63110, United States
b Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States
c Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, United States
d Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, United States

Abstract
Relentless, repetitive itching and scratching is a debilitating feature of many chronic inflammatory skin disorders such as atopic dermatitis. While well known clinically, this itch–scratch cycle has historically lacked in-depth mechanistic understanding. However, recent advances at the interface of itch neurobiology and skin immunology have shed new light on this phenomenon. In this review, we highlight recent advances in our understanding of the neuroimmunology of chronic itch centered around three key points of entry into the itch–scratch cycle: the epithelial barrier, the immune system, and the peripheral nervous system. Furthermore, we explore novel neuro-epithelial-immune interactions that may represent promising therapeutic paradigms. © 2018

Author Keywords
atopic dermatitis;  cytokines;  itch;  neuroimmunity;  proteases;  scratch;  skin barrier

Document Type: Review
Publication Stage: Final
Source: Scopus

“Development of best practices to minimize wound complications after complex tethered spinal cord surgery: A modified Delphi study” (2018) Journal of Neurosurgery: Pediatrics

Development of best practices to minimize wound complications after complex tethered spinal cord surgery: A modified Delphi study
(2018) Journal of Neurosurgery: Pediatrics, 22 (6), pp. 701-709. 

Alexiades, N.G.a s , Ahn, E.S.b , Blount, J.P.c , Brockmeyer, D.L.d , Browd, S.R.e , Grant, G.A.f , Heuer, G.G.g , Hankinson, T.C.h , Iskandar, B.J.i , Jea, A.j , Krieger, M.D.k , Leonard, J.R.l , Limbrick, D.D.m , Maher, C.O.n , Proctor, M.R.o , Sandberg, D.I.p , Wellons, J.C., IIIq , Shao, B.a r , Feldstein, N.A.a , Anderson, R.C.E.a

a Department of Neurological Surgery, Columbia University Medical Center, New York, NY, United States
b Department of Neurological Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
c Department of Neurosurgery, Division of Pediatric Neurosurgery, University of Alabama, Birmingham, AL, United States
d Department of Pediatric Neurosurgery, Primary Children’s Hospital, University of Utah, Salt Lake City, UT, United States
e Department of Neurosurgery, University of Washington Seattle Children’s Hospital, Seattle, WA, United States
f Department of Neurosurgery, Stanford University, Stanford, CA, United States
g Department of Neurosurgery, Children’s Hospital of PhiladelphiaPA, United States
h Department of Pediatric Neurosurgery, Children’s Hospital Colorado, Anschutz Medical Campus, Aurora, CO, United States
i Department of Neurosurgery, University of Wisconsin Hospitals and Clinics, Madison, WI, United States
j Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, United States
k Department of Neurological Surgery, USC Keck School of Medicine, Children’s Hospital of Los AngelesCA, United States
l Department of Neurosurgery, Nationwide Children’s Hospital, Ohio State University College of Medicine, Columbus, OH, United States
m Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, United States
n Department of Neurosurgery, University of Michigan, Ann Arbor, MI, United States
o Department of Neurosurgery, Children’s Hospital Boston, Harvard Medical School, Boston, MA, United States
p Department of Neurosurgery, McGovern Medical School, University of Texas Health Science Center, Houston, TX, United States
q Department of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN, United States
r Rutgers New Jersey Medical School, Newark, NJ, United States
s Neurological Institute of New York, New York, NY, United States

Abstract
Objective: Complications after complex tethered spinal cord (cTSC) surgery include infections and cerebrospinal fluid (CSF) leaks. With little empirical evidence to guide management, there is variability in the interventions undertaken to limit complications. Expert-based best practices may improve the care of patients undergoing cTSC surgery. Here, authors conducted a study to identify consensus-driven best practices. Methods: The Delphi method was employed to identify consensual best practices. A literature review regarding cTSC surgery together with a survey of current practices was distributed to 17 board-certified pediatric neurosurgeons. Thirty statements were then formulated and distributed to the group. Results of the second survey were discussed during an inperson meeting leading to further consensus, which was defined as ≥ 80% agreement on a 4-point Likert scale (strongly agree, agree, disagree, strongly disagree). Results: Seventeen consensus-driven best practices were identified, with all participants willing to incorporate them into their practice. There were four preoperative interventions: (1, 2) asymptomatic AND symptomatic patients should be referred to urology preoperatively, (3, 4) routine preoperative urine cultures are not necessary for asymptomatic AND symptomatic patients. There were nine intraoperative interventions: (5) patients should receive perioperative cefazolin or an equivalent alternative in the event of allergy, (6) chlorhexidine-based skin preparation is the preferred regimen, (7) saline irrigation should be used intermittently throughout the case, (8) antibiotic-containing irrigation should be used folsurlowing dural closure, (9) a nonlocking running suture technique should be used for dural closure, (10) dural graft overlay should be used when unable to obtain primary dural closure, (11) an expansile dural graft should be incorporated in cases of lipomyelomeningocele in which primary dural closure does not permit free flow of CSF, (12) paraxial muscles should be closed as a layer separate from the fascia, (13) routine placement of postoperative drains is not necessary. There were three postoperative interventions: (14) postoperative antibiotics are an option and, if given, should be discontinued within 24 hours; (15) patients should remain flat for at least 24 hours postoperatively; (16) routine use of abdominal binders or other compressive devices postoperatively is not necessary. One intervention was prioritized for additional study: (17) further study of additional gram-negative perioperative coverage is needed. Conclusions: A modified Delphi technique was used to develop consensus-driven best practices for decreasing wound complications after cTSC surgery. Further study is required to determine if implementation of these practices will lead to reduced complications. Discussion through the course of this study resulted in the initiation of a multicenter study of gram-negative surgical site infections in cTSC surgery. © AANS 2018.

Author Keywords
Cerebrospinal fluid leak;  Delphi method;  Spine;  Surgical site infection;  Tethered spinal cord

Document Type: Article
Publication Stage: Final
Source: Scopus

“De novo variants in congenital diaphragmatic hernia identify MYRF as a new syndrome and reveal genetic overlaps with other developmental disorders” (2018) PLoS genetics

De novo variants in congenital diaphragmatic hernia identify MYRF as a new syndrome and reveal genetic overlaps with other developmental disorders
(2018) PLoS genetics, 14 (12), p. e1007822. 

Qi, H.a b , Yu, L.c , Zhou, X.a c , Wynn, J.c , Zhao, H.a d , Guo, Y.a , Zhu, N.a c , Kitaygorodsky, A.a d , Hernan, R.c , Aspelund, G.e , Lim, F.-Y.f , Crombleholme, T.f , Cusick, R.g , Azarow, K.h , Danko, M.E.i , Chung, D.i , Warner, B.W.j , Mychaliska, G.B.k , Potoka, D.l , Wagner, A.J.m , ElFiky, M.n , Wilson, J.M.o p , Nickerson, D.q , Bamshad, M.q , High, F.A.o p r , Longoni, M.p r , Donahoe, P.K.p r , Chung, W.K.c s t , Shen, Y.a d u

a Department of Systems Biology, Columbia University Medical CenterNY, United States
b Department of Applied Mathematics and Applied Physics, Columbia UniversityNY, United States
c Department of Pediatrics Medical Center, Columbia UniversityNY, United States
d Department of Biomedical Informatics, Columbia University Medical CenterNY, United States
e Department of Surgery, Columbia University Medical CenterNY, United States
f Cincinnati Children’s Hospital, Cincinnati, OH, United States
g Children’s Hospital & Medical Center of Omaha, University of Nebraska College of Medicine, Omaha, NE, United States
h Department of Surgery, Oregon Health & Science University, Portland, OR, United States
i Monroe Carell Jr. Children’s Hospital, Vanderbilt University Medical Center, Nashville, TN, United States
j Washington University, St. Louis Children’s Hospital, St. Louis, MO, United States
k University of Michigan, CS Mott Children’s Hospital, Ann Arbor, MI, United States
l Children’s Hospital of Pittsburgh, Pittsburgh, PA, United States
m Medical College of Wisconsin, Milwaukee, WI, United States
n Department of Pediatric Surgery, Faculty of Medicine, Cairo University, Cairo, Egypt
o Department of Surgery, Boston Children’s Hospital, Boston, MA, United States
p Department of Surgery, Harvard Medical School, Boston, MA, United States
q University of Washington, Seattle, WA, United States
r Pediatric Surgical Research Laboratories, Department of Surgery, Massachusetts General Hospital, Boston, MA, United States
s Department of Medicine, Columbia UniversityNY, United States
t Herbert Irving Comprehensive Cancer Center, Columbia University Medical CenterNY, United States
u JP Sulzberger Columbia Genome Center, Columbia University Medical CenterNY, United States

Abstract
Congenital diaphragmatic hernia (CDH) is a severe birth defect that is often accompanied by other congenital anomalies. Previous exome sequencing studies for CDH have supported a role of de novo damaging variants but did not identify any recurrently mutated genes. To investigate further the genetics of CDH, we analyzed de novo coding variants in 362 proband-parent trios including 271 new trios reported in this study. We identified four unrelated individuals with damaging de novo variants in MYRF (P = 5.3×10-8), including one likely gene-disrupting (LGD) and three deleterious missense (D-mis) variants. Eight additional individuals with de novo LGD or missense variants were identified from our other genetic studies or from the literature. Common phenotypes of MYRF de novo variant carriers include CDH, congenital heart disease and genitourinary abnormalities, suggesting that it represents a novel syndrome. MYRF is a membrane associated transcriptional factor highly expressed in developing diaphragm and is depleted of LGD variants in the general population. All de novo missense variants aggregated in two functional protein domains. Analyzing the transcriptome of patient-derived diaphragm fibroblast cells suggest that disease associated variants abolish the transcription factor activity. Furthermore, we showed that the remaining genes with damaging variants in CDH significantly overlap with genes implicated in other developmental disorders. Gene expression patterns and patient phenotypes support pleiotropic effects of damaging variants in these genes on CDH and other developmental disorders. Finally, functional enrichment analysis implicates the disruption of regulation of gene expression, kinase activities, intra-cellular signaling, and cytoskeleton organization as pathogenic mechanisms in CDH.

Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access

“Selective D2 receptor PET in manganese-exposed workers” (2018) Neurology

Selective D2 receptor PET in manganese-exposed workers
(2018) Neurology, 91 (11), pp. e1022-e1030. 

Criswell, S.R., Warden, M.N., Searles Nielsen, S., Perlmutter, J.S., Moerlein, S.M., Sheppard, L., Lenox-Krug, J., Checkoway, H., Racette, B.A.

From the Department of Neurology (S.R.C., M.N.W., S.S.N., J.S.P., J.L.-K., B.A.R.), Department of Radiology (J.S.P., S.M.M.), Department of Neuroscience (J.S.P.), Program in Physical Therapy (J.S.P.), Program in Occupational Therapy (J.S.P.), and Department of Biochemistry and Molecular Biophysics (S.M.M.), Washington University School of Medicine, St. Louis, MO; Department of Environmental and Occupational Health Sciences (L.S.) and Department of Biostatistics (L.S.), University of Washington, School of Public Health, Seattle; Department of Family Medicine and Public Health (H.C.) and Department of Neurosciences (H.C.), University of California, San Diego, School of Medicine, La Jolla; and School of Public Health (B.A.R.), Faculty of Health Sciences, University of the Witwatersrand, Parktown, South Africa

Abstract
OBJECTIVE: To investigate the associations between manganese (Mn) exposure, D2 dopamine receptors (D2Rs), and parkinsonism using [11C](N-methyl)benperidol (NMB) PET. METHODS: We used NMB PET to evaluate 50 workers with a range of Mn exposure: 22 Mn-exposed welders, 15 Mn-exposed workers, and 13 nonexposed workers. Cumulative Mn exposure was estimated from work histories, and movement disorder specialists examined all workers. We calculated NMB D2R nondisplaceable binding potential (BPND) for the striatum, globus pallidus, thalamus, and substantia nigra (SN). Multivariate analysis of covariance with post hoc descriptive discriminate analysis identified regional differences by exposure group. We used linear regression to examine the association among Mn exposure, Unified Parkinson’s Disease Rating Scale motor subsection 3 (UPDRS3) score, and regional D2R BPND. RESULTS: D2R BPND in the SN had the greatest discriminant power among exposure groups (p < 0.01). Age-adjusted SN D2R BPND was 0.073 (95% confidence interval [CI] 0.022-0.124) greater in Mn-exposed welders and 0.068 (95% CI 0.013-0.124) greater in Mn-exposed workers compared to nonexposed workers. After adjustment for age, SN D2R BPND was 0.0021 (95% CI 0.0005-0.0042) higher for each year of Mn exposure. Each 0.10 increase in SN D2R BPND was associated with a 2.65 (95% CI 0.56-4.75) increase in UPDRS3 score. CONCLUSIONS AND RELEVANCE: Nigral D2R BPND increased with Mn exposure and clinical parkinsonism, indicating dose-dependent dopaminergic dysfunction of the SN in Mn neurotoxicity. © 2018 American Academy of Neurology.

Document Type: Article
Publication Stage: Final
Source: Scopus

“Emerging evidence for cannabis’ role in opioid use disorder” (2018) Cannabis and Cannabinoid Research

Emerging evidence for cannabis’ role in opioid use disorder
(2018) Cannabis and Cannabinoid Research, 3 (1), pp. 179-189. 

Wiese, B.a b , Wilson-Poe, A.R.b

a Department of Psychology, University of Missouri-St. Louis, St. Louis, MO, United States
b Department of Anesthesiology, Pain Center, Washington University, School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, United States

Abstract
Introduction: The opioid epidemic has become an immense problem in North America, and despite decades of research on the most effective means to treat opioid use disorder (OUD), overdose deaths are at an all-time high, and relapse remains pervasive. Discussion: Although there are a number of FDA-approved opioid replacement therapies and maintenance medications to help ease the severity of opioid withdrawal symptoms and aid in relapse prevention, these medications are not risk free nor are they successful for all patients. Furthermore, there are legal and logistical bottlenecks to obtaining traditional opioid replacement therapies such as methadone or buprenorphine, and the demand for these services far outweighs the supply and access. To fill the gap between efficacious OUD treatments and the widespread prevalence of misuse, relapse, and overdose, the development of novel, alternative, or adjunct OUD treatment therapies is highly warranted. In this article, we review emerging evidence that suggests that cannabis may play a role in ameliorating the impact of OUD. Herein, we highlight knowledge gaps and discuss cannabis’ potential to prevent opioid misuse (as an analgesic alternative), alleviate opioid withdrawal symptoms, and decrease the likelihood of relapse. Conclusion: The compelling nature of these data and the relative safety profile of cannabis warrant further exploration of cannabis as an adjunct or alternative treatment for OUD. © 2018 Beth Wiese and Adrianne R. Wilson-Poe.

Author Keywords
cannabis;  opioid addiction;  opioid treatment;  relapse prevention

Document Type: Review
Publication Stage: Final
Source: Scopus

“Meeting Update-Society for Neuro-Oncology 2017 Annual Meeting” (2018) Neuro-oncology

Meeting Update-Society for Neuro-Oncology 2017 Annual Meeting
(2018) Neuro-oncology, 20 (2), pp. 156-159. 

Strowd, R.E.a , Kim, A.H.b , Wen, P.Y.c

a Department of Neurology and Internal Medicine, Section on Hematology and Oncology, Wake Forest School of Medicine, Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC, United States
b Department of Neurological Surgery, Washington University School of Medicine, Siteman Cancer Center, St Louis, MO, United States
c Center for Neuro-Oncology, Dana Farber/Brigham and Women’s Cancer Center and Division of Neurology, Brigham and Women’s Hospital, Boston, MA, United States

Document Type: Article
Publication Stage: Final
Source: Scopus

“Demarcating depression” (2018) Ratio

Demarcating depression
(2018) Ratio, . Article in Press. 

Tully, I.

Department of Philosophy, Washington University in St. Louis, One Brookings Dr, St. Louis, MO 63130, United States

Abstract
How to draw the line between depression-as-disorder and non-pathological depressive symptoms continues to be a contested issue in psychiatry. Relatively few philosophers have waded into this debate, but the tools of philosophical analysis are quite relevant to it. In this paper, I defend a particular answer to this question, the Contextual approach. On this view, depression is a disorder if and only if it is a disproportionate response to a justifying cause or else is unconnected to any justifying cause. I present four objections to this approach and then defend it from them. Along the way, I explain why it matters whether we get this question right. © 2018 John Wiley & Sons Ltd

Author Keywords
depression;  fittingness;  mental illness;  psychiatry;  sadness

Document Type: Article in Press
Publication Stage: Article in Press
Source: Scopus

“Impaired copper transport in schizophrenia results in a copper-deficient brain state: A new side to the dysbindin story” (2018) World Journal of Biological Psychiatry

Impaired copper transport in schizophrenia results in a copper-deficient brain state: A new side to the dysbindin story
(2018) World Journal of Biological Psychiatry, . Article in Press. 

Schoonover, K.E.a , Queern, S.L.b c , Lapi, S.E.b c , Roberts, R.C.d

a Department of Psychology and Behavioral Neuroscience, University of Alabama at Birmingham, Birmingham, AL, United States
b Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, United States
c Department of Chemistry, Washington University in St. Louis, St. Louis, MO, United States
d Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, United States

Abstract
Objectives: Several schizophrenia brain regions exhibit decreased dysbindin. Dysbindin modulates copper transport crucial for myelination, monoamine metabolism and cellular homeostasis. Schizophrenia patients (SZP) exhibit increased plasma copper, while copper-decreasing agents produce schizophrenia-like behavioural and pathological abnormalities. Therefore, we sought to determine dysbindin and copper transporter protein expression and copper content in SZP. Methods: We studied the copper-rich substantia nigra (SN) using Western blot and inductively-coupled plasma mass spectrometry. We characterised specific protein domains of copper transporters ATP7A, CTR1, ATP7B and dysbindin isoforms 1 A and 1B/C in SZP (n = 15) and matched controls (n = 11), and SN copper content in SZP (n = 14) and matched controls (n = 11). As a preliminary investigation, we compared medicated (ON; n = 11) versus unmedicated SZP (OFF; n = 4). Results: SZP exhibited increased C terminus, but not N terminus, ATP7A. SZP expressed less transmembrane CTR1 and dysbindin 1B/C than controls. ON exhibited increased C terminus ATP7A protein versus controls. OFF exhibited less N terminus ATP7A protein than controls and ON, suggesting medication-induced rescue of the ATP7A N terminus. SZP exhibited less SN copper content than controls. Conclusions: These results provide the first evidence of disrupted copper transport in schizophrenia SN that appears to result in a copper-deficient state. Furthermore, copper homeostasis may be modulated by specific dysbindin isoforms and antipsychotic treatment. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.

Author Keywords
copper;  dysbindin;  post-mortem;  Schizophrenia;  substantia nigra

Document Type: Article in Press
Publication Stage: Article in Press
Source: Scopus

“Urologic chronic pelvic pain syndrome: insights from the MAPP Research Network” (2018) Nature Reviews Urology

Urologic chronic pelvic pain syndrome: insights from the MAPP Research Network
(2018) Nature Reviews Urology, . Article in Press. 

Clemens, J.Q.a , Mullins, C.b , Ackerman, A.L.c , Bavendam, T.b , van Bokhoven, A.d , Ellingson, B.M.e , Harte, S.E.f , Kutch, J.J.e g , Lai, H.H.h , Martucci, K.T.i , Moldwin, R.j , Naliboff, B.D.k , Pontari, M.A.l , Sutcliffe, S.m , Landis, J.R.n , on behalf of the MAPP Research Network Study Groupo

a Department of Urology, University of Michigan, Ann Arbor, MI, United States
b National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States
c Department of Surgery, Division of Urology, Cedars-Sinai Medical Center, Beverly Hills, CA, United States
d Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States
e Division of Digestive Diseases, University of California, Los Angeles, CA, United States
f Departments of Anesthesiology and Medicine, University of Michigan, Ann Arbor, MI, United States
g Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, CA, United States
h Division of Urologic Surgery, Department of Surgery, and Department of Anesthesiology, Washington University School of Medicine, St Louis, MO, United States
i Department of Anesthesiology, Perioperative and Pain Medicine, Division of Pain Medicine, Stanford University, Palo Alto, CA, United States
j The Arthur Smith Institute for Urology, Zucker School of Medicine at Hofstra-Northwell, Lake Success, NY, United States
k Departments of Medicine, Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at University of California, Los Angeles, CA, United States
l Department of Urology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States
m Division of Public Health Sciences, Department of Surgery, and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, United States
n Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA, United States

Abstract
Urologic chronic pelvic pain syndrome (UCPPS), which encompasses interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, is characterized by chronic pain in the pelvic region or genitalia that is often accompanied by urinary frequency and urgency. Despite considerable research, no definite aetiological risk factors or effective treatments have been identified. The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network uses a novel integrated strategy to characterize UCPPS as a systemic disorder that potentially involves multiple aetiologies. The first phase, MAPP I, included >1,000 participants who completed an intensive baseline assessment followed by a 12-month observational follow-up period. MAPP I studies showed that UCPPS pain and urinary symptoms co-vary, with only moderate correlation, and should be evaluated separately and that symptom flares are common and can differ considerably in intensity, duration and influence on quality of life. Longitudinal clinical changes in UCPPS correlated with structural and functional brain changes, and many patients experienced global multisensory hypersensitivity. Additionally, UCPPS symptom profiles were distinguishable by biological correlates, such as immune factors. These findings indicate that patients with UCPPS have objective phenotypic abnormalities and distinct biological characteristics, providing a new foundation for the study and clinical management of UCPPS. © 2018, Springer Nature Limited.

Document Type: Article in Press
Publication Stage: Article in Press
Source: Scopus

“The structure of cognition in 9 and 10 year-old children and associations with problem behaviors: Findings from the ABCD study’s baseline neurocognitive battery” (2018) Developmental Cognitive Neuroscience

The structure of cognition in 9 and 10 year-old children and associations with problem behaviors: Findings from the ABCD study’s baseline neurocognitive battery
(2018) Developmental Cognitive Neuroscience, . Article in Press. 

Thompson, W.K.a , Barch, D.M.b , Bjork, J.M.c , Gonzalez, R.d , Nagel, B.J.e , Nixon, S.J.f , Luciana, M.g

a Division of Biostatistics, Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA 92093, United States
b Departments of Psychological & Brain Sciences, Psychiatry and Radiology, Washington University, St. Louis, MO 63130, United States
c Institute for Drug and Alcohol Studies, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23219, United States
d Center for Children and Families, Department of Psychology, Florida International University, Miami, FL 33199, United States
e Departments of Psychiatry & Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, United States
f Department of Psychiatry, University of Florida, Gainesville, FL 32611, United States
g Department of Psychology, University of Minnesota, Minneapolis, MN 55455, United States

Abstract
The Adolescent Brain Cognitive Development (ABCD) study is poised to be the largest single-cohort long-term longitudinal study of neurodevelopment and child health in the United States. Baseline data on N= 4521 children aged 9–10 were released for public access on November 2, 2018. In this paper we performed principal component analyses of the neurocognitive assessments administered to the baseline sample. The neurocognitive battery included seven measures from the NIH Toolbox as well as five other tasks. We implemented a Bayesian Probabilistic Principal Components Analysis (BPPCA) model that incorporated nesting of subjects within families and within data collection sites. We extracted varimax-rotated component scores from a three-component model and associated these scores with parent-rated Child Behavior Checklist (CBCL) internalizing, externalizing, and stress reactivity. We found evidence for three broad components that encompass general cognitive ability, executive function, and learning/memory. These were significantly associated with CBCL scores in a differential manner but with small effect sizes. These findings set the stage for longitudinal analysis of neurocognitive and psychopathological data from the ABCD cohort as they age into the period of maximal adolescent risk-taking. © 2018

Author Keywords
Adolescence;  Child behavior checklist;  Externalizing;  Internalizing;  Neurocognition;  NIH toolbox;  Principal components analysis;  Stress reactivity

Document Type: Article in Press
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access

“Concurrent analysis of white matter bundles and grey matter networks in the chimpanzee” (2018) Brain Structure and Function

Concurrent analysis of white matter bundles and grey matter networks in the chimpanzee
(2018) Brain Structure and Function, . Article in Press. 

Mars, R.B.a b , O’Muircheartaigh, J.c d e f , Folloni, D.g , Li, L.h , Glasser, M.F.i , Jbabdi, S.a , Bryant, K.L.b

a Wellcome Centre for Integrative Neuroimaging, Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, United Kingdom
b Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, Netherlands
c Department of Forensic and Neurodevelopmental Sciences, Sackler Institute for Translational Neurodevelopment, London, United Kingdom
d Department of Neuroimaging, Institute of Psychiatry, Psychology, and Neuroscience, Sackler Institute for Translational Neurodevelopment, London, United Kingdom
e MRC Centre for Neurodevelopmental Disorders, King’s College London, London, United Kingdom
f Division of Imaging Sciences and Biomedical Engineering, Centre for the Developing Brain, St Thomas’ Hospital, King’s College London, London, United Kingdom
g Wellcome Centre for Integrative Neuroimaging, Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom
h Marcus Autism Center, Children’s Healthcare of Atlanta, Emory University, Atlanta, GA, United States
i Departments of Radiology and Neuroscience, Washington University Medical School, Saint Louis, MO, United States

Abstract
Understanding the phylogeny of the human brain requires an appreciation of brain organization of our closest animal relatives. Neuroimaging tools such as magnetic resonance imaging (MRI) allow us to study whole-brain organization in species which can otherwise not be studied. Here, we used diffusion MRI to reconstruct the connections of the cortical hemispheres of the chimpanzee. This allowed us to perform an exploratory analysis of the grey matter structures of the chimpanzee cerebral cortex and their underlying white matter connectivity profiles. We identified a number of networks that strongly resemble those found in other primates, including the corticospinal system, limbic connections through the cingulum bundle and fornix, and occipital–temporal and temporal–frontal systems. Notably, chimpanzee temporal cortex showed a strong resemblance to that of the human brain, providing some insight into the specialization of the two species’ shared lineage. © 2018, The Author(s).

Author Keywords
Brain organization;  Comparative;  Connectivity;  Diffusion MRI;  Frontal cortex;  Great ape;  Limbic system;  Networks;  Temporal cortex;  Tractography

Document Type: Article in Press
Publication Stage: Article in Press
Source: Scopus

“Improving pediatricians’ knowledge and skills in suicide prevention: Opportunities for social work” (2018) Qualitative Social Work

Improving pediatricians’ knowledge and skills in suicide prevention: Opportunities for social work
(2018) Qualitative Social Work, . Article in Press. 

Behrman, G.U.a , Secrest, S.b , Ballew, P.a , Matthieu, M.M.c , Glowinski, A.L.d , Scherrer, J.F.b

a CHADS Coalition for Mental Health, Saint Louis University, St. Louis, USA, United States
b Department of Family and Community Medicine, Saint Louis University School of Medicine, St. Louis, USA, United States
c School of Social Work, Saint Louis University, St. Louis, USA, United States
d Department of Psychiatry, Washington University School of Medicine, St. Louis, USA, United States

Abstract
Primary care physicians are key gatekeepers for detecting suicidal intent. However, research indicates training gaps for these providers. Standardized screening for suicide risk in primary care can detect youth with suicidal ideation and prompt a referral to behavioral health care before a suicide attempt. What is needed in adolescent primary care is further training in utilizing standardized mental health screening and employing best practices for suicide prevention. In this study, qualitative research methods were used in surfacing community and medical perspectives regarding skills, knowledge, and values that are needed in pediatric medicine to adequately assess for depression and anxiety. Five focus groups were conducted with pediatric residents, adolescents, parents of adolescents who died by suicide, parents with adolescents in the mental health system, and community mental health professionals. Four themes were identified that illustrate what is needed in pediatric training to lower the risks for adolescent suicide: broken mental health system of care; improving doctor/patient/family communication; alleviating stigma; and early detection and treatment that addresses medications, substance abuse, and recovery resources. The goals of this grant funded study were to analyze the data from these focus groups and compare findings across groups to create modules for Saint Louis University pediatric resident training in suicide prevention. This research project can serve as a springboard for social workers to partner with medical educators in their communities to train primary care physicians for early detection of depression, anxiety, and substance abuse to lower adolescent suicide risks. © 2018, The Author(s) 2018.

Author Keywords
adolescents;  Education;  suicide prevention

Document Type: Article in Press
Publication Stage: Article in Press
Source: Scopus