“Vascular endothelial growth factor is required for regeneration of auditory hair cells in the avian inner ear” (2020) Hearing Research
Vascular endothelial growth factor is required for regeneration of auditory hair cells in the avian inner ear
(2020) Hearing Research, 385, art. no. 107839, .
Wan, L.a , Lovett, M.b , Warchol, M.E.c , Stone, J.S.a
a Virginia Merrill Bloedel Hearing Research Center, Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, WA 98195, United States
b Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, United States
c Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
Hair cells in the auditory organ of the vertebrate inner ear are the sensory receptors that convert acoustic stimuli into electrical signals that are conveyed along the auditory nerve to the brainstem. Hair cells are highly susceptible to ototoxic drugs, infection, and acoustic trauma, which can cause cellular degeneration. In mammals, hair cells that are lost after damage are not replaced, leading to permanent hearing impairments. By contrast, supporting cells in birds and other non-mammalian vertebrates regenerate hair cells after damage, which restores hearing function. The cellular mechanisms that regulate hair cell regeneration are not well understood. We investigated the role of vascular endothelial growth factor (VEGF) during regeneration of auditory hair cells in chickens after ototoxic injury. Using RNA-Seq, immunolabeling, and in situ hybridization, we found that VEGFA, VEGFC, VEGFR1, VEGFR2, and VEGFR3 were expressed in the auditory epithelium, with VEGFA expressed in hair cells and VEGFR1 and VEGFR2 expressed in supporting cells. Using organotypic cultures of the chicken cochlear duct, we found that blocking VEGF receptor activity during hair cell injury reduced supporting cell proliferation as well as the numbers of regenerated hair cells. By contrast, addition of recombinant human VEGFA to organ cultures caused an increase in both supporting cell division and hair cell regeneration. VEGF’s effects on supporting cells were preserved in isolated supporting cell cultures, indicating that VEGF can act directly upon supporting cells. These observations demonstrate a heretofore uncharacterized function for VEGF signaling as a critical positive regulator of hair cell regeneration in the avian inner ear. © 2019 Elsevier B.V.
Author Keywords
Basilar papilla; Hair cell; Regeneration; Supporting cell; Vascular endothelial growth factor
Document Type: Article
Publication Stage: Final
Source: Scopus
“Preschool Depression: a Diagnostic Reality” (2019) Current Psychiatry Reports
Preschool Depression: a Diagnostic Reality
(2019) Current Psychiatry Reports, 21 (12), art. no. 128, .
Donohue, M.R.a , Whalen, D.J.a , Gilbert, K.E.a , Hennefield, L.a , Barch, D.M.a b c , Luby, J.a
a Department of Psychiatry, Washington University School of Medicine, 4444 Forest Park Avenue, Suite 2500, St. Louis, MO 63110, United States
b Department of Psychology, Washington University, St. Louis, MO, United States
c Department of Radiology, Washington University, St. Louis, MO, United States
Abstract
Purpose of Review: We review findings related to predictors, correlates, outcomes, and treatment of preschool depression that have been published in the last 3 years. Recent Findings: Preschool depression displays a chronic course through late adolescence and is associated with temperamental and personality traits, poorer physical health, and negative parenting practices. Preschool depression predicts deficits into adolescence, including social difficulties and blunted neural response to rewards. Depressed preschoolers can experience suicidal ideation and behaviors and display an accurate understanding of the finality of death. A treatment for preschool depression has now been validated that uses the parent-child relationship to enhance emotion development and reduce depressive symptoms. Summary: Preschool depression is homotypic with depression that occurs later in life. Future work elucidating mechanisms through which preschool depression develops and informs the sub-groups for which particular treatments may be most effective will have considerable implications for prevention and early intervention. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
Author Keywords
Neurobiology; Physical health; Preschool depression; Review; Social functioning; Suicidality
Document Type: Review
Publication Stage: Final
Source: Scopus
“Utilizing social media to explore overdose and HIV/HCV risk behaviors among current opioid misusers” (2019) Drug and Alcohol Dependence
Utilizing social media to explore overdose and HIV/HCV risk behaviors among current opioid misusers
(2019) Drug and Alcohol Dependence, 205, art. no. 107690, .
Cavazos-Rehg, P.a , Grucza, R.a , Krauss, M.J.a , Smarsh, A.c , Anako, N.a b , Kasson, E.a , Kaiser, N.a , Sansone, S.a , Winograd, R.d , Bierut, L.J.a
a Department of Psychiatry, Washington University School of Medicine, 660 South Euclid Avenue, Box 8134, St. Louis, MO 63110, United States
b George Warren Brown School, Washington University in St. Louis, One Brookings Drive, St. Louis, MO 63130, United States
c University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, United States
d Missouri Institute of Mental Health, University of Missouri St. Louis, 4633 World Parkway Circle, St. Louis, MO 63134, United States
Abstract
Introduction: Opioid misuse has evolved into an American health crisis over the past decade, becoming a public health epidemic. Measures need to be taken to prevent overdoses by opioid misuse as well as prevent the transition into injection drug use, a high risk factor for contracting HIV/HCV. This study utilized social media to survey individuals currently misusing opioids to identify groups of individuals with different risk and use patterns. Methods: We recruited participants for our online survey from Reddit. Five risk behaviors were used to characterize overdose and HIV/HCV risk groups. Gender, age, and socioeconomic status were also included in the analyses, as well as items outlining social media use surrounding opioids. Results: Two groups of participants were characterized by high likelihoods of different combinations of risky behaviors: (1) Overdose Risk Group and (2) Sexual Risk Group. Those in the Overdose Risk Group were more likely to be younger in age and female, and this group was more likely to desire or be ready for treatment relative to the lowest risk group. Those in the Sexual Risk Group were more likely to be of a minority race/ethnicity, to desire or be ready for treatment, and to post more often on Reddit about opioid use. Discussion: The results of this study illustrate patterns of opioid use and risk behaviors to inform tailored outreach and treatment efforts for groups of opioid misusers and suggests the potential for utilizing social media as a tool to engage these individuals into treatment and recovery activities. © 2019 Elsevier B.V.
Author Keywords
HCV; HIV; Opioids; Overdose; Prevention; Risk behavior; Sexual risk; Social media
Document Type: Article
Publication Stage: Final
Source: Scopus
“The effects of repeated lineups and delay on eyewitness identification” (2019) Cognitive Research: Principles and Implications
The effects of repeated lineups and delay on eyewitness identification
(2019) Cognitive Research: Principles and Implications, 4 (1), art. no. 16, .
Lin, W., Strube, M.J., Roediger, H.L., III
Washington University in St. Louis, One Brookings Drive, St. Louis, MO 63130-4899, United States
Abstract
A significant problem in eyewitness identification occurs when witnesses view a suspect in one venue such as a mugshot and then later in a lineup where the suspect is the only previously viewed person. Prior research has documented that the witness may select the suspect from the lineup due either to misplaced familiarity from seeing the mugshot or to their prior commitment from identifying the suspect from the mugshot. Two experiments attempted to minimize these biases by using repeated identical lineups, such that both targets and fillers were repeated, to determine if such a procedure could be useful. Across two experiments, we also varied the delay between seeing the event and the first lineup, as well as the delay between lineups. Despite the use of identical lineups, we continued to observe the effects of commitment and misplaced familiarity, so our procedure did not remove these problems. In addition, we also found that both repeated lineups and increasing delays can influence people’s tendency to choose and their willingness to maintain their decisions, regardless of accuracy. Most importantly, however, despite the negative effects of repeated lineups and the relatively long delays used in our experiments, we obtained strong relations between confidence and accuracy when using confidence-accuracy characteristic plots. High confidence responses were associated with high accuracy. © 2019, The Author(s).
Author Keywords
Confidence; Decision behaviors; Eyewitness identification
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Author Correction: The choroid plexus is an important circadian clock component (Nature Communications, (2018), 9, 1, (1062), 10.1038/s41467-018-03507-2)” (2019) Nature Communications
Author Correction: The choroid plexus is an important circadian clock component (Nature Communications, (2018), 9, 1, (1062), 10.1038/s41467-018-03507-2)
(2019) Nature Communications, 10 (1), art. no. 5253, .
Myung, J.a b c d e , Schmal, C.f , Hong, S.b , Tsukizawa, Y.g , Rose, P.f , Zhang, Y.h , Holtzman, M.J.h , De Schutter, E.b , Herzel, H.f , Bordyugov, G.f , Takumi, T.a g
a RIKEN Brain Science Institute (BSI), Wako, 351-0198, Japan
b Computational Neuroscience Unit, Okinawa Institute of Science and Technology, Okinawa, 904-0495, Japan
c Graduate Institute of Humanities in Medicine, Taipei Medical University, Taipei, 11031, Taiwan
d TMU-Research Center of Brain and Consciousness, Taipei Medical University, Taipei, 11031, Taiwan
e Laboratory of Braintime, Shuang Ho Hospital, New Taipei City, 23561, Taiwan
f Institute for Theoretical Biology, Charité-Universitätsmedizin and Humboldt Universität, Berlin, D-10115, Germany
g Department of Anatomy, Hiroshima University School of Medicine, Hiroshima, 734-8551, Japan
h Pulmonary and Clinical Care Medicine, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
Correction to: Nature Communications https://doi.org/10.1038/s41467-018-03507-2, published online 14 March 2018. The original version of this Article omitted the following from the Acknowledgements: The Takeda Science Foundation. This has now been corrected in both the PDF and HTML versions of the Article.. © 2019, The Author(s).
Document Type: Erratum
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Development and Usability Testing of the Society for Pediatric Anesthesia Pedi Crisis Mobile Application” (2019) Anesthesia and Analgesia
Development and Usability Testing of the Society for Pediatric Anesthesia Pedi Crisis Mobile Application
(2019) Anesthesia and Analgesia, 129 (6), pp. 1635-1644.
Clebone, A.a , Strupp, K.M.b , Whitney, G.b , Anderson, M.R.c , Hottle, J.d , Fehr, J.e f , Yaster, M.b , Schleelein, L.E.g , Burian, B.K.h , Galvez, J.A.i , Lockman, J.L.i , Polaner, D.i , Barnett, N.R.i , Keane, M.J.i , Manikappa, S.i , Gleich, S.i , Greenberg, R.S.i , Vincent, A.i , Oswald, S.L.i , Starks, R.i , Licata, S.i , Pedi Crisis Application Working Groupj
a From the Department of Anesthesiology and Critical Care Medicine, University of Chicago, Chicago, IL, Mexico
b Department of Anesthesiology, Children’s Hospital Colorado, University of Colorado, Aurora, CO, United States
c erson Applications Limited, Denver, CO, United States
d Denver, CO, United States
e Departments of Anesthesiology
f Pediatrics, Washington University School of Medicine, St Louis Children’s Hospital, St Louis, MO, United States
g Departments of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
h United States National Aeronautics and Space Administration, Ames Research Center, Moffett FieldCA
Abstract
When life-threatening, critical events occur in the operating room, the fast-paced, high-distraction atmosphere often leaves little time to think or deliberate about management options. Success depends on applying a team approach to quickly implement well-rehearsed, systematic, evidence-based assessment and treatment protocols. Mobile devices offer resources for readily accessible, easily updatable information that can be invaluable during perioperative critical events. We developed a mobile device version of the Society for Pediatric Anesthesia 26 Pediatric Crisis paper checklists-the Pedi Crisis 2.0 application-as a resource to support clinician responses to pediatric perioperative life-threatening critical events. Human factors expertise and principles were applied to maximize usability, such as by clustering information into themes that clinicians utilize when accessing cognitive aids during critical events. The electronic environment allowed us to feature optional diagnostic support, optimized navigation, weight-based dosing, critical institution-specific phone numbers pertinent to emergency response, and accessibility for those who want larger font sizes. The design and functionality of the application were optimized for clinician use in real time during actual critical events, and it can also be used for self-study or review. Beta usability testing of the application was conducted with a convenience sample of clinicians at 9 institutions in 2 countries and showed that participants were able to find information quickly and as expected. In addition, clinicians rated the application as slightly above “excellent” overall on an established measure, the Systems Usability Scale, which is a 10-item, widely used and validated Likert scale created to assess usability for a variety of situations. The application can be downloaded, at no cost, for iOS devices from the Apple App Store and for Android devices from the Google Play Store. The processes and principles used in its development are readily applicable to the development of future mobile and electronic applications for the field of anesthesiology.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Measuring disability in multiple sclerosis: Walking plus much more” (2019) Neurology
Measuring disability in multiple sclerosis: Walking plus much more
(2019) Neurology, 93 (21), pp. 919-920.
Sormani, M.P., Naismith, R.T.
From the Department of Health Sciences (M.P.S.), Section of Biostatistics, University of Genoa; IRCCS Ospedale Policlinico San Martino (M.P.S.), Genoa, Italy; and Department of Neurology (R.T.N.), Washington University, St. Louis, MO
Document Type: Editorial
Publication Stage: Final
Source: Scopus
“Anatomical context protects deep learning from adversarial perturbations in medical imaging” (2019) Neurocomputing
Anatomical context protects deep learning from adversarial perturbations in medical imaging
(2019) Neurocomputing, .
Li, Y.a , Zhang, H.a , Bermudez, C.b , Chen, Y.a , Landman, B.A.a , Vorobeychik, Y.c
a Electrical Engineering and Computer Science, Vanderbilt University, Nashville, TN 37235, United States
b Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, United States
c Computer Science & Engineering, Washington University, St. Louis, MO 63130, United States
Abstract
Deep learning has achieved impressive performance across a variety of tasks, including medical image processing. However, recent research has shown that deep neural networks are susceptible to small adversarial perturbations in the image. We study the impact of such adversarial perturbations in medical image processing where the goal is to predict an individual’s age based on a 3D MRI brain image. We consider two models: a conventional deep neural network, and a hybrid deep learning model which additionally uses features informed by anatomical context. We find that we can introduce significant errors in predicted age by adding imperceptible noise to an image, can accomplish this even for large batches of images using a single perturbation, and that the hybrid model is much more robust to adversarial perturbations than the conventional deep neural network. Our work highlights limitations of current deep learning techniques in clinical applications, and suggests a path forward. © 2019 Elsevier B.V.
Author Keywords
Adversarial deep learning; Medical image processing
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“The psychometric properties of the Washington Early Recognition Center Affectivity and Psychosis (WERCAP) screen in adults in the Kenyan context: Towards combined large scale community screening for affectivity and psychosis” (2019) Psychiatry Research
The psychometric properties of the Washington Early Recognition Center Affectivity and Psychosis (WERCAP) screen in adults in the Kenyan context: Towards combined large scale community screening for affectivity and psychosis
(2019) Psychiatry Research, art. no. 112569, .
Ndetei, D.a b , Pike, K.c , Mutiso, V.b , Tele, A.b , Gitonga, I.b , Rebello, T.c , Musyimi, C.b , Mamah, D.d
a Department of Psychiatry, University of Nairobi, Nairobi, Kenya
b Africa Mental Health Research and Training Foundation, Nairobi, Kenya
c Global Mental Health Program, Columbia University, New York, United States
d Washington University, St. Louis, United States
Abstract
There is a need for screening for early symptoms of psychosis and affectivity at community level to promote early diagnosis and management. Any screening instrument should have good psychometric properties. One such instrument is the Washington Early Recognition Center Affectivity and Psychosis (WERCAP) Screen that has been used in the USA, Kenya and Rwanda. However, its properties have not been studied outside the USA, and not in adults. The study aims to document the psychometric properties of the WERCAP Screen in Kenyan adults with positive screens on the WHO mental health treatment GAP- Intervention Guidelines (mhGAP-IG). We administered the WERCAP Screen and a gold standard – the Mini-International Neuropsychiatric Interview (MINI-Plus) section on psychosis to 674 Kenyan adults who had screened positive on the WHO mhGAP-IG. Out of these, 464 (68.84%) scored positive for both affectivity and psychosis sections on the MINI-Plus. The WERCAP affectivity and psychosis scales had good psychometric properties as screening measures, with a cut-off point of 22 for affectivity and 20 for psychosis. The WERCAP Screen has the potential for combined scale up screening for affectivity and psychosis in Kenyan population. © 2019 Elsevier B.V.
Author Keywords
Affective disorders; Psychometrics; Psychoses; Schizophrenia
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Sleep-Wake Disturbances After Acquired Brain Injury in Children Surviving Critical Care” (2019) Pediatric Neurology
Sleep-Wake Disturbances After Acquired Brain Injury in Children Surviving Critical Care
(2019) Pediatric Neurology, .
Williams, C.N.a b , Hartman, M.E.c , McEvoy, C.T.d , Hall, T.A.a e , Lim, M.M.f g h i j , Shea, S.A.i , Luther, M.a , Guilliams, K.P.c k , Guerriero, R.M.k , Bosworth, C.C.l , Piantino, J.A.a m
a Pediatric Critical Care and Neurotrauma Recovery Program, Oregon Health and Science University, Portland, OR, United States
b Division of Pediatric Critical Care, Department of Pediatrics, Oregon Health and Science University, Portland, OR, United States
c Division of Critical Care Medicine, Department of Pediatrics, St Louis Children’s Hospital, Washington University School of Medicine, St. Louis, MO, United States
d Division of Neonatology, Department of Pediatrics, Oregon Health and Science University, Portland, OR, United States
e Division of Pediatric Psychology, Department of Pediatrics, Oregon Health and Science University, Portland, OR, United States
f Division of Pulmonary and Critical Care Medicine, Department of Medicine, Oregon Health and Science University, Portland, OR, United States
g Department of Neurology, Oregon Health and Science University, Portland, OR, United States
h Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, United States
i Oregon Institute of Occupational Health Sciences, Oregon Health and Science University, Portland, OR, United States
j VA Portland Health Care System, Portland, OR, United States
k Division of Pediatric and Developmental Neurology, Department of Neurology, St Louis Children’s Hospital, Washington University School of Medicine, St. Louis, MO, United States
l Department of Psychology, St Louis Children’s Hospital, Washington University School of Medicine, St. Louis, MO, United States
m Division of Pediatric Neurology, Department of Pediatrics, Oregon Health and Science University, Portland, OR, United States
Abstract
Background: Sleep-wake disturbances are underevaluated among children with acquired brain injury surviving critical care. We aimed to quantify severity, phenotypes, and risk factors for sleep-wake disturbances. Methods: We performed a prospective cohort study of 78 children aged ≥3 years with acquired brain injury within three months of critical care hospitalization. Diagnoses included traumatic brain injury (n = 40), stroke (n = 11), infectious or inflammatory disease (n = 10), hypoxic-ischemic injury (n = 9), and other (n = 8). Sleep Disturbances Scale for Children standardized T scores measured sleep-wake disturbances. Overall sleep-wake disturbances were dichotomized as any total or subscale T score ≥60. Any T score ≥70 defined severe sleep-wake disturbances. Subscale T scores ≥60 identified sleep-wake disturbance phenotypes. Results: Sleep-wake disturbances were identified in 44 (56%) children and were classified as severe in 36 (46%). Sleep-wake disturbances affected ≥33% of patients within each diagnosis and were not associated with severity of illness measures. The most common phenotype was disturbance in initiation and maintenance of sleep (47%), although 68% had multiple concurrent sleep-wake disturbance phenotypes. One third of all patients had preadmission chronic conditions, and this increased risk for sleep-wake disturbances overall (43% vs 21%, P = 0.04) and in the traumatic brain injury subgroup (52% vs 5%, P = 0.001). Conclusions: Over half of children surviving critical care with acquired brain injury have sleep-wake disturbances. Most of these children have severe sleep-wake disturbances independent of severity of illness measures. Many sleep-wake disturbances phenotypes were identified, but most children had disturbance in initiation and maintenance of sleep. Our study underscores the importance of evaluating sleep-wake disturbances after acquired brain injury. © 2019 Elsevier Inc.
Author Keywords
Brain injury; Critical care outcomes; Pediatric; Sleep; Sleep-wake disorders; Trauma
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Universality and diversity in human song” (2019) Science
Universality and diversity in human song
(2019) Science, 366 (6468), art. no. eaax0868, . Cited 1 time.
Mehr, S.A.a b c , Singh, M.d , Knox, D.e , Ketter, D.M.f g , Pickens-Jones, D.h , Atwood, S.b , Lucas, C.i , Jacoby, N.j , Egner, A.A.b , Hopkins, E.J.b , Howard, R.M.b , Hartshorne, J.K.k , Jennings, M.V.k , Simson, J.b l , Bainbridge, C.M.b , Pinker, S.b , O’Donnell, T.J.m , Krasnow, M.M.b , Glowacki, L.n
a Data Science Initiative, Harvard University, Cambridge, MA 02138, United States
b Department of Psychology, Harvard University, Cambridge, MA 02138, United States
c School of Psychology, Victoria University of Wellington, Wellington, New Zealand
d Department of Human Evolutionary Biology, Harvard University, Cambridge, MA 02138, United States
e Department of Politics, Princeton University, Princeton, NJ 08544, United States
f Eastman School of Music, University of Rochester, Rochester, NY 14604, United States
g Department of Music, Missouri State University, Springfield, MO 65897, United States
h Unaffiliated scholar, Portland, OR 97212, United States
i Department of Political Science, Washington University, St. Louis, MO 63130, United States
j Computational Auditory Perception Group, Max Planck Institute for Empirical Aesthetics, Frankfurt am Main, 60322, Germany
k Department of Psychology, Boston College, Chestnut Hill, MA 02467, United States
l Department of Psychology, University of Konstanz, Konstanz, 78464, Germany
m Department of Linguistics, McGill University, Montreal, QC H3A 1A7, Canada
n Department of Anthropology, Pennsylvania State University, State CollegePA 16802, United States
Abstract
What is universal about music, and what varies? We built a corpus of ethnographic text on musical behavior from a representative sample of the world’s societies, as well as a discography of audio recordings. The ethnographic corpus reveals that music (including songs with words) appears in every society observed; that music varies along three dimensions (formality, arousal, religiosity), more within societies than across them; and that music is associated with certain behavioral contexts such as infant care, healing, dance, and love. The discography—analyzed through machine summaries, amateur and expert listener ratings, and manual transcriptions—reveals that acoustic features of songs predict their primary behavioral context; that tonality is widespread, perhaps universal; that music varies in rhythmic and melodic complexity; and that elements of melodies and rhythms found worldwide follow power laws. Copyright © 2019, American Association for the Advancement of Science
Document Type: Article
Publication Stage: Final
Source: Scopus
“Blood Pressure and Memory: Novel Approaches to Modeling Nonlinear Effects in Longitudinal Studies” (2019) Alzheimer Disease and Associated Disorders
Blood Pressure and Memory: Novel Approaches to Modeling Nonlinear Effects in Longitudinal Studies
(2019) Alzheimer Disease and Associated Disorders, 33 (4), pp. 291-298.
Liu, A.a , Sun, Z.d , McDade, E.M.e , Hughes, T.F.f , Ganguli, M.b , Chang, C.-C.H.a c
a Departments of Biostatistics, United States
b Psychiatry, Neurology, and Epidemiology, United States
c Medicine, University of Pittsburgh, 200 Meyran Ave., Pittsburgh, PA 15213, United States
d AbbVIE Pharmaceuticals, Chicago, IL, United States
e Department of Neurology, Washington University in St. Louis, St. Louis, MO, United States
f Department of Anthropology, Sociology, and Gerontology, Youngstown State University, Youngstown, OH, United States
Abstract
Background:Linear models cannot capture nonlinear associations when the relationships between cognition and risk factors vary across risk levels. We demonstrate a method of modelling nonlinear associations using the example of blood pressure (BP) and memory.Methods:We measured memory and BP (in mm Hg) annually for 10 years in a population-based cohort (N=1982) aged 65+. We evaluated the relationship between BP and memory at the same time points using both linear mixed models and generalized additive mixed models with smoothing splines, adjusting for relevant covariates.Results:Linear mixed models found no significant associations. Generalized additive mixed models detected different associations between BP and memory across baseline BP categories (normotensive, hypertensive, hypotensive). Among normotensives, systolic blood pressure (SBP)/diastolic blood pressure (DBP) around 140/80 was associated with the highest, while SBP/DBP around 110/60 was associated with the lowest, predicted memory scores. Among hypertensives, SBP/DBP around 130/85 was associated with the highest, while SBP/DBP around 150/65 was associated with the lowest, predicted memory scores. Among hypotensives, no significant association was found. Among both normotensives and hypertensives, a DBP >75 was associated with better memory.Conclusions:By modelling nonlinear associations, we showed that the relationship between BP and memory performance varied by baseline BP among normotensives and hypertensives. © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Author Keywords
blood pressure; memory; smoothing splines
Document Type: Article
Publication Stage: Final
Source: Scopus
“Disrupting insulin signaling in Schwann cells impairs myelination and induces a sensory neuropathy” (2019) GLIA
Disrupting insulin signaling in Schwann cells impairs myelination and induces a sensory neuropathy
(2019) GLIA, .
Hackett, A.R., Strickland, A., Milbrandt, J.
Department of Genetics, Washington University School of Medicine, Saint Louis, MO, United States
Abstract
Although diabetic mice have been studied for decades, little is known about the cell type specific contributions to diabetic neuropathy (DN). Schwann cells (SCs) myelinate and provide trophic support to peripheral nervous system axons. Altered SC metabolism leads to myelin defects, which can be seen both in inherited and DNs. How SC metabolism is altered in DN is not fully understood, but it is clear that insulin resistance underlies impaired lipid metabolism in many cell types throughout the body via the phosphoinositide 3-kinase/protein kinase b (PKB)/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. Here, we created an insulin resistant SC by deleting both insulin receptor (INSR) and insulin-like growth factor receptor 1 (IGF1R), to determine the role of this signaling pathway in development and response to injury in order to understand SC defects in DN. We found that myelin is thinner throughout development and adulthood in INSR/IGF1R Schwann cell specific knock out mice. The nerves of these mutant mice had reduced expression of key genes that mediate fatty acid and cholesterol synthesis due to reduced mTOR–sterol regulatory element-binding protein signaling. In adulthood, these mice show sensory neuropathy phenotypes reminiscent of diabetic mice. Altogether, these data suggest that SCs may play an important role in DN and targeting their metabolism could lead to new therapies for DN. © 2019 Wiley Periodicals, Inc.
Author Keywords
diabetes; insulin; insulin-like growth factor; metabolism; myelin; peripheral neuropathy; remyelination; Schwann cell
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Neurobiological Divergence of the Positive and Negative Schizophrenia Subtypes Identified on a New Factor Structure of Psychopathology Using Non-negative Factorization: An International Machine Learning Study” (2019) Biological Psychiatry
Neurobiological Divergence of the Positive and Negative Schizophrenia Subtypes Identified on a New Factor Structure of Psychopathology Using Non-negative Factorization: An International Machine Learning Study
(2019) Biological Psychiatry, .
Chen, J.a b , Patil, K.R.a b , Weis, S.a b , Sim, K.h i , Nickl-Jockschat, T.k l , Zhou, J.j , Aleman, A.q , Sommer, I.E.q r , Liemburg, E.J.s , Hoffstaedter, F.a b , Habel, U.c d , Derntl, B.e , Liu, X.a b , Fischer, J.M.a b , Kogler, L.e , Regenbogen, C.c d , Diwadkar, V.A.m , Stanley, J.A.m , Riedl, V.f , Jardri, R.t , Gruber, O.g , Sotiras, A.n , Davatzikos, C.o p , Eickhoff, S.B.a b , Bartels-Velthuis, A.A.u , Bruggeman, R.u , Castelein, S.u , Jörg, F.u , Pijnenborg, G.H.M.u , Knegtering, H.u , Visser, E.u , Pharmacotherapy Monitoring and Outcome Survey (PHAMOUS) Investigatorsv
a Institute of Neuroscience and Medicine, Brain and Behaviour (INM-7), Research Center Jülich, Jülich, Germany
b Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
c Department of Psychiatry, Psychotherapy and Psychosomatics, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Aachen, Germany
d Jülich Aachen Research Alliance–Institute Brain Structure Function Relationship, Research Center Jülich, and RWTH Aachen University, Aachen, Germany
e Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany
f Department of Neuroradiology, Rechts der Isar Hospital, Technical University of Munich, Munich, Germany
g Section for Experimental Psychopathology and Neuroimaging, Department of General Psychiatry, Heidelberg University, Heidelberg, Germany
h Department of General Psychiatry, Institute of Mental Health, Singapore
i Research Division, Institute of Mental Health, Singapore
j Center for Cognitive Neuroscience, Neuroscience and Behavioral Disorders Program, Duke–National University of Singapore Medical School, Singapore
k Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa, Iowa CityIA, United States
l Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa CityIA, United States
m Department of Psychiatry and Behavioral Neuroscience, Wayne State University, Detroit, MI, United States
n Department of Radiology and Institute for Informatics, School of Medicine, Washington University in St. Louis, St. Louis, MO, United States
o Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
p Department of Radiology, Section of Biomedical Image Analysis, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
q Department of Neuroscience, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
r BCN Neuroimaging Center, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
s Rob Giel Research Center, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
t University of Lille, National Centre for Scientific Research, UMR 9193, SCALab and CHU Lille, Fontan Hospital, CURE platform, Lille, France
Abstract
Background: Disentangling psychopathological heterogeneity in schizophrenia is challenging, and previous results remain inconclusive. We employed advanced machine learning to identify a stable and generalizable factorization of the Positive and Negative Syndrome Scale and used it to identify psychopathological subtypes as well as their neurobiological differentiations. Methods: Positive and Negative Syndrome Scale data from the Pharmacotherapy Monitoring and Outcome Survey cohort (1545 patients; 586 followed up after 1.35 ± 0.70 years) were used for learning the factor structure by an orthonormal projective non-negative factorization. An international sample, pooled from 9 medical centers across Europe, the United States, and Asia (490 patients), was used for validation. Patients were clustered into psychopathological subtypes based on the identified factor structure, and the neurobiological divergence between the subtypes was assessed by classification analysis on functional magnetic resonance imaging connectivity patterns. Results: A 4-factor structure representing negative, positive, affective, and cognitive symptoms was identified as the most stable and generalizable representation of psychopathology. It showed higher internal consistency than the original Positive and Negative Syndrome Scale subscales and previously proposed factor models. Based on this representation, the positive–negative dichotomy was confirmed as the (only) robust psychopathological subtypes, and these subtypes were longitudinally stable in about 80% of the repeatedly assessed patients. Finally, the individual subtype could be predicted with good accuracy from functional connectivity profiles of the ventromedial frontal cortex, temporoparietal junction, and precuneus. Conclusions: Machine learning applied to multisite data with cross-validation yielded a factorization generalizable across populations and medical systems. Together with subtyping and the demonstrated ability to predict subtype membership from neuroimaging data, this work further disentangles the heterogeneity in schizophrenia. © 2019 Society of Biological Psychiatry
Author Keywords
Brain imaging; Machine learning; Multivariate classification; Non-negative factorization; Schizophrenia; Subtyping
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
Access Type: Open Access
“Convergent Evidence for Predispositional Effects of Brain Gray Matter Volume on Alcohol Consumption” (2019) Biological Psychiatry
Convergent Evidence for Predispositional Effects of Brain Gray Matter Volume on Alcohol Consumption
(2019) Biological Psychiatry, .
Baranger, D.A.A.a , Demers, C.H.a , Elsayed, N.M.c , Knodt, A.R.d , Radtke, S.R.d , Desmarais, A.a , Few, L.R.b , Agrawal, A.b , Heath, A.C.b , Barch, D.M.a b , Squeglia, L.M.f , Williamson, D.E.c e , Hariri, A.R.d , Bogdan, R.a
a Department of Psychological and Brain Sciences, Washington University, St. Louis, MO, United States
b Department of Psychiatry, Washington University, St. Louis, MO, United States
c Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, United States
d Department of Psychology and Neuroscience, Duke University, Durham, NC, United States
e Durham VA Medical Center, Durham, NC, United States
f Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, United States
Abstract
Background: Alcohol use has been reliably associated with smaller subcortical and cortical regional gray matter volumes (GMVs). Whether these associations reflect shared predisposing risk factors or causal consequences of alcohol use remains poorly understood. Methods: Data came from 3 neuroimaging samples (N = 2423), spanning childhood or adolescence to middle age, with prospective or family-based data. First, we identified replicable GMV correlates of alcohol use. Next, we used family-based and longitudinal data to test whether these associations may plausibly reflect a predispositional liability for alcohol use or a causal consequence of alcohol use. Finally, we used heritability, gene-set enrichment, and transcriptome-wide association study approaches to evaluate whether genome-wide association study–defined genomic risk for alcohol consumption is enriched for genes that are preferentially expressed in regions that were identified in our neuroimaging analyses. Results: Smaller right dorsolateral prefrontal cortex (DLPFC) (i.e., middle and superior frontal gyri) and insula GMVs were associated with increased alcohol use across samples. Family-based and prospective longitudinal data suggest that these associations are genetically conferred and that DLPFC GMV prospectively predicts future use and initiation. Genomic risk for alcohol use was enriched in gene sets that were preferentially expressed in the DLPFC and was associated with replicable differential gene expression in the DLPFC. Conclusions: These data suggest that smaller DLPFC and insula GMV plausibly represent genetically conferred predispositional risk factors for, as opposed to consequences of, alcohol use. DLPFC and insula GMV represent promising biomarkers for alcohol-consumption liability and related psychiatric and behavioral phenotypes. © 2019 Society of Biological Psychiatry
Author Keywords
Alcohol; Gene expression; Heritability; Imaging; Longitudinal; Structure
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“In vivo identification of small molecules mediating gpr126/adgrg6 signaling during schwann cell development” (2019) Annals of the New York Academy of Sciences
In vivo identification of small molecules mediating gpr126/adgrg6 signaling during schwann cell development
(2019) Annals of the New York Academy of Sciences, 1456 (1), pp. 44-63.
Bradley, E.C.a , Cunningham, R.L.b , Wilde, C.c , Morgan, R.K.d , Klug, E.A.a , Letcher, S.M.a , Schöneberg, T.c , Monk, K.R.b d , Liebscher, I.c , Petersen, S.C.a b
a Department of Neuroscience, Kenyon College, Gambier, OH, United States
b Department of Developmental Biology, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
c Rudolf Schönheimer Institute of Biochemistry, Medical Faculty, University of Leipzig, Leipzig, Germany
d Vollum Institute, Oregon Health & Science University, Portland, OR, United States
Abstract
Gpr126/Adgrg6, an adhesion family G protein–coupled receptor (aGPCR), is required for the development of myelinating Schwann cells in the peripheral nervous system. Myelin supports and insulates vertebrate axons to permit rapid signal propagation throughout the nervous system. In mammals and zebrafish, mutations in Gpr126 arrest Schwann cells at early developmental stages. We exploited the optical and pharmacological tractability of larval zebrafish to uncover drugs that mediate myelination by activating Gpr126 or functioning in parallel. Using a fluorescent marker of mature myelinating glia(Tg[mbp:EGFP-CAAX]), we screened hypomorphic gpr126 mutant larvae for restoration of myelin basic protein (mbp) expression along peripheral nerves following small molecule treatment. Our screens identified five compounds sufficient to promote mbp expression in gpr126 hypomorphs. Using an allelic series of gpr126 mutants, we parsed the ability of small molecules to restore mbp, suggesting differences in drug efficacy dependent on Schwann cell developmental state. Finally, we identify apomorphine hydrochloride as a direct small molecule activator of Gpr126 using combined in vivo/in vitro assays and show that aporphine class compounds promote Schwann cell development in vivo. Our results demonstrate the utility of in vivo screening for aGPCR modulators and identify small molecules that interact with the gpr126-mediated myelination program. © 2019 New York Academy of Sciences.
Author Keywords
Adhesion GPCR; Gpr126/Adgrg6; Myelin; Schwann cells; Zebrafish
Document Type: Book Chapter
Publication Stage: Final
Source: Scopus
“Association of depression symptoms with receipt of healthcare provider advice on physical activity among US adults” (2019) Journal of Affective Disorders
Association of depression symptoms with receipt of healthcare provider advice on physical activity among US adults
(2019) Journal of Affective Disorders, .
Grabovac, I.a , Stefanac, S.b , Smith, L.c , Haider, S.a , Cao, C.d e , Jackson, S.E.f , Dorner, T.E.a , Waldhoer, T.g , Rieder, A.a , Yang, L.h i
a Department of Social and Preventive Medicine, Center for Public Health, Medical University of Vienna, Austria
b Institute of Outcome Research, Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Austria
c Cambridge Centre for Sport and Exercise Sciences, Anglia Ruskin University, Cambridge, United Kingdom
d Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St LouisMO, United States
e Program in Physical Therapy, Washington University School of Medicine, St LouisMO, United States
f Department of Behavioural Science and Health, University College London, London, United Kingdom
g Department of Epidemiology, Center for Public Health, Medical University of Vienna, Austria
h Department of Cancer Epidemiology and Prevention Research, Alberta Health Services, Calgary, Alberta, Canada
i Departments of Oncology and Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
Abstract
Background: Given the high burden and prevalence of depression, various guidelines underscore the role of healthcare providers in supplying advice on physical activity (PA) as a potential modifying factor influencing the incidence and severity of depressive symptoms in adults. We aimed to investigate the extent to which healthcare providers provide PA advice to adults with depressive symptoms in the US. Methods: Data on adults aged 20–64 years (n = 4971) in the National Health and Nutrition Examination Study between 2011 and 2016 were analysed. Depressive symptoms were assessed using the Patient Health Questionnaire and response options were categorised as “none or minimal”, “mild”, “moderate-severe”. Receipt of PA advice from a healthcare provider was self-reported. We restricted our study sample to adults free from chronic diseases. Results: Higher odds of receiving advice to exercise were reported among adults with mild (OR = 1.7, 95% CI: 1.3–2.3) and moderate-severe depressive symptoms (OR = 1.7, 95% CI: 1.0–2.8). Furthermore, exercise advice was more commonly reported among adults who were overweight, obese, Hispanic, Asian, being insured with private insurance, with education higher than high school, and had access to a routine place for health care. Limitations: Social and culutral aspects of overweight/obesity may prohibit generalizations. Cross sectional design does not allow for causal realtionships. Conclusions: In the US, fewer than one in three adults experiencing symptoms of depression report having received exercise advice from a healthcare provider. Providing such advice may be a sustainable clinical strategy in reducing the incidence and severity of depression symptoms. © 2019 Elsevier B.V.
Author Keywords
Advice; Depressive symptoms; Health care providers; NHANES; Physical activity
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“The AURORA Study: a longitudinal, multimodal library of brain biology and function after traumatic stress exposure” (2019) Molecular Psychiatry
The AURORA Study: a longitudinal, multimodal library of brain biology and function after traumatic stress exposure
(2019) Molecular Psychiatry, .
McLean, S.A.a , Ressler, K.b , Koenen, K.C.c , Neylan, T.d , Germine, L.b , Jovanovic, T.e , Clifford, G.D.f , Zeng, D.g , An, X.a , Linnstaedt, S.a , Beaudoin, F.h , House, S.i , Bollen, K.A.j , Musey, P.k , Hendry, P.l , Jones, C.W.m , Lewandowski, C.n , Swor, R.o , Datner, E.p , Mohiuddin, K.q , Stevens, J.S.r , Storrow, A.s , Kurz, M.C.t , McGrath, M.E.u , Fermann, G.J.v , Hudak, L.A.w , Gentile, N.x , Chang, A.M.y , Peak, D.A.z , Pascual, J.L.aa , Seamon, M.J.aa , Sergot, P.ab , Peacock, W.F.ac , Diercks, D.ad , Sanchez, L.D.ae , Rathlev, N.af , Domeier, R.ag , Haran, J.P.ah , Pearson, C.ai , Murty, V.P.aj , Insel, T.R.ak , Dagum, P.ak , Onnela, J.-P.al , Bruce, S.E.am , Gaynes, B.N.an , Joormann, J.ao , Miller, M.W.ap , Pietrzak, R.H.aq , Buysse, D.J.ar , Pizzagalli, D.A.b , Rauch, S.L.b , Harte, S.E.as , Young, L.J.r , Barch, D.M.at , Lebois, L.A.M.b , van Rooij, S.J.H.r , Luna, B.ar , Smoller, J.W.au , Dougherty, R.F.ak , Pace, T.W.W.av , Binder, E.r , Sheridan, J.F.aw , Elliott, J.M.ax , Basu, A.c , Fromer, M.ay , Parlikar, T.ay , Zaslavsky, A.M.az , Kessler, R.az
a Department of Anesthesiology, Institute of Trauma Recovery, UNC School of Medicine, Chapel Hill, NC, United States
b Department of Psychiatry, McLean Hospital, Boston, MA, United States
c Department of Epidemiology, Harvard School of Public Health, Boston, MA, United States
d Department of Psychiatry, University of California San Francisco, San Francisco, CA, United States
e Department of Psychiatry & Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, MI, United States
f Department of Biomedical Informatics, Emory University School of Medicine, Atlanta, GA, United States
g Department of Biostatistics, UNC Gillings School of Public Health, Chapel Hill, NC, United States
h Department of Emergency Medicine, Alpert Medical School of Brown University, Providence, RI, United States
i Department of Emergency Medicine, Washington University School of Medicine, St. Louis, MO, United States
j Department of Statistics and Operational Research, University of North Carolina, Chapel Hill, NC, United States
k Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN, United States
l Department of Emergency Medicine, University of Florida College of Medicine, Jacksonville, FL, United States
m Department of Emergency Medicine, Cooper University Health Care, Camden, NJ, United States
n Department of Emergency Medicine, Henry Ford Hospital, Detroit, MI, United States
o Department of Emergency Medicine, William Beaumont School of Medicine, Royal Oak, MI, United States
p Department of Emergency Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
q Department of Emergency Medicine, Einstein Health Medical Center, Philadelphia, PA, United States
r Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States
s Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
t Department of Emergency Medicine, School of Medicine, University of Alabama, Birmingham, AL, United States
u Department of Emergency Medicine, Boston University Medical Center, Boston, MA, United States
v Department of Emergency Medicine, University of Cincinnati Medical Center, Cincinnati, OH, United States
w Department of Emergency Medicine, Emory University Hospital, Atlanta, GA, United States
x Department of Emergency Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, United States
y Department of Emergency Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, United States
z Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, United States
aa Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
ab Department of Emergency Medicine, McGovern Medical School, University of Texas, Houston, TX, United States
ac Department of Emergency Medicine, Baylor College of Medicine, Houston, TX, United States
ad Department of Emergency Medicine, UT Southwestern Medical Center, Dallas, TX, United States
ae Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States
af Department of Emergency Medicine, Baystate Medical Center, Springfield, MA, United States
ag Department of Emergency Medicine, St. Joseph Mercy Ann Arbor Hospital, Ypsilanti, MI, United States
ah Department of Emergency Medicine, University of Massachusetts Medical School, Worcester, MA, United States
ai Department of Emergency Medicine, Wayne State University School of Medicine, Detroit, MI, United States
aj Department of Psychology, College of Liberal Arts, Temple University, Philadelphia, PA, United States
ak Mindstrong Health, Mountain View, CA, United States
al Department of Biostatistics, Harvard School of Public Health, Boston, MA, United States
am Department of Psychological Sciences, University of Missouri, St. Louis, MO, United States
an Department of Psychiatry, UNC School of Medicine, Chapel Hill, NC, United States
ao Department of Psychology, Yale University, New Haven, CT, United States
ap Department of Psychiatry, Boston University School of Medicine, Boston, MA, United States
aq Department of Psychiatry, Yale School of Medicine, West Haven, CT, United States
ar Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, United States
as Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI, United States
at Department of Psychological & Brain Sciences, Washington University School of Medicine, St. Louis, MO, United States
au Department of Psychiatry, Massachusetts General Hospital, Boston, MA, United States
av Department of Psychiatry, College of Medicine, University of Arizona, Tucson, AZ, United States
aw College of Dentistry, Ohio State University School of Medicine, Columbus, OH, United States
ax Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
ay Verily Life Sciences, San Francisco, CA, United States
az Department of Health Care Policy, Harvard Medical School, Boston, MA, United States
Abstract
Adverse posttraumatic neuropsychiatric sequelae (APNS) are common among civilian trauma survivors and military veterans. These APNS, as traditionally classified, include posttraumatic stress, postconcussion syndrome, depression, and regional or widespread pain. Traditional classifications have come to hamper scientific progress because they artificially fragment APNS into siloed, syndromic diagnoses unmoored to discrete components of brain functioning and studied in isolation. These limitations in classification and ontology slow the discovery of pathophysiologic mechanisms, biobehavioral markers, risk prediction tools, and preventive/treatment interventions. Progress in overcoming these limitations has been challenging because such progress would require studies that both evaluate a broad spectrum of posttraumatic sequelae (to overcome fragmentation) and also perform in-depth biobehavioral evaluation (to index sequelae to domains of brain function). This article summarizes the methods of the Advancing Understanding of RecOvery afteR traumA (AURORA) Study. AURORA conducts a large-scale (n = 5000 target sample) in-depth assessment of APNS development using a state-of-the-art battery of self-report, neurocognitive, physiologic, digital phenotyping, psychophysical, neuroimaging, and genomic assessments, beginning in the early aftermath of trauma and continuing for 1 year. The goals of AURORA are to achieve improved phenotypes, prediction tools, and understanding of molecular mechanisms to inform the future development and testing of preventive and treatment interventions. © 2019, Springer Nature Limited.
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Gall’s German enemies” (2019) Journal of the History of the Neurosciences
Gall’s German enemies
(2019) Journal of the History of the Neurosciences, .
Eling, P.a , Finger, S.b
a Department of Psychology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, Netherlands
b Department of Psychological and Brain Sciences, and Program in History of Medicine, Washington University, St. Louis, MO, United States
Abstract
Franz Joseph Gall’s (1758–1828) proposal for a new theory about how to represent the mental faculties is well known. He replaced the traditional perception-judgement-memory triad of abstract faculties with a set of 27 highly specific faculties, many of which humans share with animals. In addition, he argued that these faculties are dependent on specific cortical areas, these being his organs of mind. After several years of presenting his new views in Vienna, he was banned from lecturing for what he considered absurd reasons. The edict enticed him to make a scientific journey through the German states, both to present his ideas to targeted audiences and to collect more cases. This trip, started in 1805, was extended to include stops in Denmark, Holland, and Switzerland before finally ending in Paris in 1807. For the most part, Gall was received with great enthusiasm in what is now Germany, but there were some individuals who strongly opposed his anatomical discoveries and skull-based doctrine. In this article, we examine the concerns and arguments raised by Johann Gotlieb Walter in Berlin, Henrik Steffens in Halle, Jakob Fidelis Ackermann in Heidelberg, and Samuel Thomas Soemmerring in Munich, as well as how Gall responded to them. © 2019, © 2019 The Author(s). Published with license by Taylor & Francis Group, LLC.
Author Keywords
craniology; Franz Joseph Gall; Germany; Jakob Fidelis Ackermann; Johann Gotlieb Walter; organology; phrenology; Samuel Thomas Soemmerring Henrik Steffens
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Comparative Performance and Neuropathologic Validation of the AD8 Dementia Screening Instrument” (2019) Alzheimer Disease and Associated Disorders
Comparative Performance and Neuropathologic Validation of the AD8 Dementia Screening Instrument
(2019) Alzheimer Disease and Associated Disorders, .
Morris, G.M.a , Holden, T.R.b , Weng, H.c , Xiong, C.c , Coble, D.W.c , Cairns, N.J.d , Morris, J.C.e
a Department of Dermatology, St. Louis University School of Medicine, United States
b Department of Medicine, Division of Geriatrics and Nutritional Science, United States
c Division of Biostatistics, United States
d Department of Neurology, Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO, United States
e Department of Neurology, Knight Alzheimer Disease Research Center, Washington University School of Medicine, 4488 Forest Park Avenue, St. Louis, MO 63108, United States
Abstract
Background/Objective: The AD8 informant-based screening instrument has been validated with molecular biomarkers of Alzheimer disease (AD) but not with the gold standard of neuropathologic AD. The objective of this study was to validate the AD8 with neuropathologic AD and compare its predictive performance with that of the Mini-Mental State Examination and both participantderived and informant-derived subjective memory complaint (SMC) regarding the participant. Methods: This longitudinal cohort study at the Knight Alzheimer Disease Research Center at Washington University included 230 participants, ages 50 to 91 years, who later had a neuropathologic examination. Four dementia screening instruments from their baseline assessment were evaluated: the AD8, Mini-Mental State Examination, participant SMC, and informant SMC. The primary outcome was a neuropathologic diagnosis of AD. Results: The average participant age at baseline was 80.4 years, 48% were female. All 4 dementia screening tests were predictive of neuropathologic AD. There was no significant difference in the predictive performance of the AD8 compared with the other instruments, but the AD8 had superior sensitivity and combined positive and negative predictive values. Conclusion: The AD8 is a brief and sensitive screening instrument that may facilitate earlier and more accurate AD diagnosis in a variety of care settings. © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Author Keywords
AD8; Alzheimer disease; dementia; screening
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“A set of functionally-defined brain regions with improved representation of the subcortex and cerebellum” (2019) NeuroImage
A set of functionally-defined brain regions with improved representation of the subcortex and cerebellum
(2019) NeuroImage, art. no. 116290, .
Seitzman, B.A.a , Gratton, C.a , Marek, S.a , Raut, R.V.c , Dosenbach, N.U.F.a c d f g , Schlaggar, B.L.a b c d e , Petersen, S.E.a c e g h , Greene, D.J.b c
a Department of Neurology, Washington University in St. Louis- School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, United States
b Department of Psychiatry, Washington University in St. Louis- School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, United States
c Department of Radiology, Washington University in St. Louis- School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, United States
d Department of Pediatrics, Washington University in St. Louis- School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, United States
e Department of Neuroscience, Washington University in St. Louis- School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, United States
f Department of Occupational Therapy, Washington University in St. Louis- School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, United States
g Department of Biomedical Engineering, Washington University in St. Louis- School of Engineering and Applied Science, One Brookings Dr, St. Louis, MO 63130, United States
h Department of Psychological and Brain Sciences, Washington University in St. Louis, One Brookings Dr, St. Louis, MO 63130, United States
Abstract
An important aspect of network-based analysis is robust node definition. This issue is critical for functional brain network analyses, as poor node choice can lead to spurious findings and misleading inferences about functional brain organization. Two sets of functional brain nodes from our group are well represented in the literature: (1) 264 volumetric regions of interest (ROIs) reported in Power et al., 2011, and (2) 333 cortical surface parcels reported in Gordon et al., 2016. However, subcortical and cerebellar structures are either incompletely captured or missing from these ROI sets. Therefore, properties of functional network organization involving the subcortex and cerebellum may be underappreciated thus far. Here, we apply a winner-take-all partitioning method to resting-state fMRI data to generate novel functionally-constrained ROIs in the thalamus, basal ganglia, amygdala, hippocampus, and cerebellum. We validate these ROIs in three datasets using several criteria, including agreement with existing literature and anatomical atlases. Further, we demonstrate that combining these ROIs with established cortical ROIs recapitulates and extends previously described functional network organization. This new set of ROIs is made publicly available for general use, including a full list of MNI coordinates and functional network labels. © 2019 Elsevier Inc.
Author Keywords
Cerebellum; Functional connectivity; Networks; Resting-state; Subcortical
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Adipose tissue NAD+ biosynthesis is required for regulating adaptive thermogenesis and whole-body energy homeostasis in mice” (2019) Proceedings of the National Academy of Sciences of the United States of America
Adipose tissue NAD+ biosynthesis is required for regulating adaptive thermogenesis and whole-body energy homeostasis in mice
(2019) Proceedings of the National Academy of Sciences of the United States of America, 116 (47), pp. 23822-23828.
Yamaguchi, S.a , Franczyk, M.P.a , Chondronikola, M.a , Qi, N.b , Gunawardana, S.C.c , Stromsdorfer, K.L.a , Porter, L.C.a , Wozniak, D.F.d e , Sasaki, Y.f , Rensing, N.g , Wong, M.g , Piston, D.W.c , Klein, S.a c , Yoshino, J.a h
a Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO 63110, United States
b Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, United States
c Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, United States
d Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, United States
e Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, MO 63110, United States
f Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, United States
g Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United States
h Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
Nicotinamide adenine dinucleotide (NAD+) is a critical coenzyme for cellular energy metabolism. The aim of the present study was to determine the importance of brown and white adipose tissue (BAT and WAT) NAD+ metabolism in regulating whole-body thermogenesis and energy metabolism. Accordingly, we generated and analyzed adipocyte-specific nicotinamide phosphoribosyltransferase (Nampt) knockout (ANKO) and brown adipocyte-specific Nampt knockout (BANKO) mice because NAMPT is the rate-limiting NAD+ biosynthetic enzyme. We found ANKO mice, which lack NAMPT in both BAT and WAT, had impaired gene programs involved in thermogenesis and mitochondrial function in BAT and a blunted thermogenic (rectal temperature, BAT temperature, and whole-body oxygen consumption) response to acute cold exposure, prolonged fasting, and administration of β-adrenergic agonists (norepinephrine and CL-316243). In addition, the absence of NAMPT in WAT markedly reduced adrenergic-mediated lipolytic activity, likely through inactivation of the NAD+–SIRT1–caveolin-1 axis, which limits an important fuel source fatty acid for BAT thermogenesis. These metabolic abnormalities were rescued by treatment with nicotinamide mononucleotide (NMN), which bypasses the block in NAD+ synthesis induced by NAMPT deficiency. Although BANKO mice, which lack NAMPT in BAT only, had BAT cellular alterations similar to the ANKO mice, BANKO mice had normal thermogenic and lipolytic responses. We also found NAMPT expression in supraclavicular adipose tissue (where human BAT is localized) obtained from human subjects increased during cold exposure, suggesting our finding in rodents could apply to people. These results demonstrate that adipose NAMPT-mediated NAD+ biosynthesis is essential for regulating adaptive thermogenesis, lipolysis, and whole-body energy metabolism. © 2019 National Academy of Sciences. All rights reserved.
Author Keywords
Adipose tissue; Energy metabolism; Lipolysis; NAD; Thermogenesis
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access
“Subcortical surface morphometry in substance dependence: An ENIGMA addiction working group study” (2019) Addiction Biology
Subcortical surface morphometry in substance dependence: An ENIGMA addiction working group study
(2019) Addiction Biology, art. no. e12830, .
Chye, Y.a , Mackey, S.b , Gutman, B.A.c , Ching, C.R.K.d , Batalla, A.e f , Blaine, S.g , Brooks, S.h i , Caparelli, E.C.j , Cousijn, J.k , Dagher, A.l , Foxe, J.J.m , Goudriaan, A.E.n o , Hester, R.p , Hutchison, K.q , Jahanshad, N.d , Kaag, A.M.k , Korucuoglu, O.r , Li, C.-S.R.g , London, E.D.s , Lorenzetti, V.a t , Luijten, M.u , Martin-Santos, R.f , Meda, S.A.v , Momenan, R.w , Morales, A.s , Orr, C.b , Paulus, M.P.x y , Pearlson, G.g , Reneman, L.z , Schmaal, L.aa ab , Sinha, R.g , Solowij, N.ac ad , Stein, D.J.ae , Stein, E.A.j , Tang, D.l , Uhlmann, A.af , van Holst, R.ag , Veltman, D.J.ah , Verdejo-Garcia, A.a , Wiers, R.W.ai , Yücel, M.a , Thompson, P.M.d , Conrod, P.aj , Garavan, H.b
a Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, VIC, Australia
b Departments of Psychiatry, University of Vermont, Burlington, VT, United States
c Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, United States
d Department of Neurology, Keck School of Medicine, Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, CA, United States
e Department of Psychiatry, University Medical Centre Utrecht Brain Center, Utrecht University, Utrecht, Netherlands
f Department of Psychiatry and Psychology, Hospital Clinic, IDIBAPS, CIBERSAM, Institute of Neuroscience, University of Barcelona, Barcelona, Spain
g Departments of Psychiatry and Neuroscience, Yale University School of MedicineCT, United States
h Faculty of Health, School of Psychology, Liverpool John Moores University, Liverpool, L3 3AF, United Kingdom
i Department of Neuroscience, Section of Functional Pharmacology, Uppsala University75240, Sweden
j Neuroimaging Research Branch, Intramural Research Program, National Institute of Drug Abuse, Baltimore, MD, United States
k Department of Developmental Psychology, University of Amsterdam, Netherlands
l McConnell Brain Imaging Center, Montreal Neurological Institute, McGill University, Montreal, QC, Canada
m Department of Neuroscience & The Ernest J. Del Monte Institute for Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, NY, United States
n Amsterdam UMC, Department of Psychiatry, Amsterdam Institute for Addiction Research, University of Amsterdam, Amsterdam, Netherlands
o Department of Research and Quality of Care, Arkin Mental Health Care, Amsterdam, Netherlands
p Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, VIC, Australia
q Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, United States
r Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, United States
s Jane and Terry Semel Institute of Neuroscience and Human Behavior, David Geffen School of Medicine, Universityof California at Los Angeles, Los Angeles, CA, United States
t School of Psychology, Faculty of Health Sciences, Australian Catholic University, Melbourne, VIC, Australia
u Behavioural Science Institute, Radboud University, Nijmegen, Netherlands
v Olin Neuropsychiatry Research Center, Hartford Hospital/IOL, Hartford, CT, United States
w Clinical NeuroImaging Research Core, Division of Intramural Clinical and BiologicalResearch, National Institute of Alcohol Abuse and Alcoholism, Bethesda, MD, United States
x VA San Diego Healthcare System and Department of Psychiatry, University of California San DiegoCA, United States
y Laureate Institute for Brain Research, Tulsa, OK, United States
z Department of Radiology and Nuclear Medicine, Amsterdam UMC, location AMC, Amsterdam, Netherlands
aa Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, Australia
ab Centre for Youth Mental Health, The University of Melbourne, Parkville, Australia
ac School of Psychology and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia
ad The Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE), New Lambton HeightsNSW, Australia
ae SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa
af Department of Psychiatry and Mental Health, Faculty of Health Sciences University of Cape Town, South Africa
ag Department of Psychiatry, University of Amsterdam, Amsterdam, Netherlands
ah Department of Psychiatry, VU University Medical CenterAmsterdam, Netherlands
ai Addiction Development and Psychopathology (ADAPT) Lab, University of AmsterdamAmsterdam, Netherlands
aj Department of Psychiatry, Université de Montreal, CHU Ste Justine Hospital, Canada
Abstract
While imaging studies have demonstrated volumetric differences in subcortical structures associated with dependence on various abused substances, findings to date have not been wholly consistent. Moreover, most studies have not compared brain morphology across those dependent on different substances of abuse to identify substance-specific and substance-general dependence effects. By pooling large multinational datasets from 33 imaging sites, this study examined subcortical surface morphology in 1628 nondependent controls and 2277 individuals with dependence on alcohol, nicotine, cocaine, methamphetamine, and/or cannabis. Subcortical structures were defined by FreeSurfer segmentation and converted to a mesh surface to extract two vertex-level metrics—the radial distance (RD) of the structure surface from a medial curve and the log of the Jacobian determinant (JD)—that, respectively, describe local thickness and surface area dilation/contraction. Mega-analyses were performed on measures of RD and JD to test for the main effect of substance dependence, controlling for age, sex, intracranial volume, and imaging site. Widespread differences between dependent users and nondependent controls were found across subcortical structures, driven primarily by users dependent on alcohol. Alcohol dependence was associated with localized lower RD and JD across most structures, with the strongest effects in the hippocampus, thalamus, putamen, and amygdala. Meanwhile, nicotine use was associated with greater RD and JD relative to nonsmokers in multiple regions, with the strongest effects in the bilateral hippocampus and right nucleus accumbens. By demonstrating subcortical morphological differences unique to alcohol and nicotine use, rather than dependence across all substances, results suggest substance-specific relationships with subcortical brain structures. © 2019 Society for the Study of Addiction
Author Keywords
addiction; structural MRI; substance dependence
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“A multi-institutional analysis of clinical outcomes and patterns of care of 1p/19q codeleted oligodendrogliomas treated with adjuvant or salvage radiation therapy” (2019) Journal of Neuro-Oncology
A multi-institutional analysis of clinical outcomes and patterns of care of 1p/19q codeleted oligodendrogliomas treated with adjuvant or salvage radiation therapy
(2019) Journal of Neuro-Oncology, .
Lin, A.J.a , Kane, L.T.b , Molitoris, J.K.c , Smith, D.R.d , Dahiya, S.e , Badiyan, S.N.a , Wang, T.J.C.d , Kruser, T.J.b , Huang, J.a
a Department of Radiation Oncology, Center for Advanced Medicine, Washington University School of Medicine, 4921 Parkview Place, Campus Box #8224, St. Louis, MO 63110, United States
b Department of Radiation Oncology, Northwestern University, Chicago, IL, United States
c Department of Radiation Oncology, University of Maryland, Baltimore, MD, United States
d Department of Radiation Oncology, Columbia University, New York, NY, United States
e Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
Abstract
Purpose: Practice patterns vary for adjuvant treatment of 1p/19q-codeleted oligodendroglioma patients. This study evaluates the outcomes of adjuvant (aRT) versus salvage radiation therapy (sRT) in a multi-institutional cohort. Methods: Oligodendroglioma patients with confirmed 1p/19q codeletion who were treated with RT with or without chemotherapy from 2000 to 2017 at four tertiary centers were retrospectively reviewed. Overall survival (OS), post-RT progression-free survival (PFS), freedom-from-RT (FFRT), and radiation necrosis (RN) rates were determined using Kaplan–Meier analyses. OS1/PFS1 were defined from the initial surgery. OS2/PFS2 were defined from the RT start-date. Multivariable analyses (MVAs) of prognostic factors for OS and PFS were performed with Cox regression. Results: One hundred eighty-six patients were identified: 124(67%) received aRT and 62(33%) received sRT; of sRT patients, 58% were observed after surgery while 42% received chemotherapy without aRT. The median time from initial diagnosis to sRT was 61 months, and 74% had reoperations before sRT. sRT had longer OS1 than aRT (94% vs. 69% at 10 years, p = 0.03) and PFS1 (10-year PFS of 80% vs. 68%, p = 0.03), though sRT was not associated with significantly different OS1/PFS1 on MVAs. Chemotherapy did not delay sRT compared to observation and had worse PFS2 (42% vs. 79% at 5 years, p = 0.08). Higher RT dose was not associated with improved clinical outcomes but was associated with higher symptomatic RN rate (15% vs. 0% at 2 years, p = 0.003). Conclusions: Delaying RT for selected oligodendroglioma patients appears safe. Adjuvant chemotherapy does not delay sRT longer than observation and may be associated with worse PFS after RT. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
Author Keywords
1p/19q codeletion; Chemotherapy; Observation; Oligodendroglioma; Radiation therapy
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“The relationship between confidence and accuracy with verbal and verbal + numeric confidence scales” (2018) Cognitive Research: Principles and Implications
The relationship between confidence and accuracy with verbal and verbal + numeric confidence scales
(2018) Cognitive Research: Principles and Implications, 3 (1), art. no. 41, .
Tekin, E., Lin, W., Roediger, H.L., III
Washington University in St. Louis, One Brookings Drive, St Louis, MO 63130-4899, United States
Abstract
Police departments often use verbal confidence measures (highly confident, somewhat confident) with a small number of values, whereas psychologists measuring the confidence–accuracy relationship typically use numeric scales with a large range of values (20-point or 100-point scales). We compared verbal and verbal + numeric confidence scales for two different lineups, using either two or four levels of confidence. We found strong confidence–accuracy relationships that were unaffected by the nature of the scale at the highest level of confidence. High confidence corresponded to high accuracy with both two- and four-level scales, and the scale type (verbal only or verbal + numeric) did not matter. Police using a simple scale of “highly confident” and “somewhat confident” can, according to our results, rest assured that high confidence indicates high accuracy on a first identification from a lineup. In addition, our two lineups differed greatly in difficulty, yet the confidence–accuracy relationship was quite strong for both lineups, although somewhat lower for the more difficult lineup. © 2018, The Author(s).
Author Keywords
Confidence scales; Confidence–accuracy relationship; Eyewitness memory; Scale ranges; Scale types
Document Type: Article
Publication Stage: Final
Source: Scopus
Access Type: Open Access