Arts & Sciences Brown School McKelvey School of Engineering School of Law School of Medicine Weekly Publications

WashU weekly Neuroscience publications

“Neuronal insulin signaling and brain structure in nondemented older adults: the Atherosclerosis Risk in Communities Study” (2021) Neurobiology of Aging

Neuronal insulin signaling and brain structure in nondemented older adults: the Atherosclerosis Risk in Communities Study
(2021) Neurobiology of Aging, 97, pp. 65-72.

Walker, K.A.a , Chawla, S.b , Nogueras-Ortiz, C.b , Coresh, J.c , Sharrett, A.R.c , Wong, D.F.d , Jack, C.R., Jr.e , Spychalla, A.J.e , Gottesman, R.F.a b , Kapogiannis, D.a b

a Department of Neurology, Johns Hopkins University, Baltimore, MD, United States
b Laboratory of Clinical Investigation, National Institute on Aging, Intramural Research Program, Baltimore, MD, United States
c Department of Epidemiology, Johns Hopkins University, Baltimore, MD, United States
d Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MS, United States
e Department of Radiology, Mayo Clinic, Rochester, MN, United States

Abstract
We used plasma neuronal extracellular vesicles to examine how neuronal insulin signaling proteins relate cross-sectionally to brain structure in nondemented older adults with varying levels of cortical amyloid. Extracellular vesicles enriched for neuronal origin by anti-L1CAM immunoabsorption were isolated from plasma of Atherosclerosis Risk in Communities–Positron Emission Tomography study participants (n = 88; mean age: 77 years [standard deviation: 6]). Neuronal extracellular vesicle levels of phosphorylated insulin signaling cascade proteins were quantified. Brain volume and white matter hyperintensity (WMH) volume were assessed using 3T magnetic resonance imaging. After adjusting for demographic variables and extracellular vesicle marker Alix, higher levels of a neuronal insulin signaling composite measure were associated with lower WMH and greater temporal lobe volume. Secondary analyses found the levels of downstream protein kinases involved in cell survival (p70S6K) and tau phosphorylation/neuroinflammation (GSK-3β) to be most strongly associated with WMH and temporal lobe volume, respectively. Associations between neuronal insulin signaling and lower WMH volume were attenuated in participants with elevated cortical amyloid. These results suggest that enhanced neuronal proximal insulin signaling is associated with preserved brain structure in nondemented older adults. © 2020 Elsevier Inc.

Author Keywords
Brain;  Exosome;  Extracellular vesicle;  Insulin;  Magnetic resonance imaging;  White matter disease

Funding details
Mayo Clinic
National Institutes of Health
National Institute on Aging
National Heart, Lung, and Blood Institute
National Institutes of Health
National Institute on Aging
National Heart, Lung, and Blood InstituteHHSN268201700003I, 2U01HL096917, 2U01HL096902, HHSN268201700004I, 2U01HL096899, 2U01HL096814, HHSN268201700002I, HHSN268201700001I, U01 2U01HL096812, HHSN268201700005I
National Institute of Neurological Disorders and Stroke
National Institute on Deafness and Other Communication DisordersR01-HL70825, K24 AG052573, K23 AG064122

Document Type: Article
Publication Stage: Final
Source: Scopus

“Introducing a New Journal, Biological Psychiatry: Global Open Science” (2020) Biological Psychiatry

Introducing a New Journal, Biological Psychiatry: Global Open Science
(2020) Biological Psychiatry, 88 (12), p. 890.

Krystal, J.H.a b , Barch, D.M.c , Carter, C.S.d

a Departments of Psychiatry, Neuroscience, and Psychology, Yale University, New Haven, CT, United States
b Department of Psychiatry, Yale-New Haven Hospital, New Haven, CT, United States
c Departments of Psychological and Brain Sciences and Radiology, Washington University in St. Louis, St. Louis, MO, United States
d Departments of Psychiatry and Psychology and the Imaging Research Center, University of California, Davis, Davis, CA, United States

Document Type: Editorial
Publication Stage: Final
Source: Scopus

“It’s tricky: Rating alleviating maneuvers in cervical dystonia” (2020) Journal of the Neurological Sciences

It’s tricky: Rating alleviating maneuvers in cervical dystonia
(2020) Journal of the Neurological Sciences, 419, art. no. 117205, .

Cisneros, E.a , Stebbins, G.T.b , Chen, Q.a , Vu, J.P.a , Benadof, C.N.a , Zhang, Z.a , Barbano, R.L.c , Fox, S.H.d e , Goetz, C.G.b , Jankovic, J.f , Jinnah, H.A.g , Perlmutter, J.S.h i , Adler, C.H.j , Factor, S.A.k , Reich, S.G.l , Rodriguez, R.m , Severt, L.L.n , Stover, N.P.o , Berman, B.D.p , Comella, C.L.b , Peterson, D.A.a q

a Institute for Neural Computation, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA 92093, United States
b Department of Neurological Sciences, Rush University Medical Center, 1620 W Harrison St, Chicago, IL 60612, United States
c Department of Neurology, University of Rochester, 500 Joseph C. Wilson Blvd, Rochester, NY 14627, United States
d Movement Disorder Clinic, Toronto Western Hospital, 399 Bathurst Street, Toronto, ON M5T 2S8, Canada
e Medical Sciences Building, 1 King’s College Cir, Toronto, ON M5S 1A8, Canada
f Department of Neurology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, United States
g Departments of Neurology and Human Genetics, Emory University, 1365 Clifton Rd building b suite 2200, Atlanta, GA 30322, United States
h Department of Neurology, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, United States
i Departments of Radiology, Neuroscience, Physical Therapy, and Occupational Therapy, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, United States
j Department of Neurology, Mayo Clinic College of Medicine, 200 1st St SW, Rochester, MN 55905, United States
k Department of Neurology, Emory University School of Medicine, 201 Dowman Dr, Atlanta, GA 30322, United States
l Department of Neurology, University of Maryland Medical Centre, 22 S Greene St, Baltimore, MD 21201, United States
m UF Department of Neurology, 1149 Newell Dr, Gainesville, FL 32611, United States
n Department of Neurology, Beth Israel Medical Center, 529 W 42nd St # 6K, New York, NY 10036, United States
o Department of Neurology, The University of Alabama, Tuscaloosa, AL 35487, United States
p Department of Neurology, Virginia Commonwealth University, 1101 East Marshall Street, PO Box 980599, Richmond, VA 23298-0599, United States
q CNL-S, Salk Institute for Biological Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037, United States

Abstract
Objectives: To investigate hypothesized sources of error when quantifying the effect of the sensory trick in cervical dystonia (CD) with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS-2), test strategies to mitigate them, and provide guidance for future research on the sensory trick. Methods: Previous analyses suggested the sensory trick (or “alleviating maneuver”, AM) item be removed from the TWSTRS-2 because of its poor clinimetric properties. We hypothesized three sources of clinimetric weakness for rating the AM: 1) whether patients were given sufficient time to demonstrate their AM; 2) whether patients’ CD was sufficiently severe for detecting AM efficacy; and 3) whether raters were inadvertently rating the item in reverse of scale instructions. We tested these hypotheses with video recordings and TWSTRS-2 ratings by one “site rater” and a panel of five “video raters” for each of 185 Dystonia Coalition patients with isolated CD. Results: Of 185 patients, 23 (12%) were not permitted sufficient testing time to exhibit an AM, 23 (12%) had baseline CD too mild to allow confident rating of AM effect, and 1 site- and 1 video-rater each rated the AM item with a reverse scoring convention. When these confounds were eliminated in step-wise fashion, the item’s clinimetric properties improved. Conclusions: The AM’s efficacy can contribute to measuring CD motor severity by addressing identified sources of error during its assessment and rating. Given the AM’s sensitive diagnostic and potential pathophysiologic significance, we also provide guidance on modifications to how AMs can be assessed in future CD research. © 2020 Elsevier B.V.

Author Keywords
Cervical dystonia;  Clinimetrics;  Sensorimotor integration;  Sensory trick;  Spasmodic torticollis

Funding details
National Center for Advancing Translational SciencesU54 TR001456
Office of the Assistant Secretary for HealthW81XWH-17-1-0393
National Institute of Neurological Disorders and StrokeU54 NS065701

Document Type: Article
Publication Stage: Final
Source: Scopus

“Central Nervous System Cancers, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology” (2020) Journal of the National Comprehensive Cancer Network: JNCCN

Central Nervous System Cancers, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology
(2020) Journal of the National Comprehensive Cancer Network: JNCCN, 18 (11), pp. 1537-1570.

Nabors, L.B.a , Portnow, J.b , Ahluwalia, M.c , Baehring, J.d , Brem, H.e , Brem, S.f , Butowski, N.g , Campian, J.L.h , Clark, S.W.i , Fabiano, A.J.j , Forsyth, P.k , Hattangadi-Gluth, J.l , Holdhoff, M.e , Horbinski, C.m , Junck, L.n , Kaley, T.o , Kumthekar, P.m , Loeffler, J.S.p , Mrugala, M.M.q , Nagpal, S.r , Pandey, M.s , Parney, I.q , Peters, K.t , Puduvalli, V.K.u , Robins, I.v , Rockhill, J.w , Rusthoven, C.x , Shonka, N.y , Shrieve, D.C.z , Swinnen, L.J.e , Weiss, S.aa , Wen, P.Y.ab , Willmarth, N.E.ac , Bergman, M.A.ad , Darlow, S.D.ad

a O’Neal Comprehensive Cancer Center at UAB
b City of Hope National Medical Center
c Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
d Yale Cancer Center/Smilow Cancer Hospital
e Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
f Abramson Cancer Center at the University of Pennsylvania
g UCSF Helen Diller Family Comprehensive Cancer Center
h Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
i Vanderbilt-Ingram Cancer Center
j Roswell Park Comprehensive Cancer Center
k Moffitt Cancer Center
l UC San Diego Moores Cancer Center
m Robert H. Lurie Comprehensive Cancer Center of Northwestern University
n University of Michigan Rogel Cancer Center
o Memorial Sloan Kettering Cancer Center
p Massachusetts General Hospital Cancer Center
q Mayo Clinic Cancer Center
r Stanford Cancer Institute
s St. Jude Children’s Research Hospital/The University of Tennessee Health Science Center
t Duke Cancer Institute
u The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute
v University of Wisconsin Carbone Cancer Center
w Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
x University of Colorado Cancer Center
y Fred and Pamela Buffet Cancer Center
z Huntsman Cancer Institute at the University of Utah
aa Fox Chase Cancer Center
ab Dana-Farber Cancer Institute
ac American Brain Tumor Association; and
ad National Comprehensive Cancer Network

Abstract
The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of adult CNS cancers ranging from noninvasive and surgically curable pilocytic astrocytomas to metastatic brain disease. The involvement of an interdisciplinary team, including neurosurgeons, radiation therapists, oncologists, neurologists, and neuroradiologists, is a key factor in the appropriate management of CNS cancers. Integrated histopathologic and molecular characterization of brain tumors such as gliomas should be standard practice. This article describes NCCN Guidelines recommendations for WHO grade I, II, III, and IV gliomas. Treatment of brain metastases, the most common intracranial tumors in adults, is also described.

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

“Assessment of Neighborhood Poverty, Cognitive Function, and Prefrontal and Hippocampal Volumes in Children” (2020) JAMA Network Open

Assessment of Neighborhood Poverty, Cognitive Function, and Prefrontal and Hippocampal Volumes in Children
(2020) JAMA Network Open, 3 (11), p. e2023774.

Taylor, R.L.a , Cooper, S.R.a , Jackson, J.J.a , Barch, D.M.a b c

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 Radiology, Washington University, St Louis, MO, United States

Abstract
Importance: The association between poverty and unfavorable cognitive outcomes is robust, but most research has focused on individual household socioeconomic status (SES). There is increasing evidence that neighborhood context explains unique variance not accounted for by household SES. Objective: To evaluate whether neighborhood poverty (NP) is associated with cognitive function and prefrontal and hippocampal brain structure in ways that are dissociable from household SES. Design, Setting, and Participants: This cross-sectional study used a baseline sample of the ongoing longitudinal Adolescent Brain Cognitive Development (ABCD) Study. The ABCD Study will follow participants for assessments each year for 10 years. Data were collected at 21 US sites, mostly within urban and suburban areas, between September 2019 and October 2018. School-based recruitment was used to create a participant sample reflecting the US population. Data analysis was conducted from March to June 2019. Main Outcomes and Measures: NP and household SES were included as factors potentially associated with National Institutes of Health Toolbox Cognitive Battery subtests and hippocampal and prefrontal (dorsolateral prefrontal cortex [DLPFC], dorsomedial PFC [DMPFC], superior frontal gyrus [SFG]) volumes. Independent variables were first considered individually and then together in mixed-effects models with age, sex, and intracranial volume as covariates. Structural equation modeling (SEM) was used to assess shared variance in NP to brain structure and cognitive task associations. The tested hypotheses were formulated after data collection. Results: A total of 11 875 children aged 9 and 10 years (5678 [47.8%] girls) were analyzed. Greater NP was associated with lower scores across all cognitive domains (eg, total composite: β = -0.18; 95% CI, -0.21 to -0.15; P < .001) and with decreased brain volume in the DLPFC (eg, right DLPFC: β = -0.09; 95% CI, -0.12 to -0.07; P < .001), DMPFC (eg, right DMPC: β = -0.07; 95% CI, -0.09 to -0.05; P < .001), SFG (eg, right SFG: β = -0.05; 95% CI, -0.08 to -0.03; P < .001), and right hippocampus (β = -0.04; 95% CI, -0.06 to -0.01; P = .01), even when accounting for household income. Greater household income was associated with higher scores across all cognitive domains (eg, total composite: β = 0.30; 95% CI, 0.28 to 0.33; P < .001) and larger volume in all prefrontal and hippocampal brain regions (eg, right hippocampus: β = 0.04; 95% CI, 0.02 to 0.07; P < .001) even when accounting for NP. The SEM model was a good fit across all cognitive domains, with prefrontal regions being associated with NP relations to language (picture vocabulary: estimate [SE], -0.03 [0.01]; P < .001; oral reading: estimate [SE], -0.02 [0.01]; P < .001), episodic memory (picture sequence: estimate [SE], -0.02 [0.01]; P = .008), and working memory (dimensional card sort: estimate [SE], -0.02 [0.01]; P = .001; flanker inhibitory control: estimate [SE], -0.01 [0.01]; P = .01; list sorting: estimate [SE], -0.03 [0.01]; P < .001) and hippocampal regions being associated with NP associations with language (picture vocabulary: estimate [SE], -0.01 [0.004]; P < .001) and episodic memory (picture sequence: estimate [SE], -0.01 [0.004]; P < 0.001). Conclusions and Relevance: In this study, NP accounted for unique variance in cognitive function and prefrontal and right hippocampal brain volume. These findings demonstrate the importance of including broader environmental influences when conceptualizing early life adversity.

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

“Comparison of Two Commercially Available Fentanyl Screening Immunoassays for Clinical Use” (2020) The Journal of Applied Laboratory Medicine

Comparison of Two Commercially Available Fentanyl Screening Immunoassays for Clinical Use
(2020) The Journal of Applied Laboratory Medicine, 5 (6), pp. 1277-1286.

Budelier, M.M.a , Franks, C.E.a , Logsdon, N.a , Jannetto, P.J.b , Scott, M.G.a , Roper, S.M.a , Farnsworth, C.W.a

a Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University, St. Louis, MO
b Department of Laboratory Medicine and Pathology, Mayo Clinic, MN, Rochester

Abstract
BACKGROUND: Fentanyl is a synthetic opioid associated with illicit drug use and overdose deaths. The SEFRIA Immunalysis (IAL) and ARK fentanyl assays are both FDA-cleared, open channel immunoassays for fentanyl detection in urine. However, limited data are available in the literature comparing these assays. The objective of this study was to perform a direct comparison of these two fentanyl immunoassays. METHODS: IAL and ARK fentanyl immunoassays were performed on a Roche Cobas e602 automated chemistry analyzer. Repeatability and total imprecision were compared by diluting fentanyl into urine at concentrations above, below, and at the manufacturers’ cutoffs of 1.0 ng/mL. Cross-reactivity was assessed for norfentanyl and the fentanyl analogs acetylfentanyl, acrylfentanyl, and furanylfentanyl. Concordance was assessed in 90 patient samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as the gold standard. RESULTS: Repeatability varied from 11.4%-17.8% on the IAL assay and 2.8%-5.5% on the ARK assay. Total imprecision was 18.9%-40.7% on the IAL assay and 2.9%-6.4% on the ARK assay. Both assays cross-reacted with acetylfentanyl (∼100%), acrylfentanyl (∼100%), and furanylfentanyl (∼20%), but only the ARK assay cross-reacted with norfentanyl (∼3%). An admixture of 0.5 ng/mL fentanyl and 6 ng/mL norfentanyl produced a positive result on the ARK assay. Total concordance between IAL and ARK for 90 tested patient samples was 93% (kappa = 0.85). Relative to LC-MS/MS, the IAL assay had a concordance of 90% (kappa = 0.79) and the ARK assay had a concordance of 94% (kappa = 0.88). Including norfentanyl in the LC-MS/MS confirmation increased the concordance of the ARK to 96% (kappa = 0.90). CONCLUSIONS: The ARK assay recognized the metabolite norfentanyl, demonstrated superior precision, and had better concordance with LC-MS/MS compared to the IAL assay. © American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Author Keywords
drug screen;  Fentanyl;  method comparison

Document Type: Article
Publication Stage: Final
Source: Scopus

“Proceedings from the Fourth International Symposium on σ-2 Receptors: Role in Health and Disease” (2020) eNeuro

Proceedings from the Fourth International Symposium on σ-2 Receptors: Role in Health and Disease
(2020) eNeuro, 7 (6), .

Izzo, N.J.a , Colom-Cadena, M.b , Riad, A.A.c , Xu, J.d , Singh, M.e , Abate, C.f , Cahill, M.A.g h , Spires-Jones, T.L.b , Bowen, W.D.i , Mach, R.H.c , Catalano, S.M.a

a Cognition Therapeutics Inc, Pittsburgh, 15203, United States
b UK Dementia Research Institute and The University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom
c University of Pennsylvania, Department of Radiology, Philadelphia, 19104, United States
d Washington University School of Medicine, Department of Radiology, St. Louis, MO, 63110
e Loyola University Chicago Stritch School of Medicine, Department of Cellular and Molecular Physiology, Maywood, 60153, United States
f Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di BariBari I-70125, Italy
g School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW 2650, Australia
h Department of Cancer Biology and Therapeutics, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, 2601 Australia
i Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI 02912

Abstract
The σ-2 receptor (S2R) complex has been implicated in CNS disorders ranging from anxiety and depression to neurodegenerative disorders such as Alzheimer’s disease (AD). The proteins comprising the S2R complex impact processes including autophagy, cholesterol synthesis, progesterone signaling, lipid membrane-bound protein trafficking, and receptor stabilization at the cell surface. While there has been much progress in understanding the role of S2R in cellular processes and its potential therapeutic value, a great deal remains unknown. The International Symposium on Sigma-2 Receptors is held in conjunction with the annual Society for Neuroscience (SfN) conference to promote collaboration and advance the field of S2R research. This review summarizes updates presented at the Fourth International Symposium on Sigma-2 Receptors: Role in Health and Disease, a Satellite Symposium held at the 2019 SfN conference. Interdisciplinary members of the S2R research community presented both previously published and preliminary results from ongoing studies of the role of S2R in cellular metabolism, the anatomic and cellular expression patterns of S2R, the relationship between S2R and amyloid β (Aβ) in AD, the role of S2R complex protein PGRMC1 in health and disease, and the efforts to design new S2R ligands for the purposes of research and drug development. The proceedings from this symposium are reported here as an update on the field of S2R research, as well as to highlight the value of the symposia that occur yearly in conjunction with the SfN conference. Copyright © 2020 Izzo et al.

Author Keywords
amyloid β;  neurodegeneration;  PGRMC1;  SfN symposium;  TMEM97;  σ-2 receptor

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

“A feasibility study to evaluate early treatment response of brain metastases one week after stereotactic radiosurgery using perfusion weighted imaging” (2020) PLoS ONE

A feasibility study to evaluate early treatment response of brain metastases one week after stereotactic radiosurgery using perfusion weighted imaging
(2020) PLoS ONE, 15 (11 November), art. no. e0241835, .

Huang, J.a , Milchenko, M.b , Rao, Y.J.a , LaMontagne, P.b , Abraham, C.a , Robinson, C.G.a , Huang, Y.a , Shimony, J.S.b , Rich, K.M.c , Benzinger, T.b

a Department of Radiation Oncology, Washington University School of Medicine, Saint Louis, MO, United States
b Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO, United States
c Department of Neurosurgery, Washington University School of Medicine, Saint Louis, MO, United States

Abstract
Background To explore if early perfusion-weighted magnetic resonance imaging (PWI) may be a promising imaging biomarker to predict local recurrence (LR) of brain metastases after stereotactic radiosurgery (SRS). Methods This is a prospective pilot study of adult brain metastasis patients who were treated with SRS and imaged with PWI before and 1 week later. Relative cerebral blood volume (rCBV) parameter maps were calculated by normalizing to the mean value of the contralateral white matter on PWI. Cox regression was conducted to explore factors associated with time to LR, with Bonferroni adjusted p&lt;0.0006 for multiple testing correction. LR rates were estimated with the Kaplan-Meier method and compared using the log-rank test. Results Twenty-three patients were enrolled from 2013 through 2016, with 22 evaluable lesions from 16 patients. After a median follow-up of 13.1 months (range: 3.0–53.7), 5 lesions (21%) developed LR after a median of 3.4 months (range: 2.3–5.7). On univariable analysis, larger tumor volume (HR 1.48, 95% CI 1.02–2.15, p = 0.04), lower SRS dose (HR 0.45, 95% CI 0.21–0.97, p = 0.04), and higher rCBV at week 1 (HR 1.07, 95% CI 1.003–1.14, p = 0.04) had borderline association with shorter time to LR. Tumors &gt;2.0cm3 had significantly higher LR than if &lt;2.0cm3: 54% vs 0% at 1 year, respectively, p = 0.008. A future study to confirm the association of early PWI and LR of the high-risk cohort of lesions &gt;2.0cm3 is estimated to require 258 patients. Conclusions PWI at week 1 after SRS may have borderline association with LR. Tumors &lt;2.0cm3 have low risk of LR after SRS and may be low-yield for predictive biomarker studies. Information regarding sample size and potential challenges for future imaging biomarker studies may be gleaned from this pilot study. © 2020 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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

“Randomized Controlled Crossover Trials of the Pharmacokinetics of PRC-063, a Novel Multilayer Extended-Release Formulation of Methylphenidate, in Healthy Adults” (2020) Journal of Clinical Psychopharmacology

Randomized Controlled Crossover Trials of the Pharmacokinetics of PRC-063, a Novel Multilayer Extended-Release Formulation of Methylphenidate, in Healthy Adults
(2020) Journal of Clinical Psychopharmacology, 40 (6), pp. 579-587.

Katzman, M.A.a b c d , Mattingly, G.e f , Klassen, L.J.g , Cataldo, M.J.h , Donnelly, G.A.E.i

a From the START Clinic for Mood and Anxiety DisordersON
b Department of Psychology, Adler Professional Graduate School, Toronto, United States
c Department of Psychiatry, Northern Ontario School of Medicine
d Department of Psychology, Lakehead UniversityON, Canada
e Washington University School of Medicine, St Louis, United States
f Midwest Research Group, St Charles, MO
g Eden Mental Health Centre, Winkler, MB, Canada
h Purdue Pharma L.P., CT, Stamford
i Pickering, ON, Canada

Abstract
PURPOSE/BACKGROUND: PRC-063 is a once-daily, extended-release oral formulation of methylphenidate hydrochloride developed to provide early and prolonged symptom improvement in patients with attention-deficit/hyperactivity disorder. METHODS/PROCEDURES: We conducted 3 randomized, open-label crossover studies of the pharmacokinetics of PRC-063 in healthy, nonobese men and women aged 18 to 45 years. PRC-063 (100 mg/d) was compared with immediate-release methylphenidate (20 mg, 3 times daily) when administered on a single day under fasted and fed conditions and at steady state (day 5 of repeat dosing under fasted conditions). The pharmacokinetics of PRC-063 administered as capsule contents sprinkled on apple sauce, yoghurt, or ice cream were also investigated. FINDINGS/RESULTS: PRC-063 demonstrated biphasic absorption, with 2 distinct peak plasma concentrations. Intake of a high-fat, high-calorie meal did not increase the peak plasma methylphenidate concentration (Cmax) or extent of absorption (area under the curve), however; it resulted in slower uptake versus a fasted state. During repeated dosing, steady state was reached with no further accumulation of methylphenidate from day 3. At steady state, PRC-063 gave higher evening and trough plasma methylphenidate levels than immediate-release methylphenidate (3 times daily). The pharmacokinetics of PRC-063 sprinkled on food were comparable to that of intact capsules. Reported adverse events (AEs) were consistent with the established safety profile of methylphenidate. There were no serious AEs, but 3 subjects discontinued the repeat-dosing study because of AEs assessed as possibly related to study treatment. IMPLICATIONS/CONCLUSIONS: Our data indicate that PRC-063 can be taken with or without food or by sprinkling capsule contents on food.

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

“The Effect of Venlafaxine on Electrocardiogram Intervals During Treatment for Depression in Older Adults” (2020) Journal of Clinical Psychopharmacology

The Effect of Venlafaxine on Electrocardiogram Intervals During Treatment for Depression in Older Adults
(2020) Journal of Clinical Psychopharmacology, 40 (6), pp. 553-559.

Behlke, L.M.a , Lenze, E.J.a , Pham, V.a , Miller, J.P.b , Smith, T.W.c , Saade, Y.d , Karp, J.F.e , Reynolds, C.F., 3rde , Blumberger, D.M.f , Stefan, C.f , Mulsant, B.H.f

a From the Department of Psychiatry
b Division of Biostatistics
c Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St Louis, MO
d Department of Psychiatry, Johns Hopkins University School of Medicine, MD, Baltimore, United States
e Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, United States
f Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, ON, Canada

Abstract
PURPOSE/BACKGROUND: Venlafaxine is a commonly used antidepressant with both serotonergic and noradrenergic activity. There are concerns that it may prolong the corrected QT interval (QTc), and older adults may be at higher risk for this adverse effect, especially at higher dosages of the medication. METHODS/PROCEDURES: In this secondary analysis of a prospective clinical trial, we measured changes in QTc and other electrocardiogram (ECG) parameters in 169 adults 60 years or older with a major depressive disorder treated acutely with venlafaxine extended release up to 300 mg daily. We examined the relationship of venlafaxine dosage and ECG parameters, as well as the relationship between serum levels of venlafaxine and ECG parameters. FINDINGS/RESULTS: Venlafaxine exposure was not associated with an increase in QTc. Heart rate increased with venlafaxine treatment, whereas the PR interval shortened, and QRS width did not change significantly. The QTc change from baseline was not associated with venlafaxine dosages or serum concentrations. Age, sex, cardiovascular comorbidities, and depression remission status did not predict changes in QTc with venlafaxine. IMPLICATIONS/CONCLUSIONS: Venlafaxine treatment did not prolong QTc or other ECG parameters, even in high dosages in older depressed adults. These findings indicate that venlafaxine does not significantly affect cardiac conduction in most older patients.

Document Type: Article
Publication Stage: Final
Source: Scopus

“Anesthetic Conditioning for Secondary Brain Injury After Aneurysmal Subarachnoid Hemorrhage” (2020) World Neurosurgery

Anesthetic Conditioning for Secondary Brain Injury After Aneurysmal Subarachnoid Hemorrhage
(2020) World Neurosurgery, 143, pp. 577-578.

Athiraman, U.a , Zipfel, G.J.b

a Department of Anesthesiology, Washington University, St. Louis, MO, United States
b Department of Neurological Surgery and Neurology, Washington University, St. Louis, MO, United States

Document Type: Article
Publication Stage: Final
Source: Scopus

“Congenital neuroblastoma” (2020) NeoReviews

Congenital neuroblastoma
(2020) NeoReviews, 21 (11), pp. e716-e727.

Minakova, E.a , Lang, J.b

a Department of Pediatrics, Division of Newborn Medicine, Washington University in St Louis, St Louis, MO, United States
b Mallinckrodt Institute of Radiology, Washington University in St Louis, St Louis, MO, United States

Abstract
Neuroblastoma is the most common extracranial solid tumor diagnosed during childhood and gives rise to various heterogeneous tumors along the sympathoadrenal axis. Congenital neuroblastoma accounts for 5% of total neuroblastoma cases diagnosed annually, with the majority of cases diagnosed in the first month after birth. Interestingly, neonates demonstrate a unique disease trajectory compared with children older than 1 year of age. This article will provide information on the pathogenesis and variable clinical presentation of congenital neuroblastoma, along with the biological prognostic factors that predict long-term outcomes in affected neonates. © 2020, American Academy of Pediatrics. All rights reserved.

Document Type: Article
Publication Stage: Final
Source: Scopus

“Meningioma: A Review of Clinicopathological and Molecular Aspects” (2020) Frontiers in Oncolog

Meningioma: A Review of Clinicopathological and Molecular Aspects
(2020) Frontiers in Oncology, 10, art. no. 579599, .

Huntoon, K.a , Toland, A.M.S.b , Dahiya, S.c

a Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, United States
b Department of Pathology, Stanford University, Stanford, CA, United States
c Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States

Abstract
Meningiomas are the most the common primary brain tumors in adults, representing approximately a third of all intracranial neoplasms. They classically are found to be more common in females, with the exception of higher grades that have a predilection for males, and patients of older age. Meningiomas can also be seen as a spectrum of inherited syndromes such as neurofibromatosis 2 as well as ionizing radiation. In general, the 5-year survival for a WHO grade I meningioma exceeds 80%; however, survival is greatly reduced in anaplastic meningiomas. The standard of care for meningiomas in a surgically-accessible location is gross total resection. Radiation therapy is generally saved for atypical, anaplastic, recurrent, and surgically inaccessible benign meningiomas with a total dose of ~60 Gy. However, the method of radiation, regimen and timing is still evolving and is an area of active research with ongoing clinical trials. While there are currently no good adjuvant chemotherapeutic agents available, recent advances in the genomic and epigenomic landscape of meningiomas are being explored for potential targeted therapy. © Copyright © 2020 Huntoon, Toland and Dahiya.

Author Keywords
clinical trials;  immunotherapy;  meningioma;  molecular diagnosis;  neurosurgery;  pathology;  radiation therapy;  targeted treatment

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

“Burst mitofusin activation reverses neuromuscular dysfunction in murine cmt2a” (2020) eLife

Burst mitofusin activation reverses neuromuscular dysfunction in murine cmt2a
(2020) eLife, 9, art. no. e61119, pp. 1-42.

Franco, A.a , Dang, X.a b , Walton, E.K.a , Ho, J.N.c d , Zablocka, B.e , Ly, C.f , Miller, T.M.f , Baloh, R.H.g , Shy, M.E.h , Yoo, A.S.c d , Dorn, G.W., IIa

a Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, United States
b Department of Cardiology, The First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an, Shaanxi, China
c Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, United States
d Center for Regenerative Medicine, Washington University School of Medicine, St. Louis, MO, United States
e Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland
f Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
g Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, United States
h Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA, United States

Abstract
Charcot-Marie-Tooth disease type 2A (CMT2A) is an untreatable childhood peripheral neuropathy caused by mutations of the mitochondrial fusion protein, mitofusin (MFN) 2. Here, pharmacological activation of endogenous normal mitofusins overcame dominant inhibitory effects of CMT2A mutants in reprogrammed human patient motor neurons, reversing hallmark mitochondrial stasis and fragmentation independent of causal MFN2 mutation. In mice expressing human MFN2 T105M, intermittent mitofusin activation with a small molecule, MiM111, normalized CMT2A neuromuscular dysfunction, reversed pre-treatment axon and skeletal myocyte atrophy, and enhanced axon regrowth by increasing mitochondrial transport within peripheral axons and promoting in vivo mitochondrial localization to neuromuscular junctional synapses. MiM111-treated MFN2 T105M mouse neurons exhibited accelerated primary outgrowth and greater post-axotomy regrowth, linked to enhanced mitochondrial motility. MiM111 is the first pre-clinical candidate for CMT2A. © 2020, eLife Sciences Publications Ltd. All rights reserved.

Funding details
Foundation for Barnes-Jewish Hospital
National Institutes of HealthR41NS115184, 628906, R41NS113642, R35HL135736
CDI-COREs 2015-515, 2019-813
Muscular Dystrophy Association
Center for Cellular Imaging, Washington University

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

“Genetic architecture of reciprocal social behavior in toddlers: Implications for heterogeneity in the early origins of autism spectrum disorder” (2020) Development and Psychopathology

Genetic architecture of reciprocal social behavior in toddlers: Implications for heterogeneity in the early origins of autism spectrum disorder
(2020) Development and Psychopathology, 32 (4), pp. 1190-1205. Cited 1 time.

Marrus, N.a , Grant, J.D.a b , Harris-Olenak, B.c , Albright, J.a , Bolster, D.a , Haber, J.R.d , Jacob, T.d , Zhang, Y.a , Heath, A.C.a , Agrawal, A.a , Constantino, J.N.a , Elison, J.T.e f , Glowinski, A.L.a

a Department of Psychiatry, Washington University, St. Louis, MO, USA
b Department of Psychology, Maryville University of St. Louis, St. Louis, MO, USA
c Kaiser Permanente San Jose, CA, San Jose, United States
d Palo Alto Veterans Affairs Health Care System, Menlo Park, CA, United States
e Institute of Child Development, University of Minnesota, MN, Minneapolis, United States
f Department of Pediatrics, University of Minnesota, MN, Minneapolis, United States

Abstract
Impairment in reciprocal social behavior (RSB), an essential component of early social competence, clinically defines autism spectrum disorder (ASD). However, the behavioral and genetic architecture of RSB in toddlerhood, when ASD first emerges, has not been fully characterized. We analyzed data from a quantitative video-referenced rating of RSB (vrRSB) in two toddler samples: a community-based volunteer research registry (n = 1,563) and an ethnically diverse, longitudinal twin sample ascertained from two state birth registries (n = 714). Variation in RSB was continuously distributed, temporally stable, significantly associated with ASD risk at age 18 months, and only modestly explained by sociodemographic and medical factors (r2 = 9.4%). Five latent RSB factors were identified and corresponded to aspects of social communication or restricted repetitive behaviors, the two core ASD symptom domains. Quantitative genetic analyses indicated substantial heritability for all factors at age 24 months (h2 ≥ .61). Genetic influences strongly overlapped across all factors, with a social motivation factor showing evidence of newly-emerging genetic influences between the ages of 18 and 24 months. RSB constitutes a heritable, trait-like competency whose factorial and genetic structure is generalized across diverse populations, demonstrating its role as an early, enduring dimension of inherited variation in human social behavior. Substantially overlapping RSB domains, measurable when core ASD features arise and consolidate, may serve as markers of specific pathways to autism and anchors to inform determinants of autism’s heterogeneity.

Author Keywords
quantitative autistic traits;  reciprocal social behavior;  toddlers;  twins;  vrRSB

Document Type: Article
Publication Stage: Final
Source: Scopus

“Responsiveness to Change over Time: An Examination of the Neuro-QoL Social Function Measures in Persons with Huntington’s Disease” (2020) Journal of Huntington’s Disease

Responsiveness to Change over Time: An Examination of the Neuro-QoL Social Function Measures in Persons with Huntington’s Disease
(2020) Journal of Huntington’s Disease, 9 (1), pp. 83-97.

Carlozzi, N.E.a , Boileau, N.R.a , Hahn, E.A.b , Barton, S.K.c , Cella, D.b , McCormack, M.K.d e , Ready, R.E.f

a Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI, United States
b Department of Medical Social Sciences, Northwestern University Feinberg, School of Medicine, Chicago, IL, United States
c Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
d Department of Psychiatry, Rutgers-Robert Wood Johnson Medical School, Piscataway, NJ, United States
e Department of Pathology, Rowan School of Medicine, Stratford, NJ, United States
f Department of Psychological and Brain Sciences, University of Massachusetts, Amherst, MA, United States

Abstract
Social health is an important concern in persons with Huntington’s disease (HD); however, there is little literature examining this construct in this population. Objective: While cross-sectional data supports the clinical utility of two Neuro-QoL social health measures in persons with HD, data is still needed to establish their longitudinal validity. Methods: Participants (N = 358) completed baseline and at least one follow-up (12- and 24-month) assessment that included the completion of Neuro-QoL Social Health computer adaptive tests (CATs) and short forms (for Ability to Participate in Social Roles and Activities [SRA] and Satisfaction with SRA). Test-retest reliability was examined using intra class correlations, and one-way ANOVAs with Bonferroni post-hoc contrasts were used to determine whether there were group differences among premanifest, early- and late-stage HD participants on the Social health measures. In addition, standardized response means were used to examine longitudinal responsiveness, and mixed or general linear models were used to examine change over time (relative to self-reported change on an associated anchor item about social health and clinician-rated change based on Total Functional Capacity scores from the UHDRS). Results: Test-retest reliability of the measures was excellent (ICCs ranged from 0.82 to 0.87 across the different measures) and persons with greater disease burden reported more problems with social health than those at earlier stages in the disease process (all p < 0.0001). Responsiveness was supported for all measures except the Ability to Participate in SRA CAT; participants who had self-reported or clinician-rated declines in health generally had 12- and 24-month declines on the Neuro-QoL measures. Conclusions: Findings indicate that these measures may be useful for studies attempting to assess change in social health over time. © 2020 – IOS Press and the authors. All rights reserved.

Author Keywords
health-related quality of life;  Huntington’s disease;  patient-reported outcomes;  social health;  validity

Document Type: Article
Publication Stage: Final
Source: Scopus

“Bidirectional pathways between psychosocial risk factors and paranoid ideation in a general nonclinical population” (2020) Development and Psychopathology

Bidirectional pathways between psychosocial risk factors and paranoid ideation in a general nonclinical population
(2020) Development and Psychopathology, .

Saarinen, A.a b , Granö, N.c , Hintsanen, M.a , Lehtimäki, T.d , Cloninger, C.R.e f , Keltikangas-Järvinen, L.b

a Research Unit of Psychology, University of Oulu, Oulu, Finland
b Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland
c Department of Adolescent Psychiatry, Helsinki University Hospital, Helsinki, Finland
d Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
e Department of Psychiatry, School of Medicine, Washington University, St. Louis, MO, United States
f Anthropedia Foundation, St. Louis, MO, United States

Abstract
We investigated (a) whether psychosocial factors (experienced stress, anticipatory worry, social detachment, sleeping disturbances, alcohol use) predict the course of paranoid ideation between the ages of 24 to 50 years and (b) whether the predictive relationships are more likely to proceed from the psychosocial factors to paranoid ideation, or vice versa. The participants (N = 1534-1553) came from the population-based Young Finns study. Paranoid ideation and psychosocial factors were assessed by reliable self-report questionnaires in 2001, 2007, and 2011/2012. The data were analyzed using growth curve and structural equation models. High experienced stress, anticipatory worry, social detachment, frequent sleeping disturbances, and frequent alcohol use predicted more paranoid ideation. More risk factors predicted increasing paranoid ideation. There were bidirectional predictive relationships of paranoid ideation with experienced stress, anticipatory worry, social detachment, and sleeping disturbances. The link between alcohol use and paranoid ideation was only correlative. In conclusion, paranoid ideation increases by reciprocal interactions with stress, worry, social detachment, and sleeping disturbances. The findings support the threat-Anticipation model of paranoid ideation, providing important implications for treatment of paranoia. Copyright © The Author(s), 2020. Published by Cambridge University Press.

Author Keywords
alcohol use;  paranoid;  sleep;  social isolation;  stress

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

“Socio-demographic and trauma-related predictors of depression within eight weeks of motor vehicle collision in the AURORA study” (2020) Psychological Medicine

Socio-demographic and trauma-related predictors of depression within eight weeks of motor vehicle collision in the AURORA study
(2020) Psychological Medicine, .

Joormann, J.a , McLean, S.A.b c , Beaudoin, F.L.d e f g , An, X.b , Stevens, J.S.h , Zeng, D.i , Neylan, T.C.j k , Clifford, G.l , Linnstaedt, S.D.b , Germine, L.T.m n o , Rauch, S.L.p , Musey, P.I.q , Hendry, P.L.r , Sheikh, S.r , Jones, C.W.s , Punches, B.E.t u , Fermann, G.t , Hudak, L.A.v , Mohiuddin, K.w , Murty, V.x , McGrath, M.E.y , Haran, J.P.z , Pascual, J.aa , Seamon, M.ab , Peak, D.A.ac , Pearson, C.ad , Domeier, R.M.ae , Sergot, P.af , Merchant, R.ag , Sanchez, L.D.ah ai , Rathlev, N.K.aj , Peacock, W.F.ak , Bruce, S.E.al , Barch, D.am , Pizzagalli, D.A.n , Luna, B.an , Harte, S.E.ao , Hwang, I.ap , Lee, S.ap , Sampson, N.ap , Koenen, K.C.aq , Ressler, K.J.n ar , Kessler, R.C.ap

a Department of Psychology, Yale University, New Haven, CT, United States
b Department of Anesthesiology, Institute for Trauma Recovery, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
c Department of Emergency Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
d Department of Emergency Medicine, Alpert Medical School, Brown University, Providence, RI, United States
e Department of Health Services, Policy and Practice, Brown University School of Public Health, Providence, RI, United States
f Rhode Island Hospital, Providence, RI, United States
g Miriam Hospital, Providence, RI, United States
h Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, United States
i Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, United States
j San Francisco VA Healthcare System, San Francisco, CA, United States
k Department of Psychiatry and Neurology, University of California, San Francisco, CA, United States
l Department of Biomedical Informatics, Emory University School of Medicine, Georgia Institute of Technology, Atlanta, GA, United States
m Institute for Technology in Psychiatry, McLean Hospital, Belmont, MA, United States
n Department of Psychiatry, Harvard Medical School, Boston, MA, United States
o Many Brains Project, Acton, MA, United States
p Department of Psychiatry, McLean Hospital, Belmont, MA, United States
q Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN, United States
r Department of Emergency Medicine, University of Florida College of Medicine-Jacksonville, Jacksonville, FL, United States
s Department of Emergency Medicine, Cooper Medical School, Rowan University, Camden, NJ, United States
t Department of Emergency Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States
u University of Cincinnati College of Nursing, Cincinnati, OH, United States
v Department of Emergency Medicine, Emory University, Grady Memorial Hospital, Atlanta, GA, United States
w Department of Emergency Medicine/Internal Medicine, Einstein Medical Center, Philadelphia, PA, United States
x Department of Psychology, Temple University, Philadelphia, PA, United States
y Department of Emergency Medicine, Boston Medical Center, Boston, MA, United States
z Department of Emergency Medicine, University of Massachusetts Medical School, Worcester, MA, United States
aa Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
ab Division of Traumatology, Surgical Critical Care and Emergency Surgery, University of Pennsylvania, Philadelphia, PA, United States
ac Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, United States
ad Wayne State University, Department of Emergency Medicine, Ascension St. John Hospital, Detroit, MI, United States
ae Department of Emergency Medicine, Saint Joseph Mercy Hospital, Ann Arbor, MI, United States
af Department of Emergency Medicine, University of Texas Health Science Center, Houston, TX, United States
ag Department of Emergency Medicine, Brigham and Women’s Hospital, Boston, MA, United States
ah Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States
ai Department of Emergency Medicine, Harvard Medical School, Boston, MA, United States
aj Department of Emergency Medicine, University of Massachusetts Medical School-Baystate, Springfield, MA, United States
ak Henry JN Taub Department of Emergency Medicine, Baylor College of Medicine, Houston, TX, United States
al Department of Psychological Sciences, University of Missouri-St. Louis, St. Louis, MO, United States
am Department of Psychological and Brain Sciences, Psychiatry, and Radiology, Washington University in St. Louis, St. Louis, MO, United States
an Laboratory of Neurocognitive Development, Western Psychiatric Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
ao Department of Anesthesiology and Internal Medicine-Rheumatology, Chronic Pain and Fatigue Research Center, University of Michigan Medical School, Ann Arbor, MI, United States
ap Department of Health Care Policy, Harvard Medical School, Boston, MA, United States
aq Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, United States
ar Division of Depression and Anxiety Disorders, McLean Hospital, Belmont, MA, United States

Abstract
Background This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience. Methods We focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression. Results Eight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma. Conclusions These observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure. Copyright © The Author(s) 2020. Published by Cambridge University Press.

Author Keywords
Anxiety;  depression;  PTSD;  trauma

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

“Obsessive-Compulsive Disorder in the Adolescent Brain Cognitive Development Study: Impact of Changes From DSM-IV to DSM-5” (2020) Journal of the American Academy of Child and Adolescent Psychiatry

Obsessive-Compulsive Disorder in the Adolescent Brain Cognitive Development Study: Impact of Changes From DSM-IV to DSM-5
(2020) Journal of the American Academy of Child and Adolescent Psychiatry, .

Potter, A.S.a , Owens, M.M.a , Albaugh, M.a , Garavan, H.a , Sher, K.J.b , Kaufman, J.c , Barch, D.M.d

a University of Vermont, Burlington
b University of Missouri, Columbia
c Kennedy Krieger Institute, Baltimore, Maryland, and Johns Hopkins School of Medicine, Baltimore, MD, United States
d Washington University, St. Louis, MO, United States

Abstract
The Diagnostic and Statistical Manual of Mental Disorders (DSM), used to diagnose psychiatric disorders, was revised to DSM-5 in 2013. Changes were made to the criteria for obsessive-compulsive disorder (OCD), a disorder with a lifetime prevalence of 1% to 3% in children.1 Prior revisions to OCD criteria (from DSM-III to DSM-IV) resulted in lower reported prevalence rates,2 but this is not yet clear with DSM-5. In DSM-5, the definition of obsessions was broadened (Table 1), and the requirement that obsessions cause marked anxiety or distress was removed. Thus we examined rates of OCD within the Adolescent Brain Cognitive Development (ABCD) study3 using both DSM-IV and DSM-5 criteria. © 2020 American Academy of Child and Adolescent Psychiatry

Funding details
National Institutes of HealthU01DA041022, U01DA041028, U01DA050988, U01DA041174, U01DA041025, U01DA041156, U01DA041093, U01DA041048, U24DA041147, U24DA041123, U01DA041106, U01DA041148, U01DA051038, U01DA041134, U01DA050989, U01DA041117, U01DA051018, U01DA051039, U01DA041089, U01DA041120, U01DA051016, U01DA051037, U01DA050987

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

“A large-scale genome-wide association study meta-analysis of cannabis use disorder” (2020) The Lancet Psychiatry

A large-scale genome-wide association study meta-analysis of cannabis use disorder
(2020) The Lancet Psychiatry, . Cited 1 time.

Johnson, E.C.a , Demontis, D.d g h , Thorgeirsson, T.E.i , Walters, R.K.l m , Polimanti, R.n p bq , Hatoum, A.S.a , Sanchez-Roige, S.q s bq , Paul, S.E.u , Wendt, F.R.n p , Clarke, T.-K.v bq , Lai, D.w bq , Reginsson, G.W.i , Zhou, H.n p bq , He, J.a bq , Baranger, D.A.A.x , Gudbjartsson, D.F.j y , Wedow, R.l m bq , Adkins, D.E.z aa ac , Adkins, A.E.z aa ac , Alexander, J.ad , Bacanu, S.-A.ad bq , Bigdeli, T.B.af , Boden, J.ag bq , Brown, S.A.q r , Bucholz, K.K.a , Bybjerg-Grauholm, J.g aj , Corley, R.P.am , Degenhardt, L.ao bq , Dick, D.M.aa ab , Domingue, B.W.ap , Fox, L.a bq , Goate, A.M.ar , Gordon, S.D.as , Hack, L.M.aq , Hancock, D.B.at , Hartz, S.M.a , Hickie, I.B.au , Hougaard, D.M.g aj , Krauter, K.ak an bq , Lind, P.A.as , McClintick, J.N.av , McQueen, M.B.al , Meyers, J.L.af aw , Montgomery, G.W.ax , Mors, O.g az , Mortensen, P.B.e f g , Nordentoft, M.g ba , Pearson, J.F.ah ai , Peterson, R.E.ae , Reynolds, M.D.bb , Rice, J.P.a , Runarsdottir, V.bc , Saccone, N.L.b c , Sherva, R.bd bq , Silberg, J.L.ab ae , Tarter, R.E.bb , Tyrfingsson, T.bc , Wall, T.L.q , Webb, B.T.ad , Werge, T.g be bf , Wetherill, L.w bq , Wright, M.J.ay , Zellers, S.bg , Adams, M.J.v , Bierut, L.J.a , Boardman, J.D.bh , Copeland, W.E.bi , Farrer, L.A.bd , Foroud, T.M.w , Gillespie, N.A.ae , Grucza, R.A.a , Harris, K.M.bj bq , Heath, A.C.a , Hesselbrock, V.bk bq , Hewitt, J.K.am , Hopfer, C.J.bl , Horwood, J.ag bq , Iacono, W.G.bg , Johnson, E.O.at , Kendler, K.S.ae , Kennedy, M.A.ai , Kranzler, H.R.bm bn , Madden, P.A.F.a , Maes, H.H.ab ae , Maher, B.S.bo , Martin, N.G.as , McGue, M.bg , McIntosh, A.M.v , Medland, S.E.as , Nelson, E.C.a , Porjesz, B.af aw bq , Riley, B.P.ad , Stallings, M.C.am , Vanyukov, M.M.bb , Vrieze, S.bg bq , Walters, R.bq , Johnson, E.bq , McClintick, J.bq , Hatoum, A.bq , Wendt, F.bq , Adams, M.bq , Adkins, A.bq , Aliev, F.bq , Batzler, A.bq , Bertelsen, S.bq , Biernacka, J.bq , Bigdeli, T.bq , Chen, L.-S.bq , Chou, Y.-L.bq , Degenhardt, F.bq , Docherty, A.bq , Edwards, A.bq , Fontanillas, P.bq , Foo, J.bq , Frank, J.bq , Giegling, I.bq , Gordon, S.bq , Hack, L.bq , Hartmann, A.bq , Hartz, S.bq , Heilmann-Heimbach, S.bq , Herms, S.bq , Hodgkinson, C.bq , Hoffman, P.bq , Hottenga, J.bq , Kennedy, M.bq , Alanne-Kinnunen, M.bq , Konte, B.bq , Lahti, J.bq , Lahti-Pulkkinen, M.bq , Ligthart, L.bq , Loukola, A.bq , Maher, B.bq , Mbarek, H.bq , McIntosh, A.bq , McQueen, M.bq , Meyers, J.bq , Milaneschi, Y.bq , Palviainen, T.bq , Pearson, J.bq , Peterson, R.bq , Ripatti, S.bq , Ryu, E.bq , Saccone, N.bq , Salvatore, J.bq , Schwandt, M.bq , Streit, F.bq , Strohmaier, J.bq , Thomas, N.bq , Wang, J.-C.bq , Webb, B.bq , Wills, A.bq , Boardman, J.bq , Chen, D.bq , Choi, D.-S.bq , Copeland, W.bq , Culverhouse, R.bq , Dahmen, N.bq , Domingue, B.bq , Elson, S.bq , Frye, M.bq , Gäbel, W.bq , Hayward, C.bq , Ising, M.bq , Keyes, M.bq , Kiefer, F.bq , Kramer, J.bq , Kuperman, S.bq , Lucae, S.bq , Lynskey, M.bq , Maier, W.bq , Mann, K.bq , Männistö, S.bq , Müller-Myhsok, B.bq , Murray, A.bq , Nurnberger, J.bq , Palotie, A.bq , Preuss, U.bq , Räikkönen, K.bq , Reynolds, M.bq , Ridinger, M.bq , Scherbaum, N.bq , Schuckit, M.bq , Soyka, M.bq , Treutlein, J.bq , Witt, S.bq , Wodarz, N.bq , Zill, P.bq , Adkins, D.bq , Boomsma, D.bq , Bierut, L.bq , Brown, S.bq , Bucholz, K.bq , Cichon, S.bq , Costello, E.J.bq , de Wit, H.bq , Diazgranados, N.bq , Dick, D.bq , Eriksson, J.bq , Farrer, L.bq , Foroud, T.bq , Gillespie, N.bq , Goate, A.bq , Goldman, D.bq , Grucza, R.bq , Hancock, D.bq , Heath, A.bq , Hewitt, J.bq , Hopfer, C.bq , Iacono, W.bq , Johnson, E.bq , Kaprio, J.bq , Karpyak, V.bq , Kendler, K.bq , Kranzler, H.bq , Lichtenstein, P.bq , Lind, P.bq , McGue, M.bq , MacKillop, J.bq , Madden, P.bq , Maes, H.bq , Magnusson, P.bq , Martin, N.bq , Medland, S.bq , Montgomery, G.bq , Nelson, E.bq , Nöthen, M.bq , Palmer, A.bq , Pederson, N.bq , Penninx, B.bq , Rice, J.bq , Rietschel, M.bq , Riley, B.bq , Rose, R.bq , Rujescu, D.bq , Shen, P.-H.bq , Silberg, J.bq , Stallings, M.bq , Tarter, R.bq , Vanyukov, M.bq , Wall, T.bq , Whitfield, J.bq , Zhao, H.bq , Neale, B.bq , Gelernter, J.n o p bq , Edenberg, H.bq , Agrawal, A.a bq , Davis, L.K.s t , Bogdan, R.u , Edenberg, H.J.w av , Stefansson, K.k bp , Børglum, A.D.d g h , Psychiatric Genomics Consortium Substance Use Disorders Workgroupbr

a Department of Psychiatry, Washington University School of Medicine, St Louis, MO, United States
b Department of Genetics, Washington University School of Medicine, St Louis, MO, United States
c Division of Biostatistics, Washington University School of Medicine, St Louis, MO, United States
d Department of Biomedicine—Human Genetics and Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark
e National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark
f Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark
g The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark
h Center for Genomics and Personalized Medicine, Aarhus, Denmark
i CNS Department, Reykjavik, Iceland
j Statistics Department, Reykjavik, Iceland
k deCODE Genetics/Amgen, Reykjavik, Iceland
l Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
m Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, United States
n Division of Human Genetics, Department of Psychiatry, Yale School of Medicine, New Haven, CT, United States
o Department of Genetics, Department of Neuroscience, Yale School of Medicine, New Haven, CT, United States
p Veterans Affairs Connecticut Healthcare System, West Haven, CT, United States
q Department of Psychiatry, University of California San Diego, La Jolla, CA, United States
r Department of Psychology and Office of Research Affairs, University of California San Diego, La Jolla, CA, United States
s Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
t Department of Psychiatry and Behavioral Sciences, Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, United States
u Department of Psychological and Brain Sciences, Washington University in Saint Louis, St. Louis, MO, United States
v Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom
w Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States
x Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
y School of Engineering and Natural Sciences, Iceland University, Reykjavik, Iceland
z Department of Psychiatry, University of Utah, Salt Lake City, UT, United States
aa Department of Psychology, Virginia Commonwealth University, Richmond, VA, United States
ab Department of Human & Molecular Genetics, Virginia Commonwealth University, Richmond, VA, United States
ac College Behavioral and Emotional Health Institute, Virginia Commonwealth University, Richmond, VA, United States
ad Virginia Commonwealth University Alcohol Research Center, Virginia Commonwealth University, Richmond, VA, United States
ae Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, United States
af Department of Psychiatry and Behavioral Sciences, SUNY Downstate Health Sciences University, Brooklyn, NY, United States
ag Department of Psychological Medicine, University of Otago, Christchurch, New Zealand
ah Biostatistics and Computational Biology Unit, University of Otago, Christchurch, New Zealand
ai Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand
aj Department for Congenital Disorders, Center for Neonatal Screening, Statens Serum Institut, Copenhagen, Denmark
ak Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, CO, United States
al Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, United States
am Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, United States
an University of Colorado Boulder, Boulder, CO, United States
ao National Drug and Alcohol Research Centre, University of New South Wales, Sydney, NSW, Australia
ap Stanford University Graduate School of Education, Stanford University, Stanford, CA, United States
aq Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States
ar Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States
as QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
at GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, Durham, NC, United States
au Brain and Mind Centre, University of Sydney, Sydney, Australia
av Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, United States
aw Henri Begleiter Neurodynamics Laboratory, SUNY Downstate Health Sciences University, Brooklyn, NY, United States
ax Institute for Molecular Bioscience, University of QueenslandQLD, Australia
ay Queensland Brain Institute, University of QueenslandQLD, Australia
az Psychosis Research Unit, Aarhus University Hospital, Aarhus, Denmark
ba Mental Health Services in the Capital Region of Denmark, Mental Health Center Copenhagen, University of Copenhagen, Copenhagen, Denmark
bb School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, United States
bc SAA—National Center of Addiction Medicine, Vogur Hospital, Reykjavik, Iceland
bd Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, United States
be Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, Copenhagen, Denmark
bf Department of Clinical Medicine, Center for GeoGenetics, GLOBE Institute, University of Copenhagen, Copenhagen, Denmark
bg Department of Psychology, University of Minnesota, Minneapolis, MN, United States
bh Institute of Behavioral Science and Department of Sociology, University of Colorado Boulder, Boulder, CO, United States
bi Department of Psychiatry, University of Vermont Medical Center, Burlington, VT, United States
bj Department of Sociology, and The Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
bk Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, United States
bl Department of Psychiatry, University of Colorado Denver, Aurora, CO, United States
bm Center for Studies of Addiction, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
bn VISN 4 MIRECC, Crescenz VAMC, Philadelphia, PA, United States
bo Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
bp Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland

Abstract
Background: Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods: To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings: We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p=1·84 × 10−9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86–0·93, p=6·46 × 10−9). Cannabis use disorder and cannabis use were genetically correlated (rg 0·50, p=1·50 × 10−21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation: These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. Funding: National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain &amp; Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license

Funding details
Raymond and Beverly Sackler Foundation
Janssen Biotech
Pfizer
Eli Lilly and Company

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

“Metacognitive study strategies in a college course and their relation to exam performance” (2020) Memory and Cognition

Metacognitive study strategies in a college course and their relation to exam performance
(2020) Memory and Cognition, .

Zepeda, C.D.a , Nokes-Malach, T.J.b

a Department of Education, Washington University in St. Louis, One Brookings Drive, Campus Box 1183, St. Louis, MO 63130, United States
b Learning Research and Development Center, University of Pittsburgh, Pittsburgh, PA, United States

Abstract
Several strands of prior work have evaluated students’ study strategies and learning activities. In this work, we focus on integrating two of those strands. One has focused on student self-reports of their study practices from a cognitive psychology perspective. The other has focused on classifying student learning activities from a learning sciences perspective using the Interactive, Constructive, Active, and Passive (ICAP) framework (Chi & Wylie, 2014). The current study aims to integrate these two strands of research by testing the implications of the ICAP framework with students’ self-reports in a classroom context. Another goal was to address the measurement limitations of the metacognitive study strategy literature by using assessment-specific self-reports with both closed and open-ended questions. Across three noncumulative exams, 342 undergraduates self-reported their study practices before each exam. We then categorized their strategies as either active or constructive in alignment with the ICAP framework. Next, we examined whether these strategies were related to each other and then tested the hypothesis that constructive strategies would be positively associated with better exam performance than active strategies. Students reported using a variety of study practices in which a few active strategies were related to constructive strategies, but constructive strategies were more likely to be related to each other. Lastly, supporting the ICAP framework, many of the constructive strategies were positively related to exam performance, whereas the active strategies were not. This work provides insight into the measurement of students’ study strategies and their relations to each other and learning outcomes. © 2020, The Psychonomic Society, Inc.

Author Keywords
Learning;  Normative practices;  Performance;  Study strategies;  Time management

Funding details
National Science Foundation
DUE—1524575, 220020483

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