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American Journal of Psychiatry

Leslie G Nucifora, Matthew L MacDonald, Brian J Lee, Matthew E Peters, Alexis L Norris, Benjamin C Orsburn, Kun Yang, Kelly Gleason, Russell L Margolis, Jonathan Pevsner, Carol A Tamminga, Robert A Sweet, Christopher A Ross, Akira Sawa, Frederick C Nucifora
OBJECTIVE: The mechanisms leading to schizophrenia are likely to be diverse. However, there may be common pathophysiological pathways for subtypes of the disease. The authors tested the hypothesis that increased protein insolubility and ubiquitination underlie the pathophysiology for a subtype of schizophrenia. METHODS: Prefrontal cortex and superior temporal gyrus from postmortem brains of individuals with and without schizophrenia were subjected to cold sarkosyl fractionation, separating proteins into soluble and insoluble fractions...
May 6, 2019: American Journal of Psychiatry
Rajesh Narendran, Savannah Tollefson, Michael L Himes, Jennifer Paris, Brian Lopresti, Roberto Ciccocioppo, N Scott Mason
OBJECTIVE: Nociceptin/orphanin FQ (N/OFQ) is an antistress neuropeptide transmitter in the brain that counteracts corticotropin-releasing factor (CRF)-mediated stress and anxiety symptoms during drug and alcohol withdrawal. It also inhibits the release of a wide array of neurotransmitters, including dopamine and glutamate, which allows for it to block the rewarding properties of cocaine. Chronic cocaine administration in rodents has been shown to decrease N/OFQ and increase nociceptive opioid peptide (NOP) receptors in the nucleus accumbens...
May 6, 2019: American Journal of Psychiatry
Runyu Zou, Henning Tiemeier, Jan van der Ende, Frank C Verhulst, Ryan L Muetzel, Tonya White, Manon Hillegers, Hanan El Marroun
OBJECTIVE: The authors examined associations of exposure to maternal depressive symptoms at different developmental stages from fetal life to preadolescence with child brain development, including volumetrics and white matter microstructure. METHODS: This study was embedded in a longitudinal birth cohort in Rotterdam, the Netherlands. Participants were 3,469 mother-child pairs with data on maternal depressive symptoms and child neuroimaging at age 10. The authors also measured child emotional and behavioral problems at the time of neuroimaging...
May 6, 2019: American Journal of Psychiatry
Kenneth S Kendler, Henrik Ohlsson, Jan Sundquist, Kristina Sundquist
OBJECTIVE: The objective of this study was to clarify the etiology of substance-induced psychotic disorder and its progression to schizophrenia in a Swedish national sample. METHODS: Individuals with a registration of substance-induced psychotic disorder between 1997 and 2015 in national medical registries (N=7,606) were followed up for a mean of 84 months. Data from medical, criminal, and pharmacy registries on first-degree through third-degree relatives were used to calculate familial risk scores for nonaffective psychosis, drug abuse, and alcohol use disorder...
May 6, 2019: American Journal of Psychiatry
Alec Buchanan, Kyaw Sint, Jeffrey Swanson, Robert Rosenheck
OBJECTIVE: Violent behavior is infrequent among individuals with schizophrenia but is clinically important. The purpose of this study was to provide data on the correlates of violence, which may allow better risk assessment and care. METHODS: A total of 1,435 individuals with schizophrenia who participated in the National Institute of Mental Health's Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study and were followed for 18 months were examined...
April 24, 2019: American Journal of Psychiatry
Martine Hoogman, Ryan Muetzel, Joao P Guimaraes, Elena Shumskaya, Maarten Mennes, Marcel P Zwiers, Neda Jahanshad, Gustavo Sudre, Thomas Wolfers, Eric A Earl, Juan Carlos Soliva Vila, Yolanda Vives-Gilabert, Sabin Khadka, Stephanie E Novotny, Catharina A Hartman, Dirk J Heslenfeld, Lizanne J S Schweren, Sara Ambrosino, Bob Oranje, Patrick de Zeeuw, Tiffany M Chaim-Avancini, Pedro G P Rosa, Marcus V Zanetti, Charles B Malpas, Gregor Kohls, Georg G von Polier, Jochen Seitz, Joseph Biederman, Alysa E Doyle, Anders M Dale, Theo G M van Erp, Jeffery N Epstein, Terry L Jernigan, Ramona Baur-Streubel, Georg C Ziegler, Kathrin C Zierhut, Anouk Schrantee, Marie F Høvik, Astri J Lundervold, Clare Kelly, Hazel McCarthy, Norbert Skokauskas, Ruth L O'Gorman Tuura, Anna Calvo, Sara Lera-Miguel, Rosa Nicolau, Kaylita C Chantiluke, Anastasia Christakou, Alasdair Vance, Mara Cercignani, Matt C Gabel, Philip Asherson, Sarah Baumeister, Daniel Brandeis, Sarah Hohmann, Ivanei E Bramati, Fernanda Tovar-Moll, Andreas J Fallgatter, Bernd Kardatzki, Lena Schwarz, Anatoly Anikin, Alexandr Baranov, Tinatin Gogberashvili, Dmitry Kapilushniy, Anastasia Solovieva, Hanan El Marroun, Tonya White, Georgii Karkashadze, Leyla Namazova-Baranova, Thomas Ethofer, Paulo Mattos, Tobias Banaschewski, David Coghill, Kerstin J Plessen, Jonna Kuntsi, Mitul A Mehta, Yannis Paloyelis, Neil A Harrison, Mark A Bellgrove, Tim J Silk, Ana I Cubillo, Katya Rubia, Luisa Lazaro, Silvia Brem, Susanne Walitza, Thomas Frodl, Mariam Zentis, Francisco X Castellanos, Yuliya N Yoncheva, Jan Haavik, Liesbeth Reneman, Annette Conzelmann, Klaus-Peter Lesch, Paul Pauli, Andreas Reif, Leanne Tamm, Kerstin Konrad, Eileen Oberwelland Weiss, Geraldo F Busatto, Mario R Louza, Sarah Durston, Pieter J Hoekstra, Jaap Oosterlaan, Michael C Stevens, J Antoni Ramos-Quiroga, Oscar Vilarroya, Damien A Fair, Joel T Nigg, Paul M Thompson, Jan K Buitelaar, Stephen V Faraone, Philip Shaw, Henning Tiemeier, Janita Bralten, Barbara Franke
OBJECTIVE: Neuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonreplications are frequent. The authors sought to identify cortical characteristics related to ADHD using large-scale studies. METHODS: Cortical thickness and surface area (based on the Desikan-Killiany atlas) were compared between case subjects with ADHD (N=2,246) and control subjects (N=1,934) for children, adolescents, and adults separately in ENIGMA-ADHD, a consortium of 36 centers...
April 24, 2019: American Journal of Psychiatry
Thorhildur Halldorsdottir, Dunja Kurtoic, Bertram Müller-Myhsok, Elisabeth B Binder, Clancy Blair
OBJECTIVE: Self-regulation includes the volitional and nonvolitional regulation of emotional, cognitive, and physiological responses to stimulation. It develops from infancy through individual characteristics and the environment, with the stress hormone system as a central player. Accordingly, the authors hypothesized that genes involved in regulating the stress system, such as FK506 binding protein 5 (FKBP5), interact with early-life stress exposure, such as exposure to intimate partner violence (IPV), to predict self-regulation indicators and associated outcomes, including behavioral and learning problems in school...
April 5, 2019: American Journal of Psychiatry
Thorhildur Halldorsdottir, Charlotte Piechaczek, Ana Paula Soares de Matos, Darina Czamara, Verena Pehl, Petra Wagenbuechler, Lisa Feldmann, Peggy Quickenstedt-Reinhardt, Antje-Kathrin Allgaier, Franz Joseph Freisleder, Ellen Greimel, Tuomas Kvist, Jari Lahti, Katri Räikkönen, Monika Rex-Haffner, Eiríkur Örn Arnarson, W Edward Craighead, Gerd Schulte-Körne, Elisabeth B Binder
OBJECTIVE: Identifying risk factors for major depression and depressive symptoms in youths could have important implications for prevention efforts. This study examined the association of polygenic risk scores (PRSs) for a broad depression phenotype derived from a large-scale genome-wide association study (GWAS) in adults, and its interaction with childhood abuse, with clinically relevant depression outcomes in clinical and epidemiological youth cohorts. METHODS: The clinical cohort comprised 279 youths with major depression (mean age=14...
April 5, 2019: American Journal of Psychiatry
Sidney Zisook, Gary R Johnson, Ilanit Tal, Paul Hicks, Peijun Chen, Lori Davis, Michael Thase, Yinjun Zhao, Julia Vertrees, Somaia Mohamed
OBJECTIVE: Almost two-thirds of patients with major depressive disorder do not achieve remission with initial treatments. Thus, identifying and providing effective, feasible, and safe "next-step" treatments are clinical imperatives. This study explores patient baseline features that might help clinicians select between commonly used next-step treatments. METHODS: The authors used data from the U.S. Department of Veterans Affairs (VA) Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study, a multisite, randomized, single-blind trial of 1,522 Veterans Health Administration patients who did not have an adequate response to at least one course of antidepressant treatment meeting minimal standards for dosage and duration...
April 5, 2019: American Journal of Psychiatry
Antonio F Pardiñas, Mariana Nalmpanti, Andrew J Pocklington, Sophie E Legge, Christopher Medway, Adrian King, John Jansen, Marinka Helthuis, Stanley Zammit, James MacCabe, Michael J Owen, Michael C O'Donovan, James T R Walters
OBJECTIVE: Clozapine is the only effective medication for treatment-resistant schizophrenia, but its worldwide use is still limited because of its complex titration protocols. While the discovery of pharmacogenomic variants of clozapine metabolism may improve clinical management, no robust findings have yet been reported. This study is the first to adopt the framework of genome-wide association studies (GWASs) to discover genetic markers of clozapine plasma concentrations in a large sample of patients with treatment-resistant schizophrenia...
March 29, 2019: American Journal of Psychiatry
Jennifer L Phillips, Sandhaya Norris, Jeanne Talbot, Meagan Birmingham, Taylor Hatchard, Abigail Ortiz, Olabisi Owoeye, Lisa A Batten, Pierre Blier
OBJECTIVE: Subanesthetic ketamine doses have been shown to have rapid yet transient antidepressant effects in patients with treatment-resistant depression, which may be prolonged by repeated administration. The purpose of this study was to evaluate the antidepressant effects of a single ketamine infusion, a series of repeated ketamine infusions, and prolongation of response with maintenance infusions. METHODS: Forty-one participants with treatment-resistant depression completed a single-site randomized double-blind crossover comparison of single infusions of ketamine and midazolam (an active placebo control)...
March 29, 2019: American Journal of Psychiatry
Manish K Jha, Abu Minhajuddin, Charles South, A John Rush, Madhukar H Trivedi
OBJECTIVE: The authors evaluated improvement in irritability with antidepressant treatment and its prognostic utility in treatment-seeking adult outpatients with major depressive disorder. METHODS: Mixed-model analyses were used to assess changes in irritability (as measured with the five-item irritability domain of the Concise Associated Symptom Tracking [CAST-IRR] scale) from baseline to week 4 after controlling for depression severity (as measured with the 16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C]) in the Combining Medications to Enhance Depression Outcomes (CO-MED) trial (N=664)...
March 29, 2019: American Journal of Psychiatry
Richard Border, Emma C Johnson, Luke M Evans, Andrew Smolen, Noah Berley, Patrick F Sullivan, Matthew C Keller
OBJECTIVE: Interest in candidate gene and candidate gene-by-environment interaction hypotheses regarding major depressive disorder remains strong despite controversy surrounding the validity of previous findings. In response to this controversy, the present investigation empirically identified 18 candidate genes for depression that have been studied 10 or more times and examined evidence for their relevance to depression phenotypes. METHODS: Utilizing data from large population-based and case-control samples (Ns ranging from 62,138 to 443,264 across subsamples), the authors conducted a series of preregistered analyses examining candidate gene polymorphism main effects, polymorphism-by-environment interactions, and gene-level effects across a number of operational definitions of depression (e...
March 8, 2019: American Journal of Psychiatry
William F Martin, Christoph U Correll, Peter J Weiden, Ying Jiang, Sanjeev Pathak, Lauren DiPetrillo, Bernard L Silverman, Elliot W Ehrich
OBJECTIVE: Preclinical evidence and data from a proof-of-concept study in healthy volunteers suggest that samidorphan, an opioid antagonist, mitigates weight gain associated with olanzapine. This study prospectively compared combination therapy of olanzapine plus either samidorphan or placebo for the treatment of schizophrenia. METHODS: This was an international, multicenter, randomized phase 2 study of olanzapine plus samidorphan in patients with schizophrenia...
March 8, 2019: American Journal of Psychiatry
Willie Earley, Maria Victoria Burgess, Ludmyla Rekeda, Regan Dickinson, Balázs Szatmári, György Németh, Roger S McIntyre, Gary S Sachs, Lakshmi N Yatham
OBJECTIVE: Cariprazine, a dopamine D3 /D2 and 5-HT1A receptor partial agonist, was found to be effective in treating bipolar I depression in a previous phase 2 study. This phase 3 study further assessed the efficacy, safety, and tolerability of cariprazine in bipolar I depression. METHODS: In a double-blind placebo-controlled study, adult participants (18-65 years old) who met DSM-5 criteria for bipolar I disorder and a current depressive episode were randomly assigned to receive placebo (N=158) or cariprazine at 1...
March 8, 2019: American Journal of Psychiatry
Alan F Schatzberg
Over the past two decades, research in the biology and treatment of major depression has led to advances in our understanding of the biology of the disorder and to the development of novel treatments. While progress has been made, a number of key issues have emerged regarding diagnosis of the disorder and how we develop and test new therapies. Among these are the potential need to include new dimensions in the diagnostic criteria, the limited utility of clinical predictors of response, the moving away from traditional blinded trials in major depression, and whether preclinical models tell us much about novel drug development...
May 1, 2019: American Journal of Psychiatry
Anne R Hart, Charles H Kellner
No abstract text is available yet for this article.
May 1, 2019: American Journal of Psychiatry
Ned H Kalin
No abstract text is available yet for this article.
May 1, 2019: American Journal of Psychiatry
Marucela Juana Uscamayta Ayvar, Rodolfo Sanchez Garrafa, Javier I Escobar, Gabriel A de Erausquin
No abstract text is available yet for this article.
May 1, 2019: American Journal of Psychiatry
Michael Wang, Adam Kaplin
No abstract text is available yet for this article.
May 1, 2019: American Journal of Psychiatry
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