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Depression: HELP
Articles by Roy H. Perlis
Based on 56 articles published since 2010
(Why 56 articles?)
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Between 2010 and 2020, R. Perlis wrote the following 56 articles about Depression.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Editorial Can a Framework Be Established for the Safe Use of Ketamine? 2018

Freedman, Robert / Brown, Alan S / Cannon, Tyrone D / Druss, Benjamin G / Earls, Felton J / Escobar, Javier / Hurd, Yasmin L / Lewis, David A / López-Jaramillo, Carlos / Luby, Joan / Mayberg, Helen S / Moffitt, Terrie E / Oquendo, Maria / Perlis, Roy H / Pine, Daniel S / Rush, A John / Tamminga, Carol A / Tohen, Mauricio / Vieta, Eduard / Wisner, Katherine L / Xin, Yu. ·The authors are members of the Editorial Board of the Journal. ·Am J Psychiatry · Pubmed #29656666.

ABSTRACT: -- No abstract --

2 Review Discriminating Between Bipolar Disorder and Major Depressive Disorder. 2016

Vöhringer, Paul A / Perlis, Roy H. ·Department of Psychiatry, Tufts University School of Medicine, 800 Washington Street, Boston, MA 02111, USA; Department of Psychiatry, University of Chile, Av. Independencia 1027, Santiago 8071146, Chile. · Department of Psychiatry, Center for Experimental Drugs and Diagnostics, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, MA 02114, USA. Electronic address: rperlis@mgh.harvard.edu. ·Psychiatr Clin North Am · Pubmed #26876315.

ABSTRACT: Rates of misdiagnosis between major depressive disorder and bipolar disorder have been reported to be substantial, and the consequence of such misdiagnosis is likely to be a delay in achieving effective control of symptoms, in some cases spanning many years. Particularly in the midst of a depressive episode, or early in the illness course, it may be challenging to distinguish the 2 mood disorders purely on the basis of cross-sectional features. To date, no useful biological markers have been reliably shown to distinguish between bipolar disorder and major depressive disorder.

3 Review Pharmacogenomic testing and personalized treatment of depression. 2014

Perlis, Roy H. ·Center for Experimental Drugs and Diagnostics, Massachusetts General Hospital, Boston, MA. ·Clin Chem · Pubmed #24281779.

ABSTRACT: BACKGROUND: There is wide variation in antidepressant efficacy and tolerability during the treatment of major depressive disorder, a brain disease associated with significant morbidity and mortality risk. The ability to rapidly identify optimal treatment, thereby shortening the time to symptomatic remission, could reduce these risks and associated costs. CONTENT: Up to 42% of variance in antidepressant response is associated with common genetic variation, and there are over 10 psychotropic medications for which the US Food and Drug Administration-approved labeling reflects a genetic test. Most published studies have examined functional variations in genes of the cytochrome p450 system, relevant to metabolism of many antidepressants. However, there are few data supporting the clinical usefulness of specific pharmacogenetic tests. Randomized trials and cost-effectiveness studies are emerging, but larger-scale studies are needed. Specific challenges in translating genetic association results to clinical practice include need for replication to address risk of type I error, overestimation of effect sizes, absence of data from generalizable cohorts, and absence of comparative data that would suggest one specific intervention over another. Several opportunities to accelerate development and validation of new tools for stratification remain, including integration of these tests with clinical data or other biomarkers and application of electronic health records for test development and investigation. SUMMARY: Although common genetic variation, particularly in genes of the cytochrome p450 system, has been associated with antidepressant response, evidence that this variation may be successfully applied to guide treatment selection is just emerging. Larger-scale studies facilitated by informatics tools will clarify the usefulness of such tests.

4 Review Major depressive disorder in DSM-5: implications for clinical practice and research of changes from DSM-IV. 2014

Uher, Rudolf / Payne, Jennifer L / Pavlova, Barbara / Perlis, Roy H. ·Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada; Institute of Psychiatry, King's College London, London, UK. ·Depress Anxiety · Pubmed #24272961.

ABSTRACT: The changes in diagnostic criteria for major depressive disorder (MDD) from the fourth to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) may appear small but have important consequences for how the diagnosis is used. In DSM-5, MDD is part of the new "Depressive disorders" section, which is separate from "Bipolar disorders", marking a division in what had been known as "Mood disorders". A small wording change has expanded the core mood criterion to include hopelessness, potentially broadening the diagnosis. The replacement of an operationalized bereavement exclusion with a call for clinical judgment in distinguishing normal reactions to significant loss from a disorder in need of clinical attention makes the diagnosis less objective and complicates investigations of the relationship between adversity and depression. A new persistent depressive disorder category is intended to encompass both dysthymia and chronic depression, but its relationship to MDD is ambiguous with conflicting statements on whether the two diagnoses should be concurrent if both sets of criteria are fulfilled. Clarification is also needed on whether MDD can be concurrent with the new broad "other specified bipolar and related disorders". New specifiers of MDD "with anxious distress" and "with mixed features" allow characterization of additional symptoms. The specifier "with perinatal onset" expands on the DSM-IV "postnatal onset" to include onset during pregnancy. We review the changes in MDD definition, provide guidance on their implementation and discuss their implications for clinical practice and research.

5 Article Randomized, controlled, participant- and rater-blind trial of pharmacogenomic test-guided treatment versus treatment as usual for major depressive disorder. 2020

Perlis, Roy H / Dowd, Daniel / Fava, Maurizio / Lencz, Todd / Krause, David S. ·Department of Psychiatry and Division of Clinical Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. · Clinical Research & Development and Medical Affairs, Genomind, Inc., King of Prussia, Pennsylvania. · Department of Psychiatry, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York. ·Depress Anxiety · Pubmed #32383277.

ABSTRACT: BACKGROUND: Cohort and cost-effectiveness studies suggest that measuring variation in genes that influence metabolism of common drugs could improve antidepressant treatment outcomes. Prior randomized trials have yielded inconsistent results. METHOD: Multicenter randomized double-blind (subject and rater), controlled trial of pharmacogenomic testing among outpatients with nonpsychotic major depressive disorder. Study participants (n = 304) were randomized 1:1 to assay-guided treatment (AGT; N = 151) or treatment-as-usual (TAU; N = 153). Participants and raters were blinded to study arm; unblinded clinicians received results of a pharmacogenomic test and adjusted treatment in light of the test report. Primary outcome was change over 8 weeks in Hamilton Depression Rating Scale (SIGH-D-17). RESULTS: For the primary comparison of interest, change in SIGH-D-17, no significant difference was detected between AGT and TAU at Week 8 (p = .53). Rates of study completion also did not differ between the arms (AGT 92.7%, TAU 92.2% (χ CONCLUSION: Pharmacogenomic testing using a panel of pharmacokinetic and pharmacodynamic variants was not associated with significant improvement in the primary efficacy outcome when providers were unconstrained by the assay results. Further investigation is needed to understand the discordance with cost-effectiveness results and among randomized trials.

6 Article Activation of WNT and CREB signaling pathways in human neuronal cells in response to the Omega-3 fatty acid docosahexaenoic acid (DHA). 2019

Zhao, Wen-Ning / Hylton, Norma K / Wang, Jennifer / Chindavong, Peter S / Alural, Begum / Kurtser, Iren / Subramanian, Aravind / Mazitschek, Ralph / Perlis, Roy H / Haggarty, Stephen J. ·Chemical Neurobiology Laboratory, Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, United States of America; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States of America; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States of America. · Chemical Neurobiology Laboratory, Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, United States of America. · Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States of America; Center for Quantitative Health, Center for Genomic Medicine, Division of Clinical Research, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, United States of America. · Chemical Neurobiology Laboratory, Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, United States of America; Department of Neuroscience, Institute of Health Sciences, Dokuz Eylul University, Izmir 35210, Turkey. · Broad Institute of MIT and Harvard, Cambridge, MA 02142, United States of America. · Broad Institute of MIT and Harvard, Cambridge, MA 02142, United States of America; Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, United States of America. · Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States of America; Center for Quantitative Health, Center for Genomic Medicine, Division of Clinical Research, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, United States of America. Electronic address: rperlis@mgh.harvard.edu. · Chemical Neurobiology Laboratory, Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, United States of America; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States of America; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States of America. Electronic address: shaggarty@mgh.harvard.edu. ·Mol Cell Neurosci · Pubmed #31202891.

ABSTRACT: A subset of individuals with major depressive disorder (MDD) elects treatment with complementary and alternative medicines (CAMs), including the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Previous studies in rodents suggest that DHA modulates neurodevelopmental processes, including adult neurogenesis and neuroplasticity, but the molecular and cellular mechanisms of DHA's potential therapeutic effect in the context of human neurobiology have not been well established. Here we sought to address this knowledge gap by investigating the effects of DHA using human iPSC-derived neural progenitor cells (NPCs) and post-mitotic neurons using pathway-selective reporter genes, multiplexed mRNA expression profiling, and a panel of metabolism-based viability assays. Finally, real-time, live-cell imaging was employed to monitor neurite outgrowth upon DHA treatment. Overall, these studies showed that DHA treatment (0-50 μM) significantly upregulated both WNT and CREB signaling pathways in human neuronal cells in a dose-dependent manner with 2- to 3-fold increases in pathway activation. Additionally, we observed that DHA treatment enhanced survival of iPSC-derived NPCs and differentiation of post-mitotic neurons with live-cell imaging, revealing increased neurite outgrowth with DHA treatment within 24 h. Taken together, this study provides evidence that DHA treatment activates critical pathways regulating neuroplasticity, which may contribute to enhanced neuronal cell viability and neuronal connectivity. The extent to which these pathways represent molecular mechanisms underlying the potential beneficial effects of omega-3 fatty acids in MDD and other brain disorders merits further investigation.

7 Article Genome-wide association study identifies 30 loci associated with bipolar disorder. 2019

Stahl, Eli A / Breen, Gerome / Forstner, Andreas J / McQuillin, Andrew / Ripke, Stephan / Trubetskoy, Vassily / Mattheisen, Manuel / Wang, Yunpeng / Coleman, Jonathan R I / Gaspar, Héléna A / de Leeuw, Christiaan A / Steinberg, Stacy / Pavlides, Jennifer M Whitehead / Trzaskowski, Maciej / Byrne, Enda M / Pers, Tune H / Holmans, Peter A / Richards, Alexander L / Abbott, Liam / Agerbo, Esben / Akil, Huda / Albani, Diego / Alliey-Rodriguez, Ney / Als, Thomas D / Anjorin, Adebayo / Antilla, Verneri / Awasthi, Swapnil / Badner, Judith A / Bækvad-Hansen, Marie / Barchas, Jack D / Bass, Nicholas / Bauer, Michael / Belliveau, Richard / Bergen, Sarah E / Pedersen, Carsten Bøcker / Bøen, Erlend / Boks, Marco P / Boocock, James / Budde, Monika / Bunney, William / Burmeister, Margit / Bybjerg-Grauholm, Jonas / Byerley, William / Casas, Miquel / Cerrato, Felecia / Cervantes, Pablo / Chambert, Kimberly / Charney, Alexander W / Chen, Danfeng / Churchhouse, Claire / Clarke, Toni-Kim / Coryell, William / Craig, David W / Cruceanu, Cristiana / Curtis, David / Czerski, Piotr M / Dale, Anders M / de Jong, Simone / Degenhardt, Franziska / Del-Favero, Jurgen / DePaulo, J Raymond / Djurovic, Srdjan / Dobbyn, Amanda L / Dumont, Ashley / Elvsåshagen, Torbjørn / Escott-Price, Valentina / Fan, Chun Chieh / Fischer, Sascha B / Flickinger, Matthew / Foroud, Tatiana M / Forty, Liz / Frank, Josef / Fraser, Christine / Freimer, Nelson B / Frisén, Louise / Gade, Katrin / Gage, Diane / Garnham, Julie / Giambartolomei, Claudia / Pedersen, Marianne Giørtz / Goldstein, Jaqueline / Gordon, Scott D / Gordon-Smith, Katherine / Green, Elaine K / Green, Melissa J / Greenwood, Tiffany A / Grove, Jakob / Guan, Weihua / Guzman-Parra, José / Hamshere, Marian L / Hautzinger, Martin / Heilbronner, Urs / Herms, Stefan / Hipolito, Maria / Hoffmann, Per / Holland, Dominic / Huckins, Laura / Jamain, Stéphane / Johnson, Jessica S / Juréus, Anders / Kandaswamy, Radhika / Karlsson, Robert / Kennedy, James L / Kittel-Schneider, Sarah / Knowles, James A / Kogevinas, Manolis / Koller, Anna C / Kupka, Ralph / Lavebratt, Catharina / Lawrence, Jacob / Lawson, William B / Leber, Markus / Lee, Phil H / Levy, Shawn E / Li, Jun Z / Liu, Chunyu / Lucae, Susanne / Maaser, Anna / MacIntyre, Donald J / Mahon, Pamela B / Maier, Wolfgang / Martinsson, Lina / McCarroll, Steve / McGuffin, Peter / McInnis, Melvin G / McKay, James D / Medeiros, Helena / Medland, Sarah E / Meng, Fan / Milani, Lili / Montgomery, Grant W / Morris, Derek W / Mühleisen, Thomas W / Mullins, Niamh / Nguyen, Hoang / Nievergelt, Caroline M / Adolfsson, Annelie Nordin / Nwulia, Evaristus A / O'Donovan, Claire / Loohuis, Loes M Olde / Ori, Anil P S / Oruc, Lilijana / Ösby, Urban / Perlis, Roy H / Perry, Amy / Pfennig, Andrea / Potash, James B / Purcell, Shaun M / Regeer, Eline J / Reif, Andreas / Reinbold, Céline S / Rice, John P / Rivas, Fabio / Rivera, Margarita / Roussos, Panos / Ruderfer, Douglas M / Ryu, Euijung / Sánchez-Mora, Cristina / Schatzberg, Alan F / Scheftner, William A / Schork, Nicholas J / Shannon Weickert, Cynthia / Shehktman, Tatyana / Shilling, Paul D / Sigurdsson, Engilbert / Slaney, Claire / Smeland, Olav B / Sobell, Janet L / Søholm Hansen, Christine / Spijker, Anne T / St Clair, David / Steffens, Michael / Strauss, John S / Streit, Fabian / Strohmaier, Jana / Szelinger, Szabolcs / Thompson, Robert C / Thorgeirsson, Thorgeir E / Treutlein, Jens / Vedder, Helmut / Wang, Weiqing / Watson, Stanley J / Weickert, Thomas W / Witt, Stephanie H / Xi, Simon / Xu, Wei / Young, Allan H / Zandi, Peter / Zhang, Peng / Zöllner, Sebastian / Anonymous1281184 / Anonymous1291184 / Adolfsson, Rolf / Agartz, Ingrid / Alda, Martin / Backlund, Lena / Baune, Bernhard T / Bellivier, Frank / Berrettini, Wade H / Biernacka, Joanna M / Blackwood, Douglas H R / Boehnke, Michael / Børglum, Anders D / Corvin, Aiden / Craddock, Nicholas / Daly, Mark J / Dannlowski, Udo / Esko, Tõnu / Etain, Bruno / Frye, Mark / Fullerton, Janice M / Gershon, Elliot S / Gill, Michael / Goes, Fernando / Grigoroiu-Serbanescu, Maria / Hauser, Joanna / Hougaard, David M / Hultman, Christina M / Jones, Ian / Jones, Lisa A / Kahn, René S / Kirov, George / Landén, Mikael / Leboyer, Marion / Lewis, Cathryn M / Li, Qingqin S / Lissowska, Jolanta / Martin, Nicholas G / Mayoral, Fermin / McElroy, Susan L / McIntosh, Andrew M / McMahon, Francis J / Melle, Ingrid / Metspalu, Andres / Mitchell, Philip B / Morken, Gunnar / Mors, Ole / Mortensen, Preben Bo / Müller-Myhsok, Bertram / Myers, Richard M / Neale, Benjamin M / Nimgaonkar, Vishwajit / Nordentoft, Merete / Nöthen, Markus M / O'Donovan, Michael C / Oedegaard, Ketil J / Owen, Michael J / Paciga, Sara A / Pato, Carlos / Pato, Michele T / Posthuma, Danielle / Ramos-Quiroga, Josep Antoni / Ribasés, Marta / Rietschel, Marcella / Rouleau, Guy A / Schalling, Martin / Schofield, Peter R / Schulze, Thomas G / Serretti, Alessandro / Smoller, Jordan W / Stefansson, Hreinn / Stefansson, Kari / Stordal, Eystein / Sullivan, Patrick F / Turecki, Gustavo / Vaaler, Arne E / Vieta, Eduard / Vincent, John B / Werge, Thomas / Nurnberger, John I / Wray, Naomi R / Di Florio, Arianna / Edenberg, Howard J / Cichon, Sven / Ophoff, Roel A / Scott, Laura J / Andreassen, Ole A / Kelsoe, John / Sklar, Pamela / Anonymous1301184. ·Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. eli.stahl@mssm.edu. · Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA. eli.stahl@mssm.edu. · Medical and Population Genetics, Broad Institute, Cambridge, MA, USA. eli.stahl@mssm.edu. · MRC Social, Genetic and Developmental Psychiatry Centre, King's College London, London, UK. · NIHR BRC for Mental Health, King's College London, London, UK. · Department of Biomedicine, University of Basel, Basel, Switzerland. · Department of Psychiatry (UPK), University of Basel, Basel, Switzerland. · Institute of Human Genetics, University of Bonn School of Medicine & University Hospital Bonn, Bonn, Germany. · Centre for Human Genetics, University of Marburg, Marburg, Germany. · Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland. · Division of Psychiatry, University College London, London, UK. · Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA. · Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin, Berlin, Germany. · Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. · iSEQ, Center for Integrative Sequencing, Aarhus University, Aarhus, Denmark. · Department of Biomedicine-Human Genetics, Aarhus University, Aarhus, Denmark. · Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden. · Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Würzburg, Würzburg, Germany. · iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark. · Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen, Denmark. · Institute of Clinical Medicine, University of Oslo, Oslo, Norway. · Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. · deCODE Genetics/Amgen, Reykjavik, Iceland. · Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia. · Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia. · Medical and Population Genetics, Broad Institute, Cambridge, MA, USA. · Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, MA, USA. · Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, England. · National Centre for Register-based Research and Centre for Integrated Register-based Research, Aarhus University, Aarhus, Denmark. · Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA. · Department of Neuroscience, Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy. · Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA. · Department of Psychiatry, Berkshire Healthcare NHS Foundation Trust, Bracknell, UK. · Department of Psychiatry, Rush University Medical Center, Chicago, IL, USA. · Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark. · Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA. · Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. · Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway. · Psychiatry, UMC Utrecht Brain Center Rudolf Magnus, Utrecht, the Netherlands. · Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA. · Institute of Psychiatric Phenomics and Genomics, University Hospital, LMU Munich, Munich, Germany. · Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA. · Molecular & Behavioral Neuroscience Institute and Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI, USA. · Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA. · Instituto de Salud Carlos III, Biomedical Network Research Centre on Mental Health (CIBERSAM), Madrid, Spain. · Department of Psychiatry, Hospital Universitari Vall d´Hebron, Barcelona, Spain. · Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain. · Psychiatric Genetics Unit, Group of Psychiatry Mental Health and Addictions, Vall d´Hebron Research Institut, Universitat Autònoma de Barcelona, Barcelona, Spain. · Department of Psychiatry, Mood Disorders Program, McGill University Health Center, Montreal, Quebec, Canada. · Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA. · Division of Psychiatry, University of Edinburgh, Edinburgh, Scotland. · University of Iowa Hospitals and Clinics, Iowa City, IA, USA. · Translational Genomics, USC, Phoenix, AZ, USA. · Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany. · Centre for Psychiatry, Queen Mary University of London, London, UK. · UCL Genetics Institute, University College London, London, UK. · Department of Psychiatry, Laboratory of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, Poland. · Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA. · Department of Radiology, University of California, San Diego, La Jolla, CA, USA. · Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA. · Department of Cognitive Science, University of California, San Diego, La Jolla, CA, USA. · Applied Molecular Genomics Unit, VIB Department of Molecular Genetics, University of Antwerp, Antwerp, Belgium. · Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Department of Medical Genetics, Oslo University Hospital Ullevål, Oslo, Norway. · NORMENT, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway. · Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. · Department of Neurology, Oslo University Hospital, Oslo, Norway. · NORMENT, KG Jebsen Centre for Psychosis Research, Oslo University Hospital, Oslo, Norway. · Center for Statistical Genetics and Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA. · Department of Medical & Molecular Genetics, Indiana University, Indianapolis, IN, USA. · Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. · Center for Neurobehavioral Genetics, University of California, Los Angeles, Los Angeles, CA, USA. · Department of Molecular Medicine and Surgery, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden. · Department of Clinical Neuroscience, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden. · Child and Adolescent Psychiatry Research Center, Stockholm, Sweden. · Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany. · Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada. · Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, USA. · Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. · Department of Psychological Medicine, University of Worcester, Worcester, UK. · School of Biomedical Sciences, Plymouth University Peninsula Schools of Medicine and Dentistry, University of Plymouth, Plymouth, UK. · School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia. · Neuroscience Research Australia, Sydney, New South Wales, Australia. · Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark. · Biostatistics, University of Minnesota System, Minneapolis, MN, USA. · Mental Health Department, University Regional Hospital, Biomedicine Institute (IBIMA), Málaga, Spain. · Department of Psychology, Eberhard Karls Universität Tübingen, Tubingen, Germany. · Department of Psychiatry and Behavioral Sciences, Howard University Hospital, Washington, DC, USA. · Center for Multimodal Imaging and Genetics, University of California, San Diego, La Jolla, CA, USA. · Psychiatrie Translationnelle, Inserm U955, Créteil, France. · Faculté de Médecine, Université Paris Est, Créteil, France. · Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Onatario, Canada. · Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. · Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. · Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada. · Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt am Main, Germany. · Cell Biology, SUNY Downstate Medical Center College of Medicine, Brooklyn, NY, USA. · Institute for Genomic Health, SUNY Downstate Medical Center College of Medicine, Brooklyn, NY, USA. · ISGlobal, Barcelona, Spain. · Psychiatry, Altrecht, Utrecht, the Netherlands. · Psychiatry, GGZ inGeest, Amsterdam, the Netherlands. · Psychiatry, VU Medisch Centrum, Amsterdam, the Netherlands. · Department of, rth East London NHS Foundation Trust, Ilford, UK. · Department of Neurodegenerative Diseases and Geropsychiatry, University Hospital Bonn, Bonn, Germany. · Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. · HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA. · Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA. · Department of Psychiatry, University of Illinois at Chicago College of Medicine, Chicago, IL, USA. · Max Planck Institute of Psychiatry, Munich, Germany. · Mental Health, NHS 24, Glasgow, UK. · Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK. · Department of Psychiatry, Brigham and Women's Hospital, Boston, MA, USA. · Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany. · Department of Genetics, Harvard Medical School, Boston, MA, USA. · Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA. · Genetic Cancer Susceptibility Group, International Agency for Research on Cancer, Lyon, France. · Estonian Genome Center, University of Tartu, Tartu, Estonia. · Discipline of Biochemistry, Neuroimaging and Cognitive Genomics (NICOG) Centre, National University of Ireland, Galway, Galway, Ireland. · Neuropsychiatric Genetics Research Group, Department of Psychiatry and Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland. · Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany. · Research/Psychiatry, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA. · Department of Clinical Sciences, Psychiatry, Umeå University Medical Faculty, Umeå, Sweden. · Department of Clinical Psychiatry, Psychiatry Clinic, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina. · Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden. · Department of Psychiatry, Harvard Medical School, Boston, MA, USA. · Division of Clinical Research, Massachusetts General Hospital, Boston, MA, USA. · Outpatient Clinic for Bipolar Disorder, Altrecht, Utrecht, the Netherlands. · Department of Psychiatry, Washington University in Saint Louis, Saint Louis, MO, USA. · Department of Biochemistry and Molecular Biology II, Institute of Neurosciences, Center for Biomedical Research, University of Granada, Granada, Spain. · Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA. · Medicine, Psychiatry, Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA. · Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. · Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA. · Rush University Medical Center, Chicago, IL, USA. · Scripps Translational Science Institute, La Jolla, CA, USA. · Faculty of Medicine, Department of Psychiatry, School of Health Sciences, University of Iceland, Reykjavik, Iceland. · Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. · NORMENT, University of Oslo, Oslo, Norway. · Psychiatry and the Behavioral Sciences, University of Southern California, Los Angeles, CA, USA. · Mood Disorders, PsyQ, Rotterdam, the Netherlands. · Institute for Medical Sciences, University of Aberdeen, Aberdeen, UK. · Research Division, Federal Institute for Drugs and Medical Devices (BfArM), Bonn, Germany. · Centre for Addiction and Mental Health, Toronto, Onatario, Canada. · Neurogenomics, TGen, Phoenix, AZ, USA. · Department of Psychiatry, Psychiatrisches Zentrum Nordbaden, Wiesloch, Germany. · Computational Sciences Center of Emphasis, Pfizer Global Research and Development, Cambridge, MA, USA. · Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, Onatario, Canada. · Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada. · Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK. · Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA. · Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Institute of Clinical Medicine and Diakonhjemmet Hospital, University of Oslo, Oslo, Norway. · National Institute of Mental Health, Klecany, Czech Republic. · Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia. · Department of Psychiatry, University of Munster, Munster, Germany. · Department of Psychiatry and Addiction Medicine, Assistance Publique-Hopitaux de Paris, Paris, France. · Paris Bipolar and TRD Expert Centres, FondaMental Foundation, Paris, France. · UMR-S1144 Team 1: Biomarkers of relapse and therapeutic response in addiction and mood disorders, INSERM, Paris, France. · Department of Psychiatry, Université Paris Diderot, Paris, France. · Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA. · Division of Endocrinology, Children's Hospital Boston, Boston, MA, USA. · Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, London, UK. · Department of Psychiatry & Psychology, Mayo Clinic, Rochester, MN, USA. · School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia. · Department of Human Genetics, University of Chicago, Chicago, IL, USA. · Biometric Psychiatric Genetics Research Unit, Alexandru Obregia Clinical Psychiatric Hospital, Bucharest, Romania. · Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden. · INSERM, Paris, France. · Department of Medical & Molecular Genetics, King's College London, London, UK. · Neuroscience Therapeutic Area, Janssen Research and Development, LLC, Titusville, NJ, USA. · Cancer Epidemiology and Prevention, M. Sklodowska-Curie Cancer Center and Institute of Oncology, Warsaw, Poland. · School of Psychology, The University of Queensland, Brisbane, Queensland, Australia. · Research Institute, Lindner Center of HOPE, Mason, OH, USA. · Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. · Human Genetics Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA. · Division of Mental Health and Addiction and Institute of Clinical Medicine, Oslo University Hospital and University of Oslo, Oslo, Norway. · Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia. · Mental Health, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology-NTNU, Trondheim, Norway. · Department of Psychiatry, St Olavs University Hospital, Trondheim, Norway. · Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark. · Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. · University of Liverpool, Liverpool, UK. · Psychiatry and Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA. · Mental Health Services in the Capital Region of Denmark, Mental Health Center Copenhagen, University of Copenhagen, Copenhagen, Denmark. · Division of Psychiatry, Haukeland Universitetssjukehus, Bergen, Norway. · Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway. · Human Genetics and Computational Biomedicine, Pfizer Global Research and Development, Groton, CT, USA. · College of Medicine Institute for Genomic Health, SUNY Downstate Medical Center College of Medicine, Brooklyn, NY, USA. · Department of Clinical Genetics, Amsterdam Neuroscience, Vrije Universiteit Medical Center, Amsterdam, the Netherlands. · Department of Neurology and Neurosurgery, McGill University, Faculty of Medicine, Montreal, Quebec, Canada. · Montreal Neurological Institute and Hospital, Montreal, Quebec, Canada. · Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy. · Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. · Department of Psychiatry, Hospital Namsos, Namsos, Norway. · Department of Mental Health, Norwegian University of Science and Technology, Trondheim, Norway. · Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. · Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. · Department of Psychiatry, McGill University, Montreal, Quebec, Canada. · Department of Psychiatry, Sankt Olavs Hospital Universitetssykehuset i Trondheim, Trondheim, Norway. · Clinical Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain. · Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark. · Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. · Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA. · Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA. · Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA. jkelsoe@ucsd.edu. ·Nat Genet · Pubmed #31043756.

ABSTRACT: Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10

8 Article Peripheral and central levels of kynurenic acid in bipolar disorder subjects and healthy controls. 2019

Sellgren, Carl M / Gracias, Jessica / Jungholm, Oscar / Perlis, Roy H / Engberg, Göran / Schwieler, Lilly / Landen, Mikael / Erhardt, Sophie. ·Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. carl.sellgren@ki.se. · Center for Experimental Drugs and Diagnostics, Center for Genomic Medicine and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. carl.sellgren@ki.se. · Department of Psychiatry, Harvard Medical School, Boston, MA, USA. carl.sellgren@ki.se. · Stockholm County Council, Stockholm, Sweden. carl.sellgren@ki.se. · Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. · Center for Experimental Drugs and Diagnostics, Center for Genomic Medicine and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. · Department of Psychiatry, Harvard Medical School, Boston, MA, USA. · Stockholm County Council, Stockholm, Sweden. · Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Mölndal, Sweden. ·Transl Psychiatry · Pubmed #30696814.

ABSTRACT: Metabolites of the kynurenine pathway of tryptophan degradation, in particular, the N-Methyl-D-aspartic acid receptor antagonist kynurenic acid (KYNA), are increasingly recognized as primary pathophysiological promoters in several psychiatric diseases. Studies analyzing central KYNA levels from subjects with psychotic disorders have reported increased levels. However, sample sizes are limited and in contrast many larger studies examining this compound in blood from psychotic patients commonly report a decrease. A major question is to what extent peripheral KYNA levels reflect brain KYNA levels under physiological as well as pathophysiological conditions. Here we measured KYNA in plasma from a total of 277 subjects with detailed phenotypic data, including 163 BD subjects and 114 matched healthy controls (HCs), using an HPLC system. Among them, 94 BD subjects and 113 HCs also had CSF KYNA concentrations analyzed. We observe a selective increase of CSF KYNA in BD subjects with previous psychotic episodes although this group did not display altered plasma KYNA levels. In contrast, BD subjects with ongoing depressive symptoms displayed a tendency to decreased plasma KYNA concentrations but unchanged CSF KYNA levels. Sex and age displayed specific effects on KYNA concentrations depending on if measured centrally or in the periphery. These findings implicate brain-specific regulation of KYNA under physiological as well as under pathophysiological conditions and strengthen our previous observation of CSF KYNA as a biomarker in BD. In summary, biomarker and drug discovery studies should include central KYNA measurements for a more reliable estimation of brain KYNA levels.

9 Article Risk tolerance measured by probability discounting among individuals with primary mood and psychotic disorders. 2019

Hart, Kamber L / Brown, Hannah E / Roffman, Joshua L / Perlis, Roy H. ·Center for Quantitative Health, Massachusetts General Hospital. · Center for Quantitative Health, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School. · Massachusetts General Hospital and Harvard Medical School. ·Neuropsychology · Pubmed #30688494.

ABSTRACT: OBJECTIVE: Change in risk tolerance is a feature of multiple psychiatric disorders and may contribute to adverse outcomes. We used a probability discounting (PD) task to measure risk-taking behavior among individuals with bipolar disorder (BPAD), major depressive disorder (MDD), schizoaffective disorder (SCAD), and schizophrenia (SCZ). METHOD: A PD task was administered to 117 patients and 88 healthy controls (HCs), along with a cognitive battery using the Cambridge Neuropsychological Test Automated Battery, and relevant symptomatology scales. We examined differences in PD rates between diagnostic groups, and compared with HCs, while controlling for potential confounding factors including measures of cognitive functioning. RESULTS: Individuals with a diagnosis of BPAD or SCAD/SCZ prefer smaller, more guaranteed rewards rather than larger, less likely rewards as compared with healthy controls (p = .002 and p = .034, respectively). There was no effect of performance on cognitive tasks, antipsychotic treatment, or symptomatology on the rate of probability discounting. CONCLUSION: This study supports the transdiagnostic measurement of risk-taking behaviors, even when such behaviors are not the primary area of psychopathology. Quantifying risk-taking may enable targeted therapeutic strategies across disorders. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

10 Article Effect of cytochrome CYP2C19 metabolizing activity on antidepressant response and side effects: Meta-analysis of data from genome-wide association studies. 2018

Fabbri, Chiara / Tansey, Katherine E / Perlis, Roy H / Hauser, Joanna / Henigsberg, Neven / Maier, Wolfgang / Mors, Ole / Placentino, Anna / Rietschel, Marcella / Souery, Daniel / Breen, Gerome / Curtis, Charles / Lee, Sang-Hyuk / Newhouse, Stephen / Patel, Hamel / O'Donovan, Michael / Lewis, Glyn / Jenkins, Gregory / Weinshilboum, Richard M / Farmer, Anne / Aitchison, Katherine J / Craig, Ian / McGuffin, Peter / Schruers, Koen / Biernacka, Joanna M / Uher, Rudolf / Lewis, Cathryn M. ·Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, PO80, De De Crespigny Park, Denmark Hill United Kingdom. · College of Biomedical and Life Sciences, Cardiff University, Cardiff, United Kingdom. · Department of Psychiatry, Center for Experimental Drugs and Diagnostics, Massachusetts General Hospital, Boston, USA. · Laboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland. · Croatian Institute for Brain Research, Medical School, University of Zagreb, Zagreb, Croatia. · Department of Psychiatry, University of Bonn, Bonn, Germany. · Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark. · Biological Psychiatry Unit and Dual Diagnosis Ward, Istituto Di Ricovero e Cura a Carattere Scientifico, Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy. · Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany. · Laboratoire de Psychologie Médicale, Université Libre de Bruxelles and Psy Pluriel-Centre Européen de Psychologie Médicale, Brussels, Belgium. · Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, PO80, De De Crespigny Park, Denmark Hill United Kingdom. · MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom. · Division of Psychiatry, University College London (UCL), London, United Kingdom. · Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. · Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA. · Department of Psychiatry, University of Alberta, Edmonton, AB, Canada. · School of Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, The Netherlands. · Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; Department of Psychiatry & Psychology, Mayo Clinic, Rochester, MN, United States. · Department of Psychiatry, Dalhousie University, Halifax, Canada. · Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, PO80, De De Crespigny Park, Denmark Hill United Kingdom. Electronic address: cathryn.lewis@kcl.ac.uk. ·Eur Neuropsychopharmacol · Pubmed #30135031.

ABSTRACT: Cytochrome (CYP) P450 enzymes have a primary role in antidepressant metabolism and variants in these polymorphic genes are targets for pharmacogenetic investigation. This is the first meta-analysis to investigate how CYP2C19 polymorphisms predict citalopram/escitalopram efficacy and side effects. CYP2C19 metabolic phenotypes comprise poor metabolizers (PM), intermediate and intermediate+ metabolizers (IM; IM+), extensive and extensive+ metabolizers (EM [wild type]; EM+) and ultra-rapid metabolizers (UM) defined by the two most common CYP2C19 functional polymorphisms (rs4244285 and rs12248560) in Caucasians. These polymorphisms were genotyped or imputed from genome-wide data in four samples treated with citalopram or escitalopram (GENDEP, STAR*D, GenPod, PGRN-AMPS). Treatment efficacy was assessed by standardized percentage symptom improvement and by remission. Side effect data were available at weeks 2-4, 6 and 9 in three samples. A fixed-effects meta-analysis was performed using EM as the reference group. Analysis of 2558 patients for efficacy and 2037 patients for side effects showed that PMs had higher symptom improvement (SMD = 0.43, CI = 0.19-0.66) and higher remission rates (OR = 1.55, CI = 1.23-1.96) compared to EMs. At weeks 2-4, PMs showed higher risk of gastro-intestinal (OR = 1.26, CI = 1.08-1.47), neurological (OR = 1.28, CI = 1.07-1.53) and sexual side effects (OR = 1.52, CI = 1.23-1.87; week 6 values were similar). No difference was seen at week 9 or in total side effect burden. PMs did not have higher risk of dropout at week 4 compared to EMs. Antidepressant dose was not different among CYP2C19 groups. CYP2C19 polymorphisms may provide helpful information for guiding citalopram/escitalopram treatment, despite PMs being relatively rare among Caucasians (∼2%).

11 Article Cohort study of the relationship between individual psychotherapy and pregnancy outcomes. 2018

Snapper, Leslie A / Hart, Kamber L / Venkatesh, Kartik K / Kaimal, Anjali J / Perlis, Roy H. ·Center for Experimental Drugs and Diagnostics, Center for Human Genetic Research and Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, Unites States. · Department of Obstetrics and Gynecology, Massachusetts General Hospital and Brigham and Women's Hospital, the Division of Maternal Fetal Medicine, Boston, MA 02114, Unites States. · Center for Experimental Drugs and Diagnostics, Center for Human Genetic Research and Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, Unites States. Electronic address: rperlis@partners.org. ·J Affect Disord · Pubmed #30029152.

ABSTRACT: INTRODUCTION: Antenatal depression is associated with poor obstetric outcomes, but it has not been determined if treatment improves these outcomes. We hypothesized that psychotherapy for antenatal depression would decrease rates of low Apgar score, preterm birth, low birthweight, and high maternal weight gain. METHODS: Using longitudinal clinical data from the electronic health record (EHR) of a large academic medical center, we examined the association between exposure to psychotherapy during pregnancy among women with a history of major depressive disorder and obstetric outcomes. We compared outcomes between women with and without psychotherapy treatment during pregnancy, and included a dose response analysis. RESULTS: Of 50,856 women with pregnancies between 1998 and 2013, 5413 had a lifetime diagnosis of depression (948 had a diagnosis of depression during pregnancy), and 536 received psychotherapy at least once during pregnancy. Women who received one or more psychotherapy sessions during pregnancy had increased odds of preterm delivery and decreased odds of high maternal weight gain (more than 40 pounds). Individuals who received four or more psychotherapy sessions during pregnancy had increased odds of preterm birth and low infant birth weight and decreased odds of high maternal weight gain. LIMITATIONS: Patients may have pursued treatment outside of this hospital's EHR data, and we cannot control for the quality of treatment or type of psychotherapy. DISCUSSION: Psychotherapy was associated with negative obstetric outcomes. While treatment of depression in pregnant women has been shown to benefit the mother, the absence of benefit in terms of pregnancy outcomes merits further investigation.

12 Article Pharmacogenetic testing among patients with mood and anxiety disorders is associated with decreased utilization and cost: A propensity-score matched study. 2018

Perlis, Roy H / Mehta, Rajesh / Edwards, Alison M / Tiwari, Arun / Imbens, Guido W. ·Center for Quantitative Health, Division of Clinical Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. · Healthagen, New York City, NY, USA. · Graduate School of Business, Stanford University, Stanford, CA, USA. ·Depress Anxiety · Pubmed #29734486.

ABSTRACT: BACKGROUND: Naturalistic and small randomized trials have suggested that pharmacogenetic testing may improve treatment outcomes in depression, but its cost-effectiveness is not known. There is growing enthusiasm for personalized medicine, relying on genetic variation as a contributor to heterogeneity of treatment effects. We sought to examine the relationship between a commercial pharmacogenetic test for psychotropic medications and 6-month cost of care and utilization in a large commercial health plan. METHODS: We performed a propensity-score matched case-control analysis of longitudinal health claims data from a large US insurer. Individuals with a mood or anxiety disorder diagnosis (N = 817) who received genetic testing for pharmacokinetic and pharmacodynamic variation were matched to 2,745 individuals who did not receive such testing. Outcomes included number of outpatient visits, inpatient hospitalizations, emergency room visits, and prescriptions, as well as associated costs over 6 months. RESULTS: On average, individuals who underwent testing experienced 40% fewer all-cause emergency room visits (mean difference 0.13 visits; P < 0.0001) and 58% fewer inpatient all-cause hospitalizations (mean difference 0.10 visits; P < 0.0001) than individuals in the control group. The two groups did not differ significantly in number of psychotropic medications prescribed or mood-disorder related hospitalizations. Overall 6-month costs were estimated to be $1,948 (SE 611) lower in the tested group. CONCLUSIONS: Pharmacogenetic testing represents a promising strategy to reduce costs and utilization among patients with mood and anxiety disorders.

13 Article Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. 2018

Wray, Naomi R / Ripke, Stephan / Mattheisen, Manuel / Trzaskowski, Maciej / Byrne, Enda M / Abdellaoui, Abdel / Adams, Mark J / Agerbo, Esben / Air, Tracy M / Andlauer, Till M F / Bacanu, Silviu-Alin / Bækvad-Hansen, Marie / Beekman, Aartjan F T / Bigdeli, Tim B / Binder, Elisabeth B / Blackwood, Douglas R H / Bryois, Julien / Buttenschøn, Henriette N / Bybjerg-Grauholm, Jonas / Cai, Na / Castelao, Enrique / Christensen, Jane Hvarregaard / Clarke, Toni-Kim / Coleman, Jonathan I R / Colodro-Conde, Lucía / Couvy-Duchesne, Baptiste / Craddock, Nick / Crawford, Gregory E / Crowley, Cheynna A / Dashti, Hassan S / Davies, Gail / Deary, Ian J / Degenhardt, Franziska / Derks, Eske M / Direk, Nese / Dolan, Conor V / Dunn, Erin C / Eley, Thalia C / Eriksson, Nicholas / Escott-Price, Valentina / Kiadeh, Farnush Hassan Farhadi / Finucane, Hilary K / Forstner, Andreas J / Frank, Josef / Gaspar, Héléna A / Gill, Michael / Giusti-Rodríguez, Paola / Goes, Fernando S / Gordon, Scott D / Grove, Jakob / Hall, Lynsey S / Hannon, Eilis / Hansen, Christine Søholm / Hansen, Thomas F / Herms, Stefan / Hickie, Ian B / Hoffmann, Per / Homuth, Georg / Horn, Carsten / Hottenga, Jouke-Jan / Hougaard, David M / Hu, Ming / Hyde, Craig L / Ising, Marcus / Jansen, Rick / Jin, Fulai / Jorgenson, Eric / Knowles, James A / Kohane, Isaac S / Kraft, Julia / Kretzschmar, Warren W / Krogh, Jesper / Kutalik, Zoltán / Lane, Jacqueline M / Li, Yihan / Li, Yun / Lind, Penelope A / Liu, Xiaoxiao / Lu, Leina / MacIntyre, Donald J / MacKinnon, Dean F / Maier, Robert M / Maier, Wolfgang / Marchini, Jonathan / Mbarek, Hamdi / McGrath, Patrick / McGuffin, Peter / Medland, Sarah E / Mehta, Divya / Middeldorp, Christel M / Mihailov, Evelin / Milaneschi, Yuri / Milani, Lili / Mill, Jonathan / Mondimore, Francis M / Montgomery, Grant W / Mostafavi, Sara / Mullins, Niamh / Nauck, Matthias / Ng, Bernard / Nivard, Michel G / Nyholt, Dale R / O'Reilly, Paul F / Oskarsson, Hogni / Owen, Michael J / Painter, Jodie N / Pedersen, Carsten Bøcker / Pedersen, Marianne Giørtz / Peterson, Roseann E / Pettersson, Erik / Peyrot, Wouter J / Pistis, Giorgio / Posthuma, Danielle / Purcell, Shaun M / Quiroz, Jorge A / Qvist, Per / Rice, John P / Riley, Brien P / Rivera, Margarita / Saeed Mirza, Saira / Saxena, Richa / Schoevers, Robert / Schulte, Eva C / Shen, Ling / Shi, Jianxin / Shyn, Stanley I / Sigurdsson, Engilbert / Sinnamon, Grant B C / Smit, Johannes H / Smith, Daniel J / Stefansson, Hreinn / Steinberg, Stacy / Stockmeier, Craig A / Streit, Fabian / Strohmaier, Jana / Tansey, Katherine E / Teismann, Henning / Teumer, Alexander / Thompson, Wesley / Thomson, Pippa A / Thorgeirsson, Thorgeir E / Tian, Chao / Traylor, Matthew / Treutlein, Jens / Trubetskoy, Vassily / Uitterlinden, André G / Umbricht, Daniel / Van der Auwera, Sandra / van Hemert, Albert M / Viktorin, Alexander / Visscher, Peter M / Wang, Yunpeng / Webb, Bradley T / Weinsheimer, Shantel Marie / Wellmann, Jürgen / Willemsen, Gonneke / Witt, Stephanie H / Wu, Yang / Xi, Hualin S / Yang, Jian / Zhang, Futao / Anonymous12721124 / Anonymous12731124 / Arolt, Volker / Baune, Bernhard T / Berger, Klaus / Boomsma, Dorret I / Cichon, Sven / Dannlowski, Udo / de Geus, E C J / DePaulo, J Raymond / Domenici, Enrico / Domschke, Katharina / Esko, Tõnu / Grabe, Hans J / Hamilton, Steven P / Hayward, Caroline / Heath, Andrew C / Hinds, David A / Kendler, Kenneth S / Kloiber, Stefan / Lewis, Glyn / Li, Qingqin S / Lucae, Susanne / Madden, Pamela F A / Magnusson, Patrik K / Martin, Nicholas G / McIntosh, Andrew M / Metspalu, Andres / Mors, Ole / Mortensen, Preben Bo / Müller-Myhsok, Bertram / Nordentoft, Merete / Nöthen, Markus M / O'Donovan, Michael C / Paciga, Sara A / Pedersen, Nancy L / Penninx, Brenda W J H / Perlis, Roy H / Porteous, David J / Potash, James B / Preisig, Martin / Rietschel, Marcella / Schaefer, Catherine / Schulze, Thomas G / Smoller, Jordan W / Stefansson, Kari / Tiemeier, Henning / Uher, Rudolf / Völzke, Henry / Weissman, Myrna M / Werge, Thomas / Winslow, Ashley R / Lewis, Cathryn M / Levinson, Douglas F / Breen, Gerome / Børglum, Anders D / Sullivan, Patrick F / Anonymous12741124. ·Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. naomi.wray@uq.edu.au. · Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia. naomi.wray@uq.edu.au. · Medical and Population Genetics, Broad Institute, Cambridge, MA, USA. · Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. · Department of Psychiatry and Psychotherapy, Universitätsmedizin Berlin Campus Charité Mitte, Berlin, Germany. · Department of Biomedicine, Aarhus University, Aarhus, Denmark. · iSEQ, Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark. · iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark. · Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. · Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. · Department of Biological Psychology and EMGO+ Institute for Health and Care Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. · Division of Psychiatry, University of Edinburgh, Edinburgh, UK. · Centre for Integrated Register-Based Research, Aarhus University, Aarhus, Denmark. · National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark. · Discipline of Psychiatry, University of Adelaide, Adelaide, South Australia, Australia. · Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany. · Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. · Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA. · Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark. · Department of Psychiatry, Vrije Universiteit Medical Center and GGZ inGeest, Amsterdam, The Netherlands. · Virginia Institute for Psychiatric and Behavior Genetics, Richmond, VA, USA. · Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. · Department of Clinical Medicine, Translational Neuropsychiatry Unit, Aarhus University, Aarhus, Denmark. · Statistical Genomics and Systems Genetics, European Bioinformatics Institute (EMBL-EBI), Cambridge, UK. · Human Genetics, Wellcome Trust Sanger Institute, Cambridge, UK. · Department of Psychiatry, University Hospital of Lausanne, Prilly, Switzerland. · MRC Social Genetic and Developmental Psychiatry Centre, King's College London, London, UK. · Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia. · Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia. · Centre for Advanced Imaging, University of Queensland, Brisbane, Queensland, Australia. · Psychological Medicine, Cardiff University, Cardiff, UK. · Center for Genomic and Computational Biology, Duke University, Durham, NC, USA. · Department of Pediatrics, Division of Medical Genetics, Duke University, Durham, NC, USA. · Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. · Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. · Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. · Institute of Human Genetics, University of Bonn, Bonn, Germany. · Life & Brain Center, Department of Genomics, University of Bonn, Bonn, Germany. · Psychiatry, Dokuz Eylul University School of Medicine, Izmir, Turkey. · Epidemiology, Erasmus MC, Rotterdam, The Netherlands. · Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA. · Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. · Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Massachusetts General Hospital, Boston, MA, USA. · Research, 23andMe, Inc., Mountain View, CA, USA. · Neuroscience and Mental Health, Cardiff University, Cardiff, UK. · Bioinformatics, University of British Columbia, Vancouver, British Columbia, Canada. · Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA. · Department of Mathematics, Massachusetts Institute of Technology, Cambridge, MA, USA. · Department of Psychiatry (UPK), University of Basel, Basel, Switzerland. · Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland. · Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. · Department of Psychiatry, Trinity College Dublin, Dublin, Ireland. · Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. · Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA. · Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. · Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark. · Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, UK. · University of Exeter Medical School, Exeter, UK. · Danish Headache Centre, Department of Neurology, Rigshospitalet, Glostrup, Denmark. · Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Capital Region of Denmark, Copenhagen, Denmark. · iPSYCH, Lundbeck Foundation Initiative for Psychiatric Research, Copenhagen, Denmark. · Brain and Mind Centre, University of Sydney, Sydney, New South Wales, Australia. · Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine and Ernst Moritz Arndt University Greifswald, Greifswald, Germany. · Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche, Ltd, Basel, Switzerland. · Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA. · Statistics, Pfizer Global Research and Development, Groton, CT, USA. · Max Planck Institute of Psychiatry, Munich, Germany. · Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA. · Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA. · Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA. · Psychiatry and Behavioral Sciences, University of Southern California, Los Angeles, CA, USA. · Informatics Program, Boston Children's Hospital, Boston, MA, USA. · Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. · Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA. · Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. · Department of Endocrinology at Herlev University Hospital, University of Copenhagen, Copenhagen, Denmark. · Swiss Institute of Bioinformatics, Lausanne, Switzerland. · Institute of Social and Preventive Medicine (IUMSP), University Hospital of Lausanne, Lausanne, Switzerland. · Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA. · Mental Health, NHS 24, Glasgow, UK. · Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK. · Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany. · Statistics, University of Oxford, Oxford, UK. · Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA. · School of Psychology and Counseling, Queensland University of Technology, Brisbane, Queensland, Australia. · Child and Youth Mental Health Service, Children's Health Queensland Hospital and Health Service, South Brisbane, Queensland, Australia. · Child Health Research Centre, University of Queensland, Brisbane, Queensland, Australia. · Estonian Genome Center, University of Tartu, Tartu, Estonia. · Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada. · Statistics, University of British Columbia, Vancouver, British Columbia, Canada. · DZHK (German Centre for Cardiovascular Research), partner site Greifswald, University Medicine, University Medicine Greifswald, Greifswald, Germany. · Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. · Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia. · Humus, Reykjavik, Iceland. · MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK. · Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA. · Complex Trait Genetics, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. · Clinical Genetics, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. · Department of Psychiatry, Brigham and Women's Hospital, Boston, MA, USA. · Solid Biosciences, Boston, MA, USA. · Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, MO, USA. · Department of Biochemistry and Molecular Biology II, Institute of Neurosciences, Center for Biomedical Research, University of Granada, Granada, Spain. · Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. · Department of Psychiatry and Psychotherapy, Medical Center of the University of Munich, Campus Innenstadt, Munich, Germany. · Institute of Psychiatric Phenomics and Genomics (IPPG), Medical Center of the University of Munich, Campus Innenstadt, Munich, Germany. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. · Behavioral Health Services, Kaiser Permanente Washington, Seattle, WA, USA. · Faculty of Medicine, Department of Psychiatry, University of Iceland, Reykjavik, Iceland. · School of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia. · Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK. · deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. · Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA. · College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK. · Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany. · Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany. · KG Jebsen Centre for Psychosis Research, Norway Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. · Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA. · Medical Genetics Section, CGEM, IGMM, University of Edinburgh, Edinburgh, UK. · Clinical Neurosciences, University of Cambridge, Cambridge, UK. · Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. · Roche Pharmaceutical Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases Discovery and Translational Medicine Area, Roche Innovation Center Basel, F. Hoffmann-La Roche, Ltd, Basel, Switzerland. · Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany. · Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands. · Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA. · Computational Sciences Center of Emphasis, Pfizer Global Research and Development, Cambridge, MA, USA. · Department of Psychiatry, University of Münster, Munster, Germany. · Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Juelich, Germany. · Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland. · Amsterdam Public Health Institute, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. · Centre for Integrative Biology, Università degli Studi di Trento, Trento, Italy. · Department of Psychiatry and Psychotherapy, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany. · Psychiatry, Kaiser Permanente Northern California, San Francisco, CA, USA. · MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. · Centre for Addiction and Mental Health, Toronto, Ontario, Canada. · Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. · Division of Psychiatry, University College London, London, UK. · Neuroscience Therapeutic Area, Janssen Research and Development, LLC, Titusville, NJ, USA. · Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia. · Psychosis Research Unit, Aarhus University Hospital, Risskov, Aarhus, Denmark. · Institute of Translational Medicine, University of Liverpool, Liverpool, UK. · Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark. · Human Genetics and Computational Biomedicine, Pfizer Global Research and Development, Groton, CT, USA. · Psychiatry, Harvard Medical School, Boston, MA, USA. · Psychiatry, University of Iowa, Iowa City, IA, USA. · Human Genetics Branch, NIMH Division of Intramural Research Programs, Bethesda, MD, USA. · Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany. · Faculty of Medicine, University of Iceland, Reykjavik, Iceland. · Child and Adolescent Psychiatry, Erasmus MC, Rotterdam, The Netherlands. · Psychiatry, Erasmus MC, Rotterdam, The Netherlands. · Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada. · Division of Epidemiology, New York State Psychiatric Institute, New York, NY, USA. · Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. · Human Genetics and Computational Biomedicine, Pfizer Global Research and Development, Cambridge, MA, USA. · Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. · Department of Medical and Molecular Genetics, King's College London, London, UK. · Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA. · NIHR BRC for Mental Health, King's College London, London, UK. · Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. pfsulliv@med.unc.edu. · Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. pfsulliv@med.unc.edu. · Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. pfsulliv@med.unc.edu. ·Nat Genet · Pubmed #29700475.

ABSTRACT: Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.

14 Article Anxiety About Antidepressants. 2018

Perlis, Roy H. ·From the Department of Psychiatry, Massachusetts General Hospital, Boston. ·Am J Psychiatry · Pubmed #29690791.

ABSTRACT: -- No abstract --

15 Article New insights into the pharmacogenomics of antidepressant response from the GENDEP and STAR*D studies: rare variant analysis and high-density imputation. 2018

Fabbri, C / Tansey, K E / Perlis, R H / Hauser, J / Henigsberg, N / Maier, W / Mors, O / Placentino, A / Rietschel, M / Souery, D / Breen, G / Curtis, C / Sang-Hyuk, L / Newhouse, S / Patel, H / Guipponi, M / Perroud, N / Bondolfi, G / O'Donovan, M / Lewis, G / Biernacka, J M / Weinshilboum, R M / Farmer, A / Aitchison, K J / Craig, I / McGuffin, P / Uher, R / Lewis, C M. ·Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. · Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. · College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK. · Department of Psychiatry, Center for Experimental Drugs and Diagnostics, Massachusetts General Hospital, Boston, MA, USA. · Laboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland. · Croatian Institute for Brain Research, Medical School, University of Zagreb, Zagreb, Croatia. · Department of Psychiatry, University of Bonn, Bonn, Germany. · Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark. · Biological Psychiatry Unit and Dual Diagnosis Ward, Istituto Di Ricovero e Cura a Carattere Scientifico, Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy. · Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany. · Laboratoire de Psychologie Médicale, Université Libre de Bruxelles and Psy Pluriel-Centre Européen de Psychologie Médicale, Brussels, Belgium. · Department of Genetic Medicine and Development, University of Geneva Medical School and University Hospitals of Geneva, Geneva, Switzerland. · Department of Psychiatry, University of Geneva, Geneva, Switzerland. · MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK. · Division of Psychiatry, University College London (UCL), London, UK. · Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA. · Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA. · Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA. · Department of Psychiatry, University of Alberta, Edmonton, AB, Canada. · Department of Psychiatry, Dalhousie University, Halifax, Canada. ·Pharmacogenomics J · Pubmed #29160301.

ABSTRACT: Genome-wide association studies have generally failed to identify polymorphisms associated with antidepressant response. Possible reasons include limited coverage of genetic variants that this study tried to address by exome genotyping and dense imputation. A meta-analysis of Genome-Based Therapeutic Drugs for Depression (GENDEP) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies was performed at the single-nucleotide polymorphism (SNP), gene and pathway levels. Coverage of genetic variants was increased compared with previous studies by adding exome genotypes to previously available genome-wide data and using the Haplotype Reference Consortium panel for imputation. Standard quality control was applied. Phenotypes were symptom improvement and remission after 12 weeks of antidepressant treatment. Significant findings were investigated in NEWMEDS consortium samples and Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) for replication. A total of 7062 950 SNPs were analyzed in GENDEP (n=738) and STAR*D (n=1409). rs116692768 (P=1.80e-08, ITGA9 (integrin α9)) and rs76191705 (P=2.59e-08, NRXN3 (neurexin 3)) were significantly associated with symptom improvement during citalopram/escitalopram treatment. At the gene level, no consistent effect was found. At the pathway level, the Gene Ontology (GO) terms GO: 0005694 (chromosome) and GO: 0044427 (chromosomal part) were associated with improvement (corrected P=0.007 and 0.045, respectively). The association between rs116692768 and symptom improvement was replicated in PGRN-AMPS (P=0.047), whereas rs76191705 was not. The two SNPs did not replicate in NEWMEDS. ITGA9 codes for a membrane receptor for neurotrophins and NRXN3 is a transmembrane neuronal adhesion receptor involved in synaptic differentiation. Despite their meaningful biological rationale for being involved in antidepressant effect, replication was partial. Further studies may help in clarifying their role.

16 Article Polygenic loading for major depression is associated with specific medical comorbidity. 2017

McCoy, T H / Castro, V M / Snapper, L / Hart, K / Januzzi, J L / Huffman, J C / Perlis, R H. ·Center for Quantitative Health, Center for Human Genetic Research and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. · Partners Research Information Systems and Computing, Partners HealthCare System, One Constitution Center, Boston, MA, USA. · Cardiology Division, Massachusetts General Hospital and Harvard Clinical Research Institute, Boston, MA, USA. · Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. ·Transl Psychiatry · Pubmed #28926002.

ABSTRACT: Major depressive disorder frequently co-occurs with medical disorders, raising the possibility of shared genetic liability. Recent identification of 15 novel genetic loci associated with depression allows direct investigation of this question. In cohorts of individuals participating in biobanks at two academic medical centers, we calculated polygenic loading for risk loci reported to be associated with depression. We then examined the association between such loading and 50 groups of clinical diagnoses, or topics, drawn from these patients' electronic health records, determined using a novel application of latent Dirichilet allocation. Three topics showed experiment-wide association with the depression liability score; these included diagnostic groups representing greater prevalence of mood and anxiety disorders, greater prevalence of cardiac ischemia, and a decreased prevalence of heart failure. The latter two associations persisted even among individuals with no mood disorder diagnosis. This application of a novel method for grouping related diagnoses in biobanks indicate shared genetic risk for depression and cardiac disease, with a pattern suggesting greater ischemic risk and diminished heart failure risk.

17 Article Impact of antidepressant treatment during pregnancy on obstetric outcomes among women previously treated for depression: an observational cohort study. 2017

Venkatesh, K K / Castro, V M / Perlis, R H / Kaimal, A J. ·Department of Obstetrics and Gynecology, Massachusetts General Hospital and Brigham and Women's Hospital Boston, MA, USA. · Department of Psychiatry, Center for Experimental Drugs and Diagnostics, Massachusetts General Hospital Boston, MA, USA. · Center for Human Genetic Research, Massachusetts General Hospital Boston, MA, USA. · Harvard Medical School, Boston, MA, USA. · Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, USA. ·J Perinatol · Pubmed #28682318.

ABSTRACT: OBJECTIVE: To examine the impact of pharmacologic treatment for depression on obstetric outcomes in women treated for depression during the 2 years prior to pregnancy. STUDY DESIGN: Observational cohort study among 2859 women treated for depression during the 2 years prior to pregnancy. The primary exposure was any antidepressant treatment during pregnancy. Secondary analyses examined the impact of treatment by period of antidepressant exposure. Multivariable logistic regression models as well as propensity score analysis was utilized. RESULTS: Among 2859 women, 1648 (58%) were treated with antidepressant medication during pregnancy. Women who received antidepressants had no difference in preterm and early-term deliveries, Apgar scores, and small for gestational age (SGA); they had a lower likelihood of breastfeeding (adjusted odds ratio (AOR) 0.69, (95% confidence interval (CI): 0.51 to 0.94)). In secondary analysis, women who used antidepressants all three trimesters who delivered at term were more likely to deliver early term (AOR 1.36, (95% CI: 1.09 to 1.72)). Women who were treated with antidepressants only during the first and second trimesters had a reduced likelihood of SGA (AOR: 0.51 (95% CI: 0.32 to 0.83)). Generally similar results were observed with propensity score analysis. CONCLUSION: Antidepressant exposure during pregnancy does not confer an increased risk of preterm birth nor growth restriction in women recently treated for depression, but also does not appear to markedly improve these outcomes.

18 Article Genetic effects influencing risk for major depressive disorder in China and Europe. 2017

Bigdeli, T B / Ripke, S / Peterson, R E / Trzaskowski, M / Bacanu, S-A / Abdellaoui, A / Andlauer, T F M / Beekman, A T F / Berger, K / Blackwood, D H R / Boomsma, D I / Breen, G / Buttenschøn, H N / Byrne, E M / Cichon, S / Clarke, T-K / Couvy-Duchesne, B / Craddock, N / de Geus, E J C / Degenhardt, F / Dunn, E C / Edwards, A C / Fanous, A H / Forstner, A J / Frank, J / Gill, M / Gordon, S D / Grabe, H J / Hamilton, S P / Hardiman, O / Hayward, C / Heath, A C / Henders, A K / Herms, S / Hickie, I B / Hoffmann, P / Homuth, G / Hottenga, J-J / Ising, M / Jansen, R / Kloiber, S / Knowles, J A / Lang, M / Li, Q S / Lucae, S / MacIntyre, D J / Madden, P A F / Martin, N G / McGrath, P J / McGuffin, P / McIntosh, A M / Medland, S E / Mehta, D / Middeldorp, C M / Milaneschi, Y / Montgomery, G W / Mors, O / Müller-Myhsok, B / Nauck, M / Nyholt, D R / Nöthen, M M / Owen, M J / Penninx, B W J H / Pergadia, M L / Perlis, R H / Peyrot, W J / Porteous, D J / Potash, J B / Rice, J P / Rietschel, M / Riley, B P / Rivera, M / Schoevers, R / Schulze, T G / Shi, J / Shyn, S I / Smit, J H / Smoller, J W / Streit, F / Strohmaier, J / Teumer, A / Treutlein, J / Van der Auwera, S / van Grootheest, G / van Hemert, A M / Völzke, H / Webb, B T / Weissman, M M / Wellmann, J / Willemsen, G / Witt, S H / Levinson, D F / Lewis, C M / Wray, N R / Flint, J / Sullivan, P F / Kendler, K S. ·Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. · Department of Psychiatry, Charite Universitatsmedizin Berlin Campus Benjamin Franklin, Berlin, Germany. · Medical and Population Genetics, Broad Institute, Cambridge, MA, USA. · Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. · Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia. · Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia. · Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. · Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany. · Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. · Department of Psychiatry, VU University Medical Center and GGZ inGeest, Amsterdam, The Netherlands. · Institute of Epidemiology and Social Medicine, University of Muenster, Münster, Germany. · Division of Psychiatry, University of Edinburgh, Edinburgh, UK. · King's College London, NIHR BRC for Mental Health, London, UK. · King's College London, MRC Social Genetic and Developmental Psychiatry Centre, London, UK. · Department of Clinical Medicine, Translational Neuropsychiatry Unit, Aarhus University, Aarhus, Denmark. · Department of Biomedicine, University of Basel, Basel, Switzerland. · Division of Medical Genetics, University of Basel, Basel, Switzerland. · Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Jülich, Germany. · Institute of Human Genetics, University of Bonn, Bonn, Germany. · Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. · Centre for Advanced Imaging, University of Queensland, Brisbane, QLD, Australia. · Department of Psychological Medicine, Cardiff University, Cardiff, UK. · EMGO+ Institute, VU University Medical Center, Amsterdam, The Netherlands. · Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany. · Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA. · Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. · Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA. · Department of Psychiatry and Behavioral Sciences, State University of New York Downstate Medical Center, Brooklyn, NY, USA. · Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany. · Department of Psychiatry, Trinity College Dublin, Dublin, Ireland. · Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany. · Department of Psychiatry, Kaiser-Permanente Northern California, San Fransisco, CA, USA. · Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland. · Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. · Department of Psychiatry, Washington University in Saint Louis School of Medicine, St Louis, MO, USA. · Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland. · Brain and Mind Research Institute, University of Sydney, Sydney, NSW, Australia. · Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland. · Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst Moritz Arndt University Greifswald, Greifswald, Germany. · Max Planck Institute of Psychiatry, Munich, Germany. · Department of Psychiatry and The Behavioral Sciences, University of Southern California, Los Angeles, CA, USA. · Neuroscience Therapeutic Area, Janssen Research and Development, LLC, Titusville, NJ, USA. · School of Psychology, University of Queensland, Brisbane, QLD, Australia. · Department of Psychiatry, New York State Psychiatric Institute, Columbia University College of Physicians and Surgeons, New York, NY, USA. · Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. · Institute for Molecular Biology, University of Queensland, Brisbane, QLD, Australia. · Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark. · Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK. · Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. · Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia. · MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, UK. · Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA. · Department of Psychiatry, Harvard Medical School, Boston, MA, USA. · Medical Genetics Section, CGEM, IGMM, University of Edinburgh, Edinburgh, UK. · Department of Psychiatry, University of Iowa, Iowa, IA, USA. · Department of Psychiatry, Washington University in Saint Louis, St Louis, MO, USA. · Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. · Department of Biochemistry and Molecular Biology II, Institute of Neurosciences, Center for Biomedical Research, University of Granada, Granada, Spain. · Department of Psychiatry, University of Groningen, University of Medical Center Groningen, Groningen, The Netherlands. · Institute of Psychiatric Phenomics and Genomics, Medical Center of the University of Munich, Campus Innenstadt, Munich, Germany. · Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, The Netherlands. · Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA. · Human Genetics Branch, NIMH Division of Intramural Research Programs, Bethesda, MD, USA. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. · Division of Psychiatry, Group Health, Seattle, WA, USA. · Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany. · Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands. · Division of Epidemiology, New York State Psychiatric Institute, New York, NY, USA. · Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA. · Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA. · King's College London, Department of Medical and Molecular Genetics, London, UK. · Merton College, University of Oxford, Oxford, UK. · Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. · Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden. · Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. · Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. ·Transl Psychiatry · Pubmed #28350396.

ABSTRACT: Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30-40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log

19 Article Improving discrimination in antepartum depression screening using the Edinburgh Postnatal Depression Scale. 2017

Venkatesh, Kartik K / Kaimal, Anjali J / Castro, Victor M / Perlis, Roy H. ·Dept. of Obstetrics and Gynecology, Massachusetts General Hospital and Brigham and Women's Hospital, Boston, MA, United States. Electronic address: kvenkatesh@partners.org. · Division of Maternal Fetal Medicine, Dept. of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, MA, United States. · Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States. · Center for Experimental Drugs and Diagnostics, Dept. of Psychiatry, Massachusetts General Hospital, Boston, MA, United States; Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States. ·J Affect Disord · Pubmed #28260619.

ABSTRACT: BACKGROUND: Universal screening of pregnant women for postpartum depression has recently been recommended; however, optimal application of depression screening tools in stratifying risk has not been defined. The current study examines new approaches to improve the ability of the Edinburgh Postnatal Depression Scale (EPDS) to stratify risk for postpartum depression, including alternate cut points, use of a continuous measure, and incorporation of other putative risk factors. METHODS: An observational cohort study of 4939 women screened both antepartum and postpartum with a negative EPDS screen antepartum(i.e. EPDS<10). The primary outcome was a probable postpartum major depressive episode(EPDS cut-off ≥10). Area under the receiver operating characteristics curve(AUC), sensitivity, specificity, and predictive values were calculated. RESULTS: 287 women(5.8%) screened positive for postpartum depression. An antepartum EPDS cut-off<5 optimally identified women with a low risk of postpartum depression with a negative predictive value of 97.6%; however, overall discrimination was modest(AUC 0.66, 95%CI: 0.64-0.69); sensitivity was 78.7%, and specificity was 53.8%, and the positive predictive value was low at 9.5%. The negative predictive values were similar(>95%) at all antepartum EPDS cut-off values from 4 to 8. Discrimination was improved(AUC ranging from 0.70 to 0.73) when the antepartum EPDS was combined with a prior history of major depressive disorder before pregnancy. LIMITATIONS: An inability to assess EPDS subscales and a relatively low prevalence of depression in this cohort. CONCLUSIONS: Though an antepartum EPDS cut-off score <5 yielded the greatest discrimination identifying women at low risk for postpartum depression, the negative predictive value was insufficient to substitute for postpartum screening.

20 Article Pharmacogenetics of antidepressant response: A polygenic approach. 2017

García-González, Judit / Tansey, Katherine E / Hauser, Joanna / Henigsberg, Neven / Maier, Wolfgang / Mors, Ole / Placentino, Anna / Rietschel, Marcella / Souery, Daniel / Žagar, Tina / Czerski, Piotr M / Jerman, Borut / Buttenschøn, Henriette N / Schulze, Thomas G / Zobel, Astrid / Farmer, Anne / Aitchison, Katherine J / Craig, Ian / McGuffin, Peter / Giupponi, Michel / Perroud, Nader / Bondolfi, Guido / Evans, David / O'Donovan, Michael / Peters, Tim J / Wendland, Jens R / Lewis, Glyn / Kapur, Shitij / Perlis, Roy / Arolt, Volker / Domschke, Katharina / Anonymous5720895 / Breen, Gerome / Curtis, Charles / Sang-Hyuk, Lee / Kan, Carol / Newhouse, Stephen / Patel, Hamel / Baune, Bernhard T / Uher, Rudolf / Lewis, Cathryn M / Fabbri, Chiara. ·Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom. · College of Biomedical and Life Sciences, Cardiff University, Cardiff, United Kingdom. · Laboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland. · Croatian Institute for Brain Research, Medical School, University of Zagreb, Zagreb, Croatia. · Department of Psychiatry, University of Bonn, Bonn, Germany. · Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark. · Biological Psychiatry Unit and Dual Diagnosis Ward, Istituto Di Ricovero e Cura a Carattere Scientifico, Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy. · Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany. · Laboratoire de Psychologie Médicale, Université Libre de Bruxelles and Psy Pluriel-Centre Européen de Psychologie Médicale, Brussels, Belgium. · Institute of Public Health of the Republic of Slovenia, Ljubljana, Slovenia. · Laboratory of Psychiatric Genetics, Poznan University of Medical Sciences, Poland. · Institute of Public Health of the Republic of Slovenia, Ljubljana, Slovenia; Department of Molecular and Biomedical Sciences, Jozef Stefan Institute, Ljubljana, Slovenia. · Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark. · Department of Psychiatry, University of Alberta, Edmonton, AB, Canada. · Department of Genetic Medicine and Laboratories, University Hospitals of Geneva, Geneva, Switzerland. · Department of Psychiatry, University of Geneva, Geneva, Switzerland. · Center of Excellence for Drug Discovery in Psychiatry, GlaxoSmithKline Medicines Research Centre, Verona, Italy. · Medical Research Council CAiTE Centre, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom. · Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, United Kingdom. · School of Clinical Sciences, University of Bristol, Bristol, United Kingdom. · Pharma Research and Early Development, F. Hoffmann-La Roche, Basel, Switzerland. · Division of Psychiatry, University College London, London, UK. · Department of Psychiatry, Center for Experimental Drugs and Diagnostics, Massachusetts General Hospital, Boston, USA. · Department of Psychiatry, University of Münster, Münster, Germany. · Department of Psychiatry Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany. · Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia. · Department of Psychiatry, Dalhousie University, Halifax, Canada. · Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom. Electronic address: Cathryn.lewis@kcl.ac.uk. · Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. ·Prog Neuropsychopharmacol Biol Psychiatry · Pubmed #28159590.

ABSTRACT: BACKGROUND: Major depressive disorder (MDD) has a high personal and socio-economic burden and >60% of patients fail to achieve remission with the first antidepressant. The biological mechanisms behind antidepressant response are only partially known but genetic factors play a relevant role. A combined predictor across genetic variants may be useful to investigate this complex trait. METHODS: Polygenic risk scores (PRS) were used to estimate multi-allelic contribution to: 1) antidepressant efficacy; 2) its overlap with MDD and schizophrenia. We constructed PRS and tested whether these predicted symptom improvement or remission from the GENDEP study (n=736) to the STAR*D study (n=1409) and vice-versa, including the whole sample or only patients treated with escitalopram or citalopram. Using summary statistics from Psychiatric Genomics Consortium for MDD and schizophrenia, we tested whether PRS from these disorders predicted symptom improvement in GENDEP, STAR*D, and five further studies (n=3756). RESULTS: No significant prediction of antidepressant efficacy was obtained from PRS in GENDEP/STAR*D but this analysis might have been underpowered. There was no evidence of overlap in the genetics of antidepressant response with either MDD or schizophrenia, either in individual studies or a meta-analysis. Stratifying by antidepressant did not alter the results. DISCUSSION: We identified no significant predictive effect using PRS between pharmacogenetic studies. The genetic liability to MDD or schizophrenia did not predict response to antidepressants, suggesting differences between the genetic component of depression and treatment response. Larger or more homogeneous studies will be necessary to obtain a polygenic predictor of antidepressant response.

21 Article An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype. 2017

Direk, Nese / Williams, Stephanie / Smith, Jennifer A / Ripke, Stephan / Air, Tracy / Amare, Azmeraw T / Amin, Najaf / Baune, Bernhard T / Bennett, David A / Blackwood, Douglas H R / Boomsma, Dorret / Breen, Gerome / Buttenschøn, Henriette N / Byrne, Enda M / Børglum, Anders D / Castelao, Enrique / Cichon, Sven / Clarke, Toni-Kim / Cornelis, Marilyn C / Dannlowski, Udo / De Jager, Philip L / Demirkan, Ayse / Domenici, Enrico / van Duijn, Cornelia M / Dunn, Erin C / Eriksson, Johan G / Esko, Tonu / Faul, Jessica D / Ferrucci, Luigi / Fornage, Myriam / de Geus, Eco / Gill, Michael / Gordon, Scott D / Grabe, Hans Jörgen / van Grootheest, Gerard / Hamilton, Steven P / Hartman, Catharina A / Heath, Andrew C / Hek, Karin / Hofman, Albert / Homuth, Georg / Horn, Carsten / Jan Hottenga, Jouke / Kardia, Sharon L R / Kloiber, Stefan / Koenen, Karestan / Kutalik, Zoltán / Ladwig, Karl-Heinz / Lahti, Jari / Levinson, Douglas F / Lewis, Cathryn M / Lewis, Glyn / Li, Qingqin S / Llewellyn, David J / Lucae, Susanne / Lunetta, Kathryn L / MacIntyre, Donald J / Madden, Pamela / Martin, Nicholas G / McIntosh, Andrew M / Metspalu, Andres / Milaneschi, Yuri / Montgomery, Grant W / Mors, Ole / Mosley, Thomas H / Murabito, Joanne M / Müller-Myhsok, Bertram / Nöthen, Markus M / Nyholt, Dale R / O'Donovan, Michael C / Penninx, Brenda W / Pergadia, Michele L / Perlis, Roy / Potash, James B / Preisig, Martin / Purcell, Shaun M / Quiroz, Jorge A / Räikkönen, Katri / Rice, John P / Rietschel, Marcella / Rivera, Margarita / Schulze, Thomas G / Shi, Jianxin / Shyn, Stanley / Sinnamon, Grant C / Smit, Johannes H / Smoller, Jordan W / Snieder, Harold / Tanaka, Toshiko / Tansey, Katherine E / Teumer, Alexander / Uher, Rudolf / Umbricht, Daniel / Van der Auwera, Sandra / Ware, Erin B / Weir, David R / Weissman, Myrna M / Willemsen, Gonneke / Yang, Jingyun / Zhao, Wei / Tiemeier, Henning / Sullivan, Patrick F. ·Department of Epidemiology, Erasmus University Medical Center, Rotterdam; Department of Psychiatry, Dokuz Eylul University, Izmir, Turkey. · Department of Genetics, Genomic Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. · Department of Epidemiology, University of Michigan, Ann Arbor, Michigan. · Stanley Center for Psychiatric Research, The Broad Institute of Harvard and MIT, Cambridge; Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston; Department of Psychiatry and Psychotherapy, Charité, Campus Mitte, Berlin. · Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, South Australia. · Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen; Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, South Australia. · Genetic Epidemiology Unit, Erasmus University Medical Center, Rotterdam. · Rush Alzheimer's Disease Center & Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois. · Division of Psychiatry, University of Edinburgh, Edinburgh. · Department of Biological Psychology, VU University, Amsterdam, The Netherlands. · MRC Social, Genetic & Developmental Psychiatry Centre Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London. · Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus. · Queensland Brain Institute, University of Queensland, St. Lucia, Queensland. · Department of Biomedicine and Centre for Integrative Sequencing, Aarhus University, Aarhus; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus. · Department of Psychiatry, Lausanne University Hospital, Lausanne. · Institute of Human Genetics, University of Bonn, Bonn; Department of Genomics, Life & Brain Center, Bonn; Institute of Neuroscience and Medicine, Research Centre Jülich, Jülich; Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland. · Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois. · Department of Psychiatry and Psychotherapy, University of Münster, Münster. · Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge; Department of Neurology, Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Neurology, Harvard Medical School, Boston. · Roche Pharmaceutical Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases Discovery & Translational Medicine Area, Roche Innovation Center Basel, F Hoffman-La Roche Ltd., Basel, Switzerland; Centre for Integrative Biology, University of Trento, Trento, Italy. · Stanley Center for Psychiatric Research, The Broad Institute of Harvard and MIT, Cambridge; Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; Department of Psychiatry, Harvard Medical School, Boston. · National Institute for Health and Welfare, Department of Chronic Disease Prevention, Helsinki; Department of General Practice and Primary Health Care, University of Helsinki, Helsinki; Unit of General Practice, Helsinki University Central Hospital, Helsinki; Folkhalsan Research Centre, Helsinki; Vasa Central Hospital, Vasa, Finland. · Program in Medical and Populational Genetics, The Broad Institute of Harvard and MIT, Cambridge; Division of Endocrinology, Boston Children's Hospital, Cambridge; Department of Genetics, Harvard Medical School, Boston; Estonian Genome Center, University of Tartu, Tartu, Estonia. · Institute for Social Research, University of Michigan, Ann Arbor, Michigan. · Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland. · Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas. · Department of Psychiatry, Trinity Centre for Health Science, Dublin, Ireland. · QIMR Berghofer Medical Research Institute, Brisbane. · Department of Psychiatry and Psychotherapy, Helios Hospital Stralsund, Munich; Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Munich; German Center for Neurodegenerative Diseases, Site Rostock/Greifswald, Munich. · Department of Psychiatry, Neuroscience Campus Amsterdam and EMGO Institute of Health and Care Research, VU University, Amsterdam, The Netherlands. · Department of Psychiatry, Kaiser Permanente San Francisco Medical Center, San Francisco. · Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen. · Department of Psychiatry, Washington University, St. Louis, Missouri. · Department of Epidemiology, Erasmus University Medical Center, Rotterdam; Department of Psychiatry, Erasmus University Medical Center, Rotterdam. · Department of Epidemiology, Erasmus University Medical Center, Rotterdam. · Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Munich. · Roche Pharmaceutical Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases Discovery & Translational Medicine Area, Roche Innovation Center Basel, F Hoffman-La Roche Ltd., Basel, Switzerland. · Max Planck Institute of Psychiatry, Munich. · Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York. · Institute of Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne. · Department of Psychosomatic Medicine and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich; Institute of Epidemiology II, Mental Health Research Unit, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg. · Folkhalsan Research Centre, Helsinki; Institute of Behavioural Sciences, University of Helsinki, Helsinki. · Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California. · Division of Psychiatry, University College London, London. · Janssen Research & Development LLC, New Brunswick, New Jersey. · University of Exeter Medical School, Exeter. · Department of Biostatistics, Boston University School of Public Health, Framingham, Massachusetts; Boston University and National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts. · Estonian Genome Center, University of Tartu, Tartu, Estonia; Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia. · The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus; Research Department P, Aarhus University Hospital, Risskov, Denmark. · Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi. · Department of Medicine, Section of General Internal Medicine, Boston University School of Medicine, Boston; Boston University and National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts. · Max Planck Institute of Psychiatry, Munich; Munich Cluster for Systems Neurology, Munich; University of Liverpool, Institute of Translational Medicine, Liverpool. · Institute of Human Genetics, University of Bonn, Bonn; Department of Genomics, Life & Brain Center, Bonn. · QIMR Berghofer Medical Research Institute, Brisbane; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland. · MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom. · Department of Psychiatry, Washington University, St. Louis, Missouri; Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida. · Center for Experimental Drugs and Diagnostics, Massachusetts General Hospital and Harvard Medical School, Boston. · Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa. · Division of Psychiatric Genomics, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York. · Solid GT, Boston; Roche Pharmaceutical Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases Discovery & Translational Medicine Area, Roche Innovation Center Basel, F Hoffman-La Roche Ltd., Basel, Switzerland. · Institute of Behavioural Sciences, University of Helsinki, Helsinki. · Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim. · MRC Social, Genetic & Developmental Psychiatry Centre Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London; CIBERSAM-Universidad de Granada, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. · Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University, Munich; Department of Psychiatry and Psychotherapy, University of Göttingen, Göttingen, Germany. · Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. · Group Health, Seattle, Washington. · Department of Psychiatry and Psychiatric Neuroscience, School of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia. · Unit of Genetic Epidemiology & Bioinformatics, University Medical Center Groningen, University of Groningen, Groningen. · Institute for Community Medicine, University Medicine Greifswald, Greifswald, Munich. · MRC Social, Genetic & Developmental Psychiatry Centre Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London; Dalhousie University, Halifax, Nova Scotia, Canada. · Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Munich; German Center for Neurodegenerative Diseases, Site Rostock/Greifswald, Munich. · Department of Epidemiology, University of Michigan, Ann Arbor, Michigan; Institute for Social Research, University of Michigan, Ann Arbor, Michigan. · College of Physicians and Surgeons, Columbia University and New York State Psychiatric Institute, New York, New York. · Department of Epidemiology, Erasmus University Medical Center, Rotterdam; Department of Psychiatry, Erasmus University Medical Center, Rotterdam. Electronic address: h.tiemeier@erasmusmc.nl. · Department of Psychiatry, Genomic Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Center for Psychiatric Genomics, Genomic Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden. ·Biol Psychiatry · Pubmed #28049566.

ABSTRACT: BACKGROUND: The genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder. METHODS: We analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures. RESULTS: The SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 × 10 CONCLUSIONS: This large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression.

22 Article Tissue Type-Specific Bioenergetic Abnormalities in Adults with Major Depression. 2017

Harper, David G / Jensen, J Eric / Ravichandran, Caitlin / Perlis, Roy H / Fava, Maurizio / Renshaw, Perry F / Iosifescu, Dan V. ·Department of Psychiatry, McLean Hospital and Harvard Medical School, Belmont, MA, USA. · Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. · The Brain Institute, University of Utah, Salt Lake City, UT, USA. · Departments of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA. ·Neuropsychopharmacology · Pubmed #27585738.

ABSTRACT: Brain bioenergetic abnormalities have been observed frequently in adults with major depressive disorder (MDD); however, results have been inconsistent regarding whether decreased or increased metabolism was observed. Phosphorus-31 magnetic resonance spectroscopy (31P MRS) allows for the quantification of bioenergetic molecules, containing high-energy phosphates, over the whole brain as well as measuring the differences between gray matter and white matter. We recruited 50 subjects with a current diagnosis of MDD, not currently treated with psychotropic medication, between ages of 18 and 65 (mean±SD age: 43.4±13.6; 46% female) and 30 healthy volunteers, matched for age and gender (39.0±12.5 years of age; 36.6% female). All subjects received a T1 MP-FLASH scan for tissue segmentation followed by 31P MRS, chemical shift imaging scan with 84 voxels of data collected over the entire brain utilizing a dual-tuned, proton-phosphorus coil to minimize subject movement. Phosphocreatine and inorganic phosphate (Pi) varied in opposite directions across gray matter and white matter when MDD subjects were compared with controls. This finding suggests alterations in high-energy phosphate metabolism and regulation of oxidative phosphorylation in MDD patients. In addition, within the MDD group, gray matter Pi, a regulator of oxidative phosphorylation, correlated positively with severity of depression. These data support a model that includes changes in brain bioenergetic function in subjects with major depression.

23 Article Predicting early psychiatric readmission with natural language processing of narrative discharge summaries. 2016

Rumshisky, A / Ghassemi, M / Naumann, T / Szolovits, P / Castro, V M / McCoy, T H / Perlis, R H. ·MIT Computer Science and Artificial Intelligence Laboratory, Cambridge, MA, USA. · Department of Computer Science, University of Massachusetts Lowell, Lowell, MA, USA. · Center for Experimental Drugs and Diagnostics, Massachusetts General Hospital, Boston, MA, USA. · Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. · Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA. · Partners Research Information Systems and Computing, Partners HealthCare System, Boston, MA, USA. ·Transl Psychiatry · Pubmed #27754482.

ABSTRACT: The ability to predict psychiatric readmission would facilitate the development of interventions to reduce this risk, a major driver of psychiatric health-care costs. The symptoms or characteristics of illness course necessary to develop reliable predictors are not available in coded billing data, but may be present in narrative electronic health record (EHR) discharge summaries. We identified a cohort of individuals admitted to a psychiatric inpatient unit between 1994 and 2012 with a principal diagnosis of major depressive disorder, and extracted inpatient psychiatric discharge narrative notes. Using these data, we trained a 75-topic Latent Dirichlet Allocation (LDA) model, a form of natural language processing, which identifies groups of words associated with topics discussed in a document collection. The cohort was randomly split to derive a training (70%) and testing (30%) data set, and we trained separate support vector machine models for baseline clinical features alone, baseline features plus common individual words and the above plus topics identified from the 75-topic LDA model. Of 4687 patients with inpatient discharge summaries, 470 were readmitted within 30 days. The 75-topic LDA model included topics linked to psychiatric symptoms (suicide, severe depression, anxiety, trauma, eating/weight and panic) and major depressive disorder comorbidities (infection, postpartum, brain tumor, diarrhea and pulmonary disease). By including LDA topics, prediction of readmission, as measured by area under receiver-operating characteristic curves in the testing data set, was improved from baseline (area under the curve 0.618) to baseline+1000 words (0.682) to baseline+75 topics (0.784). Inclusion of topics derived from narrative notes allows more accurate discrimination of individuals at high risk for psychiatric readmission in this cohort. Topic modeling and related approaches offer the potential to improve prediction using EHRs, if generalizability can be established in other clinical cohorts.

24 Article Abandoning personalization to get to precision in the pharmacotherapy of depression. 2016

Perlis, Roy H. ·Center for Experimental Drugs and Diagnostics, Department of Psychiatry and Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. ·World Psychiatry · Pubmed #27717262.

ABSTRACT: Effectiveness studies and analyses of naturalistic cohorts demonstrate that many patients with major depressive disorder do not experience symptomatic remission with antidepressant treatments. In an effort to better match patients with effective treatments, numerous investigations of predictors or moderators of treatment response have been reported over the past five decades, including clinical features as well as biological measures. However, none of these have entered routine clinical practice; instead, clinicians typically personalize treatment on the basis of patient preferences as well as their own. Here, we review the reasons why it has been challenging to identify and deploy treatment-specific predictors of response, and suggest strategies that may be required to achieve true precision in the pharmacotherapy of depression. We emphasize the need for changes in how depression care is delivered, measured, and used to inform future practice.

25 Article Identification of 15 genetic loci associated with risk of major depression in individuals of European descent. 2016

Hyde, Craig L / Nagle, Michael W / Tian, Chao / Chen, Xing / Paciga, Sara A / Wendland, Jens R / Tung, Joyce Y / Hinds, David A / Perlis, Roy H / Winslow, Ashley R. ·Statistics, Pfizer Global Research and Development, Pfizer, Inc., Cambridge, Massachusetts, USA. · Human Genetics and Computational Biomedicine, Pfizer Global Research and Development, Pfizer, Inc., Cambridge, Massachusetts, USA. · 23andMe, Inc., Mountain View, California, USA. · Center for Experimental Drugs and Diagnostics, Center for Human Genetic Research and Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA. ·Nat Genet · Pubmed #27479909.

ABSTRACT: Despite strong evidence supporting the heritability of major depressive disorder (MDD), previous genome-wide studies were unable to identify risk loci among individuals of European descent. We used self-report data from 75,607 individuals reporting clinical diagnosis of depression and 231,747 individuals reporting no history of depression through 23andMe and carried out meta-analysis of these results with published MDD genome-wide association study results. We identified five independent variants from four regions associated with self-report of clinical diagnosis or treatment for depression. Loci with a P value <1.0 × 10(-5) in the meta-analysis were further analyzed in a replication data set (45,773 cases and 106,354 controls) from 23andMe. A total of 17 independent SNPs from 15 regions reached genome-wide significance after joint analysis over all three data sets. Some of these loci were also implicated in genome-wide association studies of related psychiatric traits. These studies provide evidence for large-scale consumer genomic data as a powerful and efficient complement to data collected from traditional means of ascertainment for neuropsychiatric disease genomics.

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