Philip D Harvey1,2, Tim B Bigdeli3,4, Ayman H Fanous3,4, Yuli Li5,6, Nallakkandi Rajeevan5,6, Frederick Sayward5,6, Krishnan Radhakrishnan5,7,8, Grant Huang9, Mihaela Aslan3,4. 1. Bruce W. Carter Miami Veterans Affairs (VA) Medical Center, Miami, FL. 2. University of Miami School of Medicine, Miami, FL. 3. VA New York Harbor Healthcare System, Brooklyn, NY. 4. Department of Psychiatry and Behavioral Sciences, SUNY Downstate Medical Center, Brooklyn, NY. 5. Clinical Epidemiology Research Center (CERC), VA Connecticut Healthcare System, West Haven, CT. 6. Yale University School of Medicine, New Haven, CT. 7. Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. 8. University of Kentucky School of Medicine, Lexington, KY. 9. Office of Research and Development, Veterans Health Administration, Washington, DC.
Abstract
BACKGROUND: Personalization of psychiatric treatment includes treatment of symptoms, cognition and functional deficits, suicide, and medical co-morbidities. VA Collaborative Study 572 examined a large sample of male and female veterans with schizophrenia (n=3,942) and with bipolar disorder (n=5,414) with phenotyping and genomic analyses. We present the results to date and future directions. METHODS: All veterans received a structured diagnostic interview and assessments of suicidal ideation and behavior, PTSD, and health. Veterans with schizophrenia were assessed for negative symptoms and lifetime depression. All were assessed with a cognitive and functional capacity assessment. Data for genome wide association studies were collected. Controls came from the VA Million Veteran Program. RESULTS: Suicidal ideation or behavior was present in 66%. Cognitive and functional deficits were consistent with previous studies. 40% of the veterans with schizophrenia had a lifetime major depressive episode and PTSD was present in over 30%. Polygenic risk score (PRS) analyses indicated that cognitive and functional deficits overlapped with PRS for cognition, education, and intelligence in the general population and PRS for suicidal ideation and behavior correlated with previous PRS for depression and suicidal ideation and behavior, as did the PRS for PTSD. DISCUSSION: Results to date provide directions for personalization of treatment in SMI, veterans with SMI, and veterans in general. The results of the genomic analyses suggest that cognitive deficits in SMI may be associated with general population features. Upcoming genomic analyses will reexamine the issues above, as well as genomic factors associated with smoking, substance abuse, negative symptoms, and treatment response.
BACKGROUND: Personalization of psychiatric treatment includes treatment of symptoms, cognition and functional deficits, suicide, and medical co-morbidities. VA Collaborative Study 572 examined a large sample of male and female veterans with schizophrenia (n=3,942) and with bipolar disorder (n=5,414) with phenotyping and genomic analyses. We present the results to date and future directions. METHODS: All veterans received a structured diagnostic interview and assessments of suicidal ideation and behavior, PTSD, and health. Veterans with schizophrenia were assessed for negative symptoms and lifetime depression. All were assessed with a cognitive and functional capacity assessment. Data for genome wide association studies were collected. Controls came from the VA Million Veteran Program. RESULTS: Suicidal ideation or behavior was present in 66%. Cognitive and functional deficits were consistent with previous studies. 40% of the veterans with schizophrenia had a lifetime major depressive episode and PTSD was present in over 30%. Polygenic risk score (PRS) analyses indicated that cognitive and functional deficits overlapped with PRS for cognition, education, and intelligence in the general population and PRS for suicidal ideation and behavior correlated with previous PRS for depression and suicidal ideation and behavior, as did the PRS for PTSD. DISCUSSION: Results to date provide directions for personalization of treatment in SMI, veterans with SMI, and veterans in general. The results of the genomic analyses suggest that cognitive deficits in SMI may be associated with general population features. Upcoming genomic analyses will reexamine the issues above, as well as genomic factors associated with smoking, substance abuse, negative symptoms, and treatment response.
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Authors: Csaba P Kovesdy; Keith C Norris; L Ebony Boulware; Jun L Lu; Jennie Z Ma; Elani Streja; Miklos Z Molnar; Kamyar Kalantar-Zadeh Journal: Circulation Date: 2015-09-18 Impact factor: 29.690
Authors: Max Lam; W David Hill; Joey W Trampush; Jin Yu; Emma Knowles; Gail Davies; Eli Stahl; Laura Huckins; David C Liewald; Srdjan Djurovic; Ingrid Melle; Kjetil Sundet; Andrea Christoforou; Ivar Reinvang; Pamela DeRosse; Astri J Lundervold; Vidar M Steen; Thomas Espeseth; Katri Räikkönen; Elisabeth Widen; Aarno Palotie; Johan G Eriksson; Ina Giegling; Bettina Konte; Annette M Hartmann; Panos Roussos; Stella Giakoumaki; Katherine E Burdick; Antony Payton; William Ollier; Ornit Chiba-Falek; Deborah K Attix; Anna C Need; Elizabeth T Cirulli; Aristotle N Voineskos; Nikos C Stefanis; Dimitrios Avramopoulos; Alex Hatzimanolis; Dan E Arking; Nikolaos Smyrnis; Robert M Bilder; Nelson A Freimer; Tyrone D Cannon; Edythe London; Russell A Poldrack; Fred W Sabb; Eliza Congdon; Emily Drabant Conley; Matthew A Scult; Dwight Dickinson; Richard E Straub; Gary Donohoe; Derek Morris; Aiden Corvin; Michael Gill; Ahmad R Hariri; Daniel R Weinberger; Neil Pendleton; Panos Bitsios; Dan Rujescu; Jari Lahti; Stephanie Le Hellard; Matthew C Keller; Ole A Andreassen; Ian J Deary; David C Glahn; Anil K Malhotra; Todd Lencz Journal: Am J Hum Genet Date: 2019-08-01 Impact factor: 11.025
Authors: Kenneth R Conner; Robert M Bossarte; Hua He; Jyoti Arora; Naiji Lu; Xin M Tu; Ira R Katz Journal: J Affect Disord Date: 2014-05-05 Impact factor: 4.839
Authors: Naomi R Wray; Stephan Ripke; Manuel Mattheisen; Maciej Trzaskowski; Enda M Byrne; Abdel Abdellaoui; Mark J Adams; Esben Agerbo; Tracy M Air; Till M F Andlauer; Silviu-Alin Bacanu; Marie Bækvad-Hansen; Aartjan F T Beekman; Tim B Bigdeli; Elisabeth B Binder; Douglas R H Blackwood; Julien Bryois; Henriette N Buttenschøn; Jonas Bybjerg-Grauholm; Na Cai; Enrique Castelao; Jane Hvarregaard Christensen; Toni-Kim Clarke; Jonathan I R Coleman; Lucía Colodro-Conde; Baptiste Couvy-Duchesne; Nick Craddock; Gregory E Crawford; Cheynna A Crowley; Hassan S Dashti; Gail Davies; Ian J Deary; Franziska Degenhardt; Eske M Derks; Nese Direk; Conor V Dolan; Erin C Dunn; Thalia C Eley; Nicholas Eriksson; Valentina Escott-Price; Farnush Hassan Farhadi Kiadeh; Hilary K Finucane; Andreas J Forstner; Josef Frank; Héléna A Gaspar; Michael Gill; Paola Giusti-Rodríguez; Fernando S Goes; Scott D Gordon; Jakob Grove; Lynsey S Hall; Eilis Hannon; Christine Søholm Hansen; Thomas F Hansen; Stefan Herms; Ian B Hickie; Per Hoffmann; Georg Homuth; Carsten Horn; Jouke-Jan Hottenga; David M Hougaard; Ming Hu; Craig L Hyde; Marcus Ising; Rick Jansen; Fulai Jin; Eric Jorgenson; James A Knowles; Isaac S Kohane; Julia Kraft; Warren W Kretzschmar; Jesper Krogh; Zoltán Kutalik; Jacqueline M Lane; Yihan Li; Yun Li; Penelope A Lind; Xiaoxiao Liu; Leina Lu; Donald J MacIntyre; Dean F MacKinnon; Robert M Maier; Wolfgang Maier; Jonathan Marchini; Hamdi Mbarek; Patrick McGrath; Peter McGuffin; Sarah E Medland; Divya Mehta; Christel M Middeldorp; Evelin Mihailov; Yuri Milaneschi; Lili Milani; Jonathan Mill; Francis M Mondimore; Grant W Montgomery; Sara Mostafavi; Niamh Mullins; Matthias Nauck; Bernard Ng; Michel G Nivard; Dale R Nyholt; Paul F O'Reilly; Hogni Oskarsson; Michael J Owen; Jodie N Painter; Carsten Bøcker Pedersen; Marianne Giørtz Pedersen; Roseann E Peterson; Erik Pettersson; Wouter J Peyrot; Giorgio Pistis; Danielle Posthuma; Shaun M Purcell; Jorge A Quiroz; Per Qvist; John P Rice; Brien P Riley; Margarita Rivera; Saira Saeed Mirza; Richa Saxena; Robert Schoevers; Eva C Schulte; Ling Shen; Jianxin Shi; Stanley I Shyn; Engilbert Sigurdsson; Grant B C Sinnamon; Johannes H Smit; Daniel J Smith; Hreinn Stefansson; Stacy Steinberg; Craig A Stockmeier; Fabian Streit; Jana Strohmaier; Katherine E Tansey; Henning Teismann; Alexander Teumer; Wesley Thompson; Pippa A Thomson; Thorgeir E Thorgeirsson; Chao Tian; Matthew Traylor; Jens Treutlein; Vassily Trubetskoy; André G Uitterlinden; Daniel Umbricht; Sandra Van der Auwera; Albert M van Hemert; Alexander Viktorin; Peter M Visscher; Yunpeng Wang; Bradley T Webb; Shantel Marie Weinsheimer; Jürgen Wellmann; Gonneke Willemsen; Stephanie H Witt; Yang Wu; Hualin S Xi; Jian Yang; Futao Zhang; Volker Arolt; Bernhard T Baune; Klaus Berger; Dorret I Boomsma; Sven Cichon; Udo Dannlowski; E C J de Geus; J Raymond DePaulo; Enrico Domenici; Katharina Domschke; Tõnu Esko; Hans J Grabe; Steven P Hamilton; Caroline Hayward; Andrew C Heath; David A Hinds; Kenneth S Kendler; Stefan Kloiber; Glyn Lewis; Qingqin S Li; Susanne Lucae; Pamela F A Madden; Patrik K Magnusson; Nicholas G Martin; Andrew M McIntosh; Andres Metspalu; Ole Mors; Preben Bo Mortensen; Bertram Müller-Myhsok; Merete Nordentoft; Markus M Nöthen; Michael C O'Donovan; Sara A Paciga; Nancy L Pedersen; Brenda W J H Penninx; Roy H Perlis; David J Porteous; James B Potash; Martin Preisig; Marcella Rietschel; Catherine Schaefer; Thomas G Schulze; Jordan W Smoller; Kari Stefansson; Henning Tiemeier; Rudolf Uher; Henry Völzke; Myrna M Weissman; Thomas Werge; Ashley R Winslow; Cathryn M Lewis; Douglas F Levinson; Gerome Breen; Anders D Børglum; Patrick F Sullivan Journal: Nat Genet Date: 2018-04-26 Impact factor: 38.330
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