PMID- 28494120 OWN - NLM STAT- MEDLINE DCOM- 20180313 LR - 20181202 IS - 1520-6394 (Electronic) IS - 1091-4269 (Print) IS - 1091-4269 (Linking) VI - 34 IP - 7 DP - 2017 Jul TI - Posttraumatic stress disorder symptom severity is associated with reduced default mode network connectivity in individuals with elevated genetic risk for psychopathology. PG - 632-640 LID - 10.1002/da.22633 [doi] AB - BACKGROUND: Accumulating evidence suggests that posttraumatic stress disorder (PTSD) is associated with disrupted default mode network (DMN) connectivity, but findings across studies have not been uniform. Individual differences in relevant genes may account for some of the reported variability in the relationship between DMN connectivity and PTSD. In this study, we investigated this possibility using genome-wide association study (GWAS) derived polygenic risk scores (PRSs) for relevant psychiatric traits. We hypothesized that the association between PTSD and DMN connectivity would be moderated by genetic risk for one or more psychiatric traits such that individuals with elevated polygenic risk for psychopathology and severe PTSD would exhibit disrupted DMN connectivity. METHODS: Participants were 156 white, non-Hispanic veterans of the wars in Iraq and Afghanistan who were genotyped and underwent resting state functional magnetic resonance imaging and clinical assessment. PRSs for neuroticism, anxiety, major depressive disorder, and cross-disorder risk (based on five psychiatric disorders) were calculated using summary statistics from published large-scale consortia-based GWASs. RESULTS: Cross-disorder polygenic risk influenced the relationship between DMN connectivity and PTSD symptom severity such that individuals at greater genetic risk showed a significant negative association between PTSD symptom severity and connectivity between the posterior cingulate cortex and right middle temporal gyrus. Polygenic risk for neuroticism, anxiety, and major depressive disorder did not influence DMN connectivity directly or through an interaction with PTSD. CONCLUSIONS: Findings illustrate the potential power of genome-wide PRSs to advance understanding of the relationship between PTSD and DMN connectivity, a putative neural endophenotype of the disorder. CI - (c) 2017 Wiley Periodicals, Inc. FAU - Miller, Danielle R AU - Miller DR AUID- ORCID: 0000-0002-0141-5887 AD - National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA. AD - Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA. FAU - Logue, Mark W AU - Logue MW AD - National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA. AD - Biomedical Genetics, Boston University School of Medicine, Boston, MA, USA. AD - Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA. FAU - Wolf, Erika J AU - Wolf EJ AD - National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA. AD - Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA. FAU - Maniates, Hannah AU - Maniates H AD - National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA. FAU - Robinson, Meghan E AU - Robinson ME AD - Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, MA, USA. AD - Department of Neurology, Boston University School of Medicine, Boston, MA, USA. AD - Translational Research Center for TBI and Stress Disorders, VA Boston Healthcare System, Boston, MA, USA, USA. FAU - Hayes, Jasmeet P AU - Hayes JP AD - National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA. AD - Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA. AD - Neuroimaging Research for Veterans Center, VA Boston Healthcare System, Boston, MA, USA. FAU - Stone, Annjanette AU - Stone A AD - Pharmacogenomics Analysis Laboratory, Research Service, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA. FAU - Schichman, Steven AU - Schichman S AD - Pharmacogenomics Analysis Laboratory, Research Service, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA. FAU - McGlinchey, Regina E AU - McGlinchey RE AD - Geriatric Research, Educational, and Clinical Center, VA Boston Healthcare System, Boston, MA, USA, USA. AD - Translational Research Center for TBI and Stress Disorders, VA Boston Healthcare System, Boston, MA, USA, USA. AD - Department of Psychiatry, Harvard Medical School, Boston, MA, USA. FAU - Milberg, William P AU - Milberg WP AD - Geriatric Research, Educational, and Clinical Center, VA Boston Healthcare System, Boston, MA, USA, USA. AD - Translational Research Center for TBI and Stress Disorders, VA Boston Healthcare System, Boston, MA, USA, USA. AD - Department of Psychiatry, Harvard Medical School, Boston, MA, USA. FAU - Miller, Mark W AU - Miller MW AD - National Center for PTSD, VA Boston Healthcare System, Boston, MA, USA. AD - Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA. LA - eng GR - R03 AG051877/AG/NIA NIH HHS/United States GR - R21 MH102834/MH/NIMH NIH HHS/United States GR - T32 MH019836/MH/NIMH NIH HHS/United States PT - Journal Article DEP - 20170511 PL - United States TA - Depress Anxiety JT - Depression and anxiety JID - 9708816 SB - IM MH - Adult MH - Cerebral Cortex/diagnostic imaging/*physiopathology MH - Connectome/*methods MH - Female MH - *Genome-Wide Association Study MH - Humans MH - Magnetic Resonance Imaging/methods MH - Male MH - Mental Disorders/*genetics MH - Middle Aged MH - Multifactorial Inheritance MH - Risk Assessment MH - *Severity of Illness Index MH - Stress Disorders, Post-Traumatic/diagnostic imaging/*physiopathology MH - *Veterans MH - Young Adult PMC - PMC5523965 MID - NIHMS869692 OTO - NOTNLM OT - PTSD OT - fMRI OT - genetics OT - major depressive disorder OT - psychopathology COIS- The authors declare that they have no conflicts of interest or financial disclosures. EDAT- 2017/05/12 06:00 MHDA- 2018/03/14 06:00 PMCR- 2018/07/01 CRDT- 2017/05/12 06:00 PHST- 2017/02/15 00:00 [received] PHST- 2017/03/28 00:00 [revised] PHST- 2017/03/31 00:00 [accepted] PHST- 2017/05/12 06:00 [pubmed] PHST- 2018/03/14 06:00 [medline] PHST- 2017/05/12 06:00 [entrez] PHST- 2018/07/01 00:00 [pmc-release] AID - 10.1002/da.22633 [doi] PST - ppublish SO - Depress Anxiety. 2017 Jul;34(7):632-640. doi: 10.1002/da.22633. Epub 2017 May 11.