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Posttraumatic stress disorder symptom severity is associated with reduced default mode network connectivity in individuals with elevated genetic risk for psychopathology

Citation:

Miller, D. R., Logue, M. W., Wolf, E. J., Maniates, H., Robinson, M. E., Hayes, J. P., Stone, A., et al. (2017). Posttraumatic stress disorder symptom severity is associated with reduced default mode network connectivity in individuals with elevated genetic risk for psychopathology. Depress Anxiety , 34, 632-640.

Date Published:

Jul

Abstract:

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.

Notes:

1520-6394Miller, Danielle ROrcid: 0000-0002-0141-5887Logue, Mark WWolf, Erika JManiates, HannahRobinson, Meghan EHayes, Jasmeet PStone, AnnjanetteSchichman, StevenMcGlinchey, Regina EMilberg, William PMiller, Mark WR03 AG051877/AG/NIA NIH HHS/United StatesR21 MH102834/MH/NIMH NIH HHS/United StatesT32 MH019836/MH/NIMH NIH HHS/United StatesJournal ArticleDepress Anxiety. 2017 Jul;34(7):632-640. doi: 10.1002/da.22633. Epub 2017 May 11.