Trauma and posttraumatic stress disorder modulate polygenic predictors of hippocampal and amygdala volume

Abstract

The volume of subcortical structures represents a reliable, quantitative, and objective phenotype that captures genetic effects, environmental effects such as trauma, and disease effects such as posttraumatic stress disorder (PTSD). Trauma and PTSD represent potent exposures that may interact with genetic markers to influence brain structure and function. Genetic variants, associated with subcortical volumes in two large normative discovery samples, were used to compute polygenic scores (PGS) for the volume of seven subcortical structures. These were applied to a target sample enriched for childhood trauma and PTSD. Subcortical volume PGS from the discovery sample were strongly associated in our trauma/PTSD enriched sample (n = 7580) with respective subcortical volumes of the hippocampus (p = 1.10 × 10−20), thalamus (p = 7.46 × 10−10), caudate (p = 1.97 × 10−18), putamen (p = 1.7 × 10−12), and nucleus accumbens (p = 1.99 × 10−7). We found a significant association between the hippocampal volume PGS and hippocampal volume in control subjects from our sample, but was absent in individuals with PTSD (GxE; (beta = −0.10, p = 0.027)). This significant GxE (PGS × PTSD) relationship persisted (p < 1 × 10−19) in four out of five threshold peaks (0.024, 0.133, 0.487, 0.730, and 0.889) used to calculate hippocampal volume PGSs. We detected similar GxE (G × ChildTrauma) relationships in the amygdala for exposure to childhood trauma (rs4702973; p = 2.16 × 10−7) or PTSD (rs10861272; p = 1.78 × 10−6) in the CHST11 gene. The hippocampus and amygdala are pivotal brain structures in mediating PTSD symptomatology. Trauma exposure and PTSD modulate the effect of polygenic markers on hippocampal volume (GxE) and the amygdala volume PGS is associated with PTSD risk, which supports the role of amygdala volume as a risk factor for PTSD.

Hippocampal Connectivity With the Default Mode Network Is Linked to Hippocampal Volume in the Clinical High Risk for Psychosis Syndrome and Healthy Individuals

“…Indeed, while speculative, it is possible that the associations observed between hippocampal functional connectivity and hippocampal volume in the present study reflect the influence of stress exposure. For example, the robust relations observed between the hippocampus and IPL in this study may be related to the IPL’s sensitivity to adverse environmental influence, similar to the hippocampus (e.g., Davis et al, 2017; Merz et al, 2019; Zheng et al, 2021). Research has found inverse associations between allostatic load (i.e., a quantified index of multiple stress indicators) and IPL thickness in both healthy individuals and those with schizophrenia (Chiappelli et al, 2017).…”

Genome-wide meta-analysis identifies new candidate genes for sickle cell disease nephropathy

“…To determine the maximizing P value threshold from each meta-GWAS, we generated 1001 PRSs in OMG-SCD and Walk-PHaSST with thresholds ranging from P = .0001 to P = 1, in increments of .001, as described previously. 44 Each PRS was then tested for association with proteinuria and eGFR using logistic and linear regression, respectively, in each cohort (R glm ), followed by a fixed-effects meta-analysis in R metafor . 45 A Bonferroni correction was applied to account for the 1001 thresholds examined ( P = 5 × 10 –5 ).…”

Post-Traumatic Stress Disorder (PTSD) in San Forager Theories of Disease, and Its Implications for Understanding Images of Conflict in Southern African Rock Art

“…In either event, there is an inverse relationship between subregion volumes and PTSD severity (Ben-Zion et al 2022: 666–7; cf. Zheng et al 2021, 7–8). Smaller volumes correspond with more severe progressions, suggesting that disruption or reduction in the functions of these areas underwrites PTSD symptoms (Woon & Hedges 2009; Yehuda 2002, 110).…”

“…Measurable changes in the brain ‘signify an indelible sensory imprint of a maladaptively processed experience’ which impairs cognitive and emotional capacities (Sherin & Nemeroff 2011, 274). Thereafter, symptoms reflect the roles of affected neurological substrates—there are causal relationships between the architecture of these brain areas and PTSD symptomatology (Zheng et al 2021, 7).…”