Dissecting the association of C-reactive protein levels with PTSD, traumatic events, and social support

Abstract Inflammatory markers like C-reactive protein (CRP) have been associated with posttraumatic stress disorder (PTSD) and traumatic experience, but the underlying mechanisms are unclear. We investigated the association among CRP, PTSD, and traits related to traumatic events and social support using genome-wide data from the Psychiatric Genomics Consortium (30,000 cases and 170,000 controls), the UK Biobank (UKB; up to 117,900 individuals), and the CHARGE study (Cohorts for Heart and Aging Research in Genomic Epidemiology, 148,164 individual). Linkage disequilibrium score regression, polygenic risk scoring, and two-sample Mendelian randomization analyses were used to investigate genetic overlap and causal relationships. Genetic correlations of CRP were observed with PTSD (rg=0.16, p=0.026) and behavioral and emotional response to trauma, exposure to traumatic events, and the presence of social support (−0.28<rg<0.20; p<0.008). We observed a bidirectional association between CRP and PTSD (CRP→PTSD: β=0.065, p=0.015; PTSD→CRP: β=0.008, p=0.009). CRP also showed a negative association on the “felt loved as a child” trait (UKB, β=-0.017, p=0.008). Due to the known association of socioeconomic status (SES) on PTSD and social support, a multivariable MR was performed to investigate SES as potential mediator. We found that household income (univariate MR: β=-0.22, p=1.57×10 −7 ; multivariate MR: β=-0.17, p=0.005) and deprivation index (univariate MR: β=0.38, p=1.63×10 −9 ; multivariate MR: β=0.27, p=0.016) were driving the causal estimates of “felt loved as a child” and CRP on PTSD. The present findings highlight a bidirectional association between PTSD and CRP levels, also suggesting a potential role of SES in the interplay between childhood support and inflammatory processes with respect to PTSD risk.