Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder

Abstract

Background: Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are commonly reported co-occurring mental health consequences following psychological trauma exposure. The disorders have high genetic overlap. We investigated whether the genetics of PTSD were associated with reported trauma in individuals with MDD. Since trauma is associated with recurrent MDD, we also investigated whether the genetics of PTSD are associated with episode recurrence. Methods: Genetic correlations were estimated between PTSD and MDD in the presence and MDD in the absence of reported exposure to psychological trauma, and recurrent and single-episode MDD, based on genetic data from UK Biobank Mental Health Questionnaire respondents (N=157,358). Genetic correlations were replicated using PTSD data from the Psychiatric Genomics Consortium and Million Veteran Program. Polygenic risk scores were generated to investigate whether individuals with MDD who have higher genetic risk for PTSD were more likely to report psychological trauma than those with lower genetic risk. Results: Individuals with MDD with a higher genetic risk for PTSD were significantly more likely to report exposure to psychological trauma than those with lower risk [OR=1.06 (1.03-1.09) Empricial p<0.001]. PTSD was significantly more genetically correlated with recurrent MDD than with MDD in the absence of reported psychological trauma [rg differences = ~0.2, p<0.008]. Participants who had experienced recurrent depressive episodes reported significantly higher trauma rates than participants who had experienced a single episode [chisquare>167, p<0.001]. Conclusions: Genetic risk for PTSD in individuals with MDD may influence the way in which traumatic life events are perceived, responded to and reported.

The Validity of Brief Phenotyping in Population Biobanks for Psychiatric Genome-Wide Association Studies on the Biobank Scale

“…In further research, Complex Psychiatry 2021;7:11-15 DOI: 10.1159/000516837 we have recently explored how the genetics of MDD in the presence of trauma exposure compares to the genetics of PTSD, using PTSD data both from population biobanks (UK Biobank) and from clinically ascertained samples (PGC and the Million Veteran Program). We found tentative evidence that PTSD and MDD with trauma exposure are genetically similar, but separable [27]. However, our results were similar when comparing PTSD diagnoses from population biobanks and from clinically ascertained samples.…”