Abstract
Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are commonly reported co-occurring mental health consequences of psychological trauma exposure. The disorders have high genetic overlap. Trauma is a complex phenotype but research suggests that trauma sensitivity has a heritable basis. We investigated whether sensitivity to trauma in those with MDD reflects a similar genetic component in those with PTSD. Genetic correlations between PTSD and MDD in individuals reporting trauma and MDD in individuals not reporting trauma were estimated, as well as with recurrent MDD and single-episode MDD, using genome-wide association study (GWAS) summary statistics. Genetic correlations were replicated using PTSD data from the Psychiatric Genomics Consortium and the Million Veteran Program. Polygenic risk scores were generated in UK Biobank participants who met the criteria for lifetime MDD (N = 29 471). We investigated whether genetic loading for PTSD was associated with reporting trauma in these individuals. Genetic loading for PTSD was significantly associated with reporting trauma in individuals with MDD [OR 1.04 (95% CI 1.01-1.07), Empirical-p = 0.02]. PTSD was significantly more genetically correlated with recurrent MDD than with MDD in individuals not reporting trauma (rg differences = ~0.2, p < 0.008). Participants who had experienced recurrent MDD reported significantly higher rates of trauma than participants who had experienced single-episode MDD (χ2 > 166, p < 0.001). Our findings point towards the existence of genetic variants associated with trauma sensitivity that might be shared between PTSD and MDD, although replication with better powered GWAS is needed. Our findings corroborate previous research highlighting trauma exposure as a key risk factor for recurrent MDD.
Highlights
Symptoms of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are the most commonly described co-occurring problems following exposure to psychological trauma (Ben Barnes, Hayes, Contractor, Nash, & Litz, 2018)
We investigated whether Posttraumatic stress disorder (PTSD) and MDD share a genetic component related to being exposed to traumatic events and experiencing internalising symptomatology
We addressed this by measuring the genetic overlap between PTSD and MDD with reported trauma and compared this to the genetic overlap between PTSD and MDD without reported trauma
Summary
Symptoms of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are the most commonly described co-occurring problems following exposure to psychological trauma (Ben Barnes, Hayes, Contractor, Nash, & Litz, 2018). Genetic correlations between PTSD and MDD in individuals reporting trauma and MDD in individuals not reporting trauma were estimated, as well as with recurrent MDD and single-episode MDD, using genome-wide association study (GWAS) summary statistics. We investigated whether genetic loading for PTSD was associated with reporting trauma in these individuals. Genetic loading for PTSD was significantly associated with reporting trauma in individuals with MDD [OR 1.04 (95% CI 1.01–1.07), Empirical-p = 0.02]. PTSD was significantly more genetically correlated with recurrent MDD than with MDD in individuals not reporting trauma (rg differences = ∼0.2, p < 0.008). Our findings point towards the existence of genetic variants associated with trauma sensitivity that might be shared between PTSD and MDD, replication with better powered GWAS is needed. Our findings corroborate previous research highlighting trauma exposure as a key risk factor for recurrent MDD
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