Epistasis in neurotransmitter receptors linked to posttraumatic stress disorder and major depressive disorder comorbidity in traumatized Chinese

Abstract

BackgroundPosttraumatic stress disorder (PTSD) and major depressive disorder (MDD) comorbidity occurs through exposure to trauma with genetic susceptibility. Neuropeptide-Y (NPY) and dopamine are neurotransmitters associated with anxiety and stress-related psychiatry through receptors. We attempted to explore the genetic association between two neurotransmitter receptor systems and the PTSD–MDD comorbidity.MethodsFour groups were identified using latent profile analysis (LPA) to examine the patterns of PTSD and MDD comorbidity among survivors exposed to earthquake-related trauma: low symptoms, predominantly depression, predominantly PTSD, and PTSD–MDD comorbidity. NPY2R (rs4425326), NPY5R (rs11724320), DRD2 (rs1079597), and DRD3 (rs6280) were genotyped from 1,140 Chinese participants exposed to earthquake-related trauma. Main, gene–environment interaction (G × E), and gene–gene interaction (G × G) effects for low symptoms, predominantly depression, and predominantly PTSD were tested using a multinomial logistic model with PTSD–MDD comorbidity as a reference.ResultsThe results demonstrated that compared to PTSD–MDD comorbidity, epistasis (G × G) NPY2R-DRD2 (rs4425326 × rs1079597) affects low symptoms (β = −0.66, OR = 0.52 [95% CI: 0.32–0.84], p = 0.008, pperm = 0.008) and predominantly PTSD (β = −0.56, OR = 0.57 [95% CI: 0.34–0.97], p = 0.037, pperm = 0.039), while NPY2R-DRD3 (rs4425326 × rs6280) impacts low symptoms (β = 0.82, OR = 2.27 [95% CI: 1.26–4.10], p = 0.006, pperm = 0.005) and predominantly depression (β = 1.08, R = 2.95 [95% CI: 1.55–5.62], p = 0.001, pperm = 0.001). The two G × G effects are independent.ConclusionNPY and dopamine receptor genes are related to the genetic etiology of PTSD–MDD comorbidity, whose specific mechanisms can be studied at multiple levels.