AUTHOR=Xu Ling , Zhang Jingyi , Yang Haibo , Cao Chengqi , Fang Ruojiao , Liu Ping , Luo Shu , Wang Binbin , Zhang Kunlin , Wang Li 

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

JOURNAL=Frontiers in Psychiatry

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1257911

DOI=10.3389/fpsyt.2024.1257911

ISSN=1664-0640

ABSTRACT=<sec><title>Background</title><p>Posttraumatic 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.</p></sec><sec><title>Methods</title><p>Four 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. <italic>NPY2R</italic> (rs4425326), <italic>NPY5R</italic> (rs11724320), <italic>DRD2</italic> (rs1079597), and <italic>DRD3</italic> (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.</p></sec><sec><title>Results</title><p>The results demonstrated that compared to PTSD–MDD comorbidity, epistasis (G × G) <italic>NPY2R</italic>-<italic>DRD2</italic> (rs4425326 × rs1079597) affects low symptoms (<italic>β</italic> = −0.66, <italic>OR</italic> = 0.52 [95% CI: 0.32–0.84], <italic>p</italic> = 0.008, <italic>p<sub>perm</sub></italic> = 0.008) and predominantly PTSD (<italic>β</italic> = −0.56, <italic>OR</italic> = 0.57 [95% CI: 0.34–0.97], <italic>p</italic> = 0.037, <italic>p<sub>perm</sub></italic> = 0.039), while <italic>NPY2R</italic>-<italic>DRD3</italic> (rs4425326 × rs6280) impacts low symptoms (<italic>β</italic> = 0.82, <italic>OR</italic> = 2.27 [95% CI: 1.26–4.10], <italic>p</italic> = 0.006, <italic>p<sub>perm</sub></italic> = 0.005) and predominantly depression (<italic>β</italic> = 1.08, <italic>R</italic> = 2.95 [95% CI: 1.55–5.62], <italic>p</italic> = 0.001, <italic>p<sub>perm</sub></italic> = 0.001). The two G × G effects are independent.</p></sec><sec><title>Conclusion</title><p>NPY and dopamine receptor genes are related to the genetic etiology of PTSD–MDD comorbidity, whose specific mechanisms can be studied at multiple levels.</p></sec>