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

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

doi:10.3389/fpsyt.2024.1257911

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

Front Psychiatry. 2024 Feb 29:15:1257911. doi: 10.3389/fpsyt.2024.1257911. eCollection 2024.

Authors

Ling Xu^{1

2}, Jingyi Zhang^{1

2}, Haibo Yang³, Chengqi Cao^{1

2}, Ruojiao Fang^{1

2}, Ping Liu⁴, Shu Luo⁴, Binbin Wang^{1

2}, Kunlin Zhang^{1

2}, Li Wang^{1

2}

Affiliations

¹ Laboratory for Traumatic Stress Studies and Center for Genetics and BioMedical Informatics Research, CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
² Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.
³ Academy of Psychology and Behavior, Tianjin Normal University, Tianjin, China.
⁴ People's Hospital of Deyang City, Deyang, Sichuan, China.

Abstract

Background: 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.

Methods: 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. 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.

Results: The 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, p_perm = 0.008) and predominantly PTSD (β = -0.56, OR = 0.57 [95% CI: 0.34-0.97], p = 0.037, p_perm = 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, p_perm = 0.005) and predominantly depression (β = 1.08, R = 2.95 [95% CI: 1.55-5.62], p = 0.001, p_perm = 0.001). The two G × G effects are independent.

Conclusion: NPY and dopamine receptor genes are related to the genetic etiology of PTSD-MDD comorbidity, whose specific mechanisms can be studied at multiple levels.

Keywords: PTSD-MDD comorbidity; dopamine; gene × gene interaction; neuropeptide Y; single nucleotide polymorphism.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (No. U21A20364, No. 31971020 and No. 82174237), the Key Project of the National Social Science Foundation of China (No. 20ZDA079), the Key Project of Research Base of Humanities and Social Sciences of Ministry of Education (No.16JJD190006), and the Scientific Foundation of Institute of Psychology, Chinese Academy of Sciences (No. E2CX4115CX).