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The association of proopiomelanocortin polymorphisms with the risk of major depressive disorder and the response to antidepressants via interactions with stressful life events

  • Psychiatry and Preclinical Psychiatric Studies - Original Article
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Abstract

Hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis is among the most consistent neuroendocrine abnormalities in major depressive disorder (MDD). The peptide adrenocorticotropin hormone (ACTH) mediates HPA axis function during stress and is encoded by the proopiomelanocortin (POMC) gene polycistronically. After screening 39 POMC polymorphisms, we evaluated the association of polymorphisms with susceptibility to MDD in 145 MDD patients and 193 normal subjects; in patients, we also evaluated the response to treatment with antidepressants. Additionally, we investigated the role of gene–environment interaction between POMC haplotypes and stressful life events (SLE) in the treatment response. Although genotypes and haplotypes were not significantly associated with the risk of MDD, non-remitters were more likely to carry haplotype 1 (ht1) and to have no ht2 than were remitters (corrected P = 0.010–0.035). Although observations were limited in patients without SLE, a significant haplotype–SLE interaction was observed (P = 0.020). Additionally, at 1, 2, and 8 weeks of treatment, the 21-item Hamilton Depression Rating scores of MDD subjects with POMC ht2 were significantly (P = 0.003–0.044) lower than those of patients with ht1 in subjects those did not experience SLE. MDD subjects possessing POMC ht2 achieved remission significantly (P = 0.013; survival analysis) faster than patients with ht1. This study suggests that POMC haplotypes, via an interaction with SLE, are associated with antidepressant treatment outcomes in MDD patients. Regarding SLE, haplotypes of the POMC gene could be useful markers for predicting the response to antidepressant treatment in MDD patients.

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Acknowledgments

This study was supported by a Grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (Grant no. HI12C0003).

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Authors and Affiliations

  1. Department of Medical Bioscience, Graduated School, Soonchunhyang University, Bucheon, 420-767, Republic of Korea

    Hun Soo Chang

  2. Phamacogenetic Research Center for Psychotropic Drugs, Korea University, Seoul, 136-705, Korea

    Eun Soo Won, Byung-Joo Ham, Yong-Gu Kim & Min-Soo Lee

  3. Department of Psychiatry, College of Medicine, Korea University, Seoul, 136-705, Korea

    Eun Soo Won, Byung-Joo Ham, Yong-Gu Kim & Min-Soo Lee

  4. Department of Psychiatry, Anam Hospital, Korea University College of Medicine, Anam-dong, Seongbuk-Gu, Seoul, 136-705, Korea

    Eun Soo Won, Byung-Joo Ham, Yong-Gu Kim & Min-Soo Lee

  5. Department of Psychiatry, College of Medicine, Soonchunhyang University, Cheonan, 330-721, Republic of Korea

    Hwa-Young Lee

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  1. Hun Soo Chang
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Correspondence to Min-Soo Lee.

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H. S. Chang and E. S. Won contributed equally to this work.

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Supplementary material 2 (PPTX 74 kb). Supplementary Figure S1. Kaplan–Meier survival analysis for the association of POMC haplotype 1 and haplotype 2 with the time of achieving remission after antidepressant treatment. P values were obtained using generalized Wilcoxson model

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Chang, H.S., Won, E.S., Lee, HY. et al. The association of proopiomelanocortin polymorphisms with the risk of major depressive disorder and the response to antidepressants via interactions with stressful life events. J Neural Transm 122, 59–68 (2015). https://doi.org/10.1007/s00702-014-1333-9

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  • DOI: https://doi.org/10.1007/s00702-014-1333-9

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