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Convergent genetic modulation of the endocrine stress response involves polymorphic variations of 5-HTT, COMT and MAOA

Molecular Psychiatry volume 12, pages 483–490 (2007)Cite this article

Abstract

Highly prevalent stress-related disorders such as major depression (MD) are characterised by a dysregulation of the neuroendocrine system. Although heritability for these disorders is high, the role of genes in the underlying pathophysiology is poorly understood. Here, we show that polymorphic variations in genes coding for serotonin transporter (5-HTT), catechol-O-methyl transferase (COMT) and monoamine oxidase A (MAOA) as well as sex differences influence the regulation of hypothalamic–pituitary–adrenal (HPA)-axis response to acute psychological and endocrine challenges. In our sample, the effects of COMT on the release of adrenocorticotrophin hormone (ACTH) depend on the presence of the low-expression MAOA variant in the same individual. By including individuals varying in their degree of susceptibility to MD, we showed evidence of interactions between 5-HTT and MD susceptibility in baseline cortisol, and between MAOA and MD susceptibility in baseline ACTH measures, indicating a role for these genotypes in stable-state endocrine regulation. Collectively, these results indicate that the simultaneous investigation of multiple monoaminergic genes in interaction with gender have to be measured to understand the endocrine regulation of stress. These findings point towards a genetic susceptibility to stress-related disorders.

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Acknowledgements

This work is funded by an NWO grant number 904-53-092. We especially thank Christian Keysers for valuable comments on earlier versions of the manuscript. We thank Iteke te Riet, Ruud Delissen and Roelie Nijzing for professional assistance, Magdalena Hubert, Astrid Brugman, Erik Nijboer, Janneke (DAJ) Dijck Brouwer, Henk Breukelman, Jan Koerts and colleagues for genotyping and endocrine analysis, our Ariadne colleagues for the HRP group selection, and Harm Jan Pot, Enno Hebekotte and Ernst Horwitz of the psychiatry department and our colleagues from GGZ Zuid and GGZ Stadskanaal for patient information. We acknowledge the individual participants and their families. We acknowledge Joop Clots, Ben Mulder and colleagues of the social sciences faculty for technical assistance.

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Authors and Affiliations

  1. Department of Psychiatry, University Medical Centre Groningen (UMCG), Groningen, The Netherlands

    M Jabbi, J Korf, C Hartman, G van der Pompe, J Ormel & J A den Boer

  2. UMCG Groningen, BCN NeuroImaging Centre, Antonius Deusinglaan 2, Groningen, The Netherlands

    M Jabbi

  3. Department of Pathology and Laboratory Medicine, University Medical Centre Groningen (UMCG), Groningen, The Netherlands

    I P Kema

  4. Department of Adolescent and Child psychiatry, University Medical Centre Groningen (UMCG), Groningen, The Netherlands

    C Hartman & R B Minderaa

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  1. M Jabbi
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Correspondence to M Jabbi.

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Author contributions

MJ, GvdP and IPK designed research. MJ performed research. IPK contributed reagents and performed genotyping. MJ and JK analysed the data. MJ wrote the paper with contributions of JK, IPK, CH, RBM, JO and JAdB.

Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)

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Jabbi, M., Korf, J., Kema, I. et al. Convergent genetic modulation of the endocrine stress response involves polymorphic variations of 5-HTT, COMT and MAOA. Mol Psychiatry 12, 483–490 (2007). https://doi.org/10.1038/sj.mp.4001975

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