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GABRA6 gene polymorphism and an attenuated stress response

Molecular Psychiatry volume 9, pages 998–1006 (2004)Cite this article

Abstract

The glucocorticoid component of the stress response has been the subject of intense scientific scrutiny because of the wide ranging pathological consequences resulting from excess glucocorticoid exposure, including mood and anxiety disorders, and cognitive impairment. Exposure to stress activates the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic adrenomedullary system, which are regulated by neuronal pathways, including the inhibitory GABAergic (γ-aminobutyric acid) system. Approximately 60% of the variance in glucocorticod levels may be attributable to genetic individual differences. In the present study, 56 healthy subjects underwent genotyping to determine the influence of the T1521C single nucleotide polymorphism (SNP) in the GABAAα6 receptor subunit gene (GABRA6) on the hormonal and autonomic responses to psychological stress induced by the Trier Social Stress Test (TSST). Adrenocorticotropin (ACTH), cortisol, diastolic blood pressure, and mean blood pressure responses to the TSST were significantly greater in subjects homozygous for the T allele or heterozygous compared to subjects homozygous for the C allele. Behavioral data was collected employing the Revised NEO Personality Inventory (NEO PI-R); subjects homozygous for the C allele scored significantly lower on the Extraversion factor compared to subjects homozygous for the T allele or heterozygous. These results suggest that the T1521C polymorphism in the GABRA6 gene is associated with specific personality characteristics as well as a marked attenuation in hormonal and blood pressure responses to psychological stress.

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Acknowledgements

This work was supported by NIH Grants AA 10158 (GSW), AA 12303 (GSW), and AA 12837 (MEM), and a gift from the Kenneth A Lattman Foundation (GSW).

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Authors and Affiliations

  1. Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    M Uhart & G S Wand

  2. Department of Psychiatry, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    M E McCaul, L M Oswald & G S Wand

  3. Department of Biostatistics, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD, USA

    L Choi

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  1. M Uhart
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Correspondence to G S Wand.

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Uhart, M., McCaul, M., Oswald, L. et al. GABRA6 gene polymorphism and an attenuated stress response. Mol Psychiatry 9, 998–1006 (2004). https://doi.org/10.1038/sj.mp.4001535

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