GABRA6 gene polymorphism and an attenuated stress response

Research output: Contribution to journalArticle

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 GABA Aα6 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.

Original languageEnglish (US)
Pages (from-to)998-1006
Number of pages9
JournalMolecular Psychiatry
Volume9
Issue number11
DOIs
StatePublished - Nov 2004

Fingerprint

Alleles
Blood Pressure
Exercise Test
Psychological Stress
Adrenocorticotropic Hormone
Glucocorticoids
Genes
Aminobutyrates
Personality Inventory
GABA Receptors
Anxiety Disorders
Mood Disorders
Individuality
Single Nucleotide Polymorphism
Personality
Hydrocortisone
Healthy Volunteers

Keywords

  • Cortisol
  • GABA (γ-aminobutyric acid)
  • NEO PI-R
  • Polymorphism
  • Stress

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health

Cite this

GABRA6 gene polymorphism and an attenuated stress response. / Uhart, M.; McCaul, Mary Elizabeth; Oswald, Lynn Marie; Choi, L.; Wand, Gary S.

In: Molecular Psychiatry, Vol. 9, No. 11, 11.2004, p. 998-1006.

Research output: Contribution to journalArticle

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