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01-04-2018 | Original Article

Hypothalamic-pituitary-adrenal axis variants and childhood trauma influence anxiety sensitivity in South African adolescents

Authors: Jacqueline S. Womersley, Lindi I. Martin, Lize van der Merwe, Soraya Seedat, Sian M. J. Hemmings

Published in: Metabolic Brain Disease | Issue 2/2018

Abstract

Anxiety sensitivity (AS) is characterised by the fear of anxiety-related symptoms and is a risk factor for the development of anxiety-related disorders. We examined whether genetic variation in three stress response genes, CRHR1, NR3C1, and FKBP5, interact with childhood trauma (CT) to predict AS in South African adolescents. Xhosa (n = 634) and Coloured (n = 317) students completed self-report measures of AS and CT, and a total of eighteen polymorphisms within CRHR1, NR3C1, and FKBP5 were genotyped. Differences in AS based on genetic variation and CT were analysed within population and gender groups using multiple linear regression. Associations were found between AS and FKBP5 rs9296158 (p = 0.025) and rs737054 (p = 0.045) in Coloured males. Analysis of gene x CT interactions indicated that NR3C1 rs190488 CC-genotype, NR3C1 rs10482605 G-allele addition, and FKBP5 rs3800373 C-allele addition protect against AS with increasing CT in Xhosa females (p = 0.009), Xhosa males (p = 0.036) and Coloured males (p = 0.049), respectively. We identified two different protective single nucleotide polymorphism (SNP) combinations in a four-SNP CRHR1 haplotype in Coloured males. An analysis of the interaction between CT and a six-SNP FKBP5 haplotype in Coloured males revealed both protective and risk allelic combinations. Our results provide evidence for the influence of both genetic variation in CRHR1, NR3C1 and FKBP5, as well as CT x SNP interactions, on AS in South African adolescents. This study reinforces the importance of examining the influence of gene-environment (G X E) interactions within gender and population groups.

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Title: Hypothalamic-pituitary-adrenal axis variants and childhood trauma influence anxiety sensitivity in South African adolescents
Authors: Jacqueline S. Womersley
Lindi I. Martin
Lize van der Merwe
Soraya Seedat
Sian M. J. Hemmings
Publication date: 01-04-2018
Publisher: Springer US
Published in: Metabolic Brain Disease / Issue 2/2018
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-017-0138-6

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Hypothalamic-pituitary-adrenal axis variants and childhood trauma influence anxiety sensitivity in South African adolescents

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