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Association of childhood trauma exposure and GABRA2 polymorphisms with risk of posttraumatic stress disorder in adults

Molecular Psychiatry volume 14, pages 234–235 (2009)Cite this article

Individuals who experience child abuse are at increased risk for developing posttraumatic stress disorder (PTSD) as a direct result of the abuse and upon exposure to subsequent trauma.1 A recent examination1 of PTSD symptoms in adults found evidence for a significant G × E interaction involving a quantitative measure of child abuse exposure and four single-nucleotide polymorphisms (SNPs) of FKBP5 including two SNPs for which an association of the same alleles with peritraumatic dissociative symptoms in medically ill children had been reported.2 A study3 of gene expression in the peripheral blood of trauma-exposed individuals found that FKBP5 is one of many genes whose upregulation immediately posttrauma is associated with risk for emergent PTSD at 4 months. Investigations4, 5, 6 using maternal care and separation in rodent models of child abuse have observed altered expression of genes encoding proteins involved in the stress response and, in work6 focusing on the glucocorticoid receptor (GR), have elegantly demonstrated that epigenetic mechanisms underlie these changes. Given FKBP5's role in the regulation of GR sensitivity, the G × E interaction associated with PTSD risk is likely a consequence of differential response to posttrauma alterations in gene expression resulting from one or more polymorphisms. Because animal4, 5, 7 and human3 studies have also found posttrauma changes in the expression of genes encoding GABAA (γ-aminobutyric acid) receptor subunits that affect ligand affinity at the benzodiazepine binding site, we examined whether risk for PTSD is associated with similar G × E interactions involving GABRA2 polymorphisms and childhood trauma exposure.

Interview data from twin and sibling participants (N=2594) in a recently completed family study of adult twins (only one twin from any monozygotic pair was included) with or without a history of childhood trauma were analyzed. These individuals completed a semistructured diagnostic telephone interview modified from the SSAGA-II8 that assessed Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) PTSD and which included a separate detailed assessment of child abuse modified from the Christchurch Trauma Inventory.9 MPlus10 was used to create five first-order factors for which factor loadings were allowed to vary by gender, each representing a severe childhood stressor assessed in detail (that is, sexual abuse; physical abuse by mother, by father or by other adult household member; emotional and physical partner maltreatment by a parent) from which a single second-order childhood trauma factor was created. The prevalence of PTSD in the sample was 11.5%. In logistic regression analyses that corrected for the inclusion of multiple individuals from families, significant PTSD risk was found to be associated with childhood trauma factor score (CTFS): odds ratio 8.76 (95% confidence interval 6.53–11.75).

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Authors and Affiliations

  1. Department of Psychiatry, Missouri Alcoholism Research Center, Washington University School of Medicine, St Louis, MO, USA

    E C Nelson, A Agrawal, M L Pergadia, M T Lynskey, A A Todorov, J C Wang, R D Todd, A C Heath, A M Goate & P A F Madden

  2. Queensland Institute of Medical Research, Brisbane, QLD, Australia

    N G Martin & G W Montgomery

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  1. E C Nelson
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  2. A Agrawal
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Correspondence to E C Nelson.

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

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Nelson, E., Agrawal, A., Pergadia, M. et al. Association of childhood trauma exposure and GABRA2 polymorphisms with risk of posttraumatic stress disorder in adults. Mol Psychiatry 14, 234–235 (2009). https://doi.org/10.1038/mp.2008.81

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