Cross-cultural gene− environment interactions in depression, post-traumatic stress disorder, and the cortisol awakening response: FKBP5 polymorphisms and childhood trauma in South Asia: GxE interactions in South Asia

• Published in: International review of psychiatry (Abingdon, England) England), 2015-05, Vol.27 (3), p.180-196
• Main Authors: Kohrt, Brandon A., Worthman, Carol M., Ressler, Kerry J., Mercer, Kristina B., Upadhaya, Nawaraj, Koirala, Suraj, Nepal, Mahendra K., Sharma, Vidya Dev, Binder, Elisabeth B.
• Format: Article
• Language: English
• Subjects: Genotype & phenotype; Mental depression; Mental health; Polymorphism; Post traumatic stress disorder; Psychiatry; Trauma
• ISSN: 0954-0261; 1369-1627
• DOI: 10.3109/09540261.2015.1020052

Despite increased attention to global mental health, psychiatric genetic research has been dominated by studies in high-income countries, especially with populations of European descent. The objective of this study was to assess single nucleotide polymorphisms (SNPs) in the FKBP5 gene in a population living in South Asia. Among adults in Nepal, depression was assessed with the Beck Depression Inventory (BDI), post-traumatic stress disorder (PTSD) with the PTSD Checklist-Civilian Version (PCL-C), and childhood maltreatment with the Childhood Trauma Questionnaire (CTQ). FKBP5 SNPs were genotyped for 682 participants. Cortisol awakening response (CAR) was assessed in a subsample of 118 participants over 3 days. The FKBP5 tag-SNP rs9296158 showed a main effect on depressive symptoms (p = 0.03). Interaction of rs9296158 and childhood maltreatment predicted adult depressive symptoms (p = 0.02) but not PTSD. Childhood maltreatment associated with endocrine response in individuals homozygous for the A allele, demonstrated by a negative CAR and overall hypocortisolaemia in the rs9296158 AA genotype and childhood maltreatment group (p < 0.001). This study replicated findings related to FKBP5 and depression but not PTSD. Gene-environment studies should take differences in prevalence and cultural significance of phenotypes and exposures into account when interpreting cross-cultural findings.