title: Cross-cultural gene- environment interactions in depression, post-traumatic stress disorder, and the cortisol awakening response: FKBP5 polymorphisms and childhood trauma in South Asia.
abstract: 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.
authors.affiliation: Duke Global Health Institute and Department of Psychiatry and Behavioral Sciences, Duke University , Durham, North Carolina , USA.
authors.forename: Brandon A
authors.initials: BA
authors.lastname: Kohrt
authors.forename: Carol M
authors.initials: CM
authors.lastname: Worthman
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Ressler
authors.forename: Kristina B
authors.initials: KB
authors.lastname: Mercer
authors.forename: Nawaraj
authors.initials: N
authors.lastname: Upadhaya
authors.forename: Suraj
authors.initials: S
authors.lastname: Koirala
authors.forename: Mahendra K
authors.initials: MK
authors.lastname: Nepal
authors.forename: Vidya Dev
authors.initials: VD
authors.lastname: Sharma
authors.forename: Elisabeth B
authors.initials: EB
authors.lastname: Binder
mesh_terms: D000328:Adult; D002648:Child; D002649:Child Abuse / Q000208:ethnology / Q000706:statistics & numerical data; D003863:Depression / Q000208:ethnology / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009390:Nepal / Q000208:ethnology; D012923:Social Class; D013313:Stress Disorders, Post-Traumatic / Q000208:ethnology / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000235:genetics*; D000099159:Tacrolimus Binding Protein 5
chemical_list: D006854:Hydrocortisone; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5