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

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.

Political violence and mental health in Nepal: prospective study.

BACKGROUND: Post-conflict mental health studies in low-income countries have lacked pre-conflict data to evaluate changes in psychiatric morbidity resulting from political violence. AIMS: This prospective study compares mental health before and after exposure to direct political violence during the People's War in Nepal. METHOD: An adult cohort completed the Beck Depression Inventory and Beck Anxiety Inventory in 2000 prior to conflict violence in their community and in 2007 after the war. RESULTS: Of the original 316 participants, 298 (94%) participated in the post-conflict assessment. Depression increased from 30.9 to 40.6%. Anxiety increased from 26.2 to 47.7%. Post-conflict post-traumatic stress disorder (PTSD) was 14.1%. Controlling for ageing, the depression increase was not significant. The anxiety increase showed a dose-response association with conflict exposure when controlling for ageing and daily stressors. No demographic group displayed unique vulnerability or resilience to the effects of conflict exposure. CONCLUSIONS: Conflict exposure should be considered in the context of other types of psychiatric risk factors. Conflict exposure predicted increases in anxiety whereas socioeconomic factors and non-conflict stressful life events were the major predictors of depression. Research and interventions in post-conflict settings therefore should consider differential trajectories for depression v. anxiety and the importance of addressing chronic social problems ranging from poverty to gender and ethnic/caste discrimination.

Culture in psychiatric epidemiology: using ethnography and multiple mediator models to assess the relationship of caste with depression and anxiety in Nepal.

BACKGROUND: The causes of ethnic and caste-based disparities in mental health are poorly understood. AIM: The study aimed to identify mediators underlying caste-based disparities in mental health in Nepal. SUBJECTS AND METHODS: A mixed methods ethnographic and epidemiological study of 307 adults (Dalit/Nepali, n=75; high caste Brahman and Chhetri, n=232) was assessed with Nepali versions of Beck Depression (BDI) and Anxiety (BAI) Inventories. RESULTS: One-third (33.7%) of participants were classified as depressed: Dalit/Nepali 50.0%, high caste 28.4%. One quarter (27.7%) of participants were classified as anxious: Dalit/Nepali 50.7%, high caste 20.3%. Ethnographic research identified four potential mediators: Stressful life events, owning few livestock, no household income, and lack of social support. The direct effect of caste was 1.08 (95% CI -1.10-3.27) on depression score and 4.76 (95% CI 2.33-7.19) on anxiety score. All four variables had significant indirect (mediation) effects on anxiety, and all but social support had significant indirect effects on depression. CONCLUSION: Caste-based disparities in mental health in rural Nepal are statistically mediated by poverty, lack of social support, and stressful life events. Interventions should target these areas to alleviate the excess mental health burden born by Dalit/Nepali women and men.

Cross-cultural differences in somatic presentation in patients with generalized anxiety disorder.

Little is known about cultural differences in the expression of distress in anxiety disorders. Previous cross-cultural studies of depression have found a greater somatic focus in Asian populations. We examined anxiety symptoms in patients with generalized anxiety disorder (GAD) in urban mental health settings in Nepal (N = 30) and in the United States (N = 23). Participants completed the Beck Anxiety Inventory (BAI). The overall BAI score and somatic and psychological subscales were compared. While there was no difference in total BAI scores, the Nepali group scored higher on the somatic subscale (i.e. "dizziness" and "indigestion," t[df] = -2.63[50], p < 0.05), while the American group scored higher on the psychological subscale (i.e. "scared" and "nervous," t[df] = 3.27[50], p < 0.01). Nepali patients with GAD had higher levels of somatic symptoms and lower levels of psychological symptoms than American patients with GAD. Possible explanations include differences in cultural traditions of describing distress and the mind-body dichotomy.