Financial strain and stressful social environment drive depressive symptoms, while FKBP5 variant intensifies the effect, in African Americans living in Tallahassee

Abstract

The World Health Organization estimates that almost 300 million people suffer from depression worldwide. Depression is the most common mental health disorder and shows racial disparities in disease prevalence, age of onset, severity of symptoms, frequency of diagnosis, and treatment utilization across the United States. Since depression has both social and genetic risk factors, we propose a conceptual model wherein social stressors are primary risk factors for depression, but genetic variants increase or decrease individual susceptibility to the effects of the social stressors. Our research strategy incorporates both social and genetic data to investigate variation in symptoms of depression (CES-D scores). We collected data on financial strain (difficulty paying bills) and personal social networks (a model of an individual’s social environment), and we genotyped genetic variants in five genes involved in stress reactivity ( HTR1a, BDNF, GNB3, SLC6A4, and FKBP5 ) in 135 African Americans residing in Tallahassee, Florida. We found that high financial strain and a high percentage of people in one’s social network who are a source of stress or worry were significantly associated with higher CES-D scores and explained more variation in CES-D scores than did genetic factors. Only one genetic variant (rs1360780 in FKBP5 ) was significantly associated with CES-D scores and only when the social stressors were included in the model. Interestingly, the effect of FKPB5 appeared to be strongest in individuals with high financial strain such that participants with a T allele at rs1360780 in FKBP5 and high financial strain had the highest mean CES-D scores in our study population. These results suggest that material disadvantage and a stressful social environment increases the risk of depression, but that individual-level genetic variation may increase susceptibility to the adverse health consequences of social stressors.