August 24, 2020
2 min read
Researchers have identified several actionable targets for depression prevention, according to results of an exposure-wide and Mendelian randomization study published in American Journal of Psychiatry.
“The literature to date has focused on validating a limited set of hypothesized modifiable factors for prevention of depression, such as physical activity and social support,” Karmel W. Choi, PhD, of the department of psychiatry at Massachusetts General Hospital, and colleagues wrote. “Without broader investigation, additional factors may be overlooked or unknown. Investigating a wide range of factors could help confirm existing relationships and also identify novel potential prevention targets.
“Systematically testing the relationship between many variables and a single outcome for hypothesis-free discovery is now common practice in other fields in the form of genome- or phenome-wide association studies and has led to new insights about underlying associations but has not yet been applied to identifying modifiable factors for prevention of depression,” they added.
Other unmet research needs included a lack of data on the relative influences of numerous modifiable factors among the same population; questions regarding which modifiable factors may help prevent depression among individuals at high risk; and needed insights into the association between modifiable factors and depression for noncausal reasons. In the current study, Choi and colleagues sought to systematically screen and validate numerous potential modifiable factors for depression by analyzing genomic and phenotypic data of more than 100,000 U.K. Biobank participants. They extracted baseline data for 106 factors. Variables included lifestyle (e.g., exercise, sleep, diet, media), social (e.g., support, engagement) and environmental (e.g., pollution, green space). The investigators defined incident depression as minimal baseline depressive symptoms and clinically significant depression at follow-up, and they identified those at risk for incident depression using polygenic risk scores or by reported traumatic life events. Further, in the full sample and among individuals at risk, they identified factors linked to incident depression via an exposure-wide association scan. They validated potentially causal relationships between depression and identified factors using two-sample Mendelian randomization.
Results showed an association between depression and numerous factors in domains related to sleep, media, diet and exercise. The association was also present among individuals who were at risk. However, Mendelian randomization evidence supported only a subset of factors, such as confiding in others (OR = 0.76; 95% CI, 0.67-0.86), time spent watching television (OR = 1.09; 95% CI, 1.05-1.13) and daytime napping (OR = 1.34; 95% CI, 1.17-1.53).
“Our two-stage results prioritize an array of potential targets for prevention — most robustly, social support factors, media use and circadian habits — with the potential to reduce the risk [for] depression even in the face of genetic or environmental vulnerability,” Choi and colleagues wrote. “Not all factors associated with depression in observational research may represent potent targets for prevention. A large-scale systematic approach combined with genetically informed methods for causal inference could help prioritize candidates for multimodal prevention in psychiatry.”