Ample evidence shows that lifestyle factors such as physical activity and social support help mitigate depression symptoms and lower the risk for depression. However, researchers publishing their study results in The American Journal of Psychiatry pointed out that additional modifiable factors may be “overlooked or unknown.”

Epidemiologic researchers use Mendelian randomization to examine the relationship between many variables and a single outcome, and to address questions of causality without typical biases found in other approaches. Applying this model to depression, the researchers of this study used phenotypic and genomic data from 118,378 UK Biobank participants without active depressive symptoms at baseline.

An exposure-wide association study design allowed them to test the relationship between 106 modifiable factors and clinically significant depression upon follow up. Factors included a wide range of areas from sleep and exercise to access to green space.

The researchers also factored in traumatic life events. In addition, directional effects and possible causal relationships between modifiable factors and depression were assessed using 2-sample Mendelian randomization.

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The researchers initially identified 49 factors significantly associated with depression; this number was reduced to 29 after adjusting for socioeconomic factors and physical health. They also identified 18 factors associated with reduced odds of depression, including exercise, duration of sleep, belonging to a sport or exercise club, and cereal intake, among others. Of the 11 items associated with increased odds of depression, top scorers included napping often and frequent computer, television, and mobile phone use.

Mendelian randomization showed confiding in others to reduce the risk of depression. It also linked multivitamin use with higher odds of depression. Furthermore, it showed increased computer use and B vitamin intake as more likely to be consequences of, rather than causes of, depression.

The researchers admitted that all relationships between risk factors and depression may not be straightforward, necessitating further research. They also noted limitations to their research, such as the ability to use only those variables included in the database. Modifiable psychological factors, such as coping mechanisms, were also not included in the available data. Also, their assessment of depression was based on a survey measure that, while widely used, does not constitute a clinical diagnostic interview.

Regarding further study the researchers said, “Given that depression may occur across the life course and that this was a sample of only older adults, we focused on any clinically significant incident depression over the follow-up period; however, future longitudinal research could distinguish between new-onset depression and relapse.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Choi KW, Stein MB, Nishimi KM, et al. An exposure-wide and Mendelian randomization approach to identifying modifiable factors for the prevention of depression. Am J Psychiatry. Published online August 14, 2020. doi:10.1176/appi.ajp.2020.19111158