Harvard Medical School researchers based at Massachusetts General Hospital have identified a set of modifiable factors from a field of over 100 that could represent valuable targets for preventing depression in adults.
In a study published in The American Journal of Psychiatry, the team named social connection as the strongest protective factor for depression and suggested that reducing sedentary activities such as TV watching and daytime napping could also help lower the risk of depression.
“Depression is the leading cause of disability worldwide, but until now researchers have focused on only a handful of risk and protective factors, often in just one or two domains,” said lead study author Karmel Choi, HMS clinical fellow in psychiatry at Mass General. “Our study provides the most comprehensive picture to date of modifiable factors that could impact depression risk.”
Researchers took a two-stage approach in this study. The first stage drew on a database of over 100,000 adult participants in the UK Biobank to systematically scan a wide range of modifiable factors that might be associated with the risk of developing depression, including social interaction, media use, sleep patterns, diet, physical activity and environmental exposures.
This method, known as an exposure-wide association scan (ExWAS), is analogous to genome-wide association studies (GWAS) that have been widely used to identify genetic risk factors for disease.
The second stage took the strongest modifiable candidates from ExWAS and applied a technique called Mendelian randomization (MR) to investigate which factors may have a causal relationship to depression risk. MR is a statistical method that treats genetic variation between people as a kind of natural experiment to determine whether an association is likely to reflect causation rather than just correlation.
More relevant than ever
This two-stage approach allowed the researchers to narrow the field to a smaller set of promising and potentially causal targets for depression.
“Far and away the most prominent of these factors was frequency of confiding in others, but also visits with family and friends, all of which highlighted the important protective effect of social connection and social cohesion,” said senior study author Jordan Smoller, HMS professor of psychiatry and associate chief for research in the Mass General Department of Psychiatry.
“These factors are more relevant now than ever at a time of social distancing and separation from friends and family,” Smoller added.
The protective effects of social connection were present even for individuals who were at higher risk for depression as a result of genetic vulnerability or early-life trauma.
On the other hand, factors associated with depression risk included time spent watching TV, though the authors note that additional research is needed to determine whether that association was due to media exposure per se or whether time in front of the TV was a proxy for being sedentary.
Perhaps more surprising, the tendency for daytime napping and regular use of multivitamins appeared to be associated with depression risk, though more research is needed to determine how these might contribute.
The findings demonstrate an important new approach for evaluating a wide range of modifiable factors for depression and using this evidence to prioritize targets for preventive interventions. The study’s two-stage approach could also be used to inform the prevention of other health conditions.
“Depression takes an enormous toll on individuals, families and society, yet we still know very little about how to prevent it,” said Smoller. “We’ve shown that it’s now possible to address these questions of broad public health significance through a large-scale, data-based approach that wasn’t available even a few years ago.”
“We hope this work will motivate further efforts to develop actionable strategies for preventing depression,” Smoller said.
The study was supported in part by the National Institute of Mental Health (grant T32MH017119) and the Demarest Lloyd Jr. Foundation.