- The first stage of this two-part study used data from 100,517 UK Biobank participants without active depressive symptoms at baseline to test the relationship between 106 modifiable factors and subsequent new-onset depression
- A range of factors (e.g., exercise, social activity, media use, sleep, diet) were associated with incident depression, both in the general sample and among individuals at risk because of genetic vulnerability or traumatic life experiences
- The second stage of the study, Mendelian randomization, validated frequency of confiding in others as protective against depression (OR=0.76) and television watching time as a risk factor (OR=1.09)
- Daytime napping was linked to higher odds of depression (OR=1.34) in Mendelian randomization, but there was a bidirectional effect; depression was associated with increased daytime napping (ß=0.05)
- These results may represent actionable targets for efforts to prevent depression
Two of the best substantiated risk factors for depression, genetic vulnerability and early-life adversity are unmodifiable in adults. Even though depression is the leading cause of disability worldwide, only a few modifiable preventive factors have been proposed, such as physical activity and social support. A broader investigation is needed to identify variables that may have been overlooked.
Karmel W. Choi, PhD, clinical psychologist and faculty researcher, Karestan C. Koenen, PhD, faculty researcher, and Jordan W. Smoller, MD, ScD, director of the Psychiatric and Neurodevelopmental Genetics Unit in the Department of Psychiatry at Massachusetts General Hospital, and colleagues recently used a novel two-stage approach to discover modifiable factors associated with depression. In The American Journal of Psychiatry, they describe how they validated social support as protective and television watching as a risk factor.
The initial sample for the study was 123,794 adults of white British ancestry who enrolled in the UK Biobank, did not endorse depressed mood and/or anhedonia at baseline, had high-quality genomic data available and completed an online mental health survey about six to eight years after enrollment.
Between October 2018 and August 2019, the researchers searched the participants' records for data about 106 factors considered modifiable at the individual or societal level (e.g., exercise, diet, social activities and access to green space).
The first stage of analysis was an exposure-wide association scan—hypothesis-free, systematic testing of potential relationships between the 106 variables and new-onset depression (defined as a score ≥10 on the Patient Health Questionnaire–9, administered as part of the follow-up survey). This testing was done on three groups of participants who remained enrolled in the UK Biobank in February 2020:
- The full sample (N=100,517)
- Individuals at risk of depression based on a polygenic risk score (the PRS group, n=10,093)
- Individuals at risk based on traumatic life events reported in the follow-up survey (the trauma group, n=10,154)
Relationships between identified factors and depression risk were then examined in bidirectional Mendelian randomization analyses.
After adjustment for sociodemographic factors and physical health, 18 factors were significantly associated with reduced odds of depression and 11 were significantly associated with increased odds. The top 10 included:
Six protective factors:
- Engaging in exercises like swimming or cycling
- Being part of a sports club or gym
- Walking pace
- Frequency of confiding in others
- Sleep duration
- Cereal intake
Four risk factors:
- Daytime napping
- Television watching time
- Computer use time
- Cell phone use time
The PRS Group
Among individuals at high risk of depression based on PRS, there were four significant factors after adjustment. Intriguingly, all four had been identified in the full sample (although salt intake was not in the top 10):
- Protective factors: Sleep duration; frequency of confiding in others
- Risk factors: Salt intake; computer use time
The Trauma Group
Among individuals at high risk of depression because of traumatic life events, there were four significant factors, which again had been identified in the full sample:
- Protective factors: Engaging in exercises like swimming or cycling, sleep duration and frequency of confiding in others
- Risk factor: Television watching time
Mendelian Randomization Analyses
Mendelian randomization is an epidemiologic technique that uses genetic variants to distinguish correlation from causation in observational data. In this study, the analyses generated estimates of causal relationships between depression and all factors identified in the adjusted full sample. The results supported:
- A beneficial effect of confiding in others (OR, 0.76; 95% CI, 0.67–0.86)
- A deleterious effect of television use (OR, 1.09; 95% CI, 1.05–1.13)
- A bidirectional effect of daytime napping—it was linked to higher odds of depression (OR, 1.34; 95% CI, 1.17–1.53), but depression was also associated with increased daytime napping (β, 0.05; 95% CI, 0.03–0.06)
Takeaways for Clinicians
Numerous modifiable factors seem worth targeting in efforts to prevent depression, even in the face of vulnerability due to genetics or life history. Of all the variables studied here, confiding in others was the most robust protective factor. Related factors were also protective, such as being part of group activities and frequency of visits with family/friends.
This study could not determine whether television use is a risk factor for depression because of screen time or media exposure per se because television watching time is a proxy for sedentary behavior. Regardless, clinicians should assess media use patterns in adults and educate them where appropriate about the potential mood impacts of excess television watching.
Learn more about the Psychiatric and Neurodevelopmental Genetics Unit