Depression, Mental Health, and Longevity: The Biological Link Between Mood and Lifespan
Mental disorders, including depression, are linked to substantially higher mortality: across 148 studies, people with mental disorders had 2.22 times the risk of death of comparison groups, with a median of 10 years of life lost.1 Depression is also treatable, which makes it worth taking seriously for physical health as well as wellbeing.
- Depression is linked to about 1.8 times the risk of future coronary heart disease, although the authors of the main meta-analysis say it has not been established as an independent cause, because adjustment for other risk factors was incomplete.4
- Proposed biological links include changes in the stress-hormone system and inflammation: a meta-analysis of 24 studies found higher levels of the inflammatory signals TNF-alpha and IL-6 in people with major depression.3
- Exercise treats depression: in a 2024 network meta-analysis of 218 trials, walking or jogging, yoga and strength training produced moderate reductions in depression, with larger effects at higher intensity, although confidence in the evidence was low or very low.5
- If you have symptoms of depression, talk to a doctor or mental health professional; effective treatments include psychotherapy, medication and exercise.
Health culture often separates mental from physical health, treating diet and exercise as longevity medicine and mental health care as quality-of-life medicine. The mortality data argue against that split: across 148 studies, people with mental disorders had 2.22 times the risk of death, two-thirds of those deaths were from natural causes, and an estimated 14.3% of deaths worldwide, about 8 million a year, are attributable to mental disorders.1
The Biological Cost of Depression
Stress hormones: A long-standing hypothesis holds that overactivity of corticotropin-releasing factor (CRF), the brain hormone that starts the body's stress response, contributes to depression.2 Changes in this stress-hormone system can affect sleep, metabolism and immune function, as our article on stress and cortisol explains. Whether depression also speeds biological ageing as measured by epigenetic clocks is still being studied.
Inflammation: A meta-analysis of 24 studies found significantly higher levels of TNF-alpha and IL-6 in people with major depression than in controls, with no clear difference for the other cytokines studied; individual studies had reported both positive and negative results.3 Chronic inflammation and depression may influence each other, and lower levels of BDNF, a protein that supports brain plasticity, are another proposed link.
Cardiovascular Consequences
Depression and heart disease are closely linked. In a meta-analysis, 21 studies of people without heart disease at the start found that depression was associated with 1.81 times the risk of later coronary heart disease, and 34 studies of people who already had it found 1.80 times the risk of death or a fatal coronary event. Adjusting for heart function cut that second estimate by almost half, and the authors concluded that depression has yet to be established as an independent risk factor, because adjustment for conventional risk factors and disease severity was incomplete and biased.4
Exercise as Antidepressant: The Evidence
A 2024 network meta-analysis pooled 218 randomised trials with 14,170 participants with major depression. Compared with active controls such as usual care, walking or jogging (effect size −0.62), yoga (−0.55), strength training (−0.49), mixed aerobic exercise (−0.43) and tai chi or qigong (−0.42) produced moderate reductions in depression, and effects grew with the intensity prescribed. Strength training and yoga were the best tolerated. Only one trial met the criteria for low risk of bias, however, so confidence in the results was low for walking or jogging and very low for the other forms.5
The authors concluded that these forms of exercise could be considered alongside psychotherapy and antidepressants as core treatments for depression.5 Choose an activity you can keep doing and build intensity as fitness allows; for moderate or severe depression, use exercise alongside professional care rather than instead of it.
References
- 1Walker ER, et al. "Mortality in mental disorders and global disease burden implications: a systematic review and meta-analysis." JAMA Psychiatry. 2015;72(4):334-41. PubMed · DOI
- 2Nemeroff CB. "The corticotropin-releasing factor (CRF) hypothesis of depression: new findings and new directions." Mol Psychiatry. 1996;1(4):336-42. PubMed
- 3Dowlati Y, et al. "A meta-analysis of cytokines in major depression." Biol Psychiatry. 2010;67(5):446-57. PubMed · DOI
- 4Nicholson A, et al. "Depression as an aetiologic and prognostic factor in coronary heart disease: a meta-analysis of 6362 events among 146 538 participants in 54 observational studies." Eur Heart J. 2006;27(23):2763-74. PubMed · DOI
- 5Noetel M, et al. "Effect of exercise for depression: systematic review and network meta-analysis of randomised controlled trials." BMJ. 2024;384:e075847. PubMed · DOI
