Cardiorespiratory fitness, grip strength and depression symptoms: A Mendelian Randomization study

To assess the impact of cardiorespiratory fitness (CRF) and muscle strength on depression and individual depression symptoms.

Mendelian randomisation (MR) analysis was conducted in up to 341,326 participants of European ancestry from UK Biobank (aged 37-73 years). Genetic variants from previous genome-wide association studies (GWAS) of CRF and grip strength (to proxy overall muscle strength) were utilised to instrument exposures. A broad depression phenotype based on self-report and hospital records, as well as individual measures of depression symptoms from the Patient Health Questionnaire-9 (PHQ-9) were used as outcomes. Analysis was repeated stratifying by sex and using summary statistics from a major depressive disorder (MDD) GWAS.

There was no clear evidence for association between CRF and any depression outcome. There was robust evidence suggesting greater grip was associated with lower odds of broad depression (OR per 0.1 kg increase in weight adjusted grip: 0.86, 95% CI:0.80,0.93), as well as the PHQ-9 items appetite changes (OR:0.56, 95% CI:0.49,0.65), and anhedonia (OR:0.79, 95% CI:0.69,0.90), a core symptom of depression. There was also some evidence for associations between greater grip and lower odds of depressed mood (OR:0.85, 95% CI:0.74,0.97), psychomotor changes (OR:0.79, 95% CI:0.64,0.97), fatigue (OR:0.83, 95% CI:0.74,0.93) and concentration problems (OR:0.85, 95% CI:0.74,0.98) in the MR-inverse variance weighted analysis. Effects were mostly driven by stronger associations in females and results replicated in the two-sample MR for MDD.

Muscle strength may represent an important modifiable factor for preventing and treating depression and several specific symptoms, including core symptoms such as anhedonia.