TOPLINE

People with higher objectively estimated cardiorespiratory fitness (CRF) were less likely to be diagnosed with depression or anxiety over a median of 12.6 years, a large UK Biobank study showed. Participants in the highest fitness quartile had a 24% lower risk for depression and a 17% lower risk for anxiety than those in the lowest quartile over this period.

METHODOLOGY

• Researchers conducted a prospective cohort study of 46,062 UK Biobank participants (47.3% men) with no prior diagnosis of depression or anxiety over a median follow-up of 12.6 years.
• Researchers estimated maximal oxygen consumption (VO₂max) from a standardized submaximal cycling test and categorized participants into quartiles: Q1 (≤ 23.8 mL/kg/min), Q2 (23.9-27.9 mL/kg/min), Q3 (28.0-32.5 mL/kg/min), and Q4 (≥ 32.6 mL/kg/min).
• Incident depression and anxiety disorders were identified using linked health records and diagnostic codes. The analysis was adjusted for age, sex, race, education, alcohol consumption, smoking status, overall health scores, C-reactive protein levels, BMI, and history of diabetes.
• Biological age was estimated using the Klemera-Doubal method and Phenotypic Age algorithm to test whether the associations differed by biological age.
• Proteomic profiling was performed in a subset of 3245 participants to identify differentially expressed plasma proteins.

TAKEAWAY

• During follow-up, 2190 cases of incident depression and 2483 cases of incident anxiety were noted. After full adjustment, participants in Q4 had a 24% lower risk for depression (hazard ratio [HR], 0.76; P = .002) and a 17% lower risk for anxiety (HR, 0.83; P = .026) than those in Q1.
• For every 1-SD increase in VO₂max, the risks for depression and anxiety dropped by 10% (HR, 0.90; P = .002) and 6% (HR, 0.94; P = .039), respectively.
• VO₂max had an inverse linear association with depression risk (P_overall = .006), whereas the association between VO₂max and anxiety risk was significantly nonlinear (P_overall = .005; P_nonlinear = .014). Associations between VO₂max and the risks for anxiety and the composite outcome (depressive and anxiety disorders) were stronger among participants with low biological age, but those between VO₂max and depression risk were not; none of the interactions were significant. Among individuals with BMI < 30, each 1-SD increase in VO₂max was linked to a 6% lower risk for the composite outcome (P = .022).
• Seven significantly differentially expressed plasma proteins were identified, including leptin and FABP4, which were significantly downregulated, and SPINT3 and INSL3, which were significantly upregulated (false discovery rate-adjusted P < .05).

IN PRACTICE

"These findings support promotion of cardiorespiratory fitness as a modifiable factor for mental health prevention," the authors wrote.

SOURCE

The study was led by Yuting Liu, Cancer Center, The First Hospital of Jilin University, Changchun, China. It was published online on October 8 in the Journal of Affective Disorders.

LIMITATIONS

The study was limited by its observational design, estimation of VO₂max and covariates only at baseline, lack of accounting for changes in fitness, body weight, comorbidities, and lifestyle during the long follow-up, residual confounding, lack of mediation analysis, and reliance on diagnostic codes. Additionally, the sample included predominantly White and healthy individuals, limiting generalizability. Some proteins remained unmeasured, and plasma protein levels may not have reflected actual brain-specific expression.

DISCLOSURES

The study received no specific funding. The authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.