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Individuals with depression, on average, die prematurely, have high levels of physical comorbidities and may experience accelerated biological ageing. A greater understanding of age-related changes in physiology could provide novel biological insights that may help inform strategies to mitigate excess mortality in depression. We used generalised additive models to examine age-related changes in 15 cardiovascular, body composition, grip strength and lung function measures, comparing males and females with a lifetime history of depression to healthy controls. The main dataset included 342,393 adults (mean age = 55.87 years, SD = 8.09; 52.61% females). We found statistically significant case-control differences for most physiological measures. There was some evidence that age-related changes in body composition, cardiovascular function, lung function and heel bone mineral density followed different trajectories in depression. These differences did not uniformly narrow or widen with age and differed by sex. For example, BMI in female cases was 1.1 kg/m 2 higher at age 40 and this difference narrowed to 0.4 kg/m 2 at age 70. In males, systolic blood pressure was 1 mmHg lower in depression cases at age 45 and this difference widened to 2.5 mmHg at age 65. These findings suggest that targeted screening for physiological function in middle-aged and older adults with depression is warranted to potentially mitigate excess mortality.

Introduction: Individuals with mental disorders, on average, die prematurely and may experience accelerated biological ageing. Objectives: We examined sex-specific associations between age and physiological measures in individuals with lifetime depression and healthy controls. Methods: UK Biobank recruited >500,000 participants, aged 37-73, between 2006-2010. Generalised additive models (GAMs) were used to examine associations between age and multiple cardiovascular, body composition, grip strength and lung function measures. Analyses were conducted separately in males and females with lifetime depression compared to healthy controls. Results: Analytical samples included up to 342,393 adults (mean age = 55.87 years, SD = 8.09; 52.61% females). Wefound statistically significant differences between individuals with lifetime depression and healthy controls for most physiological measures, with standardised mean differences between -0.145 and 0.156. There was some evidence that age-related changes in body composition, cardiovascular measures, lung function and heel bone mineral density followed different trajectories in individuals with lifetime depression. However, these differences did not uniformly narrow or widen with age. For example, BMI in females with lifetime depression was approximately 1.1 kg/m2 higher at age 40 and this difference narrowed to about 0.4 kg/m2 at age 70. In males, systolic blood pressure was approximately 1 mmHg lower in individuals with lifetime depression at age 45 and this difference widened to about 2.5 mmHg at age 65. Conclusions: Evidence of differences in ageing trajectories between individuals with lifetime depression and healthy controls was not uniform across physiological measures and differed by sex. [ABSTRACT FROM AUTHOR]