Lifestyle and BrainAGE in adult depression

Background: This study tested whether lifestyle and fitness features that influence brain health in the general population differentially affect adults with a history of depression. Brain health was assessed using the brain-age-gap-estimate (brainAGE), a personalized index of the brain's biological age. Methods: Medically healthy adults (44-82 years) from the UK Biobank with a history of depression (n=896) or no psychiatric history (n=36,206) were included. Heterogeneity Through Discriminative Analysis was used to cluster the depression group based on 224 lifestyle and fitness features. Global and local (voxel-based) brainAGE were computed from structural neuroimaging data. The study design and implementation involved input from the position of related lived experience. Outcomes: Four depression clusters were identified. The "balanced moderates" cluster (n=253) had good health and balanced lifestyle habits. The "optimal diet and activity" cluster (n=178) had good health, healthy diets, and regular physical activity. The "metabolic risk-sedentary" cluster (n=315) had higher body mass index, poor diet, and sedentary behaviour. The "frailty-low activity" cluster (n=150) had a varied diet coupled with physical frailty. Mood symptoms were lowest in the "balanced moderates" cluster and highest in the "metabolic risk-sedentary" cluster. The presence of a history of depression was associated with older global brainAGE and with local brainAGE in ventromedial prefrontal regions regardless of cluster assignment. The "metabolic risk-sedentary" cluster also exhibited elevated local brainAGE in the hippocampal complex and thalamus. Interpretation: This study highlights the heterogeneity in lifestyle and fitness factors among adults with a history of depression, underscoring the detrimental influence of depression as well as poor diet and physical inactivity on the biological age of the brain.