The stage‐specifically accelerated brain aging in never‐treated first‐episode patients with depression

Depression associated with structural brain abnormalities is hypothesized to be related with accelerated brain aging. However, there is far from a unified conclusion because of clinical variations such as medication status, cumulative illness burden. To explore whether brain age is accelerated in never‐treated first‐episode patients with depression and its association with clinical characteristics, we constructed a prediction model where gray matter volumes measured by voxel‐based morphometry derived from T1‐weighted MRI scans were treated as features. The prediction model was first validated using healthy controls (HCs) in two Chinese Han datasets (Dataset 1, N = 130 for HCs and N = 195 for patients with depression; Dataset 2, N = 270 for HCs) separately or jointly, then the trained prediction model using HCs (N = 400) was applied to never‐treated first‐episode patients with depression (N = 195). The brain‐predicted age difference (brain‐PAD) scores defined as the difference between predicted brain age and chronological age, were calculated for all participants and compared between patients with age‐, gender‐, educational level‐matched HCs in Dataset 1. Overall, patients presented higher brain‐PAD scores suggesting patients with depression having an “older” brain than expected. More specially, this difference occurred at illness onset (illness duration <3 months) and following 2 years then disappeared as the illness further advanced (>2 years) in patients. This phenomenon was verified by another data‐driven method and significant correlation between brain‐PAD scores and illness duration in patients. Our results reveal that accelerated brain aging occurs at illness onset and suggest it is a stage‐dependent phenomenon in depression.