Associations between age of onset and domain-specific cognitive deficits in major depressive disorder.

Background: This study aimed to examine associations between age of onset and domain-specific cognitive deficits in major depressive disorder (MDD).

Methods: We assessed 582 MDD patients (389 first-episode [FED], 193 recurrent [RMD]) and 280 healthy controls (HCs) using five cognitive domains from the MATRICS Consensus Cognitive Battery. Of these patients, 289 were reassessed after 8 weeks of antidepressant treatment. Stratified analyses compared cognitive performance across early-onset depression (EOD), late-onset depression (LOD), and HCs within FED and RMD subgroups. In the FED subgroup, linear mixed-effects models (LMM) examined interactions between age (as a proxy for onset age) and diagnostic group. Longitudinal cognitive changes were analyzed using ANCOVA and repeated-measures ANOVA, adjusting for demographic and clinical covariates.

Results: In the FED subgroup, EOD patients exhibited significantly greater deficits in processing speed, verbal learning, and composite cognitive score compared to LOD patients and HCs. LMM identified a significant age × group interaction for processing speed (F = 5.054, p = 0.025). Longitudinal analyses revealed significant treatment-related improvements across all domains, indicating comparable therapeutic efficacy between EOD and LOD. However, due to greater baseline cognitive impairments, EOD patients continued to perform significantly worse than LOD patients in processing speed at follow-up. In contrast, within the RMD subgroup, cognitive performance did not differ significantly between the EOD and LOD groups.

Conclusions: Early-onset MDD is linked to stable, domain-specific cognitive deficits-especially in processing speed-during first depressive episodes. These results underscore the need for early, targeted cognitive interventions in EOD patients, beyond mood symptom-focused pharmacotherapy.