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Associations between age of onset and domain-specific cognitive deficits in major depressive disorder
Fangmeng Hou1, Yankun Wu1, Chuan Shi1
1Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China.
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. Although both groups showed treatment-related improvements, EOD patients still performed 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.
Insights
Early-onset major depressive disorder (MDD) is associated with persistent cognitive deficits, particularly in processing speed, even after treatment. These findings highlight the need for early cognitive interventions in patients with early-onset MDD.
Area of Science:
- Neuroscience
- Psychiatry
- Cognitive Psychology
Background:
- Major Depressive Disorder (MDD) is a prevalent mental health condition.
- Cognitive deficits are common in MDD patients.
- The impact of age of onset on cognitive function in MDD requires further investigation.
Purpose of the Study:
- To investigate the association between age of onset and specific cognitive impairments in Major Depressive Disorder (MDD).
- To compare cognitive performance between early-onset depression (EOD) and late-onset depression (LOD) patients and healthy controls (HCs).
- To analyze the effects of antidepressant treatment on cognitive function in different MDD onset groups.
Main Methods:
- 582 MDD patients (389 first-episode [FED], 193 recurrent [RMD]) and 280 HCs were assessed using the MATRICS Consensus Cognitive Battery.
- Cognitive performance was compared across EOD, LOD, and HCs within FED and RMD subgroups.
- Linear mixed-effects models and ANOVA were used to analyze cross-sectional and longitudinal cognitive data.
Main Results:
- In the FED subgroup, EOD patients showed greater deficits in processing speed, verbal learning, and overall cognitive scores compared to LOD patients and HCs.
- A significant interaction between age and diagnostic group was found for processing speed in FED patients.
- While antidepressant treatment improved cognition across all domains in both EOD and LOD groups, EOD patients still exhibited slower processing speed at follow-up.
Conclusions:
- Early-onset MDD is associated with stable, domain-specific cognitive deficits, particularly in processing speed, during the first depressive episode.
- These cognitive deficits in EOD may persist despite treatment for mood symptoms.
- Targeted cognitive interventions are recommended for EOD patients to address these persistent deficits.
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