Cognitive functioning and lifetime major depressive disorder in UK Biobank

Area of Science:

• Neuroscience
• Psychiatry
• Epidemiology

Background:

• Cognitive impairment is a known correlate of major depressive disorder (MDD).
• Population-based estimates of cognitive differences in MDD are scarce.
• Previous UK Biobank studies showed limited evidence of cognitive differences in probable MDD.

Purpose of the Study:

• To investigate population-level differences in cognitive functioning associated with lifetime MDD using updated UK Biobank data.
• To examine associations between lifetime MDD and general cognitive functioning (g-factor) and specific cognitive tasks.
• To explore how recurrence, symptom severity, psychosocial impairment, and medication use modify cognitive performance in individuals with MDD.

Main Methods:

• Utilized UK Biobank data with N ranging from 7,457 to 14,836 participants (age 45-81).
• Assessed lifetime MDD using the Composite International Diagnostic Interview.
• Analyzed associations between MDD and cognitive performance (six tasks, g-factor), adjusting for demographics, education, and lifestyle.

Main Results:

• Lifetime MDD was robustly associated with a lower g-factor (β = -0.10, PFDR = 4.7 × 10-5).
• Impairments were observed in attention, processing speed, and executive functioning (β ≥ 0.06).
• Severe psychosocial impairment and psychotropic medication use were linked to worse cognitive performance, particularly in reasoning (β = -0.18, PFDR = 7.5 × 10-5).

Conclusions:

• Small but robust associations exist between lifetime MDD and reduced cognitive performance in a population sample.
• Overall effect sizes suggest limited clinical relevance for general cognitive function.
• Cognitive deficits are more pronounced in individuals with severe psychosocial impairment, highlighting clinical heterogeneity.