Abstract
Cognitive impairment associated with lifetime major depressive disorder (MDD) is well-supported by meta-analytic studies, but population-based estimates remain scarce. Previous UK Biobank studies have only shown limited evidence of cognitive differences related to probable MDD. Using updated cognitive and clinical assessments in UK Biobank, this study investigated population-level differences in cognitive functioning associated with lifetime MDD. Associations between lifetime MDD and cognition (performance on six tasks and general cognitive functioning [g-factor]) were investigated in UK Biobank (N-range 7,457-14,836, age 45-81 years, 52% female), adjusting for demographics, education, and lifestyle. Lifetime MDD classifications were based on the Composite International Diagnostic Interview. Within the lifetime MDD group, we additionally investigated relationships between cognition and (a) recurrence, (b) current symptoms, (c) severity of psychosocial impairment (while symptomatic), and (d) concurrent psychotropic medication use. Lifetime MDD was robustly associated with a lower g-factor (β= -0.10, PFDR= 4.7 × 10-5), with impairments in attention, processing speed, and executive functioning (β≥ 0.06). Clinical characteristics revealed differential profiles of cognitive impairment among case individuals; those who reported severe psychosocial impairment and use of psychotropic medication performed worse on cognitive tests. Severe psychosocial impairment and reasoning showed the strongest association (β= -0.18, PFDR=7.5 × 10-5). Findings describe small but robust associations between lifetime MDD and lower cognitive performance within a population-based sample. Overall effects were of modest effect size, suggesting limited clinical relevance. However, deficits within specific cognitive domains were more pronounced in relation to clinical characteristics, particularly severe psychosocial impairment.
Highlights
Major depressive disorder (MDD) is a highly prevalent condition, affecting around one in five people over their lifetime globally [1,2,3]
Symptoms impaired psychosocial functioning “somewhat” or Clinical characteristics Within individuals who were classified with lifetime major depressive disorder (MDD) as described above, we further identified four clinical characteristics: (a) recurrent MDD, reflecting more than one depressive episode, (b) putative current MDD symptoms concurrent with the cognitive assessment, derived from responses on the touchscreen questionnaire (Supplementary Materials 2), (c) severe psychosocial impairment, indicated by the maximum CIDI-SF symptom score of eight in combination with the maximum score for psychosocial impairment [37]; and (d) concurrent use of psychotropic medication, which was derived from reported use of antidepressant (94.6%), antipsychotic (3.9%), or anxiolytic (1.5%) medication as assessed during the nurse-led interview (Supplementary Materials 3, Figure S2)
The findings of the current study describe a robust association between lifetime MDD and lower general cognitive performance within a population-based sample
Summary
Major depressive disorder (MDD) is a highly prevalent condition, affecting around one in five people over their lifetime globally [1,2,3]. Meta-analytically derived effect sizes may overestimate cognitive impairment related to MDD compared with the general population. Understanding the degree of impairment associated with lifetime MDD (current or past diagnosis) in the general population requires further investigation within a sufficiently powered community-based sample. This summarizes the added value of population-based studies which are not biased by specific clinical characteristics and that are sufficiently powered to detect potentially modest effect sizes. Cognitive impairment associated with lifetime major depressive disorder (MDD) is well-supported by meta-analytic studies, but population-based estimates remain scarce. Using updated cognitive and clinical assessments in UK Biobank, this study investigated population-level differences in cognitive functioning associated with lifetime MDD. Deficits within specific cognitive domains were more pronounced in relation to clinical characteristics, severe psychosocial impairment
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