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Understanding cognitive impairment in mood disorders: mediation analyses in the UK Biobank cohort

  • Breda Cullen (a1), Daniel J. Smith (a2), Ian J. Deary (a3), Jill P. Pell (a4), Katherine M. Keyes (a5) and Jonathan J. Evans (a2)...



Cognitive impairment is strongly linked with persistent disability in people with mood disorders, but the factors that explain cognitive impairment in this population are unclear.


To estimate the total effect of (a) bipolar disorder and (b) major depression on cognitive function, and the magnitude of the effect that is explained by potentially modifiable intermediate factors.


Cross-sectional study using baseline data from the UK Biobank cohort. Participants were categorised as having bipolar disorder (n = 2709), major depression (n = 50 975) or no mood disorder (n = 102 931 and n = 105 284). The outcomes were computerised tests of reasoning, reaction time and memory. The potential mediators were cardiometabolic disease and psychotropic medication. Analyses were informed by graphical methods and controlled for confounding using regression, propensity score-based methods and G-computation.


Group differences of small magnitude were found on a visuospatial memory test. Z-score differences for the bipolar disorder group were in the range −0.23 to −0.17 (95% CI −0.39 to −0.03) across different estimation methods, and for the major depression group they were approximately −0.07 (95% CI −0.10 to −0.03). One-quarter of the effect was mediated via psychotropic medication in the bipolar disorder group (−0.05; 95% CI −0.09 to −0.01). No evidence was found for mediation via cardiometabolic disease.


In a large community-based sample in middle to early old age, bipolar disorder and depression were associated with lower visuospatial memory performance, in part potentially due to psychotropic medication use. Mood disorders and their treatments will have increasing importance for population cognitive health as the proportion of older adults continues to grow.

Declaration of interest

I.J.D. is a UK Biobank participant. J.P.P. is a member of the UK Biobank Steering Committee.


Corresponding author

Correspondence: Dr Breda Cullen, Mental Health and Wellbeing, Gartnavel Royal Hospital, 1055 Great Western Road, Glasgow G12 0XH, UK. Email:


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Understanding cognitive impairment in mood disorders: mediation analyses in the UK Biobank cohort

  • Breda Cullen (a1), Daniel J. Smith (a2), Ian J. Deary (a3), Jill P. Pell (a4), Katherine M. Keyes (a5) and Jonathan J. Evans (a2)...
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