Cognition and Future Depression: Associations with Risk in Those With and Without a History of Depression

IntroductionCognitive impairments are common in depression and often persist beyond mood resolution. However, the relationship between cognitive performance, its neurological underpinnings, and future depression risk is unclear, limiting strategies for primary and secondary prevention. Our objective was to determine whether cognition associates with subsequent depression, including both relapse and first-episode occurrences. Methods2094 UK Biobank participants with previous ICD-10-defined depression currently in remission (RD) (mean(SD) age: 52.4(7.25) years) were age- and sex-matched to 2094 participants without depression history or current antidepressant use. Cognitive scores were compared between groups at the composite (z-score), domain, and task levels. MRI-derived phenotypes assessed brain network structure and functional connectivity. Longitudinal associations with future depression were assessed using logistic regression models controlling for key confounders. ResultsParticipants with RD had a higher risk of future depression (30%) than controls (8.5%). Composite cognitive performance in controls was inversely associated with future depression risk (risk estimated marginal means: 0.48% at -1SD, 0.37% at mean, 0.28% at +1SD). In RD, this relationship was reversed (1.56% at -1SD, 1.80% at mean, 2.08% at +1SD). Executive functioning, processing speed, and reasoning task scores all contributed. Higher grey matter in default mode network regions was associated with better concurrent cognitive performance across all participants, but not with future depression risk. Other MRI findings were limited. ConclusionRD carried a threefold higher risk of future depression than controls. Cognitive performance was a risk marker for future depression in both groups but in opposing directions. Neuroimaging metrics provided little predictive value. What is already known on this topicNeurocognitive impairments are common in depression, even after low mood has resolved and outside of comorbid neurodegenerative processes. However, the specific relationship between cognitive performance and risk of future depression is unclear, including how this relates to previous history of depression. What this study addsCognitive performance is a differential risk marker for future depression in those with previous depression compared to matched controls: without previous history of depression, poorer cognitive scores confer the highest risk; in remitted depression, higher levels of cognitive performance are associated with greater risk of depressive relapse. How this study might affect research, practice or policyFurther research should explore targeting interventions based on specific cognitive profiles, especially in high-risk populations such as those with previous episodes of depression.