Participants with remitted depression had a higher risk of future depression compared with matched controls, while baseline cognitive performance was associated differently with later depression risk depending on depression history, according to a recent longitudinal study.

Investigators analyzed 1,862 UK Biobank participants with remitted depression and 1,862 age- and sex-matched controls without a history of depression or antidepressant use at imaging with magnetic resonance imaging (MRI). Remitted depression was defined as a prior International Classification of Diseases, 10th Revision–coded depressive episode and remission from depressive symptoms at the imaging visit. Cognitive testing and MRI were performed during imaging visits between 2014 and 2019, with longitudinal follow-up using hospital episode statistics and mental health follow-up questionnaires.

During follow-up, 33% (n = 623) of the participants with remitted depression experienced depressive relapse compared with 13% (n = 240) of controls who developed first-episode depression. In an adjusted Cox proportional hazards model accounting for temporal differences in longitudinal assessment, the participants with remitted depression had threefold higher odds of experiencing future depression compared with controls.

The primary analysis evaluated composite cognitive z scores derived from tasks assessing processing speed, reasoning, executive functioning, attention, and memory. The participants with remitted depression performed poorer overall compared with controls, with the largest deficits observed in processing speed.

Among controls, lower baseline composite cognitive performance was associated with higher future depression risk. Estimated marginal mean probability of future depression ranged from 0.25% at one standard deviation below the mean cognitive score to 0.15% at one standard deviation above the mean. Lower executive functioning, reasoning, and processing speed scores were also associated with higher depression risk in controls.

The investigators stated that among the participants with remitted depression, higher composite cognitive performance was associated with greater future depression risk. Estimated marginal mean depression risk increased from 0.74% at one standard deviation below the mean cognitive score to 1.10% at one standard deviation above the mean. Executive functioning, reasoning, and processing speed scores were associated with the same pattern, while memory performance showed limited association with future depression risk between groups.

“Those with no previous history of depression are at higher risk of future depression when cognitive performance is lower at baseline,” wrote lead study author Angharad N. de Cates, of the Institute for Mental Health at the University of Birmingham in the United Kingdom as well as the Department of Psychiatry at the University of Oxford, and colleagues. “[Remitted depression] is a high-risk group for future depression, and those with relatively higher cognitive performance may be more likely to report future depressive symptoms,” they added.

Task-level analyses showed significant group interactions for correct digit symbol matches and matrix pattern puzzles solved correctly.

The investigators also evaluated structural and functional MRI markers involving the default mode, central executive, and salience networks. The participants with remitted depression had lower overall gray matter volume and greater head movement compared with controls, but structural measures and functional connectivity measures were not associated with future depression risk. The investigators found that larger volumes in several default mode network regions were associated with better composite cognitive performance across the participants.

Sensitivity analyses using alternative depression definitions, imputed cognitive data, socioeconomic interaction terms, age subgroup analyses, and exclusions for cerebrovascular disease produced findings similar to the primary analyses.

The investigators noted several limitations, including the estimated timing of depressive episodes during follow-up, incomplete cognitive data, limited power for resting-state functional MRI analyses, and limited population representativeness within UK Biobank. More than 95% of the study population was White, which may limit generalizability.

Full disclosures can be found in the study.

Source: BMJ Mental Health