The association between cognitive function and subsequent depression: a systematic review and meta-analysis

Abstract

Despite a growing interest in understanding the cognitive deficits associated with major depressive disorder (MDD), it is largely unknown whether such deficits exist before disorder onset or how they might influence the severity of subsequent illness. The purpose of the present study was to conduct a systematic review and meta-analysis of longitudinal datasets to determine whether cognitive function acts as a predictor of later MDD diagnosis or change in depression symptoms. Eligible studies included longitudinal designs with baseline measures of cognitive functioning, and later unipolar MDD diagnosis or symptom assessment. The systematic review identified 29 publications, representing 34 unique samples, and 121 749 participants, that met the inclusion/exclusion criteria. Quantitative meta-analysis demonstrated that higher cognitive function was associated with decreased levels of subsequent depression (r = -0.088, 95% confidence interval. -0.121 to -0.054, p < 0.001). However, sensitivity analyses revealed that this association is likely driven by concurrent depression symptoms at the time of cognitive assessment. Our review and meta-analysis indicate that the association between lower cognitive function and later depression is confounded by the presence of contemporaneous depression symptoms at the time of cognitive assessment. Thus, cognitive deficits predicting MDD likely represent deleterious effects of subclinical depression symptoms on performance rather than premorbid risk factors for disorder.

Keywords: Cognitive function; depression; intelligence; longitudinal; premorbid; risk.

Figure 1. Flow Diagram of the Search Process

Figure 2. Meta-Analysis of the Association Between Cognitive Function and Subsequent Depression

A forest plot for all studies that investigated associations between cognition and later depression. Results are reported as correlation coefficients denoted by squares, and 95% confidence intervals indicated by lines (effect sizes are converted to correlation coefficients if reported as odds ratios). Meta-analysis results are displayed as the diamond. The overall analysis found a significant effect of cognition on depression (r=−0.088; 95% CI: −0.121, −0.054; p<0.001).

Figure 3. Meta-analysis Comparing Values Adjusted for Baseline Depression Symptoms vs. Unadjusted

A Forest plot for analysis comparing results from a subset of the same set of studies reported in Figure 2 when using unadjusted values compared to using values that are adjusted for baseline depression. Effects are significant for unadjusted values (r=−0.120; 95% CI: −0.169, −0.070; p<0.001), but not for adjusted values (r=−0.032; 95% CI: −0.078, 0.014; p=0.169). Results are reported as correlation coefficients denoted by squares, and 95% confidence intervals indicated by lines. Meta-analysis results are displayed as diamonds.

Figure 4. Trim and Fill Funnel Plots for All Samples

Fisher’s Z, a measure of effect size, is plotted on the x-axis and the standard error is plotted on the y-axis. Larger studies appear toward the top of the graph and smaller studies towards the bottom. In the absence of publication bias, the studies are symmetrically distributed around the mean. Actual studies are shown in open circles and imputed studies would be shown in black circles. No additional studies would be expected in the opposite direction (to the right) of the observed effect, but an additional 11 studies are imputed to the left of the mean effect size. While the calculated effect size is −0.088 (95% CI: −0.121, −0.054), using Duval and Tweedie’s Trim and Fill Method, the imputed effect size estimate is larger at −0.137 (95% CI: −0.176, −0.099; imputed studies n=11).