Domain-specific cognitive function in euthymic bipolar disorder: a systematic review and meta-analysis

Background. Euthymic bipolar disorder (BD) is associated with general and domain-specific cognitive impairment, which predicts poor occupational and social functioning. Methods. We searched Embase, Medline, and PsycInfo for articles published between database inception and June 2024, examining cognitive domains in euthymic BD. We conducted meta-analysis, meta-regressions, including premorbid IQ, demographic, and clinical variables. Newcastle Ottawa Scale, I² statistic, and funnel plots/Egger’s and Begg’s Test were used to assess quality, heterogeneity, and publication bias, respectively. The Benjamini-Hochberg (BH) procedure was utilised for multiple comparisons. Results. We identified 95 groups from 75 studies (N = 4,404 BD & 4,037 HC). BD showed significant impairment in general cognitive functioning (Hedge’s g = −0.58, 95%CI: −0.79, −0.37, p <.01), verbal memory (Hedge’s g = −0.70, 95%CI: −0.79, −0.60, p <.01), executive function (Hedge’s g = −0.69, 95%CI: −0.78, −0.60, p <.01), visuo-spatial memory (Hedge’s g = −0.68, 95%CI: −0.83, −0.53, p <.01), attention/processing speed (Hedge’s g = −0.64, 95%CI: −0.75, −0.54, p <.01), working memory (Hedge’s g = −0.61, 95%CI: −0.74, −0.49, p <.01), and premorbid IQ (Hedge’s g = −0.24, 95%CI: −0.36, −0.12, p <.01). Demographic and clinical factors were not associated with cognitive performance, except for a statistically significant, but small positive correlation between years of education and lower impairment in verbal memory, β = .066, adjusted p <.05. Conclusions. Our findings highlight cognitive domains impaired in euthymic BD, indicating targets for interventions. Substantial variance is unexplained, warranting focus on larger samples of individual-level data.