Meta-analyses of cognitive functioning in euthymic bipolar patients and their first-degree relatives

Background. Previous work suggests that impairments in executive function and verbal memory in particular may persist in euthymic bipolar patients and serve as an indicator of genetic risk (endophenotype). Method. A systematic review of the literature was undertaken. Effects sizes were extracted from selected papers and pooled using meta-analytical techniques. Results. In bipolar patients, large effect sizes (d > 0.8) were noted for executive functions (working memory, executive control, fluency) and verbal memory. Medium effect sizes (0.5 < d < 0.8) were reported for aspects of executive function (concept shifting, executive control), mental speed, visual memory, and sustained attention. Small effect sizes (d < 0.5) were found for visuoperception. In first-degree relatives, effect sizes were small (d < 0.5), but significantly different from healthy controls for executive function and verbal memory in particular. Conclusions. Executive function and verbal memory are candidate bipolar endophenotypes given large deficits in these domains in bipolar patients and small, but intermediate, cognitive impairments in first-degree relatives.