Cognitive endophenotypes of bipolar disorder: A meta-analysis of neuropsychological deficits in euthymic patients and their first-degree relatives

Background: Our aim was to delineate neuropsychological deficits related to genetic susceptibility, illness process and iatrogenic factors in bipolar disorder (BD). Methods: Following an extensive publication search on several databases, meta-analyses were conducted for 18 cognitive variables in studies that compared performances of euthymic BD patients (45 studies; 1423 subjects) or first-degree relatives of BD patients (17 studies; 443 subjects) with healthy controls. The effect of demographic variables and confounding factors like age of onset, duration of illness and medication status were analysed using the method of meta-regression. Results: While response inhibition, set shifting, executive function, verbal memory and Sustained attention deficits were common features for both patient (medium to large effect sizes) and relative groups (small to medium effect sizes), processing speed, visual memory and verbal fluency deficits were only observed in patients. Medication effects contributed to psychomotor slowing in BD patients. Earlier age of onset was associated with verbal memory impairment and psychomotor slowing. Limitation: Data related to some confounding variables was not reported in a substantial lumber of extracted studies. Conclusions: Response inhibition deficit, a potential marker of ventral prefrontal dysfunction, seems to be the most prominent endophenotype of BD. The cognitive endophenotype of BD also appears to involve fronto-temporal and fronto-limbic related cognitive impairments. Processing speed impairment is related, at least partly, to medication effects indicating the influence of confounding factors rather than genetic susceptibility. Patterns of sustained attention and processing speed impairments differ from schizophrenia. Future work in this area should differentiate cognitive deficits associated with disease genotype from impairments related to other confounding factors. (C) 2008 Elsevier B.V. All rights reserved.