Abstract

Efforts to identify genetic loci for bipolar disorder (BPD) have thus far proved elusive. The identification of processes mediating between genotype and phenotype (endophenotypes) may help resolve the carrier status of family members in genetic studies of polygenetic disorders with imperfect penetrance, such as BPD. We reviewed the literature to determine if neuropsychological measures could be used as effective endophenotypes to aid molecular genetic studies searching for genes predisposing to BPD. Four prerequisites for endophenotypic markers are described, and a critical review of relevant literature was undertaken to determine if neurocognitive measures satisfy these four requirements in BPD. We found evidence that executive functions and declarative memory may be candidate neurocognitive endophenotypes for BPD. However, we cannot exclude other areas of cognition as being affected by BPD susceptibility genes, given the limits of the current knowledge of the neuropsychology of BPD. In particular, the paucity of studies measuring cognition in healthy relatives of BPD patient limits conclusion regarding familial aggregation of particular neurocognitive deficits (i.e. attention). Furthermore, the effects of clinical state and/or medication usage on cognitive functioning in BPD probands should be further explored. Molecular genetic studies of BPD may benefit from the application of select neuropsychological measures as endophenotypic markers. The use of these markers, once defined, may improve power for detecting genes predisposing to BPD and may help to better define diagnostic criteria.

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