Clinical endophenotypes for bipolar disorder

Although twin, family, and adoption studies demonstrate that bipolar disorder (BPD) is substantially heritable, the molecular genetic basis for this illness remains elusive. Given evidence that genes predisposing to BPD may be transmitted without expression of the clinical phenotype, interest has arisen in developing endophenotypes - indicators of processes mediating between genotype and phenotype. Patients with BPD have subtle neuropsychological abnormalities, even during periods of symptom remission. Some of these neurocognitive deficits are present in unaffected family members of probands with BPD, suggesting that these measures may be quantitative endophenotypes for the disorder. Similarly, BPD is associated with specific personality traits (e.g., reduced inhibition, increased risk-taking) that have been observed in both affected individuals and their family members. In this chapter, we review the evidence for candidate neurocognitive and personality endophenotypes for BPD. We conclude that neurocognitive and personality traits appear to be appropriate endophenotypes for BPD, suggesting that these measures share some genetic factors with the illness.