Family and genetic association studies of bipolar disorder in children

The risk of bipolar disorder (BPD) (15-42%) in first-degree relatives of children with BPD are consistently larger than the 8.7% estimate of recurrence risk of BPD in first-degree relatives of adult BPD cases. There have been no family linkage studies of pediatric BPD, but secondary analyses of adult linkage samples suggest that early-onset BPD both increases the strength of associations in linkage studies. Positive associations with pediatric BPD and the BDNF gene (Vall66), the GAD1 gene (4s2241165), and the dopamine transporter gene (rs41084) have been reported but none of these associations have been replicated in independent samples. The number of informative families examined so far is quite small and studies were vastly underpowered to detect small effects. An adequately powered sample will likely require collaborative ascertainment of cases and families from multiple sites using valid and accepted measures of pediatric BPD.