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Original Article
October 2006

Controlled, Blindly Rated, Direct-Interview Family Study of a Prepubertal and Early-Adolescent Bipolar I Disorder Phenotype: Morbid Risk, Age at Onset, and Comorbidity

Author Affiliations

Author Affiliations: Department of Psychiatry, Washington University in St Louis, St Louis, Mo.

Arch Gen Psychiatry. 2006;63(10):1130-1138. doi:10.1001/archpsyc.63.10.1130

Context  A key question is whether a prepubertal and early-adolescent bipolar I disorder phenotype (PEA–BP-I) is the same illness as adult BP-I. This question arises because of the greater severity, longer current episode duration, preponderance of mania, and high rates of ultradian rapid cycling and comorbid attention-deficit/hyperactivity disorder (ADHD) in PEA–BP-I.

Objectives  To examine morbid risk (MR) of BP-I in first-degree relatives of PEA–BP-I, ADHD, and healthy control probands, as well as imprinting, sibling recurrence risk, and anticipation.

Design  Controlled, blind direct interview. There were no family psychopathology exclusions for any proband group.

Setting  University medical school research unit.

Participants  First-degree relatives 6 years and older (n = 690) of 219 probands (95 with PEA–BP-I, 47 with ADHD, and 77 healthy controls). The PEA–BP-I and ADHD probands were obtained by consecutive new case ascertainment, and healthy controls were from a random survey; proband diagnoses were validated via 4-year prospective follow-up. The PEA–BP-I probands had a mean ± SD age of 10.8 ± 2.6 years.

Main Outcome Measure  Morbid risk.

Results  The MR of BP-I was higher in relatives of PEA–BP-I probands compared with ADHD or healthy controls (P<.001 for both); the MR in relatives of ADHD and healthy controls was similar. The MR of BP-I in relatives with ADHD was higher (P<.001) and age at onset of BP-I was younger in parents with ADHD than in those without (P<.001). The MR of BP-I in relatives with oppositional, conduct, or antisocial disorders was higher than in those without (P<.001). Anticipation was evidenced by a younger age at onset of BP-I in probands than in their parents (P<.001). No imprinting was found.

Conclusions  Findings support that PEA–BP-I and adult BP-I are the same diathesis, 7 to 8× greater familiality in child vs adult BP-I, and family study validation of PEA–BP-I, including its differentiation from ADHD.