Controlled, blindly rated, direct-interview family study of a prepubertal and early-adolescent bipolar I disorder phenotype - Morbid risk, age at onset, and comorbidity

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 x greater familiality in child vs adult BP-I, and family study validation of PEA BP-I, including its differentiation from ADHD.