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

Arch Gen Psychiatry. 2006 Oct;63(10):1130-8. 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 8x greater familiality in child vs adult BP-I, and family study validation of PEA-BP-I, including its differentiation from ADHD.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Age Factors
  • Age of Onset
  • Anticipation, Genetic
  • Attention Deficit Disorder with Hyperactivity / diagnosis
  • Attention Deficit Disorder with Hyperactivity / epidemiology
  • Attention Deficit Disorder with Hyperactivity / genetics
  • Bipolar Disorder / diagnosis
  • Bipolar Disorder / epidemiology
  • Bipolar Disorder / genetics*
  • Child
  • Comorbidity
  • Disease Susceptibility / diagnosis
  • Disease Susceptibility / epidemiology
  • Family Health
  • Female
  • Follow-Up Studies
  • Genomic Imprinting
  • Humans
  • Male
  • Phenotype
  • Prevalence
  • Prospective Studies
  • Psychiatric Status Rating Scales
  • Research Design
  • Risk Factors
  • Siblings