Clinical correlates and familial aggregation of age at onset in bipolar disorder

Ping I. Lin, Melvin G. McInnis, James Bennett Potash, Virginia Willour, Dean F Mackinnon, J Raymond Depaulo, Peter P Zandi

Research output: Contribution to journalArticle


Objective: To assess whether age at onset variation reflects underlying genetic heterogeneity in bipolar disorder, the authors examined the clinical and familial characteristics of age at onset in bipolar disorder subjects from families with multiple affected members. Method: A total of 211 families with 1,856 subjects were ascertained through bipolar I disorder probands. All the subjects were assessed with the Diagnostic Interview for Genetic Studies and assigned diagnoses by trained clinicians using best estimate procedures. Admixture analysis with the 211 bipolar disorder probands was used to decompose the age-at-onset distribution into a mixture of theoretical normal distributions. Logistic regression with general estimating equations was then used to examine clinical correlates and familial aggregation of age at onset in all 717 bipolar disorder subjects. Results: The age-at-onset distribution consisted of a mixture of three normal distributions with means of 16.6 (SD=5.1), 26.0 (SD=1.4), and 34.7 (SD=6.6) years that comprised 79.7%, 7.2%, and 13.1% of the group, respectively. Cutoff points at ages 21 and 28 were derived from this analysis and used to define age-at-onset subgroups. Early-onset (age at onset ≤21) subjects had higher risks of drug abuse, alcohol abuse, rapid cycling, and suicide attempts. Affected subjects from a family with an early-onset proband were more likely than others to have an early onset (odds ratio=4.53, 95% CI=3.09-6.64). Subjects from a family with a proband whose age at onset was

Original languageEnglish (US)
Pages (from-to)240-246
Number of pages7
JournalAmerican Journal of Psychiatry
Issue number2
StatePublished - Feb 2006

ASJC Scopus subject areas

  • Psychiatry and Mental health

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