Age at onset of bipolar disorder related to parental and grandparental illness burden

Objective: The age at onset of bipolar disorder varies greatly in different countries and continents. The association between load of family history of psychiatric illness and age at onset has not been adequately explored. Methods: 979 outpatients with bipolar disorder (from 4 sites in the United States and 3 in the Netherlands and Germany) gave informed consent and completed a questionnaire about their demographics, age at onset of illness, and family history of unipolar and bipolar disorder, alcohol and substance abuse comorbidity, suicide attempts, and "other" illnesses in their parents, 4 grandparents, and any offspring. We examined how the parental and grandparental burden of these illnesses related to the age at onset of the patients? bipolar disorder. Results: The burden of family psychiatric history was strongly related to an earlier age at onset of illness in both US and European patients (F3,906 = 35.42, P < .0001). However, compared to the Europeans, patients in the United States had both more family history of most difficulties and notably earlier age at onset. Earlier age at onset was associated with a greater illness burden in the patient?s offspring (t568 = 4.1, P < .0001). Conclusions: More parental and grandparental psychiatric illness was associated with an earlier age at onset of bipolar disorder, which is earlier in the United States compared with Europe and is strongly related to a poor long-term prognosis. This apparent polygenic contribution to early onset deserves further study and therapeutic attempts at ameliorating the transgenerational impact.