We investigated the effect of the parental age at child birth on the age-of-onset (AO) of bipolar disorder in a sample of 336 bipolar I patients directly interviewed with DIGS (DSM-IV-R criteria) in connection with the type of family history (FH): 1) no family history of major psychoses (sporadic); 2) only recurrent unipolar major depression (MDD-RUP); 3) bipolar disorder, schizoaffective disorders or schizophrenia (BP/SA/SCHIZ).

Familial psychopathology data were collected through direct interview about 76% of first-degree relatives and through FH-method (FIGS-interview) about first- and second-degree relatives not available to direct investigation.

Linear/logistic regressions showed a significant effect of the paternal age (PATAGE) on AO in offspring in the total sample (p=0.040); PATAGE was negatively correlated with AO in offspring when interacting with the proband gender (p=0.026) and FH-type (p=0.003). The division of the patients by sex revealed a significant association between PATAGE and AO only in females (p=0.003); the fathers of females with FH of MDD-RUP and the fathers of sporadic females were significantly older than the fathers of females with FH of BP/SA/SCHIZ. The first two groups generated the negative correlation appearing in the total sample. No correlation between PATAGE and proband AO was observed in the third group. Maternal age had no impact on AO in offspring.

The PATAGE effect on AO in bipolar offspring was related to female sex and FH-type and it was detectable in bipolar probands with no familial loading or with milder loading like the MDD-RUP.