The early manifestations of bipolar disorder: a longitudinal prospective study of the offspring of bipolar parents.

OBJECTIVE: A major aim of this longitudinal high-risk study is to identify reliable early indicators of emerging bipolar disorder (BD) among offspring from well-characterized parents.
METHODS: High-risk offspring were recruited from families in which one parent had BD diagnosed on the basis of the Schedule for Affective Disorders and Schizophrenia - Lifetime version (SADS-L) interviews and DSM-IV diagnostic criteria and the other parent was well. Bipolar parents were further subdivided on the basis of response or non-response to long-term lithium. A comparison group of offspring was recruited from well parents diagnosed on the basis of either SADS-L interviews or the family history method. All consenting offspring from high-risk and control families were assessed longitudinally with the Schedule for Affective Disorders and Schizophrenia for School-aged Children - Present and Lifetime version (KSADS-PL) interviews and DSM-IV diagnoses were made on a blind consensus review. The offspring were reassessed on average annually, as well as at any time symptoms developed.
RESULTS: Antecedent conditions to BD in both high-risk groups included sleep and anxiety disorders, while attention-deficit hyperactivity disorder and pre-psychotic conditions were antecedents among the offspring of lithium non-responders only. Among those offspring developing BD, the index mood episode was almost always depressive.
CONCLUSIONS: Despite a specific genetic risk, BD began with non-specific psychopathology and/or depressive disorders in a majority of offspring. Therefore, diagnosis based only on cross-sectional assessment of symptoms appears to be insufficient for the accurate early detection of emerging BD. Other parameters such as family history and associated antecedents should be taken into account.