BIPOLAR SPECTRUM DISORDERS IN PATIENTS DIAGNOSED WITH VELO-CARDIO-FACIAL SYNDROME - DOES A HEMIZYGOTIC DELETION OF CHROMOSOME 22Q11 RESULT IN BIPOLAR AFFECTIVE-DISORDER

Objective: The purpose of this study was to conduct a systematic asses sment of psychiatric illness in Patients diagnosed with velo-cardio-fa cial syndrome, a genetic syndrome that involves over 40 somatic anomal ies, learning disabilities, and behavioral disorders and is associated with a microdeletion on chromosome 22q11. Method: Subjects were refer red for psychiatric diagnostic evaluation without regard to age or pre vious psychiatric history. In order to establish DSM-III-R consensus c linical diagnoses for patients who ranged in age from 5 to 34 years, t he Diagnostic Interview for Children and Adolescents-Revised or the St ructured Clinical Interview for DSM-III-R (SCID) was used. A review of available medical and Psychiatric records and a clinical interview pe rformed by two research psychiatrists to validate specific symptoms an d syndromes reported in the Diagnostic Interview for Children and Adol escents-Revised and the SCID were used to elucidate the chronological appearance and duration of symptoms. Results: Sixty-four percent (N=16 of 25) of this unselected series of patients with velo-cardio-facial syndrome met DSM-III-R criteria for a spectrum of bipolar disorders wi th full syndromal onset in late childhood or early adolescence (mean a ge at onset=12 years, SD=3). In addition, 20% (N=5) met DSM-III-R crit eria for attention deficit hyperactivity disorder (ADHD), while 16% (N =4) met criteria for attention deficit disorder without hyperactivity. In contrast to previous reports of a high prevalence of schizophrenia , none of the patients was diagnosed with schizophrenia, and only four had psychotic symptoms during a phase of their illness, all in their 20s or 30s. Conclusions: Given that the prevalence of bipolar disorder in the general population is estimated to be 1.5% and that the averag e age at onset is 24, these findings support an unusually strong assoc iation between velo-cardio-facial syndrome and early-onset bipolar dis order and suggest that a gene deleted at the 22q11 chromosomal locus m ay be involved in its pathogenesis. If confirmed, these findings may P rovide a new and fruitful line of investigation into the molecular bas is of bipolar spectrum disorders.