Bipolar spectrum disorders in patients diagnosed with velo-cardio-facial syndrome: does a hemizygous deletion of chromosome 22q11 result in bipolar affective disorder?

Am J Psychiatry. 1996 Dec;153(12):1541-7. doi: 10.1176/ajp.153.12.1541.


Objective: The purpose of this study was to conduct a systematic assessment of psychiatric illness in patients diagnosed with velo-cardio-facial syndrome, a genetic syndrome that involves over 40 somatic anomalies, learning disabilities, and behavioral disorders and is associated with a microdeletion on chromosome 22q11.

Method: Subjects were referred for psychiatric diagnostic evaluation without regard to age or previous psychiatric history. In order to establish DSM-III-R consensus clinical diagnoses for patients who ranged in age from 5 to 34 years, the Diagnostic Interview for Children and Adolescents--Revised or the Structured Clinical Interview for DSM-III-R (SCID) was used. A review of available medical and psychiatric records and a clinical interview performed by two research psychiatrists to validate specific symptoms and syndromes reported in the Diagnostic Interview for Children and Adolescents--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 with full syndromal onset in late childhood or early adolescence (mean age at onset = 12 years, SD = 3). In addition, 20% (N = 5) met DSM-III-R criteria 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 average age at onset is 24, these findings support an unusually strong association between velo-cardio-facial syndrome and early-onset bipolar disorder and suggest that a gene deleted at the 22q11 chromosomal locus may be involved in its pathogenesis. If confirmed, these findings may provide a new and fruitful line of investigation into the molecular basis of bipolar spectrum disorders.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abnormalities, Multiple / epidemiology
  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / psychology
  • Adolescent
  • Adult
  • Attention Deficit Disorder with Hyperactivity / diagnosis
  • Attention Deficit Disorder with Hyperactivity / epidemiology
  • Attention Deficit Disorder with Hyperactivity / genetics
  • Bipolar Disorder / diagnosis
  • Bipolar Disorder / epidemiology
  • Bipolar Disorder / genetics*
  • Child
  • Child, Preschool
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 22 / genetics*
  • Comorbidity
  • Dysthymic Disorder / diagnosis
  • Dysthymic Disorder / epidemiology
  • Dysthymic Disorder / genetics
  • Female
  • Humans
  • Male
  • Psychiatric Status Rating Scales
  • Psychotic Disorders / diagnosis
  • Psychotic Disorders / epidemiology
  • Psychotic Disorders / genetics
  • Syndrome