title: Bipolar spectrum disorders in patients diagnosed with velo-cardio-facial syndrome: does a hemizygous deletion of chromosome 22q11 result in bipolar affective disorder?
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Department of Psychiatry, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461, USA.
authors.forename: D F
authors.initials: DF
authors.lastname: Papolos
authors.forename: G L
authors.initials: GL
authors.lastname: Faedda
authors.forename: S
authors.initials: S
authors.lastname: Veit
authors.forename: R
authors.initials: R
authors.lastname: Goldberg
authors.forename: B
authors.initials: B
authors.lastname: Morrow
authors.forename: R
authors.initials: R
authors.lastname: Kucherlapati
authors.forename: R J
authors.initials: RJ
authors.lastname: Shprintzen
mesh_terms: D000015:Abnormalities, Multiple / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D001714:Bipolar Disorder / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D015897:Comorbidity; D019263:Dysthymic Disorder / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D013577:Syndrome