High rates of schizophrenia in velo-cardio-facial syndrome. K.C. Murphy^1,2, L.A. Jones¹, M.J. Owen¹. 1) Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK; 2) Department of Psychological Medicine, Institute of Psychiatry, King's College, London, UK.

   Velo-cardio-facial syndrome (VCFS), a syndrome characterised by distinctive dysmorphology, congenital heart disease and learning disabilities, is associated with small interstitial deletions of chromosome 22q11. In view of previous reports of a high prevalence of psychosis in VCFS, we undertook the present study to characterise the psychiatric phenotype in the largest interviewed series to date of adults with VCFS. We evaluated 50 adults with VCFS using a structured clinical interview (Schedules for Clinical Assessment in Neuropsychiatry or Psychiatric Assessment Schedule for Adults with Developmental Disability if IQ < 50) to establish a DSM-IV diagnosis. The schizophrenia phenotype in individuals with VCFS and schizophrenia was compared to a matched series of individuals with schizophrenia without VCFS (n = 12). The Kings Schizotypy Questionnaire was administered to VCFS individuals (n = 41), their first-degree relatives (n = 68) and a series of unrelated normal controls (n = 316). All VCFS individuals were genotyped for a novel promoter polymorphism in the COMT gene and also for a genetic polymorphism in the COMT gene which results in variations in enzymatic activity. Thirty per cent (n = 15) of individuals had psychotic disorder with 24% (n = 12) fulfilling DSM-IV criteria for schizophrenia. In addition, a further 12% (n = 6) had major depression without psychotic features. The individuals with schizophrenia had fewer negative symptoms and a relatively later age of onset compared to individuals with schizophrenia without VCFS. We found no evidence that either a promoter polymorphism or presence of the low activity allele of the COMT gene was associated with psychosis in our sample of individuals with VCFS. The high prevalence of schizophrenia in this group suggests that chromosome 22q11 might harbour a gene or genes of relevance to the aetiology of schizophrenia in the wider population.