High Rates of Schizophrenia in Adults With Velo-Cardio-Facial Syndrome

Abstract

Background: Velo-cardio-facial syndrome (VCFS), a syndrome characterized by an increased frequency of schizophrenia and bipolar disorder, is associated with small interstitial deletions of chromosome 22q11. Methods: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 Ͻ50) to establish a DSM-IV diagnosis. The schizophrenia phenotype in individuals with VCFS and schizophrenia was compared with a matched series of individuals with schizophrenia and without VCFS (n = 12). The King's Schizotypy Questionnaire was administered to individuals with VCFS (n = 41), their first-degree relatives (n = 68), and a series of unrelated normal controls (n = 316). All individuals with VCFS deleted for the N25 probe (n = 48) were genotyped for a genetic polymorphism in the COMT gene that results in variations in enzymatic activity.Results: Fifteen individuals with VCFS (30%) had a psychotic disorder, with 24% (n = 12) fulfilling DSM-IV criteria for schizophrenia. In addition, 6 (12%) had major depression without psychotic features. The individuals with schizophrenia had fewer negative symptoms and a relatively later age of onset compared with those with schizophrenia and without VCFS. We found no evidence that possession of the low-activity COMT allele was associated with schizophrenia in our sample of individuals with VCFS. Conclusions:The high prevalence of schizophrenia in this group suggests that chromosome 22q11 might harbor a gene or genes relevant to the etiology of schizophrenia in the wider population.

Schizophrenia and 22q11.2 deletion syndrome

“…Other psychotic disorders are also found, but sample sizes are still small (Table 2). In contrast, rates of bipolar disorder appear to be similar to those in the general population [7]. One case of bipolar disorder was found in the 105 adults with 22qDS we assessed through our center; rates of anxiety, depressive, and attention-deficit disorders are higher than population expectations (Bassett and Chow, unpublished data).…”

“…Several (but not all) reports [7,10] have indicated that with respect to schizophrenia's major clinical features, 22qDS-schizophrenia is largely indistinguishable from other forms of schizophrenia [11]. Ascertainment may play a role in differences observed.…”

“…The only study using a sample that did not include psychiatric ascertainment, which was systematically collected from a congenital cardiac clinic, reported 22.6% (95% CI, 7.0% to 38%) of adults with 22qDS had schizophrenia or schizoaffective disorder [2••]. Other studies using mixed-ascertainment strategies that included psychiatric sources reported slightly higher rates of 27% (13/48) [7] and 31% (4/13) [8]. Other psychotic disorders are also found, but sample sizes are still small (Table 2).…”

“…Ascertainment may play a role in differences observed. For example, median age at onset varies from 12 years for a sample restricted to childhood-onset schizophrenia [10] to 26 years when case identification involved parents who had transmitted the deletion to affected children [7]. The latter ascertainment strategy may also explain a finding of less severe negative symptoms [7] that was not found in a larger sample with no transmitting parents [12].…”

Discussing the psychiatric manifestations of 22q11.2 deletion syndrome: an exploration of clinical practice among medical geneticists

“…2,3 In addition, individuals with 22q11DS seem to have elevated rates of attention-deficit hyperactivity disorder, anxiety, oppositional defiant disorder, and autism spectrums disorders, and approximately 25-30% of individuals with 22q11DS develop schizophrenia or other psychotic disorders. [3][4][5][6][7][8][9][10][11][12][13] In a 2008 study, parents of individuals with 22q11DS (n = 41) reported that psychiatric disorders were their second most important cause for concern related to the syndrome (after learning disabilities) and that of all the manifestations of the condition, psychiatric disorders were the source of their greatest anxiety. 14 In addition, and crucially, many parents reported that they did not receive information about the psychiatric risks associated with 22q11DS from their health-care provider but instead obtained information about these risks from the Internet.…”