Schizophrenia and velocardio-facial syndrome

Abstract

Kieran Murphy1Murphy KC Schizophrenia and velo-cardiofacial syndrome..Lancet. 2002; 359: 426-430Summary Full Text Full Text PDF PubMed Scopus (246) Google Scholar describes VCFS as a powerful model for identifying susceptibility genes for schizophrenia. Molecular studies now suggest common genetic liability between schizophrenia and bipolar (affective) disorder at several susceptibility loci, including the chromosome 22q region implicated in VCFS.2Berrettini WH Are schizophrenic and bipolar disorders related? A review of family and molecular studies..Biol Psychiatry. 2000; 48: 531-538Summary Full Text Full Text PDF PubMed Scopus (260) Google ScholarAlthough modern diagnostic systems differentiate between these disorders, psychotic symptoms (delusions and hallucinations) are common to both, and a subgroup of patients who meet criteria for both disorders are diagnosed as having schizoaffective disorder. Since the two most common functional psychotic disorders, schizophrenia and bipolar disorder, share common epidemiological features, risk factors, and response to antipsychotic treatment. Differences between them detected by imaging or neuropathology are qualitative rather than quantitative.As an alternative, a continuum of psychosis has been proposed, in which patients described as having bipolar disorder, schizoaffective disorder, and schizophrenia represent increasingly severe psychotic symptoms.3Crow TJ The continuum of psychosis and its implication for the structure of the gene..Br J Psychiatry. 1986; 149: 419-429Crossref PubMed Scopus (228) Google Scholar The pathobiology involved is poorly understood, but may involve abnormal information processing. As described by Murphy, prepulse inhibition deficits have been widely studied in schizophrenia, and are proposed to represent a core neurobiological deficit that is expressed through psychotic symptoms. If this is the case, information-processing deficits would also be expected in other psychotic disorders, and have been confirmed in psychotic bipolar disorder.4Perry W Minassian A Feifel D Braff DL Sensorimotor gating deficits in bipolar disorder patients with acute psychotic mania..Biol Psychiatry. 2001; 50: 418-424Summary Full Text Full Text PDF PubMed Scopus (210) Google Scholar Therefore, the information-processing deficit mapped to the VCFS region in a mouse model and described by Murphy, as a phenotype associated with schizophrenia is more accurately a psychosis phenotype.On the basis of this evidence, VCFS is best represented as a model of genetic liability to functional psychosis rather than to any specific diagnosis. The chromosome 22q locus involved in VCFS has been linked to major functional psychotic disorders, and the rate of functional psychosis is increased in patients with VCFS (10–30%) compared with that in the normal population (1%). Attempts to assign a more specific psychiatric diagnosis to VCFS patients has been less successful; although most of the psychotic patients in the Murphy series had a diagnosis of schizophrenia (80%), most of the patients (64%) described by Papolos and colleagues5Papolos DF Faedda GL Veit S et al.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; 153: 1541-1547Crossref PubMed Scopus (329) Google Scholar met criteria for bipolar disorder.VCFS can be seen as a model of the phenotypic difficulties that mire psychiatric geneticists, restrained as we are by clinical diagnosis. Existing evidence may show the potential of VCFS in identifying psychosis genes and improve biological understanding of this process across several psychiatric disorders. Kieran Murphy1Murphy KC Schizophrenia and velo-cardiofacial syndrome..Lancet. 2002; 359: 426-430Summary Full Text Full Text PDF PubMed Scopus (246) Google Scholar describes VCFS as a powerful model for identifying susceptibility genes for schizophrenia. Molecular studies now suggest common genetic liability between schizophrenia and bipolar (affective) disorder at several susceptibility loci, including the chromosome 22q region implicated in VCFS.2Berrettini WH Are schizophrenic and bipolar disorders related? A review of family and molecular studies..Biol Psychiatry. 2000; 48: 531-538Summary Full Text Full Text PDF PubMed Scopus (260) Google Scholar Although modern diagnostic systems differentiate between these disorders, psychotic symptoms (delusions and hallucinations) are common to both, and a subgroup of patients who meet criteria for both disorders are diagnosed as having schizoaffective disorder. Since the two most common functional psychotic disorders, schizophrenia and bipolar disorder, share common epidemiological features, risk factors, and response to antipsychotic treatment. Differences between them detected by imaging or neuropathology are qualitative rather than quantitative. As an alternative, a continuum of psychosis has been proposed, in which patients described as having bipolar disorder, schizoaffective disorder, and schizophrenia represent increasingly severe psychotic symptoms.3Crow TJ The continuum of psychosis and its implication for the structure of the gene..Br J Psychiatry. 1986; 149: 419-429Crossref PubMed Scopus (228) Google Scholar The pathobiology involved is poorly understood, but may involve abnormal information processing. As described by Murphy, prepulse inhibition deficits have been widely studied in schizophrenia, and are proposed to represent a core neurobiological deficit that is expressed through psychotic symptoms. If this is the case, information-processing deficits would also be expected in other psychotic disorders, and have been confirmed in psychotic bipolar disorder.4Perry W Minassian A Feifel D Braff DL Sensorimotor gating deficits in bipolar disorder patients with acute psychotic mania..Biol Psychiatry. 2001; 50: 418-424Summary Full Text Full Text PDF PubMed Scopus (210) Google Scholar Therefore, the information-processing deficit mapped to the VCFS region in a mouse model and described by Murphy, as a phenotype associated with schizophrenia is more accurately a psychosis phenotype. On the basis of this evidence, VCFS is best represented as a model of genetic liability to functional psychosis rather than to any specific diagnosis. The chromosome 22q locus involved in VCFS has been linked to major functional psychotic disorders, and the rate of functional psychosis is increased in patients with VCFS (10–30%) compared with that in the normal population (1%). Attempts to assign a more specific psychiatric diagnosis to VCFS patients has been less successful; although most of the psychotic patients in the Murphy series had a diagnosis of schizophrenia (80%), most of the patients (64%) described by Papolos and colleagues5Papolos DF Faedda GL Veit S et al.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; 153: 1541-1547Crossref PubMed Scopus (329) Google Scholar met criteria for bipolar disorder. VCFS can be seen as a model of the phenotypic difficulties that mire psychiatric geneticists, restrained as we are by clinical diagnosis. Existing evidence may show the potential of VCFS in identifying psychosis genes and improve biological understanding of this process across several psychiatric disorders. Schizophrenia and velocardio-facial syndromeAuthor's reply Full-Text PDF