Assuntos
Transtorno Bipolar/genética , Proteínas de Ligação a DNA/genética , Proteínas Nucleares/genética , Polimorfismo Genético , Idade de Início , Predisposição Genética para Doença , Humanos , Regiões Promotoras Genéticas , Fatores de Transcrição de Fator Regulador X , Fatores de Transcrição , Proteína 1 de Ligação a X-BoxRESUMO
OBJECTIVE: The authors previously reported an association between the D-amino acid oxidase activator (DAOA)/G30 locus and both schizophrenia and bipolar affective disorder. Given the presumed role of DAOA/G30 in the neurochemistry of psychosis and its localization in a schizophrenia and bipolar affective disorder linkage region (13q34), it was hypothesized that the bipolar affective disorder finding would be mainly due to an association with psychotic features. METHOD: The marker/haplotype associations obtained in a subset of 173 bipolar affective disorder patients with psychotic features were similar to those in the overall patient group, suggesting that stratification on the basis of psychotic features in general might be too crude a procedure. The authors therefore tested whether confining caseness to specific psychotic features would improve detection of genotype-phenotype correlations. RESULTS: In a logistic regression, "persecutory delusions" were found to be the only significant explanatory variable for the DAOA/G30 risk genotype among 21 OPCRIT symptoms of psychosis. The authors therefore tested for association between DAOA/G30 and bipolar affective disorder in the 90 cases with a history of persecutory delusions. Whereas this subset showed strong association (odds ratio=1.83 for the best marker), the remaining larger sample of 165 patients with no such history did not differ from comparison subjects, suggesting that the association between DAOA/G30 and bipolar affective disorder is due to persecutory delusions. This was confirmed in an independent study of 294 bipolar affective disorder patients and 311 comparison subjects from Poland, in which an association between bipolar affective disorder and DAOA/G30 was only seen when case definition was restricted to cases with persecutory delusions. CONCLUSIONS: These data suggest that bipolar affective disorder with persecutory delusions constitutes a distinct subgroup of bipolar affective disorder that overlaps with schizophrenia.
Assuntos
Transtorno Bipolar/classificação , Transtorno Bipolar/genética , Proteínas de Transporte/genética , Delusões/genética , Fenótipo , Adulto , Transtorno Bipolar/psicologia , Mapeamento Cromossômico , Cromossomos Humanos Par 13/genética , Delusões/classificação , Delusões/diagnóstico , Feminino , Ligação Genética , Marcadores Genéticos , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Biologia Molecular/métodos , Transtornos Paranoides/classificação , Transtornos Paranoides/diagnóstico , Transtornos Paranoides/genética , Esquizofrenia/genética , Psicologia do EsquizofrênicoRESUMO
The proline dehydrogenase locus must be considered as a positional and functional candidate in schizophrenia. It is located in the chromosomal region of the velocardiofacial syndrome on 22q11 that is suspected to contain genes relevant to schizophrenia, and is involved in the metabolism of neurotransmitters. Positive association between single-nucleotide polymorphisms at the proline dehydrogenase locus and schizophrenia further supported the role of proline dehydrogenase in the development of schizophrenia. In order to replicate these findings, we analyzed three single-nucleotide polymorphisms in a sample comprising 299 schizophrenic patients and 300 controls. In addition, we assessed whether proline dehydrogenase also contributes to bipolar affective disorder, because chromosome 22q11 is also implicated in bipolar affective disorder. We therefore included 300 patients with bipolar affective disorder. This is the first study on a potential involvement of the proline dehydrogenase locus in bipolar affective disorder. Neither single marker nor haplotype analysis revealed an association between variants at the proline dehydrogenase locus and schizophrenia or bipolar affective disorder.
Assuntos
Transtorno Bipolar/genética , Polimorfismo de Nucleotídeo Único , Prolina Oxidase/genética , Esquizofrenia/genética , HumanosRESUMO
We previously reported an association of DRD4 exon 3 long alleles with delusional symptomatology, independently from psychiatric diagnoses [Am. J. Med. Genet. 105 (2001) 283; Psychiatry Res. 80 (1998) 129]. The aim of this investigation was to replicate these results in an independent sample from Germany. We studied 394 subjects, affected by bipolar disorder (n = 32), schizoaffective disorder (n = 45), and schizophrenia (n = 317). All affected subjects were evaluated using the Operational Criteria for Psychotic Illness (OPCRIT) checklist. DRD4 variants were not associated with symptomatology of major psychosis. Our present results, obtained in an independent German sample, did not confirm the association between DRD4 variants and delusional symptomatology. However it should be considered that the original sample included a much higher rate of mood disorders and this could partially explain the discrepancy.