摘要:

Australian research in psychiatric genetics covers molecular genetic studies of depression, anxiety, alcohol dependence, Alzheimer's disease, bipolar disorder, schizophrenia, autism, and attention deficit hyperactivity disorder. For each disorder, a variety of clinical cohorts have been recruited including affected sib pair families, trios, case/controls, and twins from a large population-based twin registry. These studies are taking place both independently and in collaboration with international groups. Microarray studies now complement DNA investigations, while animal models are in development. An Australian government genome facility provides a high throughput genotyping and mutation detection service to the Australian scientific community, enhancing the contribution of Australian psychiatric genetics groups to gene discovery.

ISSN:0955-8829    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectivesSeveral studies reported contradictory findings regarding the association of major psychosis with CAG repeats in the KCNN3 gene. We investigated the contribution of the CAG repeat at the KCNN3 gene, localized to chromosome 1q21.3, to the genetic susceptibility for schizophrenia, schizoaffective and bipolar disorders.MethodsAnalysis of the number of CAG repeats and the differences in allele length were performed for Israeli Ashkenazi Jews, non-Ashkenazi Jews, and Arabs diagnosed with major psychosis (n=181) versus matched ethnic controls (n=207).ResultsWe found no significant difference in the number of CAG repeats between the entire sample of patients and controls. However, an analysis of the differences of allele length revealed a significantly greater number of patients with identical allele length (43.1%) when compared with normal controls (30.4%). Furthermore, an earlier age of non-paranoid schizophrenia onset was found associated with differences in allele sizes. There were no significant differences in the number of CAG repeats and the differences in allele length when subjects were grouped according to gender, ethnic origins of their parents, family history, and diagnostic groups.ConclusionsOur results support the hypothesis that a contribution of the KCNN3 gene to genetic susceptibility to major psychosis and their phenotypic polymorphism may be related to the difference of allele length rather than to the number of CAG repeats.

ISSN:0955-8829    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectivesAlterations in the level of the serotonin, serotonin uptake and the number of binding sites have been linked to affective illness. We investigated the association of tryptophan hydroxylase gene polymorphisms and unipolar depression in a case–control study design.MethodsPatients and ethnically matched controls were genotyped for three polymorphisms of the tryptophan hydroxylase gene.ResultsSignificant difference in genotype frequency between patient and control groups was observed for the IVS7+218A>C polymorphism but not for the two promoter polymorphisms −1067G>A and −347T>G. Strong linkage disequilibrium among the three polymorphisms was also observed.ConclusionsAs the sample size was small, the positive association would need to be replicated by family-based association studies or in a larger set of samples. As our results did not indicate association with either of the two promoter polymorphisms, there is a need to continue the search for the causative variant directly involved in the susceptibility to unipolar depression in Chinese as this polymorphism within the intron might not be the true susceptibility variant.

ISSN:0955-8829    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveSelective breeding has been employed to develop replicate high-alcohol-drinking (HAD1 and HAD2) and low-alcohol-drinking (LAD1 and LAD2) rat lines from the heterogeneous N/Nih rat. Within-family selection and a rotational breeding design were used to discourage inbreeding (Li et al., 1993). A genome screen was previously performed using 459 HAD1×LAD1 F2 progeny to identify quantitative trait loci (QTLs) on rat chromosomes 5, 10, 12 and 16 that contribute to alcohol preference and consumption in these non-inbred rat models of alcoholism.MethodsTo confirm these QTLs in the replicate lines, 16 HAD2 and 16 LAD2 rats were genotyped for microsatellite markers within each of these QTL intervals.ResultsReview of the genotypic data support confirmation of the QTLs on chromosomes 5 and 10; several markers in the QTL region display different alleles in the HAD2 and LAD2 rats, suggesting linkage disequilibrium between the microsatellite markers and the QTL. Although the QTL on chromosome 12 had the highest LOD score in the HAD1 and LAD1 studies, little evidence supported confirmation of this QTL based on the genotyped markers.ConclusionsFurther evaluation of each of these QTL regions is ongoing in a sample of HAD2×LAD2 F2 progeny currently being generated that will be used to assess the evidence of linkage in each of these QTL regions.

ISSN:0955-8829    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveThe purpose of this study was to examine whether the neuroleptic-induced extrapyramidal symptoms are associated with the CYP2D6 activity.MethodsThe CYP2D6 gene polymorphisms (CYP2D6*2, CYP2D6*3, CYP2D6*4, CYP2D6*10, and CYP2D6*12) were genotyped in 196 normal controls and 320 schizophrenic patients receiving neuroleptics. The relationships with susceptibility to extrapyramidal symptoms (EPS) and tardive dyskinesia, and with steady-state serum haloperidol levels in maintenance therapy, were investigated.ResultsThe allele frequency of CYP2D6*2 was significantly higher, while that of CYP2D6*10 tended to be higher in the schizophrenic patients susceptible to acute EPS. The steady-state serum haloperidol levels per daily dosage were observed to be significantly higher in schizophrenic patients with the mutant-type homozygote of CYP2D6*2, while this difference was trend level in those of CYP2D6*10. However, no significant difference was observed in the distribution of both CYP2D6*2 (C2938T) and CYP2D6*10 (C188T) polymorphisms between schizophrenic patients with or without tardive dyskinesia.ConclusionThe present results suggest that the homozygotes of CYP2D6*2 and CYP2D6*10 appear to be a susceptibility factor for developing acute EPS in schizophrenic patients and for impaired neuroleptic metabolism in Japanese schizophrenic patients.

ISSN:0955-8829    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectivesTwin, family and adoption studies have suggested that vulnerability to opioid dependence may be a partially inherited trait (Cadoret et al., 1986;Merikangas et al., 1998;Tsuang et al., 1998, 2001). Studies using animal models also support a role for genetic factors in opioid dependence, and point to a locus of major effect on mouse chromosome 10 (Berrettini et al., 1994;Alexander et al., 1996), which harbors the mu opioid receptor gene (Mor1) (Kozak et al., 1994). The gene encoding the human mu opioid receptor (OPRM1) is thus an obvious candidate gene for contributing to opioid dependence. A recent report (Hoehe et al., 2000) found a significant association between a specific combination of OPRM1 single nucleotide polymorphisms (SNPs) and substance dependence.MethodsIn the current study, we genotyped 213 subjects with severe opioid dependence (89 African-Americans, 124 European-Americans) and 196 carefully screened ‘supercontrol’ subjects (96 African-Americans, 100 European-Americans) at five SNPs residing in the OPRM1 gene. The polymorphisms include three in the promoter region (T–1793A,–1699T insertion and A–1320G) and two in exon 1 (C+17T [Ala6Val] and A+118G [Asp40Asn]).ResultsStatistical analysis of the allele frequency differences between opioid-dependent and control subjects for each of the polymorphisms studied yielded P values in the range of 0.444–1.000. Haplotype analysis failed to identify any specific combination of SNPs associated with the phenotype.ConclusionsDespite reasonable statistical power we found no evidence of association between the five mu opioid receptor polymorphisms studied and severe opioid dependence in our sample. There were, however, significant allele frequency differences between African-Americans and European-Americans for all five polymorphisms, irrespective of drug-dependent status. Linkage disequilibrium analysis of the African-American genotypes indicated linkage disequilibrium (P<0.0001) across the five-polymorphism, 1911 base pair region. In addition, only four haplotypes of these five polymorphisms are predicted to exist in African-Americans.

ISSN:0955-8829    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveDisturbances in catecholamine transmission have been implicated in schizophrenia. Dopamine &bgr;-hydroxylase catalyses the conversion of dopamine to norepinephrine in noradrenergic cells. We attempted to investigate a putative functional promoter polymorphism in the dopamine &bgr;-hydroxylase gene (DBH) for association with schizophrenia.MethodsUnrelated schizophrenic patients (n=155) and control subjects (n=436) were analysed with regard to the DBH –1021 C/T variant.ResultsNo significant allele or genotype differences were found.ConclusionsThe present results do not support a major involvement of the DBH gene in schizophrenia in the Swedish population investigated.

ISSN:0955-8829    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveThe present study was aimed at examining the association between the –G308A tumour necrosis factor-&agr; gene polymorphism and major depressive disorder (MDD) in the Korean population.MethodsOne hundred and eight in-patients with MDD and 125 healthy controls participated in this study. Genotyping was performed by polymerase chain reaction–restriction fragment length polymorphism.ResultsGenotype and allele distributions in patients with MDD (P=0.024 andP=0.0125, respectively), were significantly different from those of the controls. In particular, subjects with MDD had an increased frequency of the TNF2 (A) allele.ConclusionThe present study suggests that the –G308A tumour necrosis factor-&agr; gene polymorphism may have a potential role for susceptibility to MDD in the Korean population.

ISSN:0955-8829    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectivesThere has been a recent resurgence in interest in the role of autoimmunity in childhood neuropsychiatric disorders. Significant association between HLA-DRB1 and attention deficit hyperactivity disorder (ADHD) in a case–control study of 31 subjects has been reported but there have been no other published studies following up these results. We attempted to replicate these findings.MethodsIn a well-characterized sample of 173 children with ADHD, using a fully automated sequence-specific oligonucleotide method for HLA genotyping, association between ADHD and HLA-DRB1 was tested for using the Transmission Disequilibrium Test and case–control analysis.ResultsTransmission Disequilibrium Test analysis yielded a chi-square of 10.694 with a simulated globalPvalue of 0.1641 for the full sample, and a chi-square value of 11.307 with a simulated globalPvalue of 0.1323 for the complete trios only.ConclusionThere was no evidence of association of HLA-DRB1 and ADHD.

ISSN:0955-8829    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectivesTo investigate the influence of a functional polymorphism of the dopamine D3 receptor (DRD3), and assess its interaction with a Mn superoxide dismutase (MnSOD) polymorphism, in contributing to tardive dyskinesia in a chronic inpatient population with schizophrenia.MethodsChinese Han patients with schizophrenia were assessed for abnormal involuntary movements, and subgroups of 42 patients with persistent tardive dyskinesia and 59 consistently without dyskinesias were assessed for the DRD3 ser9gly and the MnSOD ala-9val polymorphisms.ResultsA higher, but not significant, frequency of DRD3 ser/gly heterozygotes was observed in the tardive dyskinesia group (0.52 versus 0.33, χ2=5, degrees of freedom=2,P=0.08). However, assessment of the combined influence of the two polymorphisms demonstrated a significant effect (χ2=8.09, degrees of freedom=3,P=0.04), whereby the combination of the MnSOD -9val and DRD3 9ser alleles was associated with tardive dyskinesia.ConclusionsThese results indicate a possible synergistic effect of genetic factors influencing mitochondrial free radical scavenging and dopamine receptor function on the susceptibility to tardive dyskinesia.

ISSN:0955-8829    

出版商:OVID    

年代:2003

数据来源: OVID