摘要:

ObjectiveTo further evaluate the controversial putative association between a Ser9Gly variant in the first exon of the dopamine D3 receptor gene (DRD3) and schizophrenia.MethodsSwedish patients with schizophrenia (n=156) and control subjects (n=463) were assessed for the DRD3 Ser9Gly variant. Meta-analyses including previous and the present Swedish case–control results were performed.ResultsNo significant difference between the Swedish patients and controls were found, but there was an association between DRD3 Ser9Gly Ser/Ser and homozygous genotypes and response to anti-psychotic drugs. This finding was supported by an incomplete meta-analysis. In a meta-analysis of all case–control studies comprising 8761 subjects the association between DRD3 Ser9Gly homozygosity and schizophrenia (χ2=4.96, degree of freedom=1,p<0.05, odds ratio=1.10, 95% confidence interval=1.01–1.20) persisted. However, the previously proposed association between the Ser/Ser genotype and schizophrenia was not significant (χ2=2.71, degree of freedom=1,p>0.05, odds ratio=1.08, 95% confidence interval=0.99–1.17).ConclusionsWhereas the present Swedish case-control analysis did not yield any evidence for association with the diagnosis, the present meta-analysis suggests that the DRD3 gene confer susceptibility to schizophrenia. Reasons for the discrepancies between prior studies are discussed.

ISSN:0955-8829    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveThe short variant of the serotonin transporter gene-linked functional polymorphic region (5-HTTLPR) has been associated with personality traits related to anxiety, hostility, and depression. We attempted to replicate findings suggesting a positive relation between the short allele variant of 5-HTTLPR and Neuroticism, and a negative association between the short allele variant and Agreeableness.MethodsParticipants in the present study were 103 geriatric depressed patients and 99 non-depressed age matched controls. Depression status and gender were examined as potential modifiers of the association between 5-HTTLPR and personality.ResultsNeuroticism was associated with allele frequency such that individuals with the short variant of the allele (ss or sl, group S) were significantly lower on Neuroticism (P<0.04) compared with individuals with the long allele variant (group L), a pattern opposite to that of previous reports. The association did not vary by clinical group (depressed or controls) but was conditional on gender (P<0.01): the mean Neuroticism for males in group S was 48.2, whereas the mean Neuroticism for males in group L was 55.9; and the mean Neuroticism for females did not differ by allele group. In the total sample, Agreeableness was not associated with allele frequency; however, there was a significant allele group×clinical group×gender interaction (P<0.01).ConclusionsThe present findings failed to replicate prior work suggesting that the short variant of the 5-HTTLPR allele is associated with higher Neuroticism and lower Agreeableness.

ISSN:0955-8829    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveGender comparison in epidemiological studies has consistently demonstrated a greater prevalence for major depressive disorders (MDD) in females. Several lines of evidence have implicated oestrogen pathways in this gender difference. Furthermore, there is evidence that attempted suicides are more frequent in women. A population-based association study was used to test the hypothesis that the genetic variants (PvuII andXbaI polymorphisms) of the oestrogen receptor &agr; gene (ER-&agr;) confer susceptibility to MDD.MethodsThe ER-&agr; was genotyped for 154 patients with MDD and 226 controls in a Chinese population.ResultsStatistical analysis showed a significant difference in thePvuII genotype and allele frequencies between the female MDD patients and the female controls (P=0.010 andP=0.004, respectively). However, no significant differences in ER-&agr; genotype or allele frequencies were found between male MDD patients and male controls. Furthermore, the ER-&agr; genotypes were not associated with suicide-attempt history for MDD cases.ConclusionsOur results suggest that the ER-&agr; may play a role in the susceptibility of MDD in females.

ISSN:0955-8829    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

BackgroundRecently, linkage disequilibrium mapping of the major histocompatibility complex region on the short arm of human chromosome 6 suggested that the NOTCH4 locus is highly associated with schizophrenia.Objectives and methodsWe analysed two polymorphisms in this gene in Swedish schizophrenic patients (n=74) and control subjects (n=135). The NOTCH4 variants were also analysed in schizophrenic patients with regard to subdiagnosis, age at first hospitalization, abuse/dependence of alcohol, solvents, or drugs, previous suicide attempts, extrapyramidal symptoms, treatment with anticholinergic drugs, and response to anti-psychotic drug treatment. Control subjects were scrutinized with regard to personality, another partially heritable trait suggested being of importance in schizophrenia. In addition, two intermediate endophenotypes suggested being of importance in schizophrenia, dopamine D2receptor density in striatum and monoamine metabolites in cerebrospinal fluid, respectively, were investigated with regard to the two NOTCH4 variants.ResultsThere was no significant association between the patients and the controls for the two investigated polymorphisms neither for the parameters analysed in the schizophrenia material. The NOTCH4 SNP2 variant, an A→G substitution, was associated with the Karolinska Scales of Personality Irritability scale. The NOTCH4 (CTG)nvariant was associated with the revised NEO personality inventory Extraversion and Activity (E4) scales. However, after correction for multiple testing, no difference remained significant. The results for the endophenotypes and the polymorphisms were non-significant.ConclusionsThe present study does not support that the investigated NOTCH4 variants have a major influence on susceptibility to schizophrenia or related neurobiological traits.

ISSN:0955-8829    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

BackgroundWolfram syndrome is a neurodegenerative disorder that is inherited in an autosomal recessive mode and characterized by the presence of diabetes mellitus and optic atrophy. Patients and heterozygote carriers are at an increased risk of suffering psychiatric disorders. Mutations in the Wolfram gene (WFS1) (4p16.1) are responsible for the development of the disease, and mRNA and protein expression ofWFS1have recently been found in areas of the rat brain that can be related to the psychiatric symptoms.ObjectiveTo test the hypothesis thatWFS1mutations in heterozygote carriers or other variants ofWFS1can predispose to mental illness.MethodsStage 1: Exons 2, 4 and 8 ofWFS1that harbour mutations in Spanish Wolfram syndrome families were examined by Single Strand Conformation Polymorphism and sequencing analysis in 43 patients with affective disorder to identify variants and mutations. Stage 2: two variants identified in stage 1 were analysed in 152 psychiatric patients (118 schizophrenia and 34 affective disorder) and 177 control subjects.ResultsSix variants (I333V Ile→Val, F341, N500, R708, K774, K811) and aWFS1mutation (R818C, Arg→Cys) were found in the 43 patients analysed in stage 1 of the study. In stage 2, the R818C mutation was not found in the group of psychiatric patients but it was present in one control subject. The association study conducted with the I333V variant did not find significant differences in allele or genotype frequencies between patients and control subjects.ConclusionsOur results suggest thatWFS1is not a major susceptibility gene for the development of psychiatric disorders in our population.

ISSN:0955-8829    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveWomen are more prone to anxiety than men. The catechol-O-methyltransferase functional polymorphism, Val158Met, is likely to be implicated in anxiety vulnerability. We hypothesized that, particularly in women, the low-activity Met158 allele would be associated with higher anxiety scores and a biological trait, low-voltage alpha resting electroencephalogram (EEG), previously associated with alcoholism and anxiety disorders.MethodsDNA was obtained from two independent groups of participants ascertained as community samples: 149 predominantly Caucasian individuals (92 women, 57 men), and 252 Plains American Indians (149 women, 103 men). Dimensional measures of anxiety (Tridimensional Personality Questionnaire harm avoidance subscales HA1 and HA2) were obtained and DSM-III-R lifetime psychiatric diagnoses were determined. EEGs were recorded and EEG phenotypes assigned.ResultIn both populations, women showed significant associations between catechol-O-methyltransferase genotype and elevated harm avoidance scores, and the Met158/Met158 genotype was most strongly associated: predominantly Caucasian participants: HA1,P=0.03, HA2,P=0.03; and Plains American Indians: HA2,P=0.01. This was also the case with low-voltage alpha resting EEG: predominantly Caucasian participants:P=0.01, odds ratio=5.0 (95% confidence interval, 1.3–18.7); Plains American Indians:P=0.03, odds ratio=3.7 (95% confidence interval, 1.1–12.7).ConclusionsThe results of the present study suggest that an inherited difference in catecholamine metabolism is important in the pathogenesis of anxiety in women.

ISSN:0955-8829    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

BackgroundFRAXE is a second locus associated with X chromosome fragility. Similar to FRAXA, the common mutation is a GCC expansion located in the 5′ untranslated region, leading to the hypermethylation of the region and to the subsequent inactivation of specific genes (FMR1 and FMR2, respectively). Unlike FRAXA, FRAXE has a rare occurrence and is less currently studied in routine analyses. The phenotype associated with FRAXE is usually considered as mild or moderate mental retardation, with incomplete penetrance. However, phenotype/genotype relations have been less characterized.ObjectiveWe report a French family with three members affected with mental retardation, including a female suffering from West syndrome, and two mentally retarded males.MethodsAfter exclusion of the FRAXA expansion by Southern blot analysis, we performed a karyotype using folate-thymidine-deficient medium and a southern blot to search for FRAXE expansion.ResultsAll three mentally retarded patients had a number of repeats over 800 GCC and expressed more than 20% of fragile sites in their leukocytes. Another carrier female with a full expansion had a subnormal mental impairment.ConclusionsClinical features and both the cytogenetic and molecular findings seem to correlate in this family. We discuss the bias encountered when studying such families and some of the mechanisms that may explain part of the clinical variability.

ISSN:0955-8829    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectivesTo attempt to replicate previous reports that polymorphic variation in the DCP1 gene causes increased susceptibility to the development of Alzheimer's disease, either on its own or in interaction with the effects of the gene for apolipoprotein E (APOE).MethodSubjects older than 65 years of age consisting of 81 dementia patients diagnosed as having possible or probable Alzheimer's disease and 68 controls were obtained from Camden, Islington and Harlow psychiatric services. Subjects were genotyped for APOE alleles e2, e3 and e4, and the common insertion/deletion polymorphisms for DCP1* I/D were genotyped.ResultsThere was no statistically significant difference in the frequency of the DCP1* insertion/deletion alleles between the cases and controls (X2=0.04, 1 degree of freedom, not significant). When subjects were subdivided according to whether they possessed at least one copy of the APOE e4 allele, there were still no differences in DCP1 allele frequencies between cases and controls.ConclusionsFurther research is needed to elucidate any role that the DCP1 polymorphism may play in relation to Alzheimer's disease. Previous studies may be false positive, or inconsistency in replication may be due to heterogeneity.

ISSN:0955-8829    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveIt has been demonstrated that the P300 components, a positive event-related potential, are heritable and are influenced by dopaminergic activity. We tested the genetic effects of the dopaminergic system in P300 components by association study.MethodsIn a sample population consisting of 120 normal young Han-Chinese females, we explored the association between the P300 components, and, the genetic polymorphisms including the dopamine D3 receptor (serine-to-glycine polymorphism in exon I), the dopamine D4 receptor (variable number tandem repeat polymorphism in exon III), and the dopamine transporter (variable number tandem repeat polymorphism in promoter region).ResultsNo associations were demonstrated between the polymorphisms of these three genes and the P300 components.ConclusionsOur negative findings suggest that these genetic polymorphisms do not play a major role in the modulation of P300 event-related potentials.

ISSN:0955-8829    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

ObjectiveThe molecular basis of neuroleptic malignant syndrome (NMS) is unclear, but clinical studies have noted a genetic predisposition. A recent genetic study suggested an association between NMS and theTaqI A polymorphism in the dopamine D2receptor (DRD2) gene. We further examined the association in a larger number of subjects.MethodsWe studied 49 Japanese patients previously diagnosed with NMS, and 123 schizophrenic patients treated with neuroleptics without occurrence of NMS. PCR and RFLP analyses were performed to screen theTaqI A polymorphism.ResultsTheTaqI A1 allele frequency was 0.408 in NMS patients and 0.415 in patients without NMS. No significant differences in allelic or genotypic frequencies were observed between the two groups.ConclusionsWe cannot conclude that theTaqI A polymorphism is associated with development of NMS.

ISSN:0955-8829    

出版商:OVID    

年代:2003

数据来源: OVID