Efficacy of cognitive behavioural therapy with medication for patients with obsessive-compulsive disorder: A multicentre randomised controlled trial in China.

BACKGROUND: Meta-analyses support the efficacy of cognitive behavioural therapy (CBT) for obsessive-compulsive disorder (OCD) in Western cultures. However, there are no adequately powered multicentre studies in China. This study aimed to compare the effectiveness of treatment with CBT combined with medication and medication alone in OCD patients in China. METHODS: OCD patients (N = 167) were recruited from outpatient clinics at three large tertiary psychiatric hospitals and one general hospital in China. Participants were randomly allocated to receive either CBT combined with medication (n = 92) or medication alone (n = 75) for a 24-week treatment period. Participants' symptoms and social functioning were assessed using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Hamilton Anxiety Rating Scale (HAM-A), Global Assessment of Functioning (GAF) and Clinical Global Impression Scale for Severity (CGI-S) at 0, 4, 8, 12 and 24 weeks, and the effectiveness of the two treatments compared using linear mixed-effects models. RESULTS: At 24 weeks, both groups showed large within-group effects in all measures. Significantly more patients receiving combined therapy than medication alone had a decrease in symptom severity of at least 35% (based on Y-BOCS total score). The CGI-S and GAF scores decreased in both groups, and significant differences were found between the groups. LIMITATIONS: Study limitations included lack of consideration of medication types and dosages, and the absence of a CBT-only arm. CONCLUSIONS: CBT combined with medication may be effective in alleviating symptoms and social functioning impairment associated with OCD, and is more effective than medication alone in China, particularly for the treatment of compulsive behaviours.

An intronic CYP46A1 polymorphism is associated with Alzheimer disease in a Chinese Han population.

Excess cholesterol is removed from the brain via hydroxylation mediated by cholesterol 24S-hydroxylase (CYP46), which is a mechanism of maintaining cholesterol homeostasis in the brain. The CYP46A1 gene has been suggested as a genetic risk factor for sporadic late-onset Alzheimer's disease (AD). In this report, we analyzed an intronic CYP46A1 single nucleotide polymorphism (SNP) in 508 sporadic AD patients and 549 controls in a Chinese Han population. Our results indicated that the distribution of CYP46A1 SNP rs754203 genotypes was significantly different in AD patients compared to controls (χ(2) = 6.59, P = 0.037). The frequency of at least one of CYP46A1 T allele (C/T or T/T) was higher in AD patients compared to controls (χ(2) = 6.58, P = 0.01). The age- and sex-adjusted odds ratio for the risk of AD in carriers of CYP46A1 T allele (C/T + T/T) was 1.69 (95 % confidence interval, 1.12-2.56). We conclude that this intronic polymorphism in CYP46A1 gene is associated with AD in a Chinese Han population, and the CYP46A1 T allele might be a risk factor for AD.

Lack of association of neprilysin gene polymorphisms with Alzheimer's disease in a southern Chinese community.

BACKGROUND: Increasing evidence suggests that neprilysin (NEP) may be the major degrading enzyme of amyloid beta (Abeta) in the brain and the NEP gene has been proposed as a candidate gene for Alzheimer's disease (AD). Association results between the NEP gene and AD are still preliminary. This study investigates the effect of the polymorphisms of -204G/C and 159C/T in the NEP gene on the development of sporadic Alzheimer's disease (SAD) in a southern Chinese community. METHOD: 236 sporadic late-onset AD patients were recruited from Guangzhou Psychiatric Hospital in southern China, and 332 healthy elderly controls were enrolled from three old age homes in suburban Guangzhou. NEP and ApoE genotype were determined by PCR-RFLP. RESULTS: No differences in genotypic and allelic frequencies of -204G/C and 159C/T polymorphisms in NEP were found between AD and control group (for -204G/C genotype: chi2 = 2.34, P > 0.05; for allele: chi2 = 2.31, P > 0.05; for 159C/T genotype: chi2 = 1.34, P > 0.05; for allele: chi2 = 0.88, P > 0.05). Neither was any difference found in genotypic and allelic frequency when stratified by sex or by ApoE epsilon4 allele (P > 0.05). CONCLUSIONS: Our results suggest that -204G/C and 159C/T polymorphisms of the NEP gene may not be associated with SAD. Moreover, both sex and ApoE epsilon4 allele do not affect the distribution of NEP gene polymorphisms.

Genetic association between low-density lipoprotein receptor-related protein gene polymorphisms and Alzheimer's disease in Chinese Han population.

Alzheimer's disease (AD) is the most common neurodegenerative disorders in the elderly. Low-density lipoprotein receptor-related protein (LRP), as a receptor of apolipoprotein E (APOE), APP, and alpha2 macroglobulin (alpha2-M), keeps the balance between degeneration and production of beta-amyloid protein (Abeta) clearance. Its gene had been defined as a candidate gene for AD, but the results were not universal. Total 496 AD patients and 478 controls were recruited in Chinese Han population and real-time PCR was used to detect the polymorphism of LRP C766T. Multiple logistic regression, Chi-square test and survival analysis were performed to explore the association. The distribution of LRP genotypes and alleles was significantly different between cases and controls, and T allele could reduce the risk for developing AD (OR of CT genotype: 0.57; 95% CI: 0.38-0.85, rho=0.003; OR of T allele: 0.57; 95% CI: 0.39-0.83, rho=0.003). TT genotype carriers had 5 years later for developing AD compared with CC genotype carriers, but survival analysis did not conform this (LRP TT vs. CT and CC log rank chi(2)=2.71, rho=0.26). The distribution of LRP C766T genotypes and alleles was different among different severity stratified by MMSE yet (rho=0.26). Our data suggested that the polymorphism of LRP C766T was strongly associated with AD and T allele might be a protective factor for AD in Chinese Han population.

Lack of association between the BDNF gene Val66Met polymorphism and Alzheimer disease in a Chinese Han population.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by excessive neuronal loss in specific regions of the brain. Among the areas most severely affected are the basal forebrain cholinergic neurons and their projection regions, the hippocampus and the cortex. Several lines of evidence have made brain-derived neurotrophic factor (BDNF) an important candidate gene conferring risk for AD. Recently, several reports investigated the association between a single nucleotide polymorphism (Val66Met, rs6265) of the BDNF gene and AD but yielded ambiguous results. To figure out the association of this single nucleotide polymorphism in the BDNF gene with sporadic AD in a Chinese Han population, we analyzed 513 patients with AD and 575 controls for the genetic association studies. Our results indicated that the distribution of the BDNF genotypes and alleles did not differ significantly. Similar results were observed when the AD and control groups were stratified by age/age at onset and sex. Our data also showed that in the Chinese Han population, the frequencies of the BDNF Met allele (46.5%) and Val allele (53.5%) were significantly different from ethnic groups from Italy, Japan and the USA. The present data revealed no significant effect of the genotypes on the age at onset for developing AD, and no significant association between the genotypes and the severity of the disease.

Gln192Arg polymorphism in paraoxonase 1 gene is associated with Alzheimer disease in a Chinese Han ethnic population.

BACKGROUND: Oxidative stress such as low-density lipoprotein (LDL) oxidation is thought to be an important mechanism in Alzheimer's disease (AD). Paraoxonase 1 (PON1), an enzyme located on high-density lipoprotein, can prevent LDL from oxidation to some extent. It is also a potent cholinesterase inhibitor and an arylesterase, combating organophosphate poisoning and metabolization of environmental neurotoxins which might be responsible for neurodegeneration with aging. We evaluated the association of Gln192Arg polymorphism in the PON1 gene with AD in a Chinese Han ethnic population. METHODS: Patients and age-matched controls were recruited from outpatient clinics and a population-based epidemiological survey, respectively. Gln192Arg polymorphism in the PON1 gene was detected by allele-specific PCR technique in 521 patients with AD and 578 healthy controls. RESULTS: The presence of at least one of PON1 R alleles (Q/R or R/R) was lower in AD patients than in the controls (82.7% vs 87.4%; chi(2) = 4.68, P = 0.03). PON1 gene R allele frequency was lower in AD patients than in the controls (60.7% vs 64.7%; chi(2) = 3.85, P = 0.05). One-way ANOVA showed that PON1 genotype had no effect on the age of onset for developing AD. Logistic regression analysis demonstrated the age and sex-adjusted odds ratio (OR) for the risk of AD in PON1 of PON1 R allele carriers was 0.71 (P = 0.044, 95% CI, 0.51 - 0.99). CONCLUSION: Our results indicate that Gln192Arg polymorphism in the PON1 gene is associated with AD, and PON1 R allele might be a protective factor for AD in a Chinese Han ethnic population.

[Paraoxonase 1 gene Gln192Arg polymorphism in and Alzheimer disease].

OBJECTIVE: The aim of this study was to evaluate the association of Gln192Arg polymorphism in paraoxonase 1 (PON1) gene with Alzheimer's disease (AD) in Chinese Han population. METHODS: Gln192Arg polymorphism in PON1 gene was detected with real-time PCR (RT-PCR) technique in 521 patients with AD and 578 healthy controls. RESULTS: The presence of at least one of PON1 R allele (Q/R or R/R) was lower in AD patients as compared with the controls (82.7% vs 87.4%; chi(2) = 4.68, P = 0.03). PON1 gene R allele frequency was lower in AD patients as compared with the controls (60.7% vs 64.7%; chi(2) = 3.85, P = 0.05). One-Way ANOVA showed that PON1 genotype had no effect on the age of onset of AD. Logistic regression analysis demonstrated that the age and sex-adjusted OR for the risk of AD in PON1 R allele carriers was 0.71 (P = 0.044, 95% CI = 0.51 - 0.99). CONCLUSION: Our results indicate that Gln192Arg polymorphism in PON1 gene is associated with AD and PON1 R allele might be a protective factor for AD in Chinese Han population.

The Fas gene A-670G polymorphism is not associated with sporadic Alzheimer disease in a Chinese Han population.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by excessive neuronal loss, intracellular neurofibrillary tangles and extracellular deposition of amyloid beta-peptide (Abeta). The Fas antigen is a cell surface receptor-mediating cell apoptosis. Several lines of evidence have made Fas/Fas ligand induced apoptosis play an important role in the pathogenesis of AD. Moreover, the Fas gene is located on chromosome 10q24.1, a region of linkage to late-onset AD. Several reports have investigated the association between a single nucleotide polymorphism (SNP) that is located at position -670 of Fas gene and AD, but yielded ambiguous results. To figure out the association of this SNP with sporadic AD in Chinese Han population, we have analyzed 509 patients with AD and 561 controls for the genetic association studies. Our results indicate that the distribution of the Fas genotypes (chi(2) = 0.66, P = 0.72) and alleles (chi(2) = 0.70, P = 0.40) did not differ significantly. The similar results were observed when AD and control groups were stratified by age/age at onset and sex (P > 0.10). The present data revealed no significant effect of the genotypes on the age of onset for developing AD, and no significant association between the genotypes and the severity of the disease.

[Gln192Arg polymorphism of the paraoxonase-1 gene is not associated with Alzheimer's disease in Chinese].

OBJECTIVE: To explore the relationship between paraoxonase-1 (PON1) gene Gln192Arg polymorphism and sporadic Alzheimer's disease (AD) in Chinese. METHODS: A total of 165 AD patients and 174 age-matched control subjects were enrolled in this study for examination of PON1 Gln192Arg and apolipoprotein E gene polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The distribution of PON1 allelic and genotypic frequencies did not significantly differ between AD patients and the control subjects, even after the stratification by ApoE-epsilon4 status. CONCLUSION: Gln192Arg polymorphism of the PON1 gene is not associated with sporadic AD in Chinese.