Effects of PM2.5 pollution and single nucleotide polymorphisms of neurotrophin signaling pathway genes acting together on schizophrenia relapse.

PURPOSE: The objective of this study was to investigate the co-effect of long-term exposure to atmospheric particulate matter PM2.5 and single nucleotide polymorphisms on schizophrenia relapse. METHODS: A total of 332 patients with schizophrenia were recruited. Genotyping of eight SNPs for five genes along the neurotrophin signaling pathway was performed by the Sequenom Massarray technology platform. Based on the data from the monitoring stations, the PM2.5 level of each patient's residence was assessed by the inverse distance weighting method using Arc GIS software. Cox regression analysis was used to determine independent risk factors. The relationship between PM2.5 levels and the risk of schizophrenia relapse was evaluated using the restricted cubic spline (RCS) method. RESULTS: In this study, a total of 191 of 332 patients with schizophrenia relapsed with hospitalization. The risk of schizophrenia relapse was 13.62 (95% CI 8.29 to 22.37) in areas with PM2.5 concentrations of 48.43 to 75.35 µg/m3. The risk of schizophrenia relapse was 5.81 (95% CI 3.58-9.42, p < 0.001) and 13.62 (95% CI 8.29-22.37, p < 0.001) in the exposure categories Q3 and Q4, respectively, compared with Q1, and non-linear relationship between cumulative PM2.5 exposure and risk of schizophrenia relapse. A greater association was observed in the YWHAB gene polymorphic locus rs6031849 genotype TG (Hazard ratio 16.62, 95% CI 5.73 to 48.24). CONCLUSIONS: PM2.5 levels, YWHAB gene polymorphism locus rs6031849, and gender jointly influenced schizophrenia relapse, with long-term exposure to high levels of PM2.5 having the greatest effect on schizophrenia relapse.

Rs7219 Regulates the Expression of GRB2 by Affecting miR-1288-Mediated Inhibition and Contributes to the Risk of Schizophrenia in the Chinese Han Population.

In the present study, we examined a potential genetic association between the variant rs7219 within the 3'-UTR of GRB2 and the susceptibility to schizophrenia (SCZ) and bipolar disorder (BD) in the Chinese Han population. A genetic association study, including 548 SCZ patients, 512 BD patients, and 598 normal controls, was conducted in the Chinese Han population. Genotyping was performed through the Sequenom MassARRAY technology platform. The expression of GRB2 was detected using quantitative real-time polymerase chain reaction (qRT-PCR). A dual-luciferase reporter assay was performed to determine whether miR-1288 could bind to the 3'-UTR region of GRB2 containing rs7219. We found that rs7219 was significantly associated with the susceptibility to SCZ under different genetic models, including additive [OR (95% CI) = 1.24 (1.02-1.49), P = 0.027], dominant [OR (95% CI) = 1.31 (1.04-1.66), P = 0.025], and allelic models[OR (95% CI) = 1.24 (1.03-1.49), P = 0.027]. However, no significant associations were found between rs7219 and the risk for BD (all P > 0.05). Moreover, we observed that the expression of GRB2 significantly decreased in SCZ patients compared with the controls (P = 0.004). The dual-luciferase reporter assay showed that the minor allele C of rs7219 significantly decreased the luciferase activity by binding miR-1288 (P < 0.001). In summary, we are the first to reveal that rs7219 is significantly associated with the susceptibility to SCZ in the Chinese Han population. Moreover, the minor allele C of rs7219 is identified as a risk allele for SCZ because it generates a binding site for miR-1288, thereby resulting in decreased expression of GRB2 and ultimately increasing the risk of SCZ.

Influence of NRGN rs12807809 polymorphism on symptom severity in individuals with schizophrenia in the Han population but not the Zhuang population of south China.

BACKGROUND: NRGN is one of the most promising candidate genes for schizophrenia based on function and position. Therefore, this study aimed to examine the genetic association of this polymorphism with schizophrenia in the Zhuang and Han populations of south China. Subjects and methods A total of 282 patients (188 Han and 94 Zhuang) and 282 healthy subjects (188 Han and 94 Zhuang) were recruited. Of these, 246 schizophrenia patients underwent an assessment of psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS). A TaqMan genotyping assay method was used to determine the genotypes. RESULTS: We did not find a significant association of rs12807809 polymorphism with schizophrenia in the total pooled samples, or in the separate ethnic groups. However, in Han schizophrenia patients, quantitative data analyses showed that the CC genotype of the rs12807809 polymorphism was associated with PANSS aggression subscale score and activation subscale score. Furthermore, carriers of the C allele of rs12807809 polymorphism among Han schizophrenia patients had higher scores of general, activation, depression, aggression, and global symptoms than the T allele carriers. CONCLUSION: In conclusion rs12807809 polymorphism may not contribute to the risk of schizophrenia but influence the clinical symptoms of schizophrenia in the Han population.

Smoking and major depressive disorder in Chinese women.

OBJECTIVE: To investigate the risk factors that contribute to smoking in female patients with major depressive disorder (MDD) and the clinical features in depressed smokers. METHODS: We examined the smoking status and clinical features in 6120 Han Chinese women with MDD (DSM-IV) between 30 and 60 years of age across China. Logistic regression was used to determine the association between clinical features of MDD and smoking status and between risk factors for MDD and smoking status. RESULTS: Among the recurrent MDD patients there were 216(3.6%) current smokers, 117 (2.0%) former smokers and 333(5.6%) lifetime smokers. Lifetime smokers had a slightly more severe illness, characterized by more episodes, longer duration, more comorbid illness (panic and phobias), with more DSM-IV A criteria and reported more symptoms of fatigue and suicidal ideation or attempts than never smokers. Some known risk factors for MDD were also differentially represented among smokers compared to non-smokers. Smokers reported more stressful life events, were more likely to report childhood sexual abuse, had higher levels of neuroticism and an increased rate of familial MDD. Only neuroticism was significantly related to nicotine dependence. CONCLUSIONS: Although depressed women smokers experience more severe illness, smoking rates remain low in MDD patients. Family history of MDD and environmental factors contribute to lifetime smoking in Chinese women, consistent with the hypothesis that the association of smoking and depression may be caused by common underlying factors.

Association between the NOTCH4 gene rs3131296 polymorphism with schizophrenia risk in the Chinese Zhuang population and Chinese Han population.

BACKGROUND: Schizophrenia (SZ) is a common severe psychiatric disorder and a complex polygenic inherited disease that has not yet been fully interpreted. Heredity was proven to play an important role in the development of SZ. The association between the NOTCH4 gene rs3131296 polymorphism and SZ was reported to reach significance at the genome-wide level; therefore, it is necessary to replicate this association in other different populations. METHODS: To evaluate the association of the NOTCH4 gene rs3131296 polymorphism with the risk for SZ, and to explore whether a significant association could be replicated in different ethnic groups of China, we conducted this case-control study on 282 SZ cases (188 Han and 94 Zhuang) and 282 controls (188 Han and 94 Zhuang) among the Chinese Zhuang and Han populations. RESULTS: The results showed no statistically significant difference in the genotype or allele frequencies of the NOTCH4 gene variant rs3131296 between SZ patients and healthy controls in either the Zhuang or Han samples (p > 0.05). In addition, no significant difference was found in genotype or allele frequencies of the NOTCH4 gene variant rs3131296 between cases and controls in the combined samples including Zhuang and Han samples. CONCLUSIONS: Our study failed to replicate the significant association between the NOTCH4 gene rs3131296 polymorphism and the risk for SZ.

Epidemiology of major depressive disorder in mainland china: a systematic review.

BACKGROUND: Major depressive disorder (MDD) is one of the important causes of disease burden in the general population. Given the experiencing rapid economic and social changes since the early 1990s and the internationally recognized diagnostic criteria and interview instruments across the surveys during 2001-2010 in china, the epidemiological studies on MDD got varied results. We performed this meta-analysis to investigate current, 12-month and lifetime prevalence rates of MDD in mainland China. METHODS: PubMed, Embase, Chinese Biological Medical Literature database (CBM), Chinese National Knowledge Infrastructure database (CNKI), and the Chinese Wanfang and Chongqing VIP database were searched for associated studies. We estimated the overall prevalence of MDD using meta-analysis. CONCLUSIONS: Seventeen eligible studies were included. Our study showed that the overall estimation of current, 12-month and lifetime prevalence of MDD was 1.6, 2.3, 3.3%, respectively. The current prevalence was 2.0 and 1.7% in rural and urban areas, respectively; between female and male, it was 2.1 and 1.3%, respectively. In addition, the current prevalence of MDD diagnosed with SCID (Structured Clinical Interview for DSM-IV) was 1.8% and that diagnosed with CIDI (Composite International Diagnostic Interview) was 1.1%. In conclusion, our study revealed a relatively high prevalence rate in the lifetime prevalence of MDD. For current prevalence, MDD diagnosed with SCID had a higher prevalence rate than with CIDI; males showed a lower rate than females, rural residents seemed to have a greater risk of MDD than urban residents.

HTR2A-1438A/G polymorphism influences the risk of schizophrenia but not bipolar disorder or major depressive disorder: a meta-analysis.

The incidence of psychiatric disorders has been shown to have a strong genetic component, and we conducted this study to investigate whether the -1438A/G polymorphism of the HTR2A gene was associated with susceptibility to schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). Pooled odd ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using data obtained from a total 27 studies that investigated an association between the HTR2A -1438A/G polymorphism and SZ (15), BD (7), and MDD (4). We failed to observe an association between the HTR2A -1438A/G polymorphism and BD and MDD, and we found contrary results with regard to SZ. Our results showed that the -1438A/G polymorphism was a risk factor for SZ, especially in Caucasians (allele model: OR, 1.12; 95% CI, 1.05-1.20; I(2) = 17.3%; dominant model: OR, 1.14; 95% CI, 1.03-1.27; I(2) = 15.3%; recessive model: OR, 1.20; 95% CI, 1.06-1.37; I(2) = 0.0%; codominant model 1: OR, 1.16; 95% CI, 1.01-1.32; I(2) = 0.0%). We found that the association of the HTR2A -1438A/G polymorphism with SZ depends on the ethnic origin of the study population, and this genetic variant does not modify the susceptibility to BD or MDD. © 2013 Wiley Periodicals, Inc.