[Show abstract][Hide abstract] ABSTRACT: Complement pathway activation was found to occur frequently in schizophrenia, and complement 3 (C3) plays a major role in this process. Previous studies have provided evidence for the possible role of C3 in the development of schizophrenia. In this study, we hypothesized that the gene encoding C3 (C3) may confer susceptibility to schizophrenia in Han Chinese. We analyzed 7 common single nucleotide polymorphisms (SNPs) of C3 in 647 schizophrenia patients and 687 healthy controls. Peripheral C3 mRNA expression level was measured in 23 drug-naïve patients with schizophrenia and 24 controls. Two SNPs (rs1047286 and rs2250656) that deviated from Hardy-Weinberg equilibrium were excluded for further analysis. Among the remaining 5 SNPs, there was no significant difference in allele and genotype frequencies between the patient and control groups. Logistic regression analysis showed no significant SNP-gender interaction in either dominant model or recessive model. There was no significant difference in the level of peripheral C3 expression between the drug-naïve schizophrenia patients and healthy controls. In conclusion, the results of this study do not support C3 as a major genetic susceptibility factor in schizophrenia. Other factors in AP may have critical roles in schizophrenia and be worthy of further investigation.
[Show abstract][Hide abstract] ABSTRACT: Schizophrenia is a prevalent psychiatric disorder with a complex etiology. Mitochondrial dysfunction has been frequently reported in schizophrenia. Phosphatase and tension homologue-induced kinase 1 (PINK1) and presenilin-associated rhomboid-like protease (PARL) are mitochondrial proteins, and genetic variants of these two genes may confer genetic susceptibility to schizophrenia by influencing mitochondrial function. In this study, we conducted a two-stage genetic association study to test this hypothesis. We genotyped 4 PINK1 and 5 PARL genetic variants and evaluated the potential association of the 9 SNPs with schizophrenia in two independent case-control cohorts of 2510 Han Chinese individuals. No positive association of common genetic variants of the PINK1 and PARL genes with schizophrenia was identified in our samples after Bonferroni correction. Re-analysis of the newly updated Psychiatric Genetics Consortium (PGC) data sets confirmed our negative result. Intriguingly, one PINK1 SNP (rs10916832), which showed a marginally significant association in only Hunan samples (P = 0.032), is associated with the expression of a schizophrenia susceptible gene KIF17 according to the expression quantitative trait locus (eQTL) analysis. Our study indicated that common genetic variants of the PINK1 and PARL genes are unlikely to be involved in schizophrenia. Further studies are essential to characterize the role of the PINK1 and PARL genes in schizophrenia.
Full-text · Article · Oct 2014 · Molecular Genetics and Genomics
[Show abstract][Hide abstract] ABSTRACT: Background
With the recent attention to evidence-based medicine in psychiatry, a number of treatment guidelines for bipolar disorders have been published. This survey investigated prescribing patterns and predictors for guideline disconcordance in the acute treatment of a manic and mixed episode across mainland China.
The pharmacological treatments of 2828 patients with a recent hypomanic/manic episode or mixed state were examined. Guidelines disconcordance was determined by comparing the medication(s) patients were prescribed with the recommendation(s) in the guidelines of the Canadian Network for Mood and Anxiety Treatments.
The most common pattern of pharmacological treatments for an acute manic or mixed episode was a mood stabilizer plus an atypical antipsychotic (n = 1345, 47.6%), and the rate of guideline-disconcordant treatments was 11.1%. The patients who were treated in general hospitals were more likely to receive guideline-disconcordant treatments than those who were treated in psychiatric hospitals, with an OR of 1.84 (95% CI 1.44-2.36). Similarly, the patients with a mixed episode at study entry were more likely to receive guideline-disconcordant treatments than those with a manic episode, with an OR of 1.69 (95% CI 1.22-2.35). In contrast, the patients with a longer duration of disease (>5 years) were less likely to receive guideline-disconcordant treatments than those with a short duration, with an OR of 0.47 (95% CI 0.36-0.60).
In mainland China, the disconcordance with treatment guidelines for a most recent acute manic or mixed episode was modest under naturalistic conditions. The higher risk for disconcordance in general hospitals than in psychiatric hospitals suggests that special education based on treatment guidelines to practitioners in general hospitals is necessary in order to reduce the risk for disconcordant treatments.
[Show abstract][Hide abstract] ABSTRACT: In this pilot study, we aimed to examine whether iPad-assisted cognitive training could be beneficial in ameliorating some of the cognitive impairment that accompany schizophrenia. Totally, 20 first-episode schizophrenia patients were randomly assigned to an experiment group (with cognitive training) or to a control group (without cognitive training). The N-back task was assessed at baseline and after intervention, to see what effects iPad-assisted training might have (week 4). The experimental group exhibited significant improvement in the accuracy rate at 2-back, and reaction time at 0, 1 and 2-back tasks. These findings suggest that iPad- or other technically-assisted cognitive training may potentially be a valid strategy for pursuing cognitive rehabilitation among those with schizophrenia.
Full-text · Article · Jun 2014 · Archives of Psychiatric Nursing
[Show abstract][Hide abstract] ABSTRACT: Early identification of patients with bipolar disorder during their first depressive episode is beneficial to the outcome of the disorder and treatment, but traditionally this has been a great challenge to clinicians. Recently, brain-derived neurotrophic factor (BDNF) has been suggested to be involved in the pathophysiology of bipolar disorder and major depressive disorder (MDD), but it is not clear whether BDNF levels can be used to predict bipolar disorder among patients in their first major depressive episode.
To explore whether BDNF levels can differentiate between MDD and bipolar disorder in the first depressive episode.
A total of 203 patients with a first major depressive episode as well as 167 healthy controls were recruited. After 3 years of bi-annual follow-up, 164 patients with a major depressive episode completed the study, and of these, 21 were identified as having bipolar disorder and 143 patients were diagnosed as having MDD. BDNF gene expression and plasma levels at baseline were compared among the bipolar disorder, MDD and healthy control groups. Logistic regression and decision tree methods were applied to determine the best model for predicting bipolar disorder at the first depressive episode.
At baseline, patients in the bipolar disorder and MDD groups showed lower BDNF mRNA levels (P<0.001 and P = 0.02 respectively) and plasma levels (P = 0.002 and P = 0.01 respectively) compared with healthy controls. Similarly, BDNF levels in the bipolar disorder group were lower than those in the MDD group. These results showed that the best model for predicting bipolar disorder during a first depressive episode was a combination of BDNF mRNA levels with plasma BDNF levels (receiver operating characteristics (ROC) = 0.80, logistic regression; ROC = 0.84, decision tree).
Our findings suggest that BDNF levels may serve as a potential differential diagnostic biomarker for bipolar disorder in a patient's first depressive episode.
Full-text · Article · Apr 2014 · The British journal of psychiatry: the journal of mental science
[Show abstract][Hide abstract] ABSTRACT: With the recent attention to the importance of evidence-based medicine in psychiatry, a number of treatment guidelines have been published. This survey investigated prescribing pattern and predictors for guideline disconcordance in the acute treatment of bipolar depression across mainland China. Pharmacological treatments of 1078 patients with bipolar depression were examined. Guidelines disconcordance was determined by comparing the medication(s) patients were prescribed with the recommendation(s) in the guidelines of the Canadian Network for Mood and Anxiety Treatments. Predictors for guidelines discordance were analyzed with logistic regression. Of the 1078 patients, 50.2% patients were treated against treatment guidelines recommendations. The patients who were treated in general hospitals (OR = 1.53, 95% CI 1.18-1.97), with a depressive episode (OR = 1.67, 95% CI 1.27-2.19) and an older age at first onset (OR = 1.62, 95% CI 1.15-2.28) were more likely to receive guideline-disconcordant treatment than their counterparts. In contrast, the patients with current mental comorbidity, an older age at study entry, a longer duration of disease, and more frequent episodes in past year were less likely to receive guideline-disconcordant treatments than their counterparts with an OR of 0.43 (95% CI 0.24-0.77), 0.52 (95CI% 0.36-0.75), 0.48 (95% CI 0.36-0.65), and 0.50 (95% CI 0.38-0.64), respectively. Our finding suggested the disconcordance with treatment guidelines in patients with an acute bipolar depression is common under naturalistic conditions in mainland China, and the predicting factors correlated with guidelines disconcordance include both psychiatrist-specific (clinicians from general hospitals) and patient-specific features (a depressive episode at first onset, no current co-morbidity with mental disorders, a younger age at study entry, an older age at first onset, shorter duration of disease, and non-frequent episodes in past year).
[Show abstract][Hide abstract] ABSTRACT: Mitochondrial dysfunction was widely reported in schizophrenia patients in recent studies. Leucine-rich repeat kinase 2 (LRRK2) is a mitochondrial protein, and mutations in the LRRK2 gene can induce mitochondrial dysfunction. LRRK2 mutations have been reported to be the most frequent genetic cause of Parkinson's disease (PD). We were interested in whether LRRK2 variants also play a role in schizophrenia. In this study, we genotyped 12 genetic variants (including 4 tag SNPs and 8 disease-associated variants) in the LRRK2 gene in a total of 2449 samples composed of two independent Han Chinese schizophrenia case-control cohorts (486 schizophrenia patients and 480 healthy controls from Hunan Province; 624 schizophrenia patients and 859 healthy controls from Shanghai). We compared the genotype, allele and haplotype frequencies of those SNPs between cases and controls. Statistical analyses revealed no association between LRRK2 variants/haplotypes and schizophrenia in these two schizophrenia case-control cohorts and the combined samples. Our results indicated that the LRRK2 variants are unlikely to be actively involved in schizophrenia in Han Chinese.
Full-text · Article · Mar 2014 · Neuroscience Letters
[Show abstract][Hide abstract] ABSTRACT: Neuropsychological endophenotype approach is an emerging strategy in schizophrenia research to understand and identify the functional importance of genetically transmitted, brain-based deficits present in this disorder. Accumulating evidence indicated that working memory deficit is a core neuropsychological dysfunction in schizophrenia and a primary endophenotype indexing the liability to develop schizophrenia. Genetic variation in ankyrin 3 gene (ANK3) is likely to have widespread cognitive effects. Our previous study has identified a significant association of ANK3 SNPs and schizophrenia. In this study, we aimed to examine whether the schizophrenia-risk SNPs within ANK3 may affect working memory deficits in schizophrenia patients. Herein, we assess the working memory performance in 163 patients with first-episode, antipsychotic-naïve schizophrenia and 42 sex, age-matched healthy subjects using N-back task. Two SNPs rs10761482 and rs10994336 were genotyped among the patients and 209 controls. Our results showed that schizophrenia patients showed significantly poorer performance than healthy controls on N-back task (ps<0.01). After adjusting for the scores of intelligence quotient, memory quotient and the demographic factors, there was a significant genotype effect of the rs10994336 on the accuracy rate and reaction time of 2-back item (p=0.048 and 0.024, respectively). Post-hoc analyses showed that patients with rs10994336T/T genotype had significantly lower accuracy rate and more reaction time at 2-back task than those with T/C and C/C genotypes. The association of SNP rs10994336 with schizophrenia was replicated in our sample (genotypic p=0.024 and allelic p=0.006). However, we did not find any significant association of rs10761482 with schizophrenia and parameters in N-back task. Our results indicated that genetic variation within ANK3 may exert gene-specific modulating effects on working memory deficits in schizophrenia.
Full-text · Article · Dec 2013 · Progress in Neuro-Psychopharmacology and Biological Psychiatry
[Show abstract][Hide abstract] ABSTRACT: The leucine-rich repeat kinase-2 (LRRK2) gene has been regarded as 1 of the most common genetic causes of Parkinson's disease (PD). We hypothesized that LRRK2-susceptible allele(s) for PD might pose a risk for Alzheimer's disease (AD). In this study, we screened 12 LRRK2 gene variants in 2 independent cohorts from southwestern China (341 AD patients and 435 normal individuals) and eastern China (297 AD patients and 384 normal individuals), to discern the potential association between this gene and AD. No variant was identified to be associated with AD in either case-control sample. As both of the cohorts were of Han Chinese origin, we combined the LRRK2 variant data for the 2 sample sets together (a total of 638 AD patients and 819 normal individuals) and still found no association between the LRRK2 gene and AD, suggesting that LRRK2 gene variants may not affect the development of AD in Han Chinese individuals.
No preview · Article · Sep 2013 · Neurobiology of aging
[Show abstract][Hide abstract] ABSTRACT: In this study, we analyzed four single nucleotide polymorphisms (SNPs) (rs10491734, rs2228622, rs301430 and rs301443) of the solute carrier family 1 gene (SLC1A1) in a set of 616 schizophrenia patients and 638 matched healthy controls of Han Chinese descent. No significant differences of genotype or allele distribution were identified between the patients and controls. Our data suggest that SLC1A1 is unlikely to be a major susceptibility gene for schizophrenia in Han Chinese.
[Show abstract][Hide abstract] ABSTRACT: The gene coding for the calcium channel, voltage-dependent, L type, alpha 1C subunit (CACNA1C) has been reported to be associated with bipolar disorder (BD) in our previous study. Broad evidence suggests some degree of shared genetic susceptibility between BD and schizophrenia. In this study, we aimed to determine whether the BD-associated gene CACNA1C confers susceptibility to schizophrenia. The association was assessed using a cross section study of 696 schizophrenia patients and 1,114 matched control subjects of Han Chinese origin. Between-group comparisons of genotypic or allelic frequencies showed no statistically significant differences. CACNA1C is unlikely to play a major role in the pathophysiology of schizophrenia in Han Chinese. Further large-scale replication studies using a haplotype-tagging single-nucleotide polymorphism selection approach are required to obtain more conclusive results of any potential association.
[Show abstract][Hide abstract] ABSTRACT: Rationale
Clinical observations indicate that atypical antipsychotics, especially clozapine, induce obsessive–compulsive (OC) symptoms in schizophrenia patients. Recent data from neuroimaging and clinical trials suggest a role for altered glutamate neurotransmission in the etiology of OC disorder (OCD), and SLC1A1, GRIN2B, and GRIK2 have all been reported to regulate glutamate transmission and affect OCD pathophysiology.
This study aimed to determine whether SLC1A1, GRIN2B, and GRIK2 are associated with clozapine-induced OC symptoms.
A total of 250 clinically stable schizophrenia patients receiving clozapine treatment were recruited. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was used to evaluate the severity of OC symptoms. Based on their Y-BOCS scores, 250 patients were divided into the OC and non-OC groups (patients with or without OC symptoms, respectively). Additionally, three reported OCD susceptibility polymorphisms, SLC1A1 (rs2228622), GRIN2B (rs890), and GRIK2 (rs1556995), were genotyped.
Trends of association with OC symptoms were observed in rs2228622A and rs890T alleles. SLC1A1 and GRIN2B interaction was found in the significant two-locus gene–gene interaction model (p = 0.0021), using the multifactor dimensionality reduction method. Further analysis showed a significant interaction between SLC1A1 and GRIN2B on the Y-BOCS score (F
6, 137 = 7.650, p < 0.001), and individuals with AA/TT genotypes had a significantly higher mean Y-BOCS score than those with other genotypes, except AG/TT.
These results suggest that SLC1A1, GRIN2B, and interactions between the two may potentially confer a susceptibility to OC symptoms in schizophrenia patients receiving clozapine.
Full-text · Article · May 2013 · Psychopharmacology
[Show abstract][Hide abstract] ABSTRACT: Accumulating evidence indicates that chronic treatment with atypical antipsychotics (AAPs) leads to metabolic syndrome (MetS) and cognitive dysfunction. It has been found that patients receiving antipsychotic treatment with MetS have significantly worse cognitive function when compared to those without the MetS, suggesting an intrinsic relationship between MetS and cognitive dysfunction. Thus, investigating the reasons for the side effects induced by AAPs is an important step in the effort to understand the patholophysiology of this condition. The 5-HT2c receptor (5-HT2cR) antagonist properties of AAPs are likely to contribute to AAP-induced MetS. There is crosstalk between phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and 5-HT2cR. PTEN negatively regulates the activity of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, which plays an important role in obesity-induced insulin resistance in peripheral tissue. In the central nervous system, PI3K/AKT signaling modulates synaptic plasticity, a mechanism underlying learning and memory processes. This suggests that PI3K/AKT signaling contributes to both metabolic and cognitive activities. Since PTEN negatively regulates PI3K/AKT signaling and has crosstalk with 5-HT2cR, we hypothesized that the 5-HT2cR antagonism of AAPs may disrupt its crosstalk with PTEN and then trigger the PI3K/AKT signaling, and AAP-induced MetS and cognitive impairments may occur via this analogous signaling pathway.
Full-text · Article · Jan 2013 · Medical Hypotheses
[Show abstract][Hide abstract] ABSTRACT: Introduction
Several lines of evidence have indicated that serotonin 2A receptor (HTR2A) may be involved in the pathophysiology of schizophrenia. One functional polymorphism in HTR2A (T102C) has been widely investigated; however, the results have been inconsistent. The purpose of this study was to evaluate the association between HTR2A T02C polymorphism and schizophrenia in a Chinese Han population.
We performed a case-control study, using an early onset sample, which may be an attractive subgroup for genetic studies. In addition, we performed a meta-analysis of the combined sample groups in Han Chinese.
Our study, based on 385 schizophrenic patients and 399 controls, found a significant genotype-wise association of T102C and schizophrenia (P = 0.02). After applying stratified analyses, the dominant model for T allele produced significant association (OR = 1.60, 95%CI = 1.11–2.30, P = 0.01). In the meta-analysis including all of the published population-based association studies in Han Chinese and the present association study, the pooled genotype-wise result in a dominant model was statistically significant with a summary OR of 1.25 (95%CI = 1.04–1.50, P = 0.02).
Our results suggest that the HTR2A T102C polymorphism may confer susceptibility to schizophrenia in Han Chinese.
Full-text · Article · Jan 2013 · Asia-Pacific Psychiatry
[Show abstract][Hide abstract] ABSTRACT: Cognitive impairment is one of the core symptoms in schizophrenia, which reflects the neurodevelopmental deficits in the etiology of this disease. Brain-derived neurotrophic factor (BDNF) plays an important role in various neurodevelopmental processes. Growing evidence has shown that BDNF may be involved in the etiology of schizophrenia. The aim of this study was to examine the association of the BDNF Val66Met polymorphism with cognition in patients with schizophrenia. Various neuropsychological tests including the Wechsler Adult Intelligence Scale-Revised, the Wechsler Memory Scale-Revised, and the Wisconsin Card Sorting Test (WCST) were employed in a sample of 112 antipsychotic-naïve patients with schizophrenia and 63 healthy controls. We examined the Val66Met polymorphism in the 112 patients and 394 controls. Among the patients, cognition was compared between Met allele carriers and non-Met allele carriers. A wide range of cognitive deficits were demonstrated in the schizophrenic patients, compared with the controls (Ps < 0.01). No significant differences of genotype or allele distribution were identified between patients and controls. The patients with Met allele showed more percent WCST perseverative errors than those without Met allele (P = 0.007). After stratification based on gender, an association between the Met allele and a higher percentage of perseverative errors was found in male patients (P = 0.014), but not in females (P = 0.09). Cognitive performance is broadly impaired in schizophrenic patients. The BDNF Val66Met polymorphism may be involved in the impaired executive function. This effect may have gender-specific characteristics.
[Show abstract][Hide abstract] ABSTRACT: Serotonergic system-related genes may be good candidates in investigating the genetic basis of schizophrenia. Our previous study suggested that promoter region of tryptophan hydroxylase 2 gene (TPH2) may confer the susceptibility to paranoid schizophrenia. In this study, we investigated whether common variants within TPH2 promoter may predispose to paranoid schizophrenia in Han Chinese. A total of 509 patients who met DSM-IV criteria for paranoid schizophrenia and 510 matched healthy controls were recruited for this study. Five polymorphisms within TPH2 promoter region were tested. No statistically significant differences were found in allele or genotype frequencies between schizophrenic patients and healthy controls. The frequency of the rs4448731T-rs6582071A-rs7963803A-rs4570625T-rs11178997A haplotype was significantly higher in cases compared to the controls (P = 0.003; OR = 1.49; 95% CI, 1.15-1.95). Our results suggest that the common variants within TPH2 promoter are associated with paranoid schizophrenia in Han Chinese. Further studies in larger samples are warranted to elucidate the role of TPH2 in the etiology of paranoid schizophrenia.
Full-text · Article · Mar 2012 · Journal of Molecular Neuroscience