Luxian Lv

Xinxiang University, Sinsiang-hsien, Henan Sheng, China

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Publications (43)162.22 Total impact

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    ABSTRACT: Accumulating evidence indicates a putative association of telomere length and mitochondrial function with antipsychotics response in schizophrenia (SCZ). However, pharmacological findings were limited and no previous work has assessed this in a prospective longitudinal study. This study assessed telomere length and mitochondrial DNA copy number in first-episode antipsychotic-naive SCZ patients with 8-week risperidone treatment to evaluate the association between these biomarkers and clinical treatment response. We recruited 137 first-episode antipsychotic-naive SCZ patients (and 144 controls) at baseline and 89 patients completed the 8-week follow-up. Patients, completed follow-up, were divided into Responders (N = 46) and Non-Responders (N = 43) according to the percentage of symptoms improvement. Linear regression analyses show that SCZ patients had significantly lower mtDNA copy number (beta = -0.108, p = 0.002), and no alteration of telomere length when compared with healthy controls. In addition, compared with Non-Responders, Responders had significantly lower mtDNA copy number (beta = -0.178, p = 0.001), and longer telomere length (beta = 0.111, p = 0.071) before the 8-week treatment. After treatment, Responders persisted lower mtDNA copy number comparing with No-Responders (partial eta(2) = 0.125, p = 0.001). These findings suggest that telomere length and mtDNA copy number may hold the potential to serve as predictors of antipsychotic response of SCZ patients.
    Full-text · Article · Dec 2015 · Scientific Reports
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    ABSTRACT: Background: Antipsychotic-induced weight gain (AIWG) is a serious concern in therapy with antipsychotic medications. To identify single nucleotide polymorphisms (SNPs) associated with AIWG, we conducted a genome-wide association study (GWAS) for antipsychotic treatment. Methods: The discovery cohort consisted of 534 patients with schizophrenia, who underwent 8-week treatment with antipsychotics and were genotyped using the Illumina Human 610-Quad BeadChip. The independent replication cohort consisted of 547 patients with schizophrenia, treated with similar antipsychotics, and genotyped using the Sequenom MassARRAY platform. Two hundred and thirty-six drug-naive patients treated with risperidone or quetiapine were analyzed independently. Additionally, we conducted pathway and expression analyses using several public bioinformatics databases. Results: After correction for age and gender, the top 2 genome-wide significant SNPs with AIWG were located in the PTPRD gene (protein tyrosine phosphatase, receptor type D, 9p24-p23; rs10977144, P GWAS = 9.26E-09; rs10977154, P GWAS = 4.53E-08). The third most significant SNP was in the GFPT2 gene (glutamine-fructose-6-phosphate amidotransferase 2, 5q35.3; rs12386481, P GWAS = 1.98E-07). These results were validated in the replication cohort (rs10977144, P Replication = 4.30E-03; rs10977154, P Replication = 6.33E-03; rs12386481, P Replication =7.65E-03). These results were also verified in those patients initially exposed to risperidone and quetiapine (rs10977144, P = 1.97E-05; rs10977154, P = 2.04E-05; rs12386481, P = 1.97E-04). Pathway analyses showed that AIWG may involve in multiple pathways related to metabolic processes. Moreover, PTPRD mRNA might be highly expressed in brain regions, and the SNPs (rs10977144, rs1097154) also showed significant expression quantitative trait locus effects. Conclusions: Our findings indicate that PTPRD polymorphisms might modulate AIWG.
    No preview · Article · Dec 2015 · Schizophrenia Bulletin
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    ABSTRACT: Aim: We carried out a pharmacogenomic study in order to identify susceptible genes for antipsychotics induced weight gain within the Chinese Han population. Materials & methods: We enrolled 216 patients with schizophrenia in our study. All of them underwent risperidone monotherapy, and fulfilled 4-week follow-up. Weight gain was measured before treatment and 4 weeks later. Seven hundred and sixty-eight SNPs from 85 genes were calculated for association with weight gain percentage. Results: Fifty-seven SNPs located at 16 genes with a p-value less than 0.05.4 SNPs located on serotonin transporter gene (solute carrier family 6, member 4, SLC6A4) remained significant after multitest correction (rs3813034, p = 0.000357, q = 0.08, rs1042173, rs4325622, rs9303628, p = 0.000451, q = 0.08). Conclusion: SLC6A4 might be susceptible gene for risperidone-induced weight gain within the Chinese Han population.
    No preview · Article · Nov 2015 · Pharmacogenomics
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    ABSTRACT: Objective The present study aimed to evaluate the efficacy and safety of adjunctive aripiprazole treatment in schizophrenia patients with risperidone-induced hyperprolactinemia. Methods One hundred and thirteen patients who were receiving a stable dose of risperidone were randomly assigned to either adjunctive aripiprazole treatment (10 mg/day) (aripiprazole group) or no additional treatment (control group) at a 1: 1 ratio for 8 weeks. Schizophrenia symptoms were measured using the Positive and Negative Syndrome Scale (PANSS). Rating scales and safety assessments (RSESE, BARS, UKU) were performed at baseline and at weeks 4 and 8. Serum levels of prolactin were determined at baseline and at weeks 2, 4, 6 and 8. Metabolic parameters were determined at baseline and again at weeks 4 and 8. Results One hundred and thirteen patients were enrolled in this study, and 107 patients completed the study (54 in the aripiprazole group, and 53 in the control group). PANSS-total scores in the aripiprazole group decreased significantly at week 4 (P = 0.003) and week 8 (P = 0.007) compared with the control group. PANSS-negative scores in the aripiprazole group also decreased significantly at week 4 (P = 0.005) and week 8 (P< 0.001) compared with the control group. Serum levels of prolactin in the aripiprazole group decreased significantly at week 2 (P< 0.001), week 4 (P< 0.001), week 6 (P< 0.001) and week 8 (P< 0.001) compared with the control group. There were no significant differences in changes of Fasting Plasma Glucose, Total cholesterol, Triglycerides and High Density Lipoprotein within each group at week 4 and 8 execpt low density lipoproteins. There was no significant difference in the incidence of adverse reactions between the two groups. Conclusions Adjunctive aripiprazole treatment may be beneficial in reducing serum levels of prolactin and improving negative symptoms in schizophrenia patients with risperidone-induced hyperprolactinemia.
    Preview · Article · Oct 2015 · PLoS ONE
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    ABSTRACT: Individuals with adolescent-onset schizophrenia (AOS) are a subgroup of patients who present clinical symptoms between 13 and 18years of age. Little is known about neurodevelopmental abnormalities in this patient population. The present study was to examine possible resting-state dysfunctional connectivity of brain regions with altered gray matter volume in AOS. Gray matter volume was investigated by voxel-based morphometry (VBM) analysis. Resting-state functional connectivity analysis was used to examine the correlations between regions with structural deficits and the remaining regions. Thirty-seven first-episode schizophrenia adolescents and 30 healthy controls were enrolled. Compared to the controls, the patients showed significantly decreased gray matter volumes in the right superior temporal gyrus (STG) and middle temporal gyrus (MTG) (ps<0.05). With the right STG as seed, significantly reduced connectivities were found within the frontal-temporal networks in the patient group (ps<0.05). With the right MTG as seed, the patient group showed significantly reduced connectivities in the default-mode networks and visual networks (ps<0.05). Compared to significant correlations in the controls (p=0.02), the patients had no observed correlations between functional connectivity of the right STG and gray matter volume of this region. Significant positive correlations were found between functional connectivity of the right STG with the left middle frontal gyrus and the Positive and Negative Syndrome Scale total scores (p=0.048) after controlling the confounding variables. These findings show dysfunctional resting-state connectivities of the right STG and MTG with decreased gray matter volume in adolescents with AOS, suggesting that neurodevelopmental abnormalities may be present in AOS. Copyright © 2015 Elsevier B.V. All rights reserved.
    No preview · Article · Aug 2015 · Schizophrenia Research
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    ABSTRACT: The ataxin-2 binding protein 1 (A2BP1) gene is reported to be one of the susceptibility genes in schizophrenia, autism, and obesity. The aim of this study was to explore the association of A2BP1 gene polymorphisms with antipsychotic induced weight gain (AIWG) in Chinese Han population. Three hundred and twenty-eight patients with schizophrenia were followed- up for an 8-week period of treatment with olanzapine. The fasting weights of 328 patients were measured before and after the 8-week course of treatment. Four single nucleotide polymorphisms (SNPs: rs8048076, rs1478697, rs10500331, and rs4786847) of the A2BP1 gene were genotyped by polymerase chain reaction (PCR). We analyzed putative association of A2BP1 polymorphisms with AIWG of olanzapine using linear regression analysis and found that SNP rs1478697 was significantly associated with AIWG caused by olanzapine (p=0.0012; Bonferroni corrected p=0.0048). The association was replicated in another independent sample including 208 first-episode and drug-naïve patients presenting with schizophrenia after a 4-week treatment with olanzapine (p=0.0092; Bonferroni corrected p=0.0368; meta p=5.33×10(-5)). To explore the biological plausibility of A2BP1 in the pathogenesis of AIWG, we made expression analyses and eQTL analyses; these analyses showed that A2BP1 was highly expressed in whole brain tissues using the HBT database, and that rs1478697 has an expression quantitative trait locus effect in human cerebellar cortex tissues using the BRAINEAC database (p=2.50E-04). In conclusion, the rs1478697 in A2BP1 may be associated with AIWG induced by 8-week treatment with olanzapine. Copyright © 2015. Published by Elsevier Ltd.
    No preview · Article · Jun 2015 · Pharmacological Research
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    ABSTRACT: Schizophrenia (SZ) is a common and complex psychiatric disorder that has a significant genetic component. The glutamatergic system is the major excitatory neurotransmitter system in the central nervous system, and is mediated by N-methyl-D-aspartate (NMDA) receptors. Disturbances in this system have been hypothesized to play a major role in SZ pathogenesis. Several studies have revealed that the NMDA receptor subunit 2B (GRIN2B) potentially associates with SZ and its psychiatric symptoms. In this study, we performed a case-control study to identify polymorphisms of the GRIN2B gene that may confer susceptibility to SZ in the Han Chinese population. Thirty-four single nucleotide polymorphisms (SNPs) were genotyped in 528 paranoid SZ patients and 528 control subjects. A significant association was observed in allele and genotype between SZ and controls at rs2098469 (χ2 = 8.425 and 4.994; p = 0.025 and 0.014, respectively). Significant associations were found in the allele at rs12319804 (χ2 = 4.436; p = 0.035), as well as in the genotype at rs12820037 and rs7298664 between SZ and controls (χ2 = 11.162 and 38.204; p = 0.003 and 4.27×10-8, respectively). After applying the Bonferroni correction, rs7298664 still had significant genotype associations with SZ (p = 1.71×10-7). In addition, rs2098469 genotype and allele frequencies, and 12820037 allele frequencies were nominally associated with SZ. Three haplotypes, CGA (rs10845849-rs12319804-rs10845851), CC (rs12582848-rs7952915), and AAGAC (rs2041986-rs11055665-rs7314376-rs7297101-rs2098469), had significant differences between SZ and controls (χ2 = 4.324, 4.582, and 4.492; p = 0.037, 0.032, and 0.034, respectively). In addition, three SNPs, rs2098469, rs12820037, and rs7298664, were significantly associated with cognition factors PANSS subscores in SZ (F = 16.799, 7.112, and 13.357; p = 0.000, 0.017, and 0.000, respectively). In conclusion, our study provides novel evidence for an association between GRIN2B polymorphisms and SZ susceptibility and symptoms in the Han Chinese population.
    Full-text · Article · May 2015 · PLoS ONE

  • No preview · Article · May 2015 · Neuroscience Bulletin
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    ABSTRACT: Adversity, particularly in early life, can cause illness. Clues to the responsible mechanisms may lie with the discovery of molecular signatures of stress, some of which include alterations to an individual's somatic genome. Here, using genome sequences from 11,670 women, we observed a highly significant association between a stress-related disease, major depression, and the amount of mtDNA (p = 9.00 × 10(-42), odds ratio 1.33 [95% confidence interval [CI] = 1.29-1.37]) and telomere length (p = 2.84 × 10(-14), odds ratio 0.85 [95% CI = 0.81-0.89]). While both telomere length and mtDNA amount were associated with adverse life events, conditional regression analyses showed the molecular changes were contingent on the depressed state. We tested this hypothesis with experiments in mice, demonstrating that stress causes both molecular changes, which are partly reversible and can be elicited by the administration of corticosterone. Together, these results demonstrate that changes in the amount of mtDNA and telomere length are consequences of stress and entering a depressed state. These findings identify increased amounts of mtDNA as a molecular marker of MD and have important implications for understanding how stress causes the disease. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
    No preview · Article · Apr 2015 · Current biology: CB
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    ABSTRACT: This study aimed to investigate the effects of modified electroconvulsive therapy (MECT) on cognitive function and blood parameters in female patients with schizophrenia. Female patients with schizophrenia (n = 23) received MECT while maintaining antipsychotic therapy. 1) White blood cell (WBC), alanine aminotransferase (ALT), creatine kinase (CK) and creatine kinase MB (CKMB) were measured at 10 min before and after MECT. 2) The severity of symptoms was evaluated before and after MECT by using the Positive and Negative Symptoms Scale (PANSS) and then the therapeutic effects of MECT were assessed. 3) Single nerve psychology test was used to assess the cognitive function. 1) There were no significant differences in WBC, ALT, CK and CKMB before and after MECT (P > 0.05). 2) WBC, ALT and CKMB remained stable at different time points after MECT treatment (P > 0.05). But CK had statistical differences at different times before or after MECT treatment (P < 0.05). CK decreased since the first MECT and thereafter increased after the 7th treatment (P < 0.05). 3) The total score of PANSS decreased significantly after MECT (P < 0.05). 4) Digit span test showed no statistically significant differences in different time points (P > 0.05); Digital sign test and verbal fluency test showed significant differences in different times (P < 0.05). The CK figure decreased from the first to sixth MECT treatment and increased in the 7th MECT treatment, and the CKMB also increased in the 7th treatment. MECT treatment had significant effects on female patients with schizophrenia and could obviously improve patient's cognitive function.
    No preview · Article · Mar 2015 · International Journal of Clinical and Experimental Medicine
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    ABSTRACT: It is unclear whether N-acetylaspartate (NAA) depletions documented in schizophrenia patients might be due to the disease progression or medications. Here we investigated longitudinal NAA changes in drug-naïve first-episode patients (FEP) who are relatively free from chronicity. Forty-two drug-naïve FEP and 38 controls were enrolled in this study to explore the effect of 8-week risperidone monotherapy on NAA. All spectra were obtained from the medial prefrontal cortex (MPFC) on a 3.0 T MRI and analyzed with LCModel. At baseline, patients presented no significant differences in NAA (P = 0.084) or NAA/Cr + Pcr (P = 0.500) compared to controls; NAA levels were negatively correlated with PANSS total scores (P = 0.001) and WCST-PE (P = 0.041). After treatment, patients demonstrated significant reductions of NAA (P < 0.001) and NAA/Cr + Pcr (P < 0.001), and significant improvement in PANSS-P (P < 0.001) and PANSS-G (P < 0.001) symptoms. We detected no significant correlations between NAA alterations and PANSS-P (P = 0.679) or PANSS-G (P = 0.668) symptom changes; nor did NAA/Cr + Pcr changes with alterations in PANSS-P (P = 0.677) and PANSS-G (P = 0.616). This is the first evidence that short-term risperidone treatment induces an acute reduction of MPFC NAA during the early phase of schizophrenia, which may be a previously unavailable biomarker to indicate risperidone with a similar pharmacological mechanism, although the functional significance is still unclear.
    Full-text · Article · Mar 2015 · Scientific Reports
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    ABSTRACT: Obesity induced by antipsychotics severely increases the risk of many diseases and significantly reduces quality of life. Genome Wide Association Studies has identified fat-mass and obesity-associated (FTO) gene associated with obesity. The relationship between the FTO gene and drug-induced obesity is unclear. Two hundred and fifty drug naïve, Chinese Han patients with first-episode schizophrenia were enrolled in the study, and genotyped for four single nucleotide polymorphisms (SNPs rs9939609, rs8050136, rs1421085 and rs9930506) by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing. Body weight and body mass index (BMI) were measured at baseline and six months after risperidone treatment. At baseline, body weight and BMI of TT homozygotes were lower than those of A allele carriers in rs9939609; body weight of AA homozygotes was higher than those of G allele carriers in rs9930506 (p’s < 0.05). After 6 months of risperidone treatment, body weight and BMI of TT homozygotes were lower than those of A allele carriers in rs9939609 (p’s <0.01); body weight and BMI of CC homozygotes were lower than those of A allele carriers in rs8050136 (p’s < 0.05); body weight of AA homozygotes was higher than those of G allele carriers in rs9930506 (p’s < 0.05). After controlling for age, gender, age of illness onset, disease duration, weight at baseline and education, weight gain of TT homozygotes at 6 months remained to be lower than those of A allele carriers in rs9939609 (p < 0.01); weight gain of CC homozygotes at 6 months was lower than those of A allele carriers in rs8050136 (p = 0.01). Stepwise multiple regression analysis suggested that, among 4 SNPs, rs9939609 was the strongest predictor of weight gain after 6 months of risperidone treatment (p = 0.001). The FTO gene polymorphisms, especially rs9939609, seem to be related to weight gain after risperidone treatment in Chinese Han patients with first episode schizophrenia.
    Preview · Article · Oct 2014 · Behavioral and Brain Functions
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    ABSTRACT: Objective The present study was to examine serum levels of brain-derived neurotrophic factor (BDNF), folate, homocysteine (Hcy), and their relationships with hippocampal volume and psychopathology in drug naïve, first episode schizophrenia. Method Drug naïve, first episode schizophrenia patients and healthy controls were enrolled in the study. Serum levels of BDNF, folate and Hcy were measured using enzyme-linked immunosorbent assay (ELISA), electrochemiluminescence immunoassay (ECLIA), and enzymatic cycling method respectively. Hippocampus was parcellated and bilateral hippocampal volumes were measured using FreeSurfer. Results Forty-six patients with drug naïve, first episode schizophrenia (SZ group) and 30 healthy controls (control group) were enrolled. The SZ group had significantly lower serum levels of BDNF and folate, and significantly higher serum levels of Hcy compared with the control group (p = 0.013, p < 0.001, p = 0.003 respectively). There were no significant differences in hippocampal volumes between the two groups (ps > 0.2). Within the SZ group, there were significant positive relationships between serum levels of BDNF and both left and right hippocampal volumes (r = 0.327, p = 0.026; r = 0.338, p = 0.022 respectively). In contrast, such relationships did not exist in the control group. Within the SZ group, there were significant negative relationships between serum levels of folate and PANSS-total scores and PANSS-negative symptom scores (r = 0.319, p = 0.031; r = 0.321, p = 0.030 respectively); and there was a positive relationship between serum levels of Hcy and PANSS-total scores (r = 0.312, p = 0.035). Controlling for potential confounding variables resulted in similar findings. Conclusions Drug naïve, first episode schizophrenia presents decreased serum levels of BDNF, folate and increased serum levels of Hcy, which may play an important role in the neurodevelopmental process and clinical manifestation of schizophrenia.
    Full-text · Article · Oct 2014 · Schizophrenia Research
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    ABSTRACT: This study was to examine cortical thickness in drug naïve, first episode schizophrenia patients, and to explore its relationship with serum levels of brain-derived neurotrophic factor (BDNF). Forty-five drug naive schizophrenia patients and 28 healthy controls were enrolled in the study. Freesurfer was used to parcellate cortical regions, and vertex-wise group analysis was used for whole brain cortical thickness. The clusters for the brain regions that demonstrated group differences were extracted, and the mean values of thickness were calculated. Serum levels of BDNF were measured using enzyme-linked immunosorbent assay (ELISA). After controlling for age and gender, significantly thinner cortical thickness was found in left insula and superior temporal gyrus in the patient group compared with the healthy control group (HC group) (p's < 0.001). Lower serum levels of BDNF were also found in the patient group compared with the HC group (p = 0.001). Correlation analysis showed a significant positive relationship between thickness of left insula and serum levels of BDNF within the HC group (r = 0.396, p = 0.037) but there was no such relationship within the patient group (r = 0.035, p = 0.819). Cortical thinning is present in drug naïve, first episode schizophrenia patients, indicating neurodevelopmental abnormalities at the onset of schizophrenia. Left insula might be an imaging biomarker in detecting the impaired protective role of neurotrophic factor for the brain development in schizophrenia.
    Full-text · Article · Sep 2014 · Journal of Psychiatric Research
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    ABSTRACT: Objectives: MicroRNA137 (miRNA137) regulates several gene expressions involved in brain development, and a recent large genome wide association study (GWAS) revealed a possible association between miRNA137 and schizophrenia. Methods: The allelic variants of rs66642155, a variable number tandem repeat polymorphism, and the single nucleotide polymorphism rs1625579 A/C in the miRNA137 host gene fragment were compared between 300 schizophrenic patients and 300 healthy controls from the Han Chinese population. The association of these polymorphisms with clinical characteristics of schizophrenia was also tested. Results: Genotype and allele frequencies of these polymorphisms were not significantly different between patient and control populations. In patients, however, age at onset was much later in wild type rs66642155 carriers than in mutation carriers. Total positive score on the Positive and Negative Symptom Scale (PANSS), total five-factor model positive score, and the delusions symptom score were all significantly higher in wild type rs66642155 carriers with schizophrenia, while the disturbance of volition symptom score was significantly higher in the mutation carriers with schizophrenia. Conclusions: MiRNA137 may not be a significant susceptibility gene for schizophrenia, but in patients, rs66642155 allelic variant of miRNA137 appears to influence age at onset and the severity of positive symptoms.
    Full-text · Article · Aug 2014 · The International Journal of Psychiatry in Medicine
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    ABSTRACT: Objectives. The present study was to examine the relationship between serum levels of prolactin and the inflammatory status in drug-naive, first-episode schizophrenia patients with normal weight. Methods. Patients with normal weight, drug-naive, first-episode schizophrenia and healthy controls were enrolled in the study. Serum levels of prolactin (PRL) were measured using electrical chemiluminescence immunoassay. Serum levels of interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were examined using enzyme-linked immunosorbent assay (ELISA). Results. Sixty patients with normal weight, drug-naive, first-episode schizophrenia and 60 healthy controls were enrolled. The schizophrenia group had higher serum levels of PRL, IL-1beta, IL-6 and TNF-alpha compared with the control group. There was a gender difference of hyperprolactinemia in schizophrenia group. There were positive relationships between serum levels of PRL and serum levels of IL-1beta, IL-6 and TNF-alpha within the schizophrenia group. Within the schizophrenia group, TNF-alpha was the strongest predictor among the three cytokines for serum levels of prolactin after controlling for gender, age, education, smoking status and disease duration. Conclusions. Patients with normal weight, drug-naive, first-episode schizophrenia present elevated serum levels of PRL, which might be related to the up-regulated inflammatory status in this patient population.
    No preview · Article · Jun 2014 · The World Journal of Biological Psychiatry
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    ABSTRACT: The purpose of this study was to investigate the change in plasma protein expression in first episode schizophrenia after an 8-week treatment with risperidone, and to explore potential biomarkers for metabolic side effects associated with risperidone treatment. Eighty first-episode schizophrenia patientswere enrolled in the study. Fifteen of the 80 patients were randomly selected to undergo proteomic analysis. Plasma proteins were obtained before and after the 8-week risperidone treatment, and measured using two-dimensional gel electrophoresis (2-DE), Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry(MALDI-TOF/TOF) and peptide mass fingerprinting.Proteins with the highest fold changes after risperidone treatment were then measured for all 80 patients using enzyme linked immunosorbent assay (ELISA). The relationship between changes in plasma protein levels and changes in metabolic parameters after risperidone treatment was examined. In 15 randomly selected patients, approximately 1,500 protein spots were detected in each gel by 2-DE. Of those proteins, 22 spots showed significant difference in abundance after risperidone treatment (p's < 0.05). After MALDI-TOF peptide mass fingerprinting, apolipoprotein A-I (APOA-I) and Guanine Nucleotide Binding Protein, Alpha Stimulating (GNAS), were found to have the highest fold changes.The content of APOA-I was significantly increased, and the content of GNAS was significantly decreased after risperidone treatment (p's
    Full-text · Article · Apr 2014 · PLoS ONE
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    ABSTRACT: The present study was to examine the role of pro-inflammatory T helper 17 (Th17) cells in drug naïve, first episode schizophrenia. Patients with normal weight, drug naïve, first episode schizophrenia and healthy controls were enrolled in the study. Flow cytometric analysis was performed to analyze the proportion of Th17 cells among the CD4+ T cells. Plasma levels of interleukin-17 (IL-17), interferon-γ (IFN-γ) and interleukin-6 (IL-6) were examined using enzyme-linked immunosorbent assay (ELISA). Psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). All measures were repeated for the patient group after 4 weeks of risperidone treatment. Sixty-nine patients with normal weight, drug naïve, first episode schizophrenia and 60 healthy controls were enrolled. At baseline, the patient group had significantly higher proportions of Th17 cells and plasma levels of IFN-γ and IL-6 compared with the control group (p's<0.01). Within the patient group, there were significant positive relationships between the proportion of Th17 cells, plasma levels of IL-17, IFN- γ, IL-6 and the PANSS total score after controlling for potential confounding variables (p's<0.05). After 4 weeks of risperidone treatment, the proportion of Th17 cells decreased significantly (p<0.001), there was a significant positive relationship between the PANSS total score change rate and the change in proportion of Th17 cells (p=0.039). Patients with normal weight, drug naïve, first episode schizophrenia present activation of Th17 cells, which might be associated with therapeutic response after risperidone treatment.
    No preview · Article · Jan 2014 · Progress in Neuro-Psychopharmacology and Biological Psychiatry
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    ABSTRACT: CACNA1C (12p13.3) has been implicated as a susceptibility gene for schizophrenia by several replicated genome wide association studies. While these results have been consistent among studies in European populations, the findings in East Asian populations have varied. To test whether CACNA1C is a risk gene for schizophrenia, we conducted a case-control study in 5897 schizophrenic patients and 6323 healthy control subjects selected from Han Chinese population. Our study replicated the positive associations of rs1006737 (P=0.0108, OR=1.16, 95% CI: 1.03-1.29) and rs1024582 (P=0.0062, OR=1.18, 95% CI: 1.05-1.33), and identified a novel risk locus, rs2007044 (P=0.0053, OR=1.08, 95% CI: 1.02-1.14). A meta-analysis of rs1006737 combining our study and previous studies was conducted in a total of 8222 schizophrenia cases and 24,661 healthy controls. In the meta-analysis, the association between rs1006737 and schizophrenia remained significant (OR=1.14, 95% CI: 1.07-1.22, P=0.0001). Stratified analysis showed no heterogeneity between East Asian and European ancestries (χ(2)[1]=0.07, P=0.795), and the difference in pooled ORs between ancestries was not significant (Z=0.25, P=0.801). Our results provide further support for associations of rs1006737 and rs1024582 with schizophrenia, identify a new risk locus rs2007044 in a Han Chinese population, and further establish CACNA1C as an important susceptibility gene for the disease across world populations.
    No preview · Article · Dec 2013 · Schizophrenia Research
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    ABSTRACT: The present study aimed to examine the changes in pro-inflammatory cytokines and body weight during 6-month risperidone treatment in drug naïve, first-episode schizophrenia. Sixty-two drug naïve, first-episode schizophrenia (SZ group) and 60 healthy individuals (control group) were enrolled in the study. Serum interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) levels, and body weight were measured at baseline for both groups, and repeated for the SZ group at five different time points during 6-month risperidone treatment. At baseline, serum IL-1β, IL-6, and TNF-α levels in the SZ group (53.28 ± 12.62, 33.98 ± 14.13, 50.08 ± 12.86 pg/mL, respectively) were significantly higher than those in the control group (23.49 ± 15.27, 15.53 ± 7.16, 32.12 ± 15.23 pg/mL, respectively) (p's < 0.001). Within the SZ group, serum IL-1β levels decreased significantly at 2 weeks (48.02 ± 16.00 pg/mL, p < 0.01) and 1 month (44.70 ± 16.63 pg/mL, p < 0.001), but then gradually increased at 2 months (48.49 ± 18.87 pg/mL), 3 months (50.59 ± 18.48 pg/mL) and 6 months (53.64 ± 16.22 pg/mL) to the levels comparable to baseline; serum IL-6 levels changed significantly over the course of treatment (p = 0.001), but reached the levels comparable to baseline at 6 months (37.13 ± 13.23 pg/mL); serum levels of TNF-α increased significantly at 3 months (55.02 ± 16.69 pg/mL, p < 0.01) and 6 months (58.69 ± 13.57 pg/mL, p < 0.001); steady and significant weight gain was observed at each follow-up time point (p's < 0.001), from 56.71 ± 9.25 kg at baseline to 62.72 ± 9.53 kg at 6 months. Risperidone treatment is associated with changes in serum pro-inflammatory cytokines levels and weight. There is an initial anti-inflammatory effect that reduces with treatment, potentially due to its weight gain side effect.
    No preview · Article · Dec 2013 · Psychopharmacology