Xiangyang Zhang

Yale-New Haven Hospital, New Haven, Connecticut, United States

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Publications (7)12.7 Total impact

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    ABSTRACT: Controversial results concerning insulin resistance and lipid metabolism have been reported in antipsychotic-naive first-episode psychosis (AN-FEP) patients with schizophrenia of different countries. We aimed at determining whether schizophrenia-related psychopathology was associated with insulin resistance and/or dyslipidaemia in Chinese patients with AN-FEP schizophrenia. A cross-sectional study was performed in Chinese patients newly diagnosed with schizophrenia (n = 49, antipsychotic-naïve or antipsychotic medications< 2 weeks) and healthy volunteers (n = 30). The serum levels of insulin and triglyceride levels as well as homeostasis model of assessment-insulin resistance (HOMA-IR) index were significantly increased in AN-FEP patients, when compared with healthy volunteers. The gender difference had a significant impact on the insulin resistance and dyslipidaemia in these AN-FEP subjects. Multiple linear regression analysis demonstrated that the severity of positive symptoms of schizophrenia was negatively related to insulin resistance. No difference of serum glucose level, total cholesterol content, body mass index (BMI) and smoking status was detected between patients with schizophrenia and healthy controls. In conclusion, Chinese AN-FEP patients were more prone to insulin resistance and dyslipidaemia as compared to the healthy population, which is negatively correlated to positive symptoms. The results may contribute to the understanding of the relationship between the glucose/lipidaemia metabolic dysfunction and the psychopathology in patients with schizophrenia.
    Psychiatry research. 10/2013;
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    ABSTRACT: Background and Objectives We previously reported a risk genomic region (ie, PTP4A1-PHF3-EYS) for alcohol dependence in a genome-wide association study (GWAS). We also reported a rare variant constellation across this region that was significantly associated with alcohol dependence. In the present study, we significantly increased the marker density within this region and examined the specificity of the associations of common variants for alcohol dependence. Methods One African-American discovery sample (681 cases with alcohol dependence and 508 controls), one European-American replication sample (1,409 alcohol dependent cases and 1,518 controls), and one European-Australian replication sample (a total of 6,438 family subjects with 1,645 alcohol dependent probands) underwent association analysis. A total of 38,714 subjects from 18 other cohorts with 10 different neuropsychiatric disorders served as contrast groups. ResultsWe found 289 SNPs that were nominally associated with alcohol dependence in the discovery sample (p < .05). Fifty-six associations of them were significant after correction (1.9 × 10−6 ≤ p ≤ 1.6 × 10−5). No markers were significantly associated with other neuropsychiatric disorders after experiment-wide correction. Conclusions and Scientific SignificanceWe confirmed with our previous findings that PTP4A1-PHF3-EYS variants were significantly associated with alcohol dependence, which were replicable across multiple independent populations and were specific for alcohol dependence. These findings suggested that this region might harbor a causal variant(s) for alcohol dependence. (Am J Addict 2013;XX:1–4)
    American Journal on Addictions 09/2013; · 1.74 Impact Factor
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    ABSTRACT: Alcohol dependence is more common among men than among women. Potential explanations for this include the role of genes in sex chromosomes (X and Y). In the present study, we scanned the entire Y chromosome and its homologs on the X chromosome in men to identify male-specific risk genes for alcohol dependence. Two thousand nine hundred and twenty-seven individuals in two independent cohorts were analyzed. The European-American male cohort (883 cases with alcohol dependence and 445 controls) served as the discovery cohort and the European-American female cohort (526 cases and 1073 controls) served as a contrast group. All individuals were genotyped on the Illumina Human 1M beadchip. Two thousand two hundred and twenty-four single nucleotide polymorphisms (SNPs) on the Y chromosome or in the homologs on the X chromosome were analyzed. The allele frequencies were compared between cases and controls within each cohort using logistic regression analysis. We found that, after experiment-wide correction, two SNPs on the X chromosome were associated significantly with alcohol dependence in European-American men (P=1.0×10 for rs5916144 and P=5.5×10 for rs5961794 at 3' UTR of NLGN4X), but not in the women. A total of 26 SNPs at 3'UTR of or within NLGN4X were nominally associated with alcohol dependence in men (5.5×10≤P≤0.05), all of which were not statistically significant in women. We conclude that NLGN4X was a significant male-specific risk gene for alcohol dependence in European-Americans. NLGN4X might harbor a causal variant(s) for alcohol dependence. A defect of synaptogenesis in neuronal circuitry caused by NLGN4X mutations is believed to play a role in alcohol dependence.
    Psychiatric genetics 07/2013; · 2.33 Impact Factor
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    ABSTRACT: Objective: In the present study, we scanned the whole exome in three independent samples to search for replicable risk nonsynonymous (ns) variants (ns single-nucleotide polymorphisms [nsSNPs]) for alcohol dependence. Method: A total of 10,554 subjects in three independent samples were analyzed for association with alcohol dependence, including one European American sample (1,409 cases with alcohol dependence and 1,518 controls), one African American sample (681 cases and 508 controls), and one European Australian sample (a total of 6,438 family subjects with 1,645 alcohol-dependent probands). RNA expression of the risk genes in human, mouse, and rat brains was also explored. Results: We identified a total of 70 nsSNPs at 65 genes with nominally replicable associations; 22 nsSNPs at 21 genes among them survived corrections for multiple testing in meta-analysis (α = .0007). By incorporating the information from bioinformatics and RNA expression analyses, we identified at least two of the most promising risk genes for alcohol dependence: APOER2 and UBAP2. Conclusions: The gene coding for apolipoprotein E receptor 2 (APOER2) and the gene coding for ubiquitin-associated protein-2 (UBAP2) are among the most appropriate for follow-up in human and nonhuman species as contributors to risk for alcohol dependence. (J. Stud Alcohol Drugs, 74, 622-625, 2013).
    Journal of studies on alcohol and drugs 07/2013; 74(4):622-5. · 1.68 Impact Factor
  • Journal of Human Genetics 01/2013; · 2.37 Impact Factor
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    ABSTRACT: Objective To explore the deficits of acoustic startle reflex (ASR) that might exist in Chinese patients with schizophrenia and the effects of antipsychotics on ASR.Methods Participants included 25 male patients with chronic schizophrenia treated with typical antipsychotics (typical group), 25 who were treated with atypical antipsychotic clozapine (clozapine group) and 25 healthy male subjects (control group) matched for age and years of education. Startle reflex to acoustic stimuli were examined in all subjects from the three groups. At the same day of startle testing, psychopathological symptoms of the patients were assessed with the Positive and Negative Syndrome Scale (PANSS).Results(1) Startle response (SR) was significantly reduced in typical group as compared to control group [(553.6 ± 516.9) mV vs. (942.0 ± 447.3) mV, P = 0.009]. SR of clozapine group [(755.9 ± 439.4) mV] was greater than that of typical group and less than that of control group, but there was no significant difference between the clozapine group and the other two. (2) Habituation (HAB) of startle reflex in typical group was significantly lower than in control group [(17.8 ± 35.8)% vs. (44.9 ± 28.9)%, P = 0.027]. HAB of clozapine group [(22.9 ± 34.1)%] was higher than that of typical group and less than that of control group, but there was no significant difference between clozapine group and the other groups. (3) Compared with healthy controls, patients of typical group exhibited the significant reduction in prepulse inhibition (PPI) of startle reflex (P = 0.024) when prepulse interval (LI) was 120 ms. PPI of clozapine group was higher than typical group and less than control group, but no significant differences in PPI were found between clozapine group and the other groups. While LI was 30- or 120-ms, PPI among the three groups showed not significantly different (P > 0.05). (4) No significant relationship was found between PPI of different LIs and symptom scores assessed with PANSS in patients with schizophrenia (P > 0.05).Conclusion Our findings suggest impaired PPI in Chinese patients with schizophrenia; Atypical antipsychotic clozapine might partly improve disinhibition of startle reflex in schizophrenic patients.
    Asian Journal of Psychiatry 03/2012; 5(1):54–57.
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    ABSTRACT: Mounting evidence suggest that astrocytes might be involved in the pathogenesis of schizophrenia. Of particular interest is S100B, a protein produced primarily by astrocytes that plays a critical role in the maintenance of functional neuronal and astroglial activation. Abnormalities in S100B levels have been associated with schizophrenia. In this study, we examined serum S100B protein levels and the relationship between S100B levels and psychopathological symptoms in first-episode, drug-naïve patients with schizophrenia (SCZ). Sixty-four patients with schizophrenia were compared with 66 age- and sex-matched healthy controls (HCs). Psychopathology in the SCZ group was assessed by the Positive and Negative Syndrome Scale (PANSS). Serum S100B protein levels were measured by sandwich enzyme-linked immunosorbent assay (ELISA). The results showed that S100B protein-like immunoreactivity was significantly higher in the SCZ group than the HC group. S100B-like immunoreactivity was correlated with age, duration of illness, and PANSS subscale scores for negative and general psychopathology and total scores. In the SCZ group, serum S100B levels in residual subtypes were significantly higher than in the paranoid and disorganized subtypes. Our findings suggest an upregulation of a marker for astrocyte activity, i.e., S100B, in first-episode medication-free patients with schizophrenia, and thus support the involvement of astrocytes in the pathogenesis of schizophrenia.
    Schizophrenia Research 02/2010; · 4.59 Impact Factor

Publication Stats

7 Citations
12.70 Total Impact Points

Institutions

  • 2013
    • Yale-New Haven Hospital
      • Department of Laboratory Medicine
      New Haven, Connecticut, United States
  • 2010
    • Baylor College of Medicine
      Houston, Texas, United States