Lisheng Song

Common Variants in the TPH2 Promoter Confer Susceptibility to Paranoid Schizophrenia

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.

Metabolic adverse effects of olanzapine on cognitive dysfunction: A possible relationship between BDNF and TNF-alpha

OBJECTIVE There is accumulating evidence indicating that long-term treatment with second-generation antipsychotics (SGAs) results in metabolic syndrome (MetS) and cognitive impairment. This evidence suggests an intrinsic link between antipsychotic-induced MetS and cognitive dysfunction in schizophrenia patients. Olanzapine is a commonly prescribed SGA with a significantly higher MetS risk than that of most antipsychotics. In this study, we hypothesized that olanzapine-induced MetS may exacerbate cognitive dysfunction in patients with schizophrenia. METHODS A sample of 216 schizophrenia patients receiving long-term olanzapine monotherapy were divided into two groups, MetS and non-MetS, based on the diagnostic criteria of the National Cholesterol Education Programs Adult Treatment Panel III. We also recruited 72 healthy individuals for a control group. Cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Plasma brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-alpha (TNF-alpha) were measured by an enzyme-linked immunosorbent assay for 108 patients and 47 controls. RESULTS Among the 216 schizophrenia patients receiving olanzapine monotherapy, MetS was found in 95/216 (44%). Patients with MetS had more negative symptoms, higher total scores in PANSS (Ps<0.05) and lower immediate memory, attention, delayed memory and total scores in RBANS (Ps<0.01). Stepwise multivariate linear regression analysis revealed that increased glucose was the independent risk factor for cognitive dysfunction (t=-2.57, P=0.01). Patients with MetS had significantly lower BDNF (F=6.49, P=0.012) and higher TNF-alpha (F=5.08, P=0.026) levels than those without MetS. There was a negative correlation between the BDNF and TNF-alpha levels in the patients (r=-0.196, P=0.042). CONCLUSION Our findings provide evidence suggesting that the metabolic adverse effects of olanzapine may aggravate cognitive dysfunction in patients with schizophrenia through an interaction between BDNF and TNF-alpha.

Genetic association analysis of microRNA137 and its target complex 1 with schizophrenia in Han Chinese

Recent genome-wide association studies (GWAS) have identified a strong association signal of microRNA137 host gene (MIR137) with schizophrenia. MIR137 dysfunction results in downregulation of presynaptic target gene complexin 1 (CPLX1) and impairs synaptic plasticity in the hippocampus. In this study, we aimed to investigate whether the variants of MIR137 and CPLX1 confer susceptibility to schizophrenia in Han Chinese. This study employed 736 patients with schizophrenia patients and 751 well-matched healthy subjects for genetic analysis, and genotyped 12 SNPs within MIR137 and CPLX1. SZDB database was used to performed brain eQTL analysis. There were no significant differences of CPLX1 expression in hippocampus, prefrontal cortex or stratum between the schizophrenia patients and control subjects. No significant differences were observed in allele and genotype frequencies in studied SNPs between the case and control groups. Gene interaction analysis showed that MIR137 SNP rs1625579 did not affect schizophrenia susceptibility in interaction with the CPLX1 polymorphic variants. Our findings do not support MIR137 and CPLX1 conferring susceptibility to schizophrenia in Han Chinese.

Interaction between BDNF and TNF-α genes in schizophrenia

OBJECTIVE Our recent work reported that tumor necrosis factor-α (TNF-α) is negatively correlated with brain-derived neurotrophic factor (BDNF) in patients with schizophrenia. A previous study has shown that TNF-α could regulate the extracellular secretion of BDNF. Therefore, we hypothesized that the TNF-α gene (TNF-α) may interact with the BDNF gene (BDNF) to influence schizophrenia risk. METHODS We recruited 694 patients with schizophrenia from three mental hospitals in Eastern China and 725 healthy controls. The Positive and Negative Syndrome Scale (PANSS) was employed to evaluate symptom severity. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess cognitive function. The SNPs rs6265 in BDNF and rs1799964 in TNF-α were genotyped. RESULTS There were no significant differences in allele and genotype frequencies in either rs6265 or rs1799964 between the case and control groups. A significant association of rs6265 AA + AG × rs1799964 CC + CT with schizophrenia was observed (OR = 1.14, 95%CI: 1.02-1.27; P = .02). There were significant differences in the RBANS attention and total scores between the patients with rs6265A and rs1799964C alleles and those without these two alleles (P = .03 and P = .03 after Bonferroni correction, respectively). CONCLUSION Our findings provided preliminary evidence that the interaction of BDNF and TNF-α may confer susceptibility to schizophrenia and cognitive dysfunction.