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Yang Y.,Xinxiang Medical University | Yang Y.,Henan Key Laboratory of Biological Psychiatry | Li W.,Xinxiang Medical University | Li W.,Henan Key Laboratory of Biological Psychiatry | And 14 more authors.
Behavioral and Brain Functions | Year: 2012

Background: Ghrelin (GHRL) is a pivotal peptide regulator of food intake, energy balance, and body mass. Weight gain (WG) is a common side effect of the atypical antipsychotics (AAPs) used to treat schizophrenia (SZ). Ghrelin polymorphisms have been associated with pathogenic variations in plasma lipid concentrations, blood pressure, plasma glucose, and body mass index (BMI). However, it is unclear whether GHRL polymorphisms are associated with WG due to AAPs. Furthermore, there is no evidence of an association between GHRL polymorphisms and SZ or the therapeutic response to AAPs. We explored these potential associations by genotyping GHRL alleles in SZ patients and controls. We also examined the relation between these SNPs and changes in metabolic indices during AAP treatment in SZ subgroups distinguished by high or low therapeutic response.Methods: Four SNPs (Leu72Met, -501A/C, -604 G/A, and -1062 G > C) were genotyped in 634 schizophrenia patients and 606 control subjects.Results: There were no significant differences in allele frequencies, genotype distributions, or the distributions of two SNP haplotypes between SZ patients and healthy controls (P > 0.05). There was also no significant difference in symptom reduction between genotypes after 8 weeks of AAP treatment as measured by positive and negative symptom scale scores (PANSS). However, the -604 G/A polymorphism was associated with a greater BMI increase in response to AAP administration in both APP responders and non-responders as distinguished by PANSS score reduction (P < 0.001). There were also significant differences in WG when the responder group was further subdivided according to the specific AAP prescribed (P < 0.05).Conclusions: These four GHRL gene SNPs were not associated with SZ in this Chinese Han population. The -604 G/A polymorphism was associated with significant BW and BMI increases during AAP treatment. Patients exhibiting higher WG showed greater improvements in positive and negative symptoms than patients exhibiting lower weight gain or weight loss. © 2012 Yang et al; licensee BioMed Central Ltd. Source

Chen Y.,Peking University | Tian L.,Peking University | Zhang F.,Peking University | Liu C.,Peking University | And 15 more authors.
Psychiatry Research | Year: 2013

Myosin Vb (. MYO5B) has recently been implicated in the etiology of bipolar disorder in a genome-wide association study (GWAS). This gene is involved in amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunit glutamate receptor 1 (GluR1) recycling and plays an important role in the primary excitatory neurotransmission. Dysfunction of the brain glutamate system has been postulated to be involved in the pathophysiology in schizophrenia. To further investigate the association between MYO5B polymorphisms and schizophrenia, we genotyped nine single nucleotide polymorphisms (SNPs) in an independent sample of 1463 individuals with schizophrenia and 1563 healthy control subjects, and detected three SNPs and two haplotype blocks which displayed significant association with schizophrenia. This association was further strengthened by the results of meta-analysis. Our data strongly supported that the MYO5B gene might be associated with schizophrenia in the Chinese Han population and they have implications for understanding the glutamate hypothesis of schizophrenia. © 2013 Elsevier Ireland Ltd. Source

Li X.,Xinxiang Medical University | Han H.,Xinxiang Medical University | Hou R.,Xinxiang Medical University | Wei L.,Xinxiang Medical University | And 4 more authors.
Neuroscience Bulletin | Year: 2013

Progesterone is an efficient candidate for treating stroke and traumatic brain damage. The current study was designed to investigate the effects of progesterone on glucose transporter proteins (GLUT1 and GLUT3) during hypoxic-ischemic injury in a neonatal rat model. We demonstrated strong staining for GLUT1 in the walls of blood vessels and GLUT3 immunoreactivity in hippocampal neurons after hypoxiaischemia. Hypoxia-ischemia elevated GLUT1 and GLUT3 at both the mRNA and protein levels in the hippocampus, and pre-treatment with progesterone (8 mg/kg) further enhanced their accumulation until 24 h after hypoxic-ischemic injury. These results showed that progesterone treatment induced the accumulation of both GLUT1 and GLUT3 transporters, and an energy-compensation mechanism may be involved in the neuroprotective effect of progesterone during hypoxic-ischemic injury after cerebral ischemic attacks. © 2013 Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag Berlin Heidelberg. Source

Dong L.,Peking University | Dong L.,Min Of Health And National Clinical Research Centerfor Mental Disorders | Yan H.,Peking University | Yan H.,Min Of Health And National Clinical Research Centerfor Mental Disorders | And 37 more authors.
Pharmacological Research | Year: 2015

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. © 2015 Elsevier Ltd. All rights reserved. Source

Yue W.,Peking University | Yue W.,Key Laboratory for Mental Health | Yang Y.,Xinxiang Medical University | Yang Y.,Henan Key Laboratory of Biological Psychiatry | And 14 more authors.
Behavioral and Brain Functions | Year: 2011

Recent research has implicated that mutations in the neurexin-1 (NRXN1) gene on chromosome 2p16.3 might play a role in schizophrenia, autism, and nicotine dependence. In order to explore the association of NRXN1 polymorphisms with schizophrenia, we made a case-control association study in Chinese Han population.Methods: We examined six tag single nucleotide polymorphisms (SNPs) spanning 116.7 kb of NRXN1 in 768 schizophrenic patients and 738 healthy control subjects. The association of NRXN1 polymorphisms with schizophrenia and the age-at-onset of this disease were explored.Results: Our results showed that four SNPs of NRXN1 gene were significantly associated with schizophrenia (rs10490168: G > A, p = 0.017; rs2024513: A > G, p = 0.006; rs13382584: T > C, p = 0.009; and rs1558852: G > A, p = 0.031). Furthermore, the association of SNP rs2024513 with schizophrenia remained significance after the Bonferroni correction. Haplotypes consisting of above six SNPs also showed significantly associated with schizophrenia (global chi-square = 14.725, p = 0.022). A protective haplotype AGTGCA remained associated with schizophrenia, even after 10,000 permutation tests (empirical p-value = 0.043). However, we did not find any association with age-at-onset of schizophrenia with NRXN1 polymorphisms.Conclusions: Our findings suggest that NRXN1 might represent a major susceptibility gene for schizophrenia in Chinese Han population. © 2011 Yue et al; licensee BioMed Central Ltd. Source

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