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Influence of CFH gene on symptom severity of schizophrenia.

ABSTRACT: OBJECTIVE:Recent advances have provided compelling evidence for the role of excessive complement activity in the pathophysiology of schizophrenia. In this study, we aimed to detect the association of the gene encoding complement factor H (CFH), a regulator in complement activation, with schizophrenia. MATERIALS AND METHODS:A sample of 1783 individuals with or without schizophrenia was recruited for genetic analysis. Genomic DNA samples were extracted from peripheral blood cells using multiplex polymerase chain reaction and the SNaPshot assay. A Database for Schizophrenia Genetic Research (SZDB) was used to detect the association of brain CFH expression with schizophrenia. Next, we performed a genotype-phenotype analysis to identify the relationship between CFH Y402H polymorphism and clinical features of schizophrenia. RESULTS:There was a significant association of hippocampal CFH expression with schizophrenia (P=0.017), whereas this significance did not survive after adjusting for false discovery rate (P=0.105). Comparing the genotype and allele frequencies of the genotyped single-nucleotide polymorphisms between case and control groups showed no significant difference. There were significant differences in the scores of negative symptoms and delayed memory between the patients with C allele and those without C allele (P<0.01 and P=0.04 after Bonferroni correction, respectively). Furthermore, we observed a marginally significant association between the Y402H polymorphism and CFH expression in the hippocampus (P=0.051); however, this significance was lost after multiple testing correction (P=0.51, after Bonferroni correction). CONCLUSION:Our findings provide suggestive evidence for the role of CFH in the development of negative symptoms and cognitive dysfunction in schizophrenia.

SUBMITTER: Zhang C

PROVIDER: S-EPMC5342610 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Influence of <i>CFH</i> gene on symptom severity of schizophrenia.

Zhang Chen C Lv Qinyu Q Fan Weixing W Tang Wei W Yi Zhenghui Z

Neuropsychiatric disease and treatment 20170302

<h4>Objective</h4>Recent advances have provided compelling evidence for the role of excessive complement activity in the pathophysiology of schizophrenia. In this study, we aimed to detect the association of the gene encoding complement factor H (<i>CFH</i>), a regulator in complement activation, with schizophrenia.<h4>Materials and methods</h4>A sample of 1783 individuals with or without schizophrenia was recruited for genetic analysis. Genomic DNA samples were extracted from peripheral blood c ...[more]

PMID: 28293111

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Project description:CONTEXT The single-nucleotide polymorphism rs1344706 in the gene ZNF804a has been associated with schizophrenia and with quantitative phenotypic features, including brain structure volume and the core symptoms of schizophrenia. OBJECTIVE To evaluate associations of rs1344706 with brain structure and the core symptoms of schizophrenia. DESIGN Case-control analysis of covariance. SETTING University-based research hospital. PARTICIPANTS Volunteer sample of 335 individuals with schizophrenia spectrum disorders (306 with core schizophrenia) and 198 healthy volunteers. MAIN OUTCOME MEASURES Cerebral cortical gray matter and white matter (WM) volumes (total and frontal, parietal, temporal, and occipital lobes), lateral ventricular cerebrospinal fluid volume, and symptom severity from the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms divided into 3 domains: psychotic, negative, and disorganized. RESULTS The rs1344706 genotype produced significant main effects on total, frontal, and parietal lobe WM volumes (F = 3.98, P = .02; F = 4.95, P = .007; and F = 3.08, P = .05, respectively). In the schizophrenia group, rs1344706 produced significant simple effects on total (F = 3.93, P = .02) and frontal WM volumes (F = 7.16, P < .001) and on psychotic symptom severity (F = 6.07, P = .003); the pattern of effects was concordant with risk allele carriers having larger volumes and more severe symptoms of disease than nonrisk homozygotes. In the healthy volunteer group, risk allele homozygotes had increased total WM volume compared with nonrisk allele carriers (F = 4.61, P = .03), replicating a previously reported association. CONCLUSIONS A growing body of evidence suggests that the risk allele of rs1347706 is associated with a distinctive set of phenotypic features in healthy volunteers and individuals with schizophrenia. Our study supports this assertion by finding that specific genotypes of the polymorphism are associated with brain structure volumes in individuals with schizophrenia and healthy volunteers and with symptom severity in schizophrenia.

Project description:BackgroundThe gut microbiome and microbiome-gut-brain (MGB) axis have been receiving increasing attention for their role in the regulation of mental behavior and possible biological basis of psychiatric disorders. With the advance of next-generation sequencing technology, characterization of the gut microbiota in schizophrenia (SZ) patients can provide rich clues for the diagnosis and prevention of SZ.MethodsIn this study, we compared the differences in the fecal microbiota between 82 SZ patients and 80 demographically matched normal controls (NCs) by 16S rRNA sequencing and analyzed the correlations between altered gut microbiota and symptom severity.ResultsThe alpha diversity showed no significant differences between the NC and SZ groups, but the beta diversity revealed significant community-level separation in microbiome composition between the two groups (pseudo-F =3.337, p < 0.001, uncorrected). At the phylum level, relatively more Actinobacteria and less Firmicutes (p < 0.05, FDR corrected) were found in the SZ group. At the genus level, the relative abundances of Collinsella, Lactobacillus, Succinivibrio, Mogibacterium, Corynebacterium, undefined Ruminococcus and undefined Eubacterium were significantly increased, whereas the abundances of Adlercreutzia, Anaerostipes, Ruminococcus and Faecalibacterium were decreased in the SZ group compared to the NC group (p < 0.05, FDR corrected). We performed PICRUSt analysis and found that several metabolic pathways differed significantly between the two groups, including the Polyketide sugar unit biosynthesis, Valine, Leucine and Isoleucine biosynthesis, Pantothenate and CoA biosynthesis, C5-Branched dibasic acid metabolism, Phenylpropanoid biosynthesis, Ascorbate and aldarate metabolism, Nucleotide metabolism and Propanoate metabolism pathways (p < 0.05, FDR corrected). Among the SZ group, the abundance of Succinivibrio was positively correlated with the total Positive and Negative Syndrome Scale (PANSS) scores (r = 0.24, p < 0.05, uncorrected) as well as the general PANSS scores (r = 0.22, p < 0.05, uncorrected); Corynebacterium was negatively related to the negative scores of PANSS (r = 0.22, p < 0.05, uncorrected).ConclusionsOur findings provided evidence of altered gut microbial composition in SZ group. In addition, we found that Succinvibrio and Corynebacterium were associated with the severity of symptoms for the first time, which may provide some new biomarkers for the diagnosis of SZ.

Project description:MicroRNA-137 (miRNA-137; miR-137) is one of the important post-transcriptional regulators of the nervous system development, and its MIR137 gene rs1625579 polymorphism was reported to be a potential regulator for schizophrenia susceptibility. However, schizophrenia characteristics controlled by MIR137 rs1625579 polymorphism are still insufficiently understood. There were 3 groups included in the study: (a) subjects with diagnosis of schizophrenia (n = 150; 81-females, 69-males), (b) mentally healthy people (control group; n = 102; 66-females, 36-males) and (c) Belarusian indigenous male group (n = 295). Associations of rs1625579 with schizophrenia, symptom's severity and cognitive performance [by using Positive and Negative Syndrome Scale (PANSS) and Wisconsin Card Sorting Test (WCST), respectively] were studied, when compared to controls. Allele and genotype frequencies were investigated in Belarusian indigenous males. Rs1625579 displayed no association with schizophrenia in Belarusian population. Significant "symptom severity-genotype" interactions were revealed for schizophrenia patients. Patients with T/G genotype displayed lower severity of positive symptoms and general psychopathology compared to homozygous subjects. T/T genotype was associated with the highest symptom's severity. The negative symptom scores and the total PANSS-score were significantly higher in females carrying genotype T/T vs. T/G+G/G; no significant gene-phenotype associations were found in males. WCST parameters did not show any association with rs1625579 polymorphism. MIR137 rs1625579 polymorphism might be an important sex-dependent factor influencing severity of schizophrenia psychopathological manifestations. These findings also contribute to the knowledge on candidate gene effects on characteristics related to schizophrenia phenotype. As miR 137 is considered to be cancer therapeutic target, miR-137 may also explain the lower incidence of cancer in schizophrenia patients. Further studies with larger sample size are needed to confirm these novel findings.

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Influence of CFH gene on symptom severity of schizophrenia.

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Influence of <i>CFH</i> gene on symptom severity of schizophrenia.

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