| 1 | Schizophr. Res. 2009 Apr 109: 94-7 |
|---|---|
| PMID | 19268543 |
| Title | Polymorphisms in SLC6A4, PAH, GABRB3, and MAOB and modification of psychotic disorder features. |
| Abstract | We tested four genes [phenylalanine hydroxylase (PAH), the serotonin transporter (SLC6A4), monoamine oxidase B (MAOB), and the gamma-aminobutyric acid A receptor beta-3 subunit (GABRB3)] for their impact on five schizophrenia symptom factors: delusions, hallucinations, mania, depression, and negative symptoms. In a 90 family subset of the Irish Study of High Density schizophrenia Families, the PAH 232 bp microsatellite allele demonstrated significant association with the delusions factor using both QTDT (F=8.0, p=.031) and QPDTPHASE (chi-square=12.54, p=.028). Also, a significant association between the GABRB3 191 bp allele and the hallucinations factor was detected using QPDTPHASE (chi-square=15.51, p=.030), but not QTDT (chi-square=2.07, p=.560). |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2010 Oct 153B: 1347-9 |
| PMID | 20583128 |
| Title | Variation at the GABAA receptor gene, Rho 1 (GABRR1) associated with susceptibility to bipolar schizoaffective disorder. |
| Abstract | We have previously reported evidence that variation at GABA(A) receptor genes is associated with susceptibility to bipolar disorder with schizophrenia-like psychotic features (Research Diagnostic Criteria (RDC) schizoaffective disorder, bipolar type) with gene-wide significance at GABRB1, GABRA4, GABRB3, GABRA5, and GABRR3. Here we provide suggestive evidence implicating a sixth member of the gene family, GABRR1 (gene-wide P?=?0.0058; experiment-wide corrected significance P?=?0.052). |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Fa Yi Xue Za Zhi 2012 Jun 28: 195-7 |
| PMID | 22812221 |
| Title | [Polymorphisms of rs4906902 and rs8179184 loci in the promoter of the GABRB3 gene and their relevance with schizophrenia]. |
| Abstract | To investigate the polymorphisms of rs4906902 and rs8179184 loci in the promoter of the gamma-aminobutyric acid(GABA) receptor A, beta3 subunit gene (GABRB3), and their relevance with schizophrenia. PCR and DNA sequencing were used to detect the polymorphisms of rs4906902 and rs8179184 loci in 210 healthy individuals (control group) and 206 schizophrenic patients (case group) of the Han population in northern China. The chi2 test was used to identify Hardy-Weinberg equilibrium of the genotype distribution in the control group followed by comparing differences in genotype and haplotype frequency distributions between two groups. Distributions of the genotype frequencies fit the law of Hardy-Weinberg equilibrium in the control group. rs4906902 and rs8179184 loci were in linkage disequilibrium and showed two haplotypes which were T-G and C-A. The differences of genotypic frequencies and haplotype frequencies were statistically significant between the two groups (P < 0.05). The frequency of haplotype C-A in the case group was significantly higher than in the control group. Genotypic and haplotype frequencies in the maternal line and paternal line were statistically significant in the case group (P < 0.05). The haplotype of C-A in rs4906902 and rs8179184 loci in the promoter of GABRB3 gene may be maternally inherited and positively associated with schizophrenia and may be a useful tool in the forensic identification of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Fa Yi Xue Za Zhi 2012 Jun 28: 195-7 |
| PMID | 22812221 |
| Title | [Polymorphisms of rs4906902 and rs8179184 loci in the promoter of the GABRB3 gene and their relevance with schizophrenia]. |
| Abstract | To investigate the polymorphisms of rs4906902 and rs8179184 loci in the promoter of the gamma-aminobutyric acid(GABA) receptor A, beta3 subunit gene (GABRB3), and their relevance with schizophrenia. PCR and DNA sequencing were used to detect the polymorphisms of rs4906902 and rs8179184 loci in 210 healthy individuals (control group) and 206 schizophrenic patients (case group) of the Han population in northern China. The chi2 test was used to identify Hardy-Weinberg equilibrium of the genotype distribution in the control group followed by comparing differences in genotype and haplotype frequency distributions between two groups. Distributions of the genotype frequencies fit the law of Hardy-Weinberg equilibrium in the control group. rs4906902 and rs8179184 loci were in linkage disequilibrium and showed two haplotypes which were T-G and C-A. The differences of genotypic frequencies and haplotype frequencies were statistically significant between the two groups (P < 0.05). The frequency of haplotype C-A in the case group was significantly higher than in the control group. Genotypic and haplotype frequencies in the maternal line and paternal line were statistically significant in the case group (P < 0.05). The haplotype of C-A in rs4906902 and rs8179184 loci in the promoter of GABRB3 gene may be maternally inherited and positively associated with schizophrenia and may be a useful tool in the forensic identification of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Psychiatry Res 2012 Jul 198: 202-6 |
| PMID | 22414661 |
| Title | Investigating association of four gene regions (GABRB3, MAOB, PAH, and SLC6A4) with five symptoms in schizophrenia. |
| Abstract | Recently, microsatellite polymorphisms have been reported to be associated with four genes, GABRB3, MAOB, PAH, and SLC6A4, and their relationships have been tested to five symptom factors: hallucinations, delusions, negative symptoms, mania, and depression. These factors were frequently present in schizophrenia spectrum disorders in the Irish Study of High Density schizophrenia Families (ISHDSF) with a proband with the diagnosis of schizophrenia (Bergen et al., 2009). Of these, GABRB3 and PAH were reported to be significantly associated with hallucinations and delusions in a 90-family subset of the ISHDSF, respectively. In this study, we tested the association of genetic markers from these four gene regions with the approximate five clinical symptoms, based upon 256 schizophrenia patients, with genotypic data obtained by higher resolution single nucleotide polymorphism (SNP) genotyping. We found one GABRB3 SNP (rs1426891, 70.8kb downstream of this gene) and haplotype constructed by three SNPs (rs1426891, rs2912602, and rs2912600) were significantly associated with hallucinations in Caucasians after Bonferroni correction for multiple testing (Bonferroni corrected P: 0.032 and 0.016, respectively). Additionally, we found one haplotype constructed by two SNPs, rs5905587-rs37615860, in MAOB/NDP gene region was significantly associated with delusions in all samples tested (Bonferroni corrected P: 0.048). These results provide additional evidence that GABRB3 and MAOB/NDP gene regions might constitute risk factors for hallucinations and delusions in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | Front Behav Neurosci 2014 -1 8: 388 |
| PMID | 25414651 |
| Title | Addiction and reward-related genes show altered expression in the postpartum nucleus accumbens. |
| Abstract | Motherhood involves a switch in natural rewards, whereby offspring become highly rewarding. Nucleus accumbens (NAC) is a key CNS region for natural rewards and addictions, but to date no study has evaluated on a large scale the events in NAC that underlie the maternal change in natural rewards. In this study we utilized microarray and bioinformatics approaches to evaluate postpartum NAC gene expression changes in mice. Modular Single-set Enrichment Test (MSET) indicated that postpartum (relative to virgin) NAC gene expression profile was significantly enriched for genes related to addiction and reward in five of five independently curated databases (e.g., Malacards, Phenopedia). Over 100 addiction/reward related genes were identified and these included: Per1, Per2, Arc, Homer2, Creb1, Grm3, Fosb, GABRB3, Adra2a, Ntrk2, Cry1, Penk, Cartpt, Adcy1, Npy1r, Htr1a, Drd1a, Gria1, and Pdyn. ToppCluster analysis found maternal NAC expression profile to be significantly enriched for genes related to the drug action of nicotine, ketamine, and dronabinol. Pathway analysis indicated postpartum NAC as enriched for RNA processing, CNS development/differentiation, and transcriptional regulation. Weighted Gene Coexpression Network Analysis (WGCNA) identified possible networks for transcription factors, including Nr1d1, Per2, Fosb, Egr1, and Nr4a1. The postpartum state involves increased risk for mental health disorders and MSET analysis indicated postpartum NAC to be enriched for genes related to depression, bipolar disorder (BPD), and schizophrenia. Mental health related genes included: Fabp7, Grm3, Penk, and Nr1d1. We confirmed via quantitative PCR Nr1d1, Per2, Grm3, Penk, Drd1a, and Pdyn. This study indicates for the first time that postpartum NAC involves large scale gene expression alterations linked to addiction and reward. Because the postpartum state also involves decreased response to drugs, the findings could provide insights into how to mitigate addictions. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | Psychiatr. Genet. 2014 Aug 24: 151-7 |
| PMID | 24865167 |
| Title | Genetic analysis of GABRB3 at 15q12 as a candidate gene of schizophrenia. |
| Abstract | Copy number variations encompassing the chromosome 15q11-q13 region have been implicated in the pathogenesis of several neurodevelopmental disorders including schizophrenia. The study aimed to investigate whether the GABRB3 gene mapped to 15q12 was associated with schizophrenia. We resequenced the promoter and all the exonic regions of the GABRB3 gene in 349 patients with schizophrenia and 386 control participants from Taiwan using the Sanger sequencing method. We also used a reporter gene assay to assess the functional impact of variants identified from the promoter region. We identified a total of six common single nucleotide polymorphisms and eight rare variants in this sample. No genetic association of these common single nucleotide polymorphisms with schizophrenia was detected. A missense mutation Y402H at exon 9 was detected in two patients and two controls. Polyphen-2 predicted that the impact of this variant was benign. In addition, we identified two patient-specific variants at the promoter of GABRB3 that showed significantly increased promoter activity in a reporter gene assay. The identification of two private patient-only variants at the promoter region with enhanced promoter activity supports the rare allele hypothesis of schizophrenia and suggests that increased GABRB3 expression may confer an increased risk of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 8 | J. Mol. Neurosci. 2016 May 59: 36-47 |
| PMID | 26894264 |
| Title | Aripiprazole Increases the PKA Signalling and Expression of the GABAA Receptor and CREB1 in the Nucleus Accumbens of Rats. |
| Abstract | The GABAA receptor is implicated in the pathophysiology of schizophrenia and regulated by PKA signalling. Current antipsychotics bind with D2-like receptors, but not the GABAA receptor. The cAMP-responsive element-binding protein 1 (CREB1) is also associated with PKA signalling and may be related to the positive symptoms of schizophrenia. This study investigated the effects of antipsychotics in modulating D2-mediated PKA signalling and its downstream GABAA receptors and CREB1. Rats were treated orally with aripiprazole (0.75 mg/kg, ter in die (t.i.d.)), bifeprunox (0.8 mg/kg, t.i.d.), haloperidol (0.1 mg/kg, t.i.d.) or vehicle for 1 week. The levels of PKA-C? and p-PKA in the prefrontal cortex (PFC), nucleus accumbens (NAc) and caudate putamen (CPu) were detected by Western blots. The mRNA levels of Gabrb1, Gabrb2, GABRB3 and Creb1, and their protein expression were measured by qRT-PCR and Western blots, respectively. Aripiprazole elevated the levels of p-PKA and the ratio of p-PKA/PKA in the NAc, but not the PFC and CPu. Correlated with this elevated PKA signalling, aripiprazole elevated the mRNA and protein expression of the GABAA (?-1) receptor and CREB1 in the NAc. While haloperidol elevated the levels of p-PKA and the ratio of p-PKA/PKA in both NAc and CPu, it only tended to increase the expression of the GABAA (?-1) receptor and CREB1 in the NAc, but not the CPu. Bifeprunox had no effects on PKA signalling in these brain regions. These results suggest that aripiprazole has selective effects on upregulating the GABAA (?-1) receptor and CREB1 in the NAc, probably via activating PKA signalling. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 9 | Neuroscientist 2016 Apr 22: 119-31 |
| PMID | 25686622 |
| Title | Genetic and Developmental Perspective of Language Abnormality in Autism and Schizophrenia: One Disease Occurring at Different Ages in Humans? |
| Abstract | Language and communication through it are two of the defining features of normally developed human beings. However, both these functions are often impaired in autism and schizophrenia. In the former disorder, the problem usually emerges in early childhood (~2 years old) and typically includes a lack of communication. In the latter condition, the language problems usually occur in adolescence and adulthood and presents as disorganized speech. What are the fundamental mechanisms underlying these two disorders? Is there a shared genetic basis? Are the traditional beliefs about them true? Are there any common strategies for their prevention and management? To answer these questions, we searched PubMed by using autism, schizophrenia, gene, and language abnormality as keywords, and we reconsidered the basic concepts about these two diseases or syndromes. We found many functional genes, for example, FOXP2, COMT, GABRB3, and DISC1, are actually implicated in both of them. After observing the symptoms, genetic correlates, and temporal progression of these two disorders as well as their relationships more carefully, we now infer that the occurrence of these two diseases is likely developmentally regulated via interaction between the genome and the environment. Furthermore, we propose a unified view of autism and schizophrenia: a single age-dependently occurred disease that is newly named as Systemic Integral Disorder: if occurring in children before age 2, it is called autism; if in adolescence or a later age, it is called schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |