Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Psychotic features, defined as delusions or hallucinations, commonly occur in bipolar disorder (BP) and may be indicative of a more homogeneous form of the illness, with possible etiologic ties to schizophrenia. Several studies have shown that psychotic features aggregate in bipolar families, and increased interest in the molecular genetics of psychotic BP is emerging. Although preliminary, linkage studies of psychotic BP show replicated evidence for suggestive genome-wide linkage to chromosomes 8p and 13q, which have been implicated in prior linkage studies of schizophrenia and BP. Association studies of psychotic BP and subtypes such as mood-incongruent psychotic BP have uncovered modest positive results for several candidate schizophrenia susceptibility genes, including dysbindin, DAOA/G30, Disrupted-in-Schizophrenia-1, and neuregulin 1. These tentative results are consistent with the hypothesis that the subphenotype of psychotic BP may represent a clinical manifestation of "overlap" genes between schizophrenia and mood disorder syndromes.
 ...
PMID:The genetics of psychotic bipolar disorder. 1847 12

Schizophrenia is a highly debilitating mental disorder that affects approximately 1% of the general population, yet it continues to be poorly understood. Recent studies have identified variations in several genes that are associated with this disorder in diverse populations, including those that encode neuregulin 1 (NRG1) and its receptor ErbB4. The past few years have witnessed exciting progress in our knowledge of NRG1 and ErbB4 functions and the biological basis of the increased risk for schizophrenia that is potentially conferred by polymorphisms in the two genes. An improved understanding of the mechanisms by which altered function of NRG1 and ErbB4 contributes to schizophrenia might eventually lead to the development of more effective therapeutics.
 ...
PMID:Neuregulin 1 in neural development, synaptic plasticity and schizophrenia. 1847 32

On the basis of epidemiological as well as neurobiological evidence, schizophrenia has been conceptualized as a neurodevelopmental disorder. It is also known to have a large heritable component and a complex genetic architecture. Many putative susceptibility genes have recently been identified, arising both from positional cloning and candidate gene approaches. The evidence is strong for neuregulin 1, dysbindin and DISC1, and moderate for several others. However, there are key unanswered questions. For example, concerning the molecular basis of genetic association, multiple, mostly non-coding, variants have been found within the genes, complicating discussion as to the strength and interpretation of the data. Second, there is speculation whether the genes converge on common pathways, notably glutamatergic synaptic transmission. Additional questions concern the emerging evidence for epistasis, the clinico-genetic correlates, and the extent to which the genes confer schizophrenia risk via their roles in neurodevelopment. Here, the genetic advances and their neurodevelopmental implications are summarised, with a particular focus on neuregulin 1.
 ...
PMID:Schizophrenia susceptibility genes and their neurodevelopmental implications: focus on neuregulin 1. 1849 63

Major psychiatric disorders, including schizophrenia, bipolar disorder and substance addiction, are partly heritable and show a multifactorial pattern of heredity. Although the introduction of explicit diagnostic criteria has improved clinical research on psychiatric disorders, the concept is only of limited use for exploring their genetic underpinnings. On the behavioral level, psychopathological symptoms can hardly separate the many pathophysiological subgroups. Contrary to nosological categories, biologically based phenotypes - referred to as intermediate phenotypes - consisting of neuropsychological, electrophysiological, functional and structural brain imaging parameters, could represent the genetic basis more directly. Thus intermediate phenotypes are being targeted in current molecular genetic investigations. In this article, we review existing data on the effects of genetic variation in the dopamine and serotonin systems (catechol-O-methyltransferase, the serotonin-transporter-linked polymorphic region) on the morphometric, metabolic and functional characteristics of the cerebral cortex and limbic structures. The gene-driven modulation of these brain circuits is discussed with regard to their behavioral correlates and their role for psychiatric diseases. Furthermore, recently identified putative susceptibility genes for schizophrenia (neuregulin 1, dysbindin, G72) are briefly discussed.
 ...
PMID:Genes and neuroimaging: advances in psychiatric research. 1852 Jan 62

A single nucleotide polymorphism of the neuregulin 1 gene (SNP8NRG243177/rs6994992) increases the risk of psychosis, affects prefrontal activation and structural connectivity in the brain, and is related to the expression of a specific neuregulin 1 isoform. The purpose of this study was to investigate the interaction between this polymorphism and reactivity to psychosocial stress. Two hundred patients with schizophrenia were genotyped. The patients and one of their family members participated in neutral and conflict-related interactions in which the number of relatives' criticisms and patients' unusual thoughts was assessed. Patients with the risk T/T genotype expressed more unusual thoughts than C-carriers (C/T and C/C) during conflict-related interactions but not during neutral interactions. Two controls polymorphisms of the neuregulin 1 gene (rs10954867 and rs7005288) showed no such effect. These results raise the possibility that there is a significant gene by environment interaction regarding SNP8NRG243177/rs6994992 and psychosocial stress.
 ...
PMID:A polymorphism of the neuregulin 1 gene (SNP8NRG243177/rs6994992) affects reactivity to expressed emotion in schizophrenia. 1854 75

The genetic basis of complex diseases is expected to be highly heterogeneous, with many disease genes, where each gene by itself has only a small effect. Based on the nonlinear contributions of disease genes across the genome to complex diseases, we introduce the concept of single nucleotide polymorphism (SNP) synergistic blocks. A two-stage approach is applied to detect the genetic association of synergistic blocks with a disease. In the first stage, synergistic blocks associated with a complex disease are identified by clustering SNP patterns and choosing blocks within a cluster that minimize a diversity criterion. In the second stage, a logistic regression model is given for a synergistic block. Using simulated case-control data, we demonstrate that our method has reasonable power to identify gene-gene interactions. To further evaluate the performance of our method, we apply our method to 17 loci of four candidate genes for paranoid schizophrenia in a Chinese population. Five synergistic blocks are found to be associated with schizophrenia, three of which are negatively associated (odds ratio, OR < 0.3, P < 0.05), while the others are positively associated (OR > 2.0, P < 0.05). The mathematical models of these five synergistic blocks are presented. The results suggest that there may be interactive effects for schizophrenia among variants of the genes neuregulin 1 (NRG1, 8p22-p11), G72 (13q34), the regulator of G-protein signaling-4 (RGS4, 1q21-q22) and frizzled 3 (FZD3, 8p21). Using synergistic blocks, we can reduce the dimensionality in a multi-locus association analysis, and evaluate the sizes of interactive effects among multiple disease genes on complex phenotypes.
 ...
PMID:Two-stage designs to identify the effects of SNP combinations on complex diseases. 1858 17

Genetically, schizophrenia is a complex disease whose pathogenesis is likely governed by a number of different risk factors. While substantial efforts have been made to identify the underlying susceptibility alleles over the past 2 decades, they have been of only limited success. Each year, the field is enriched with nearly 150 additional genetic association studies, each of which either proposes or refutes the existence of certain schizophrenia genes. To facilitate the evaluation and interpretation of these findings, we have recently created a database for genetic association studies in schizophrenia ("SzGene"; available at http://www.szgene.org). In addition to systematically screening the scientific literature for eligible studies, SzGene also reports the results of allele-based meta-analyses for polymorphisms with sufficient genotype data. Currently, these meta-analyses highlight not only over 20 different potential schizophrenia genes, many of which represent the "usual suspects" (eg, various dopamine receptors and neuregulin 1), but also several that were never meta-analyzed previously. All the highlighted loci contain at least one variant showing modest (summary odds ratios approximately 1.20 [range 1.06-1.45]) but nominally significant risk effects. This review discusses some of the strengths and limitations of the SzGene database, which could become a useful bioinformatics tool within the schizophrenia research community.
 ...
PMID:Genetic research in schizophrenia: new tools and future perspectives. 1864 54

Human genetic studies have demonstrated that the neuregulin 1 gene (NRG1) is involved in the development of schizophrenia. Alternative splicing of NRG1 results in at least 15 distinct isoforms and all contain an extracellular epidermal growth factor (EGF)-like domain, which is sufficient for Nrg1's biological activity. Here, we characterize a heterozygous mutant model for mouse EGF-like domain neuregulin 1 (Nrg1) regarding schizophrenia-related behavioral domains. A comprehensive, multitiered phenotyping strategy was used to investigate locomotion, exploration, anxiety-related behaviors, and sensorimotor gating. Nrg1 mutant mice exhibited a hyper-locomotive phenotype and an improved ability to habituate to a new environment. Extensive analysis of anxiety-related behaviors revealed a wild type-like phenotype in this domain. However, a moderate impairment in sensorimotor gating was found after pharmacological challenge using psychoactive substances. Our study adds to the increasing behavioral data available from a variety of animal models for Nrg1 isoforms. We suggest a standardized and comprehensive behavioral phenotyping approach to distinguish between the different models and to clarify their relevance for schizophrenia research. Future behavioral investigations will focus on the negative and cognitive symptoms of schizophrenia.
 ...
PMID:Behavioral profile of a heterozygous mutant mouse model for EGF-like domain neuregulin 1. 1872 27

Both the neuregulin 1 (Nrg1) and alpha7 nicotinic acetylcholine receptor (alpha7*nAChRs) genes have been linked to schizophrenia and associated sensory-motor gating deficits. The prominence of nicotine addiction in schizophrenic patients is reflected in the normalization of gating deficits by nicotine self-administration. To assess the role of presynaptic type III Nrg1 at hippocampal-accumbens synapses, an important relay in sensory-motor gating, we developed a specialized preparation of chimeric circuits in vitro. Synaptic relays from Nrg1(tm1Lwr) heterozygote ventral hippocampal slices to wild-type (WT) nucleus accumbens neurons (1) lack a sustained, alpha7*nAChRs-mediated phase of synaptic potentiation seen in comparable WT/WT circuits and (2) are deficient in targeting alpha7*nAChRs to presynaptic sites. Thus, selective alteration of the level of presynaptic type III Nrg1 dramatically affects the modulation of glutamatergic transmission at ventral hippocampal to nucleus accumbens synapses.
 ...
PMID:Presynaptic type III neuregulin 1 is required for sustained enhancement of hippocampal transmission by nicotine and for axonal targeting of alpha7 nicotinic acetylcholine receptors. 1878 91

Schizophrenia is a highly complex and heritable psychiatric disorder in which multiple genes and environmental factors interact to cause the schizophrenia phenotype. A new generation of molecular studies has yielded numerous candidate genes with a putative role in risk for schizophrenia, whereas other genes regulate putative pathophysiological mechanisms. Mutant mice having either deletion (knockout) or insertion (knockin/transgenesis) of schizophrenia risk genes now allow the functional role of these genes to be investigated. In the present mini-review, we outline the advantages and limitations of various approaches to phenotypic assessment of mutant mouse models, including ethologically based methods. Thereafter, we consider recent findings, with a particular focus on, first, dopaminergic and glutamatergic pathophysiological models and, secondly, putative roles for DISC1 (disrupted in schizophrenia 1) and NRG1 (neuregulin 1) as susceptibility genes for schizophrenia. Finally, we identify current challenges associated with the use of genetic mutant models and highlight their potential value for exploring gene-gene and gene-environment interactions in relation to schizophrenia.
 ...
PMID:Mutant models for genes associated with schizophrenia. 1914 53


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>