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

The study population comprised 94 Finnish patients with DSM-IV diagnosis of schizophrenia. The patients were placed into two subgroups according to medication response to conventional neuroleptics. The aim of the study was to examine the frequency of tumor necrosis factor -308 (G > A) polymorphism in these patients and their 98 control subjects who were age- and gender-matched blood donors. Associations between TNFalpha -308 polymorphism alone and between the interaction of TNFalpha and epidermal growth factor gene polymorphisms, and medication response and age at onset of schizophrenia were also studied. The frequencies of TNFalpha A-allele were 11.7 % in patients and 12.8% in controls. The difference was not significant (p = 0.75). TNFalpha -308 polymorphism was not associated with medication response. However, patients with EGF AA and TNFalpha AG/AA genotype had a lower age at onset of schizophrenia compared with the rest of the patients not having this combination (20.0 years, 3.3 vs. 30.2 years, 10.1 mean + SD; p < 0.001). The results support earlier findings according to which TNFalpha polymorphism is not associated with the incidence of schizophrenia. On the other hand, the role of cytokines in schizophrenia may involve genetic interactions predisposing early onset of illness.
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PMID:Interaction of tumor necrosis alpha - G308A and epidermal growth factor gene polymorphisms in early-onset schizophrenia. 1561 91

In the central nervous system (CNS), neuregulin-1 (NRG-1) proteins function in neuronal migration, differentiation, and survival of oligodendrocytes. The NRG-1 gene codes for at least 15 different isoforms, which may be classified on the basis of their molecular structure. At least two different haplotypes of the NRG-1 gene may be associated with schizophrenia. An abnormal expression pattern of NRG-1 mRNA was found in the prefrontal cortex of schizophrenic patients in comparison to controls. We here show that the NRG-1alpha isoform is significantly reduced in white matter of the prefrontal cortex in schizophrenia but not in affective disorder. In the prefrontal gray matter, the density of NRG-1alpha expressing neurons was reduced in individuals with schizophrenia and in unipolar patients. We studied brains of 22 schizophrenics, 12 patients with affective disorders (7 unipolar and 5 bipolar), and 22 matched controls. NRG-1alpha immunoreactive material was detected with a polyclonal antiserum against the synthetic peptide from alpha-type EGF-like domain of human NRG. The demonstrated decreased number of NRG-1 immunoreactive neurons in the brains of schizophrenics and patients with unipolar depression points to an important role of this NRG-1alpha splice variant in neuropsychiatric disorders. Reduced NRG-1alpha protein concentrations were found in brains of schizophrenics after Western blot analysis. The diminished expression of NRG-1alpha strongly supports an early neurodevelopmental component to schizophrenia.
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PMID:Immunohistochemical evidence for impaired neuregulin-1 signaling in the prefrontal cortex in schizophrenia and in unipolar depression. 1740 26

Neuregulins (NRGs) comprise a large family of EGF-like signaling molecules involved in cell-cell communication during development and disease. The neuregulin family of ligands has four members: NRG1, NRG2, NRG3, and NRG4. Relatively little is known about the biological functions of the NRG2, 3, and 4 proteins. In contrast, the NRG1 proteins have been demonstrated to play important roles during the development of the nervous system, heart, and mammary glands. For example, NRG1 has essential functions in the development of neural crest cells and some of their major derivatives, like Schwann cells and sympathetic neurons. NRG1 controls the trabeculation of the myocardial musculature and the ductal differentiation of the mammary epithelium. Moreover, there is emerging evidence for the involvement of NRG signals in the development and function of several other organ systems, and in human disease, including breast cancer and schizophrenia. Many different isoforms of the Neuregulin-1 gene are synthesized. Such isoforms differ in their tissue-specific expression patterns and their biological activities, thereby contributing to the great diversity of the in vivo functions of NRG1. Neuregulins transmit their signals to target cells by interacting with transmembrane tyrosine kinase receptors of the ErbB family. This family includes four members, the epidermal growth factor receptor (EGF-R, ErbB1, ErbB2, ErbB3, and ErbB4). Receptor-ligand interaction induces the heterodimerization of receptor monomers, which in turn results in the activation of intracellular signaling cascades and the induction of cellular responses including proliferation, migration, differentiation, and survival or apoptosis. In vivo, functional NRG1 receptors are heterodimers composed of ErbB2 with either an ErbB3, or ErbB4 molecule. The tissue-specific distribution of the different receptor types further contributes to the diversity and specificity of the biological functions of this signaling pathway. It is a typical feature of the Neuregulin-1/ErbB signaling pathway to control sequential steps during the development of a particular organ system. For example, this pathway functions in early precursor proliferation, maturation, as well as in the myelination of Schwann cells. The systematic analysis of genetic models that have been established by the help of conventional as well as conditional gene targeting strategies in mice was instrumental for the uncovering of the multitude of biological functions of this signaling system. In this review the basic biology of the Neuregulin-1/ErbB system and how it relates to the in vivo functions were discussed with special emphasis to transgenic techniques in mice.
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PMID:The neuregulin-I/ErbB signaling system in development and disease. 1743 14

Neuregulin-1 (NRG-1), a replicated gene in schizophrenia-association studies, exhibits six mRNA-types and two types of the EGF-like domain, alpha and beta. The beta-isoform was extensively studied, less is known about the extent and specific localization of adult brain NRG-1alpha. NRG-1alpha protein levels were reported reduced in postmortem prefrontal-cortex of schizophrenia patients. NRG-1 type I mRNA levels were found higher in postmortem brain in schizophrenia. In an attempt to decipher between a genetic or environmental involvement in the differences in NRG-1 levels in postmortem brain in schizophrenia, and since obstetric complications were suggested non-genetic risk-factors of schizophrenia, we studied the effect of perinatal hypoxia in rats on brain NRG-1alpha protein levels. Seven-day-old rats were exposed to hypoxia versus air. Frontal-cortex levels of NRG-1alpha isoform were quantified at adulthood by Western blotting. Frontal-cortex NRG-1alpha was 32% elevated in hypoxia-exposed rats. The data support the role of non-genetic factors, e.g. oxygen restriction, in the expression of genes associated with schizophrenia.
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PMID:Oxygen restriction of neonate rats elevates neuregulin-1alpha isoform levels: possible relationship to schizophrenia. 1763 47

Tyrosine kinase receptors and their ligands allow communication between cells in the developing and adult organism. An extensive line of research has revealed that 'neuregulins', a family of EGF-like factors that signal via ErbB receptors, are used frequently for cell communication during nervous system development, and control a spectacular spectrum of developmental processes. For instance, during development of the peripheral nervous system, Schwann cells require neuronally-produced neuregulin (Nrg1) for growth, migration and myelination, neural crest cells rely on mesenchymally-generated Nrg1 signals for migration, while muscle requires neuronally-produced Nrg1 for the differentiation of a muscle spindle. In the central nervous system, neuregulin signals allow cells to act as guideposts or as barriers for axons during pathfinding. Neuregulin signals are also important in other organs, but the nervous system functions have received recently considerable attention due to the finding that particular haplotypes of Nrg1 and ErbB4 predispose to schizophrenia. Understanding the neuregulin signaling system can thus contribute to define causes of this devastating mental disorder.
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PMID:ErbB receptors and the development of the nervous system. 1904 66

A health economics study was carried out from 1995 ? 1997 on the public sector of psychiatry in order to explore the variables which contribute to the differences in the cost of psychiatric care. The results show that the costs are independent of the pathology, but they correlate to the level of medical-social dependence and to the existence (or not) of family and social support structures. The most expensive care per year is that of patients diagnosed with dementia, intellectual deficiencies, or problems of schizophrenia. If the sociological variables of sex, age and professional category are highly significant in the redistribution of cost, these are independent of the quality and provision of care, measured by a comprehensive, overall operational scale (EGF). 10% of patients consume 75% of the available resources but only 50% of the ambulatory care. The definitive costs are ultimately influenced by hospitalization. The increase in the number of patients actively seeking treatment and the increase in ambulatory care provided levels out year after year for which there is a noted decrease in full time hospitalization. Regardless of the diagnosis, full time hospital care carries the same cost. Therefore, the 10% of patients for whom care is most expensive are those who have been diagnosed with CIM 10, schizophrenic patients representing less than half of them.
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PMID:[Results from a health economics evaluation of a sector of psychiatry (1995-1997).]. 1943 39

Neuregulin 1 (NRG1) has been implicated in the pathophysiology of psychotic disorders. NRG1 exerts its effects via the Ras-MAPK and phosphatidylinositol-3 kinase-protein kinase B (PI3K-PKB/AKT) intracellular signaling pathways through ErbB receptors. The aim of this study was to investigate the relationship between NRG1-stimulated AKT phosphorylation and neurocognitive functions in patients with schizophrenia and in patients with other psychotic disorders. B lymphoblasts of patients (n=40) and controls (n=20) were stimulated with NRG1a (65 amino-acid residue recombinant protein from the epidermal growth factor [EGF] domain) for 30-min. The protein isolated from the cells was analyzed by Western blotting. The dependent measure was the ratio of phosphorylated AKT (pAKT) and total AKT at baseline (without NRG1 stimulation) and after NRG1 stimulation (pAKT/AKT). The neurocognitive functions (attention, immediate and long-term memory, language, visual-spatial skills) were evaluated by the repeatable brief assessment of neuropsychological status (RBANS) battery. The results revealed a significantly reduced pAKT/AKT ratio in patients with schizophrenia as compared with healthy controls and with patients with other psychotic disorders. The patients with other psychotic disorders did not differ from the healthy controls. Despite the fact that neurocognitive functions were significantly impaired in the patients, these functions did not reveal significant correlations with the pAKT/AKT ratio. In conclusion, NRG1-induced AKT phosphorylation is decreased in schizophrenia but not in other psychotic disorders. This peripheral marker is not related to neurocognitive functions.
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PMID:Neuregulin 1-stimulated phosphorylation of AKT in psychotic disorders and its relationship with neurocognitive functions. 1952 2

NRG1 (neuregulin 1) belongs to the NRG family of EGF (epidermal growth factor)-like signalling molecules involved in cell-cell communication during development and disease. It plays important roles in the developing tissues of the nerves, heart and mammary glands. Particularly in neurobiology, NRG1 signalling is associated with synaptic transmission, myelination of Schwann cells and the human disease of schizophrenia. Many different isoforms of NRG1 make the molecule highly sophisticated in biological activities and a great diversity of in vivo functions. The nervous system is a common trait in all bilateria (higher animals), but based on the BLAST information from the currently available databases it appears that NRG1 orthologues can only be identified in vertebrates. The gene was analysed in silico for type I-IV CDSs (coding sequences) from ten vertebrate genomes. The gene loci, structures of coding-intronic sequences, ClustalW program analyses, phylogenetic trees and conserved motifs in ecto- and cyto-plasmic domains were analysed and compared. Here, we conclude that non-mammalian vertebrates mainly carry type I (may have evolved a spacer different from mammalian isoforms), II and III NRG1s. The type IV NRG1 N-terminal CDSs can be identified from most of the mammalian genomes studied; however, the corresponding rodent sequences lack the start codon. The evolutionary conservation of a CDS59-CDS24-CDS103 domain, intracellular phosphorylation sites and bipartite nuclear localization signals is of physiological significance.
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PMID:In silico analysis of neuregulin 1 evolution in vertebrates. 1968 57

Recently, neurotrophic factors and cytokines have been shown to be associated in psychiatric disorders, such as schizophrenia, bipolar disorder, and depression. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family, serves as a neurotrophic molecular and plays a significant role in the brain. We generated mice in which HB-EGF activity is disrupted specifically in the ventral forebrain. These knockout mice showed (a) behavioral abnormalities similar to those described in psychiatric disorders, which were ameliorated by typical or atypical antipsychotics, (b) altered dopamine and serotonin levels in the brain, (c) decreases in spine density in neurons of the prefrontal cortex, (d) reductions in the protein levels of the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor and post-synaptic protein-95 (PSD-95), (e) decreases in the EGF receptor, and in the calcium/calmodulin-dependent protein kinase II (CaMK II) signal cascade. These results suggest the alterations affecting HB-EGF signaling could comprise a contributing factor in psychiatric disorder.
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PMID:Generation and characterization of conditional heparin-binding EGF-like growth factor knockout mice. 1982 4

Despite significant research efforts aimed at understanding the neurobiological underpinnings of psychiatric disorders, the diagnosis and the evaluation of treatment of these disorders are still based solely on relatively subjective assessment of symptoms. Therefore, biological markers which could improve the current classification of psychiatry disorders, and in perspective stratify patients on a biological basis into more homogeneous clinically distinct subgroups, are highly needed. In order to identify novel candidate biological markers for major depression and schizophrenia, we have applied a focused proteomic approach using plasma samples from a large case-control collection. Patients were diagnosed according to DSM criteria using structured interviews and a number of additional clinical variables and demographic information were assessed. Plasma samples from 245 depressed patients, 229 schizophrenic patients and 254 controls were submitted to multi analyte profiling allowing the evaluation of up to 79 proteins, including a series of cytokines, chemokines and neurotrophins previously suggested to be involved in the pathophysiology of depression and schizophrenia. Univariate data analysis showed more significant p-values than would be expected by chance and highlighted several proteins belonging to pathways or mechanisms previously suspected to be involved in the pathophysiology of major depression or schizophrenia, such as insulin and MMP-9 for depression, and BDNF, EGF and a number of chemokines for schizophrenia. Multivariate analysis was carried out to improve the differentiation of cases from controls and identify the most informative panel of markers. The results illustrate the potential of plasma biomarker profiling for psychiatric disorders, when conducted in large collections. The study highlighted a set of analytes as candidate biomarker signatures for depression and schizophrenia, warranting further investigation in independent collections.
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PMID:Plasma protein biomarkers for depression and schizophrenia by multi analyte profiling of case-control collections. 2016 99


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