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)

Fear of strangers ( FOS ) during the infant's first year was studied in 46 "high-risk" offspring of index mothers with a history of nonorganic psychosis and in 80 demographically similar control offspring. FOS was measured in the home by a standardized test at 1 year of age and by repeated interviews with the mother during the first year. As compared with controls, the total index group, and the subgroups of offspring of mothers with Schizophrenia and Cycloid Psychosis, significantly more often showed a total absence of FOS in the test at 1 year, as well as during the entire first year. FOS at 1 year was unrelated both to serious active psychiatric disturbance in index mothers during the infant's first year of life, and the infant's sex, in index and control groups.
 ...
PMID:Offspring of women with nonorganic psychosis: fear of strangers during the first year of life. 673 Oct

Extensive evidence suggests that 5-HT2 receptors may play a role in mental disorders including schizophrenia. In addition, several studies indicate that G(q)-coupled 5-HT(2A) receptors are likely targets for the initiation of events leading to the hallucinogenic behavior elicited by lysergic acid diethylamide (LSD), (+/-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), and related drugs. However, 5-HT(2A) receptors couple to other G proteins in addition to G(q) protein. To evaluate the role of the G(q) signaling pathway in DOI-induced behaviors, we utilized two behavioral models of 5-HT(2A) receptor activation: induction of head-twitches by DOI, a common response to hallucinogenic drugs in rodents, and DOI elicited anxiolytic-like effects in the elevated plus maze. Experimental subjects were genetically modified mice [Galpha(q)(-/-)] in which the G(q) alpha gene was eliminated. Galpha(q)(-/-) mice exhibited a decrease in DOI-induced head-twitches, when compared to wild-type littermates. In addition, the DOI-induced increase in anxiolytic-like behavior was abolished in Galpha(q)(-/-) mice. These results, combined with our finding that DOI-induced FOS expression in the medial prefrontal cortex was also eliminated in Galpha(q)(-/-) mice, suggests a key role for G(q) protein in hallucinogenic drug effects.
 ...
PMID:Role of G(q) protein in behavioral effects of the hallucinogenic drug 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane. 1749 41

Anxiety disorders are prevalent and disabling yet understudied from a genetic standpoint, compared with other major psychiatric disorders such as bipolar disorder and schizophrenia. The fact that they are more common, diverse and perceived as embedded in normal life may explain this relative oversight. In addition, as for other psychiatric disorders, there are technical challenges related to the identification and validation of candidate genes and peripheral biomarkers. Human studies, particularly genetic ones, are susceptible to the issue of being underpowered, because of genetic heterogeneity, the effect of variable environmental exposure on gene expression, and difficulty of accrual of large, well phenotyped cohorts. Animal model gene expression studies, in a genetically homogeneous and experimentally tractable setting, can avoid artifacts and provide sensitivity of detection. Subsequent translational integration of the animal model datasets with human genetic and gene expression datasets can ensure cross-validatory power and specificity for illness. We have used a pharmacogenomic mouse model (involving treatments with an anxiogenic drug--yohimbine, and an anti-anxiety drug--diazepam) as a discovery engine for identification of anxiety candidate genes as well as potential blood biomarkers. Gene expression changes in key brain regions for anxiety (prefrontal cortex, amygdala and hippocampus) and blood were analyzed using a convergent functional genomics (CFG) approach, which integrates our new data with published human and animal model data, as a translational strategy of cross-matching and prioritizing findings. Our work identifies top candidate genes (such as FOS, GABBR1, NR4A2, DRD1, ADORA2A, QKI, RGS2, PTGDS, HSPA1B, DYNLL2, CCKBR and DBP), brain-blood biomarkers (such as FOS, QKI and HSPA1B), pathways (such as cAMP signaling) and mechanisms for anxiety disorders--notably signal transduction and reactivity to environment, with a prominent role for the hippocampus. Overall, this work complements our previous similar work (on bipolar mood disorders and schizophrenia) conducted over the last decade. It concludes our programmatic first pass mapping of the genomic landscape of the triad of major psychiatric disorder domains using CFG, and permitted us to uncover the significant genetic overlap between anxiety and these other major psychiatric disorders, notably the under-appreciated overlap with schizophrenia. PDE10A, TAC1 and other genes uncovered by our work provide a molecular basis for the frequently observed clinical co-morbidity and interdependence between anxiety and other major psychiatric disorders, and suggest schizo-anxiety as a possible new nosological domain.
 ...
PMID:Convergent functional genomics of anxiety disorders: translational identification of genes, biomarkers, pathways and mechanisms. 2283 4

We investigated whether male inpatients with schizophrenia and a history of hands-on violent offences (forensic schizophrenic, FOS) are more impaired in emotion recognition than matched schizophrenia patients without any history of violence (general psychiatric schizophrenic, GPS). This should become apparent in performance in psychometry and in scalp event-related brain potentials (ERPs) evoked by pictures of facial affect. FOS and GPS (each n = 19) were matched concerning age, intelligence, comorbid addiction, medication and illness duration. FOS revealed significantly poorer affect recognition (AR) performance, especially of neutral and fear stimuli. Analysis of ERPs revealed a significant interaction of hemisphere, electrode position and group of the N250 component. Post hoc analysis of group effect showed significantly larger amplitudes in FOS at FC3. These results support the hypothesis that in FOS emotional faces are more salient and evoke higher arousal. Larger impairment in AR performance combined with higher salience and arousal may contribute to the occurrence of violent acts in schizophrenia patients.
...
PMID:Facial affect recognition performance and event-related potentials in violent and non-violent schizophrenia patients. 2405 42

Psychosis-proneness or schizotypy is a personality organisation mirroring individual risk for schizophrenia-development. Believed to be a fully dimensional construct sharing considerable geno- and phenotypal variance with clinical schizophrenia, it has become an increasingly promising tool for basic psychosis-research. Although many studies show genetic commonalities between schizotypy and schizophrenia, changes in regulation of gene expression have never been examined in schizotypy before. We therefore extracted RNA from the blood, a valid surrogate for brain tissue, of a large sample of 67 healthy male volunteers and correlated the activities of all genes relevant for dopaminergic neurotransmission with the positive schizotypy-scale of the O-LIFE. We found significant negative correlations regarding the expression of the genes COMT, MAOB, DRD4, DRD5 and FOS, indicating that increased schizotypy coincides with higher levels of dopaminergic dysregulation on the mRNA-level. Considering the advantages of this method, we suggest that it be applied more often in fundamental psychosis-research.
...
PMID:Psychosis-proneness correlates with expression levels of dopaminergic genes. 2463 Jul 41

Prenatal stress (PS) is a known risk factor for several psychiatric diagnoses, including schizophrenia, attention deficit hyperactivity disorder, autism, anxiety, and depression which have been associated with serotonin transporter (SERT) dysregulation. Moreover, long-term effects in animal models associate with higher levels of immediate early genes, e.g. c-FOS (up-regulated in response to neuronal activity), in the brain of PS offspring. We therefore quantified the expression of both protein related mRNAs in adolescent BALB/c mice subjected to mild auditory stress on two separate days in mid gestation. SERT and c-FOS consistently correlated in most brain regions of PS mice and controls. Moreover, two-way ANOVAs revealed concomitantly increased levels of proteins, as well as of FOSL1 and FOSL2 mRNA, especially in the striatum and hippocampus of the PS offspring. Sex affected only and less consistently mRNA expression, yet interacted with PS, demonstrating that glucocorticoid receptor mRNA expression decreased in PS males but increased in PS females compared to the respective controls. This first finding of a correlation between SERT and c-FOS protein expression affected by PS, together with related mRNAs, may be considered a new target for behavioral and treatment studies in offspring.
...
PMID:Prenatal stress increases the striatal and hippocampal expression of correlating c-FOS and serotonin transporters in murine offspring. 2510 10

Alterations in neuronal plasticity and immune system play a key role in pathogenesis of schizophrenia. Identification of genetic factors contributing to these alterations will significantly encourage elucidation of molecular etiopathomechanisms of this disorder. Transcription factors c-Fos, c-Jun, and Ier5 are the important regulators of neuronal plasticity and immune response. In the present work we investigated a potential association of schizophrenia with a number of single nucleotide polymorphisms of c-Fos-,c-Jun and Ier5 encoding genes (FOS, JUN, and IER5 respectively). Genotyping of DNA samples of patients with schizophrenia and healthy individuals was performed using polymerase chain reaction with allele specific primers. The results obtained demonstrated association between schizophrenia and FOS rs1063169, FOS rs7101, JUN rs11688, and IER5 rs6425663 polymorphisms. Namely, it was found that the inheritance of FOS rs1063169*T, JUN rs11688*A, and IER5 rs6425663*T minor variants decreases risk for development of schizophrenia whereas the inheritance of FOS rs7101*T minor variant, especially its homozygous form, increases risk for development of this disorder.
 ...
PMID:[Association of schizophrenia with variations in genes encoding transcription factors]. 2671 Jul 78

Schizophrenia is a chronic, debilitating neuropsychiatric disorder. Multiple transcriptomic gene expression profiling analysis has been used to identify schizophrenia-associated genes, unravel disease-associated biomarkers, and predict clinical outcomes. We aimed to identify gene expression regulation, underlying pathways, and their roles in schizophrenia pathogenesis. We searched the Gene Expression Omnibus (GEO) database for microarray studies of fibroblasts, lymphoblasts, and post-mortem brains of schizophrenia patients. Our analysis demonstrated high FOS expression in non-neural peripheral samples and low FOS expression in brain tissues of schizophrenia patients compared with healthy controls. FOS exhibited predictive value for schizophrenia patients in these datasets. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that "amphetamine addiction" was among the top 10 significantly enriched KEGG pathways. FOS and FOSB, which are implicated in the amphetamine addiction pathway, were up-regulated in schizophrenia fibroblast samples. Protein-protein interaction (PPI) network analysis revealed that proteins closely interacting with FOS-encoded protein were also involved in the amphetamine addiction pathway. Pearson correlation test indicated that FOS showed positive correlation with genes in the amphetamine pathway. The results revealed that FOS was acceptable as a biomarker for schizophrenia and may be involved in schizophrenia pathogenesis.
 ...
PMID:Central and Peripheral Changes in FOS Expression in Schizophrenia Based on Genome-Wide Gene Expression. 3096 96