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)

Vitamin A (retinoid), an essential nutrient for fetal and subsequent mammalian development, is involved in gene expression, cell differentiation, proliferation, migration, and death. Retinoic acid (RA) the morphogenic derivative of vitamin A is highly teratogenic. In humans retinoid excess or deficit can result in brain anomalies and psychosis. This review discusses chromosomal loci of genes that control the retinoid cascade in relation to some candidate genes in schizophrenia. The paper relates the knowledge about the transport, delivery, and action of retinoids to what is presently known about the pathology of schizophrenia, with particular reference to the dopamine hypothesis, neurotransmitters, the glutamate hypothesis, retinitis pigmentosa, dermatologic disorders, and craniofacial anomalies.
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PMID:Chromosomal locations and modes of action of genes of the retinoid (vitamin A) system support their involvement in the etiology of schizophrenia. 748 72

Vitamin A (all-trans-retinol) is the parent compound of a family of natural and synthetic compounds, the retinoids. Retinoids regulate gene transcription in numerous cells and tissues by binding to nuclear retinoid receptor proteins, which act as transcription factors. Much of the research conducted on retinoid signalling in the nervous system has focussed on developmental effects in the embryonic or early postnatal brain. Here, we review the increasing body of evidence indicating that retinoid signalling plays an important role in the function of the mature brain. Components of the metabolic pathway for retinoids have been identified in adult brain tissues, suggesting that all-trans-retinoic acid (ATRA) can be synthesized in discrete regions of the brain. The distribution of retinoid receptor proteins in the adult nervous system is different from that seen during development; and suggests that retinoid signalling is likely to have a physiological role in adult cortex, amygdala, hypothalamus, hippocampus, striatum and associated brain regions. A number of neuronal specific genes contain recognition sequences for the retinoid receptor proteins and can be directly regulated by retinoids. Disruption of retinoid signalling pathways in rodent models indicates their involvement in regulating synaptic plasticity and associated learning and memory behaviours. Retinoid signalling pathways have also been implicated in the pathophysiology of Alzheimer's disease, schizophrenia and depression. Overall, the data underscore the likely importance of adequate nutritional Vitamin A status for adult brain function and highlight retinoid signalling pathways as potential novel therapeutic targets for neurological diseases.
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PMID:Role of retinoid signalling in the adult brain. 1588 77

Vitamin A is necessary for normal embryonic development, but its role in the adult brain is poorly understood. Vitamin A derivatives, retinoids, are involved in a complex signaling pathway that regulates gene expression and, in the central nervous system, controls neuronal differentiation and neural tube patterning. Although a major functional implication of retinoic signaling has been repeatedly suggested in synaptic plasticity, learning and memory, sleep, schizophrenia, depression, Parkinson disease, and Alzheimer disease, the targets and the underlying mechanisms in the adult brain remain elusive.
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PMID:Functional implication of the vitamin A signaling pathway in the brain. 1807 Oct 33

Vitamin A (retinol), in the biologically active form of retinoic acid (RA), has been proposed as involved in the pathogenesis of schizophrenia. We hypothesized that genetic basis of genes encoding RA metabolism enzymes, which control the cellular RA level, might be associated with this disease. This cascade genetic association model, using markers in genes of synthesis and degradation enzymes within the retinoid cascade, would better fit the biological character of the retinoid hypothesis than the single gene strategy. In the present study we chose to investigate 7 genes involved in the synthesis, degradation and transportation of RA, ALDH1A1, ALDH1A2, ALDH1A3, CYP26A1, CYP26B1, CYP26C1 and Transthyretin (TTR), for their roles in the development of schizophrenia. We genotyped 18 single nucleotide polymorphisms (SNPs) in the regulatory and coding regions of these 7 genes using LDR technology in the 617 Chinese Han subjects. Case-control analyses were performed to detect association of these 7 genes with schizophrenia. Association analyses using both allelic and genotypic single-locus tests revealed no significant association between the risk for each of investigated gene and schizophrenia. However, analyses of multiple-locus haplotypes indicated that the overall frequency of rs4646642-rs4646580 of ALDH1A2 gene showed significant difference between patients and control subjects (p=0.0055). We also employed multifactor dimensionality reduction method to detect multilocus effects. In summary, in this work we show multiple candidate genes involved in retinoid cascade in schizophrenics. In addition, our results suggest a positive association between ALDH1A2 and schizophrenics in the Chinese population and support the retinoid hypothesis of schizophrenia.
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PMID:Positive association between ALDH1A2 and schizophrenia in the Chinese population. 1970 8

This review highlights morphological and functional anomalies found along the entire visual pathway in schizophrenia, from the retina to the cortex. Based on the evidence of widespread anatomical and functional visual abnormalities, we posited that a neurodevelopmental anomaly occurring early in life was likely to explain those. Incidentally, support to the neurodevelopmental theory of schizophrenia is strongly emerging from many neurobiological domains. In vertebrates, the first visual structures migrate toward the orbit position at the end of the fourth week of gestation. A neurodevelopmental defect around that time on these embryonic structures could account for the visual anomalies in schizophrenia. Retinol activity might be involved in the process. Future research in schizophrenia should focus on early visual testing, on trials combining multiple visual anomaly assessments and a closer look to retinol activity during the pregnancy.
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PMID:Revisiting visual dysfunctions in schizophrenia from the retina to the cortical cells: A manifestation of defective neurodevelopment. 2593 88

The atypical antipsychotic clozapine is one of the most potent drugs of its class, yet its precise mechanisms of action remain insufficiently understood. Recent evidence points toward the involvement of endogenous retinoic acid (RA) signaling in the pathophysiology of schizophrenia. Here we investigated whether clozapine may modulate RA-signaling. Effects of clozapine on the catabolism of all-trans RA (at-RA), the biologically most active metabolite of Vitamin A, were assessed in murine and human brain tissue and peripheral blood-derived mononuclear cells (PBMC). In patients with schizophrenia with and without clozapine treatment and matched healthy controls, at-RA serum levels and blood mRNA expression of retinoid-related genes in PBMCs were quantified. Clozapine and its metabolites potently inhibited RA catabolism at clinically relevant concentrations. In PBMC-derived microsomes, we found a large interindividual variability of the sensitivity toward the effects of clozapine. Furthermore, at-RA and retinol serum levels were significantly lower in patients with schizophrenia compared with matched healthy controls. Patients treated with clozapine exhibited significantly higher at-RA serum levels compared with patients treated with other antipsychotics, while retinol levels did not differ between treatment groups. Similarly, in patients without clozapine treatment, mRNA expression of RA-inducible targets CYP26A and STRA6, as well as at-RA/retinol ratio, were significantly reduced. In contrast, clozapine-treated patients did not differ from healthy controls in this regard. Our findings provide the first evidence for altered peripheral retinoid homeostasis in schizophrenia and suggest modulation of RA catabolism as a novel mechanism of action of clozapine, which may be useful in future antipsychotic drug development.
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PMID:Clozapine modulates retinoid homeostasis in human brain and normalizes serum retinoic acid deficit in patients with schizophrenia. 3248 28