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 corpus callosum (CC) is the brain's most important connection between cortical areas of both hemispheres. Due to the hemispheric lateralisation of brain function, information transfer between both hemispheres is vital for an optimal performance in tasks, in which several psycho-motor functions have to be integrated. Dysfunction of the CC can lead to deficits in neuropsychological tasks and could contribute to pathologies underlying psychiatric illnesses. In this review the normal and abnormal development of the CC as well as its macro- and microscopic anatomy will be outlined. Then the detrimental effects of operative callosomy on different modalities, e. g. on vision, the somatosensory and the auditory system, will be discussed. Two electrophysiological methods will be introduced, with which interhemispheric communication can be studied: hemispheric transfer in rapid visuo-motoric tasks (CUD) and transcallosal inhibition (TI), a phenomenon which occurs in a special paradigm of transcranial magnetic stimulation. A first study found TI to be reduced in unmedicated schizophrenic patients. This suggests that an inhibition between motor cortices could be reduced in schizophrenic patients. Further results of other studies, which have analysed the CC and interhemispheric transfer in schizophrenic patients, will be introduced and discussed. In future experiments, the contribution of dysfunctions of transcallosal transfer to psychopathological symptoms and neuropsychological deficits in schizophrenia should be studied.
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PMID:[Interhemispheric transfer and its implications for neurology and psychiatry]. 1297 30

Several studies have reported on structural abnormalities, decreased myelination and oligodendrocyte dysfunction in post-mortem brains from schizophrenic patients. Glia-derived cholesterol is essential for both myelination and synaptogenesis in the CNS. Lipogenesis and myelin synthesis are thus interesting etiological candidate targets in schizophrenia. Using a microarray approach, we here demonstrate that the antipsychotic drugs clozapine and haloperidol upregulate several genes involved in cholesterol and fatty acid biosynthesis in cultured human glioma cells, including HMGCR (3-hydroxy-3-methylglutaryl-coenzyme A reductase), HMGCS1 (3-hydroxy-3-methylglutaryl-coenzyme A synthase-1), FASN (fatty acid synthase) and SCD (stearoyl-CoA desaturase). The changes in gene expression were followed by enhanced HMGCR-enzyme activity and elevated cellular levels of cholesterol and triglycerides. The upregulated genes are all known to be controlled by the sterol regulatory element-binding protein (SREBP) transcription factors. We show that clozapine and haloperidol both activate the SREBP system. The antipsychotic-induced SREBP-mediated increase in glial cell lipogenesis could represent a novel mechanism of action, and may also be relevant for the metabolic side effects of antipsychotics.
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PMID:Antipsychotic drugs activate SREBP-regulated expression of lipid biosynthetic genes in cultured human glioma cells: a novel mechanism of action? 1602 36

Although emerging evidence suggests that schizophrenia (SZ) is associated with peripheral and central polyunsaturated fatty acid (PUFA) deficits, there is currently nothing known about the expression of genes that mediate PUFA biosynthesis in SZ patients. Here we determined Delta5 desaturase (FADS1), Delta6 desaturase (FADS2), elongase (HELO1 [ELOVL5]), peroxisomal (PEX19), and Delta9 desaturase (stearoyl-CoA desaturase, SCD) mRNA expression, and relevant fatty acid product:precursor ratios as estimates of enzyme activities, in the postmortem prefrontal cortex (PFC) of patients with SZ (n=20) and non-psychiatric controls (n=20). After correction for multiple comparisons, FADS2 mRNA expression was significantly greater in SZ patients relative to controls (+36%, p=0.002), and there was a positive trend found for FADS1 (+26%, p=0.15). No differences were found for HELO1 (+10%, p=0.44), PEX19 (+12%, p=0.44), or SCD (-6%, p=0.85). Both male (+34%, p=0.02) and female (+42%, p=0.02) SZ patients exhibited greater FADS2 mRNA expression relative to same-gender controls. Drug-free SZ patients (+37%, p=0.02), and SZ patients treated with typical (+40%, p=0.002) or atypical (+31%, p=0.04) antipsychotics, exhibited greater FADS2 mRNA expression relative to controls. Consistent with increased Delta6 desaturase activity, SZ patients exhibited a greater 20:3/18:2 ratio (+20%, p=0.03) and a positive trend was found for 20:4/18:2 (+13%, p=0.07). These data demonstrate abnormal, potentially compensatory, elevations in Delta6 desaturase (FADS2) expression in the PFC of SZ patients that are independent of gender and antipsychotic medications. Greater Delta6 desaturase expression and activity could have implications for central prostaglandin synthesis and proinflammatory signaling.
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PMID:Elevated delta-6 desaturase (FADS2) expression in the postmortem prefrontal cortex of schizophrenic patients: relationship with fatty acid composition. 1919 43