Treatment of schizophrenia

Kane, John M.; McGlashan, Thomas H.

doi:10.1016/s0140-6736(95)91630-x

Cited by 91 publications

(49 citation statements)

References 28 publications

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“…57 Moreover, some schizophrenic patients are susceptible to relapse due to psychological stressors, even when maintained on antipsychotic medication. 58 The difference in the modulation of BDNF expression following stress might depend upon several mechanisms. It is known that stress not only increases the levels of circulating corticosteroids but also induces the release of several neurotransmitters.…”

Section: Discussionmentioning

confidence: 99%

Developmental and stress-related changes of neurotrophic factor gene expression in an animal model of schizophrenia

Molteni

Lipska²,

Weinberger³

et al. 2001

Mol Psychiatry

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The neonatal (PND 7) lesion of the ventral hippocampus (VH) with ibotenic acid represents a well-established experimental paradigm that recapitulates many schizophrenia-like phenomena. In order to investigate molecular changes that could contribute to long lasting consequences on brain function, we have investigated the effects of the VH lesion on the expression for the trophic factors FGF-2 and BDNF. We used RNase protection assay to measure their mRNA levels in cortical regions of prepubertal (PND 35) and young adult (PND 56) animals, both under basal condition as well as in response to an acute restraint stress. The expression of BDNF was not altered by the VH lesion in prefrontal (PFC) and frontal cortex (FC) of PND 35 or PND 56 rats. An acute restraint stress at PND 35 produced a significant increase of the neurotrophin expression in PFC of sham as well as lesioned animals. However in young adult animals a significant elevation of BDNF expression was observed only in sham rats. We also found that the VH lesion produced a significant reduction of basal BDNF mRNA levels in the cingulate cortex of young adult, but not prepubertal rats. This effect was not accompanied by changes in the acute modulation of the neurotrophin, which was up-regulated by stress in both experimental groups. Conversely the expression of FGF-2 at PND 35 and PND 56 was not altered by early postnatal VH lesion, and there were no major differences between sham and lesioned animals in response to the acute stress. The changes in trophic factor expression may be relevant for the long-term effects of VH lesion on synaptic plasticity and may determine an increased vulnerability of the brain under challenging situations. Molecular Psychiatry (2001) 6, 285-292.

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Section: Discussionmentioning

confidence: 99%

Developmental and stress-related changes of neurotrophic factor gene expression in an animal model of schizophrenia

Molteni

Lipska²,

Weinberger³

et al. 2001

Mol Psychiatry

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“…Interest in cholinergic systems in schizophrenia was reawakened with the demonstration that drugs such as clozapine and olanzapine, both of which bind to muscarinic receptors, 3 are of therapeutic benefit in treating symptoms of the disorder. 4,5 Thus, from therapeutic pharmacology, postmortem tissue research and other lines of evidence it has now been suggested that muscarinic receptors are important in the pathology of schizophrenia. 2 Five muscarinic receptors have been identified in the human CNS 2 but investigations on the involvement of changes in muscarinic receptors in schizophrenia have been hampered by the lack of receptor-specific radioligands and drugs.…”

Section: Introductionmentioning

confidence: 99%

Decreased muscarinic1 receptors in the dorsolateral prefrontal cortex of subjects with schizophrenia

et al. 2002

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To test the hypothesis that muscarinic receptors are involved in the pathology of schizophrenia, we measured muscarinic 1 (M1R) and muscarinic 4 (M4R) protein and mRNA as well as [ 3 H]pirenzepine binding in Brodmann's areas (BA) 9 and 40 obtained postmortem from 20 schizophrenic and 20 age/sex-matched control subjects. There was a significant decrease in [ 3 H]pirenzepine binding to BA 9 (mean ± SEM: 151 ± 15 vs 195 ± 10 fmol mg −1 ETE; P Ͻ 0.02), but not BA 40 (143 ± 13 vs 166 ± 11 fmol mg −1 ETE), from subjects with schizophrenia. The level of M1R protein (0.11 ± 0.007 vs 0.15 ± 0.008 OD; P Ͻ 0.01), but not M4R protein, was decreased in BA9 from schizophrenic subjects with neither receptor protein being altered in BA 40. The level of M1R mRNA was decreased in BA 9 (30 ± 7.0 vs 79 ± 14 dpm × 10 3 mg −1 ETE, P Ͻ 0.01) and BA 40 (28 ± 5.9 vs 99 ± 14, P Ͻ 0.01) with schizophrenia but M4R mRNA was only decreased in BA 40 (48 ± 6.6 vs 89 ± 9.9, P Ͻ 0.005). These data suggest that the M1R, at least in the dorsolateral prefrontal cortex, may have a role in the pathology of schizophrenia.

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“…It has been shown to be beneficial in approximately 30% of patients who do not respond to typical antipsychotic therapy, without producing extrapyramidal syndrome (EPS) (Kane et al 1988;Buchanan 1995;Ashby and Wang 1996;Meltzer et al 1999). Despite these advantages, the clinical use of clozapine is limited because of a significant incidence of lethal agranulocytosis (Grohmann et al 1989;Kane and McGlashan 1995;Borison 1997). Furthermore, it is known that clozapine also is associated with a range of other side effects such as weight gain, hypersalivation, sedation, cardiovascular side effects, lowering of seizure threshold (Miller 2000).…”

mentioning

confidence: 99%

Neuropharmacological Profile of a Novel Potential Atypical Antipsychotic Drug Y-931 (8-fluoro-12-(4-methylpiperazin-1-yl)- 6H-[1]benzothieno[2,3-b][1,5] benzodiazepine maleate)

Morimoto¹,

Hashimoto²,

Yasumatsu³

et al. 2002

Neuropsychopharmacology

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Treatment of schizophrenia

Cited by 91 publications

References 28 publications

Developmental and stress-related changes of neurotrophic factor gene expression in an animal model of schizophrenia

Developmental and stress-related changes of neurotrophic factor gene expression in an animal model of schizophrenia

Decreased muscarinic1 receptors in the dorsolateral prefrontal cortex of subjects with schizophrenia

Neuropharmacological Profile of a Novel Potential Atypical Antipsychotic Drug Y-931 (8-fluoro-12-(4-methylpiperazin-1-yl)- 6H-[1]benzothieno[2,3-b][1,5] benzodiazepine maleate)

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