Biochemical Findings of Negative Symptoms in Schizophrenia and Their Putative Relevance to Pharmacological Treatment

Mv, Rao; Møller, Henrik

doi:10.1159/000119156

Cited by 49 publications

(21 citation statements)

References 49 publications

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“…In addition, Van Kammen et al (1986) has reported the occurrence of decreased noradrenaline and MHPG concentrations in the cerebrospinal fluid (CSF) of schizophrenic patients with negative symptoms. Therefore, these negative symptoms may be attributable to dysfunction of the prefrontal cortex, including hypofunction of the noradrenergic network (Rao and Moller 1994). To support this, idazoxan, a selective ␣2-antagonist, is reported to augment therapeutic effect of typical neuroleptics in treatment of schizophrenia (Litman et al 1993(Litman et al , 1996.…”

Section: Discussionmentioning

confidence: 99%

Clozapine- and Olanzapine-induced Fos Expression in the Rat Medial Prefrontal Cortex is Mediated by β-Adrenoceptors

Ohashi

Hamamura

Lee

et al. 2000

Neuropsychopharmacology

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The atypical neuroleptics, clozapine and olanzapine, have superior therapeutic efficacy against the negative symptoms of schizophrenia, compared with the typical neuroleptics. Recently, it has been suggested that the ability of clozapine and olanzapine to induce Fos expression in the medialClozapine, a prototype atypical antipsychotic compound, is effective not only against the positive, but also against the negative symptoms of schizophrenia (Claghorn et al. 1987;Kane et al. 1988) which are usually resistant to typical neuroleptics. The mechanisms underlying this action, although investigated intensively, remain to be established. Recent studies involving the Fos protein have demonstrated that clozapine induces a much larger increase in the number of neurons that exhibit Fos-like immunoreactivity (LI) in the medial prefrontal cortex (mPFC) than do typical neuroleptics (Deutch and Duman 1996; Fink-Jensen and Kristensen 1994; Fink-Jensen et al. 1995;Guo et al. 1995;Kurokawa et al. 1997;Robertson and Fibiger 1992;Robertson et al. 1994;Wan et al. 1995). This regionally specific clozapine effect sets it apart from typical neuroleptics.Although simple neuronal depolarization or increase in firing rate per se are not enough to induce c-fos in many neurons, other factors such as phenotype of neuronal cell are also required for c-fos expression, Fos protein is thought to be a marker of activated neurons in specified subset of neurons (Sagar et al. 1988; Dragunow and Faull 1989;Grant et al. 1992;Sharp et al. 1993). Therefore, it can be postulate that clozapine may enhance neuronal activity in the mPFC. In connection with the hypothesis that hypofrontality may be responFrom the Department of Neuropsychiatry (KO, TH, YL, HS, SK), Okayama University Medical School, Shikata-cho Okayama, Japan; and Takaoka Hospital (YF), Nishi-imazyuku Himeji, Japan.Address correspondence to: Dr. T. Hamamura, Department of Neuropsychiatry, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama, 700-8558 Japan.Received November 9, 1999; revised February 8, 2000; accepted February 17, 2000. N EUROPSYCHOPHARMACOLOGY 2000 -VOL . 23 , NO . 2 Clozapine-and Olanzapine-induced Fos in mPFC 163 sible for the negative or deficit symptoms of schizophrenia (Weinberger 1988), the preferential induction of Fos-LI in the mPFC is postulated to be one of the mechanisms by which clozapine reduces the negative symptoms of schizophrenia (Robertson et al. 1994). If this is the case, it is important to determine the neuropharmacological mechanisms by which clozapine induces Fos expression in the mPFC. Although clozapine is known to have an affinity for various neurotransmitter receptors, such as noradrenergic, dopaminergic, histaminergic, muscarinic and 5-hydroxytryptamine (5-HT) receptors, the precise neuropharmacological action of clozapine that results in the induction of Fos expression in the mPFC is unknown. Since clozapine administration increases the firing rate of noradrenergic cells in the locus coeruleus (LC) and noradrenaline release from...

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Section: Discussionmentioning

confidence: 99%

Clozapine- and Olanzapine-induced Fos Expression in the Rat Medial Prefrontal Cortex is Mediated by β-Adrenoceptors

Ohashi

Hamamura

Lee

et al. 2000

Neuropsychopharmacology

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“…This observation correlates with the activity of these compounds in behavioral tests for anxiolytic activity (see below) and may contribute to a favorable effect on negative symptoms. Antagonist activity at the serotonin 5-HTzA receptor has also been suggested to predict efficacy against negative symptoms (50,72). The high affinity of iloperidone for serotonin 5-HT2, receptors indicates that it should be effective against negative symptoms.…”

Section: In Viiro Receptor Bindingmentioning

confidence: 99%

Iloperidone: Preclinical Profile and Early Clinical Evaluation

Corbett¹,

Griffiths²,

Shipley³

et al. 1997

CNS Drug Reviews

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“…Siris et al (1990) found that imipramine maintenance adjunctive to fluphenazine was superior to fluphenazine and placebo for preventing relapse into psychotic depression or negative symptom states. Monoamine oxidase inhibitors have also been suggested in the treatment of negative symptoms (Rao and Moller, 1994). The efficacy of adjunctive fluvoxamine for the treatment of negative symptoms of schizophrenia has been demonstrated in two clinical trials of 30 (Silver and Nassar, 1992) and 53 participants (Silver et al, 2000), respectively.…”

Section: Introductionmentioning

confidence: 99%

Mirtazapine add‐on therapy in the treatment of schizophrenia with atypical antipsychotics: a double‐blind, randomised, placebo‐controlled clinical trial

Berk

Gama

Sundram

et al. 2009

Human Psychopharmacology

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Biochemical Findings of Negative Symptoms in Schizophrenia and Their Putative Relevance to Pharmacological Treatment

Cited by 49 publications

References 49 publications

Clozapine- and Olanzapine-induced Fos Expression in the Rat Medial Prefrontal Cortex is Mediated by β-Adrenoceptors

Clozapine- and Olanzapine-induced Fos Expression in the Rat Medial Prefrontal Cortex is Mediated by β-Adrenoceptors

Iloperidone: Preclinical Profile and Early Clinical Evaluation

Mirtazapine add‐on therapy in the treatment of schizophrenia with atypical antipsychotics: a double‐blind, randomised, placebo‐controlled clinical trial

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