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)

This study examined serotonin (5-hydroxytryptamine; 5HT) receptor responsivity in 22 chronic schizophrenic patients and 17 healthy control subjects. The 5HT agonist meta-chlorophenylpiperazine (MCPP) was used as a probe of serotonergic function. MCPP (0.35 mg/kg) or placebo was administered orally after a 3-week drug-free period in a randomized double-blind design. Hormonal (adrenocorticotropic hormone and prolactin), temperature, and behavioral responses and MCPP blood levels were assessed for 210 minutes after administration of the capsules. The schizophrenic patients had blunted temperature responses compared with those of the healthy control subjects: MCPP raised body temperature in the control subjects, but not in the patients. Behavioral responses also differed in the two groups: MCPP increased the total Brief Psychiatric Rating Scale (BPRS) score in the control subjects and tended to decrease it in the patients. In patients, MCPP decreased the BPRS psychosis subscore. Hormonal responses did not differ significantly in the two groups. These findings suggest that further exploration of 5HT function in schizophrenia is warranted.
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PMID:Serotonin function in schizophrenia: effects of meta-chlorophenylpiperazine in schizophrenic patients and healthy subjects. 133 94

Several classes of drugs that modify serotonin (5-HT) neurotransmission are either currently used, or are being evaluated for their potential use in the treatment of anxiety, schizophrenia, and depression. 5-HT1A agonists are considered potential anxiolytics, while some atypical antipsychotics are potent 5-HT2 antagonists (and also have modest dopamine D2 affinity). Furthermore, there is a diverse group of serotonergic drugs that may be effective antidepressants. Secretion of ACTH, corticosterone/cortisol, prolactin, renin, oxytocin and vasopressin are stimulated by activation of different 5-HT receptor subtypes, while other neurotransmitter receptors also influence the secretion of these hormones. We compared the receptor binding profiles of 5-HT anxiolytics, antipsychotics and antidepressants with their endocrine effects. These comparisons could aid in understanding both the therapeutic and side effects of these drugs.
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PMID:Endocrine and receptor pharmacology of serotonergic anxiolytics, antipsychotics and antidepressants. 135 27

Chronic macrophage activation with subsequent failure of activated macrophages to properly control T-lymphocyte secretion of interleukin-2 and interleukin-2 receptors is proposed as the basic biological mechanism of schizophrenia. Fundamental to this theory are the clinical observations on interleukin-2 provoking the active phase symptoms of schizophrenia in psychiatrically normal human volunteers and macrophage cytokines producing the prodromal and residual phase symptoms. This theory provides a completely new and unified mechanisms for the antipsychotic action of typical and atypical neuroleptics, bromocriptine, naloxone and DMSO. Furthermore, this hypothesis reveals why the dopamine theory of schizophrenia was a false lead. The effects of prolactin, estrogens and androgens are consistent with the model. Age of onset, male/female incidence, course of the disease from prodromal to active to residual phase, the protection afforded by rheumatoid arthritis and the close relationship between depression and schizophrenia can be explained by this theory. The gastrointestinal tract is suggested as the preferred site to investigate for the cause of the immune activation in schizophrenia.
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PMID:A comprehensive macrophage-T-lymphocyte theory of schizophrenia. 136 59

Twenty-one patients with schizophrenia who met criteria for neuroleptic treatment resistance or intolerance participated in a crossover, placebo-controlled, double-blind comparison of long-term typical neuroleptic and clozapine treatment. Clozapine significantly reduced total as well as positive and negative symptoms in comparison with both fluphenazine and placebo. Of the 21 patients, eight (38%) showed clozapine superiority on the basis of prospective response criteria. High levels of extrapyramidal side effects during fluphenazine treatment and later onset of illness were clinical predictors of clozapine superiority. Clozapine and fluphenazine equally reduced plasma homovanillic acid levels in comparison with placebo, although fluphenazine but not clozapine increased plasma prolactin level. A striking biologic difference between clozapine and fluphenazine was clozapine's enhancement of indexes of noradrenergic activity. Superior clozapine response was predicted by low ratios of cerebrospinal fluid homovanillic acid to 5-hydroxyindoleacetic acid, consistent with the notion that balance between dopaminergic and serotoninergic systems is important for clozapine's mechanism of action.
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PMID:Clinical and biologic response to clozapine in patients with schizophrenia. Crossover comparison with fluphenazine. 768 12

A low plasma prolactin concentration has been reported to be associated with an increased risk of subsequent relapse in patients with schizophrenia. Prolactin concentration was measured in samples from stable schizophrenic men who were outpatients just prior to neuroleptic withdrawal. No relationship between prolactin concentration and time to subsequent relapse was found. Prolactin concentration may predict time to relapse only in populations characterized by specific demographic features or medication history.
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PMID:Plasma prolactin as a predictor of relapse in drug-free schizophrenic outpatients. 146 85

We have previously reported that prolactin (PRL) responses to haloperidol 0.5 mg IV were blunted in subjects characterized by several diagnostic systems of schizophrenia compared to controls (Keks et al 1990). However, an attempt to find a diagnostic system most different from controls was unsuccessful due to inherent difficulties in the statistical analysis of multidiagnostic data. In this paper we present new methodologies. A test for differences in dependent correlations demonstrated that most of the variance in stimulated PRL was accounted for by Kraepelinian, and least by Schneiderian and M. Bleulerian, schizophrenias (p < 0.001). The main symptomatic difference between nonKraepelinian and Kraepelinian patients was the presence of association disturbance and feelings of passivity. Patients with both symptoms had a lower stimulated PRL than controls. Further findings and possible implications are discussed.
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PMID:Multidiagnostic evaluation of prolactin response to haloperidol challenge in schizophrenia: maximal blunting in Kraepelinian patients. 148 48

The clinical profile of clozapine (CAS 5786-21-0) is characterized by superior efficacy in reducing the positive and negative symptoms of schizophrenia and a greatly reduced propensity to elicit acute extrapyramidal symptoms (e.g., Parkinsonian symptoms), long-term effects (e.g., tardive dyskinesia) and hyperprolactinemia. For these reasons clozapine is considered the prototypic atypical antipsychotic. The failure of clozapine to elevate serum prolactin concentrations may be related to the stimulatory effect of clozapine on tuberoinfundibular dopamine neurons and/or the failure of clozapine to achieve effective blockade of pituitary dopamine D2 receptors. The lack of acute blockade of striatal D2 receptors by clozapine and the failure of chronic clozapine treatment to suppress striatal dopamine release, relative to that produced by typical antipsychotic agents, may account for the lack of acute extrapyramidal symptoms and tardive dyskinesia, respectively, associated with the use of clozapine. Although the neurochemical substrates that subserve the unique preclinical and clinical profile of clozapine have not been determined unequivocally, clozapine and other purported atypical antipsychotic agents produce a greater antagonism of 5-HT2 receptors relative to D2 receptors than is the case for typical antipsychotics. Clozapine also exerts antagonism of D1 receptors. It is proposed that the selective interaction of clozapine among D2, D1, D4 and 5-HT2 receptors results in a distinctive alteration in the function of pre- and post-synaptic dopamine elements.
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PMID:Dopaminergic and serotonergic effects of clozapine. Implications for a unique clinical profile. 158 97

Measurement of plasma prolactin (PRL) concentration and plasma homovanillic acid (HVA) concentration was performed in 24 patients with schizophrenia during maintenance haloperidol treatment. A significant inverse correlation was found between plasma PRL and ratings of both dyskinesia and thought disorder. Plasma PRL was also correlated with negative symptoms. No relationship was found between plasma HVA and any symptom grouping. Twelve patients received an apomorphine challenge; a trend toward a significant inverse relationship was found between baseline dyskinesia and apomorphine-induced decreases in plasma PRL. Plasma PRL and plasma HVA may reflect different elements of dopamine function in the central nervous system during maintenance treatment; plasma PRL may be the useful marker under these conditions.
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PMID:Plasma prolactin and homovanillic acid as markers for psychopathology and abnormal movements during maintenance haloperidol treatment in male patients with schizophrenia. 159 6

Plasma prolactin concentration (pPRL), plasma homovanillic acid concentration (pHVA), and symptomatology were measured in 24 male subjects with schizophrenia during maintenance haloperidol treatment. Fourteen subjects subsequently underwent 50 percent dose decreases under placebo-controlled, double-blind conditions. At baseline, a significant inverse correlation was found between pPRL and both tardive dyskinesia (TD) and "thinking disorder"; pPRL was directly correlated with negative symptoms. No such relationship was found with pHVA. In the patients who underwent a dose decrease, no relationship was found between baseline pPRL or pHVA and any clinical variable after the decrease. These data do not support the use of baseline pPRL or pHVA as markers of central dopamine function subsequent to a neuroleptic dose decrease.
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PMID:Plasma prolactin and homovanillic acid as markers for psychopathology and abnormal movements after neuroleptic dose decrease. 160 34

A case of schizophrenia with neuroleptic malignant syndrome (NMS) presented difficulties in differential diagnosis. However, the presence of severe galactorrhea contributed decisively to relate the clinical picture with the administration of neuroleptics. We propose that presence of galactorrhea or disorders in prolactin (PRL) secretion should be investigated in NMS.
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PMID:Galactorrhea in the neuroleptic malignant syndrome. 163 77


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