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)

Substantial evidence supports an important role for the excitatory neurotransmitter L-glutamate as a modulator of dopamine release in the central nervous system. All of the established glutamate receptor subtypes identified to date have been implicated in the regulation of dopamine release. It appears that glutamate can exert both facilitatory and inhibitory control over dopamine release and that this may be both phasic and tonic in nature. This regulatory role suggests that drugs acting at glutamate receptors may be potentially useful therapeutic agents in neurological disorders such as parkinsonism and schizophrenia.
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PMID:Glutamatergic control over brain dopamine release in vivo and in vitro. 919 6

The use of classic anti-psychotic drugs in the long-term treatment of schizophrenia is associated with risk for extrapyramidal side-effects, such as akathisia, parkinsonism and tardive dyskinesia (TD). Approximately 5-10% of European Caucasians lack the cytochrome P450 enzyme CYP2D6 (so-called poor metabolizers; PM), which normally metabolizes several drugs including many neuroleptics. PM subjects may achieve high or toxic plasma levels upon standard drug therapy. In this study we have examined 100 subjects from the Nithsdale cohort of schizophrenic patients in South-west Scotland receiving long-term neuroleptic medication, which enabled us to perform both a cross-sectional and longitudinal evaluation of extrapyramidal side-effects in relation to the genetically impaired CYP2D6 metabolism. We identified ten (10%) schizophrenic subjects with the PM genotype. In the cross-sectional study, the prevalence of TD, parkinsonism and akathisia was 51%, 38% and 15%, respectively. Patients with TD or parkinsonism were significantly older than patients without these side-effects. In contrast, patients with akathisia were significantly younger than patients without akathisia. There was a non-significant tendency for PM subjects to have more severe ratings for TD and parkinsonism. In the long-term evaluation based on repeated ratings since 1981, there was a non-significant 3-fold higher frequency of PM subjects among schizophrenic patients with longitudinal TD, as compared with the group of patients with fluctuating or no TD. These results indicate that genetically impaired CYP2D6 metabolism may be a contributing factor for the development of persistent TD.
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PMID:Non-functional CYP2D6 alleles and risk for neuroleptic-induced movement disorders in schizophrenic patients. 920 6

The previously common occurrence of catatonic schizophrenia and catatonic symptoms among schizophrenic patients has diminished sharply; catatonic symptoms now occur more frequently in association with severe affective disorders or with general medical conditions. Catatonia is generally viewed as a peculiar and puzzling syndrome and attracts limited attention. Yet significant catatonic symptoms tend to be present in close to 10% of patients admitted to psychiatric inpatient facilities. The dynamic significance of catatonia can be recognized by considering the original biologic role of catatonia in schizophrenia as an opposite to the paranoid disorder. Szondi viewed catatonia as an attempt at self-healing of the paranoid psychosis with its threatening total expansion, by extreme constriction of the ego. The previously predominant primary association of catatonia with schizophrenia has been eclipsed as neuroleptics have supplanted the endogenous self-healing attempt of catatonia, preventing the occurrence of catatonic symptoms in schizophrenia. Neuroleptics in fact duplicate or approximate the symptoms of catatonia by producing mental immobilization, hypokinesis (parkinsonism and dystonia), hyperkinesis (akathisia), and pernicious catatonia in the modern guise of the neuroleptic malignant syndrome (NMS). Patients with past or present catatonic symptoms are particularly vulnerable to NMS, and treatment of catatonia requires avoidance of neuroleptics and the use of benzodiazepines or electroconvulsive therapy (ECT). The extreme negativism and constriction of consciousness in catatonia suggest a primary role of the frontal lobes, with secondary involvement of the extrapyramidal system and its movement disorders. In an attempt to integrate clinical, psychologic, neuropharmacologic, and neurochemical findings, a modern dynamic neuropsychiatry must appreciate the major significance of catatonia.
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PMID:Catatonia and the neuroleptics: psychobiologic significance of remote and recent findings. 920 76

Amisulpride is an atypical antipsychotic drug. Low doses increase dopaminergic transmission via presynaptic blockade and are effective in patients with predominantly negative (deficit) symptoms of schizophrenia. In three double-blind studies, two short-term and one medium/long-term, comparing amisulpride with placebo, 272 patients with schizophrenia were carefully selected for a predominance of negative symptoms (low severity of positive symptoms, depression and extrapyramidal side effects). Fixed daily doses of amisulpride (100 and 300 mg) were used in a 6-week dose-range finding study (104 patients). Daily doses of between 50 and 100 mg amisulpride were used in a second 6-week study (27 patients), and in a third study, 100 mg amisulpride was administered for 6 months (141 patients) with an extension of up to 1 year. Mean total scores for the Scale for the Assessment of Negative Symptoms (SANS) at baseline in the different treatment groups varied from 98 to 74, and improved significantly in the amisulpride groups (mean change from 24 to 40 points) compared with the placebo groups. Positive symptoms measured by the Scale for the Assessment of Positive Symptoms (SAPS) were low at baseline, and the change at the end of the studies was minimal. Extrapyramidal side effects were of low severity in these studies and parkinsonism scores for amisulpride were not different from placebo. Overall, these findings indicate that the improvement in negative symptoms was not linked to a concomitant improvement in positive symptoms, parkinsonism or depressive symptoms as would be expected in the case of secondary negative symptoms. The results of these studies thus confirm the efficacy of amisulpride in schizophrenic patients with primary negative or deficit symptoms at a dose of 100 mg/day.
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PMID:Clinical update on amisulpride in deficit schizophrenia. 921 64

The purpose of this study was to determine the prevalence of extrapyramidal signs or symptoms (EPS) and clinical symptoms in first-episode schizophrenia, before any treatment, during and after treatment with a novel antipsychotic, risperidone. Twenty-two (17 men; 5 women) patients were examined using the Extrapyramidal Symptom Rating Scale, Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions-Severity of Illness and Improvement, and Global Assessment of Functioning. Three patients (14%) had distinct EPS at baseline, whereas all were free of EPS after treatment with risperidone. On the maximum dose of risperidone (5-8 mg), 32% of the total sample developed mild akathisia or parkinsonism, both of which diminished with dosage reduction. No clinically significant EPS were observed in patients receiving 2 to 4 mg of risperidone. Analysis of symptom response of the lower (2-4 mg) versus the higher (5-8 mg) doses of risperidone resulted in superior outcome in the 2- to 4-mg group for all three symptom clusters of the PANSS. In addition, 91% of the low-dose group achieved a 20% or greater reduction in total PANSS score compared with 27% for the high-dose group. These findings have clinical relevance directed at the early and longer-term treatment of schizophrenia.
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PMID:Extrapyramidal signs and clinical symptoms in first-episode schizophrenia: response to low-dose risperidone. 924 Oct 11

Clinical safety data for treatment of acute schizophrenia with olanzapine, a new atypical antipsychotic agent, are summarized. The primary clinical trial safety database included 2500 patients treated with olanzapine, 810 with haloperidol, and 236 with placebo. The overall discontinuation rate from olanzapine treatment was low. Significant adverse events included somnolence, weight gain, and asymptomatic treatment-emergent transaminase elevation. Minimal parkinsonism and akathisia with rare dystonia were noted. No hematotoxicity was noted. The incidence of seizures and sexual dysfunction was rare.
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PMID:Safety of olanzapine. 926 11

Amisulpride is a substituted benzamide with high selectivity for dopaminergic D2 and D3 receptors. This study compared 800 mg/day amisulpride and 20 mg/day haloperidol in patients with acute exacerbations of schizophrenia. This multicenter, double-blind trial involved 191 patients allocated, after a 1 to 7-day wash-out period, to amisulpride (n = 95) or haloperidol (n = 96) for 6 weeks. Improvement of mean BPRS total score was 48% for amisulpride and 38% for haloperidol (NS), whereas improvement in the Negative PANSS subscale was greater in the amisulpride group (37%) compared to haloperidol (24%) (P = 0.038). CGI scores showed a higher number of responders in the amisulpride (62%) than in the haloperidol group (44%) (P = 0.014). More extrapyramidal symptoms measured with the Simpson-Angus scale were provoked in the haloperidol group (P = 0.0009). Amisulpride is at least as effective as haloperidol in the treatment of acute exacerbations of schizophrenia, and is more effective in the treatment of negative symptoms whilst causing less parkinsonism.
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PMID:Improvement of acute exacerbations of schizophrenia with amisulpride: a comparison with haloperidol. PROD-ASLP Study Group. 929 18

In this paper we suggest a new method, conceived by Maher, to assess lateralized motor performance in schizophrenia. Subjects draw two straight lines with each hand. The lines are scanned into a computer, and a regression is run on the points of the line. The root mean squared error (RMS) of the regression equation indicates the deviation from straightness of the line. The average RMS of all four lines is taken as an overall measure of motor disorder, and the difference in performance between the two hands serves as an index of motoric laterality. Scores on the motor disorder index were significantly positively related to clinical ratings of Parkinsonism among schizophrenic inpatients. A marginal relation was found to ratings of voluntary movement disorders, and the task was not associated with dyskinetic movements. Scores on the motor disorder measure were significantly worse for schizophrenic subjects than for staff controls. The laterality index significantly differentiated right- and left-handed subjects, but did not differentiate schizophrenic from control subjects. Maher's simple line drawing task yields objective continuous ratings of motor disorder and handedness and may be a useful tool for examining associations between motor functioning and cognition and symptomatology in schizophrenia.
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PMID:Line drawing as a possible measure of lateralized motor performance in schizophrenia. 937 34

Neuroleptic treatment of psychotic symptoms or agitated behavior in elderly patients diagnosed with dementia is associated with reduced efficacy and increased rates of neuroleptic-induced parkinsonism in comparison to younger patients with schizophrenia. We report the first study to examine the relationship between an in vivo measure of dopaminergic function, plasma homovanillic acid (pHVA), and ratings of psychosis, agitation, and parkinsonism before and after neuroleptic treatment in dementia patients. Pretreatment pHVA was significantly correlated with parkinsonian rigidity, with a trend observed with agitation and hostility. Though mean pHVA did not change during perphenazine treatment, intraindividual change in pHVA at day 15 was correlated with improvement in hostility, with a similar trend for improvement in agitation. These preliminary findings are consistent with reports associating dopaminergic function with agitated, but not psychotic, symptoms in patients diagnosed with dementia, and with a reduced responsivity of dopaminergic systems to neuroleptic treatment in these patients.
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PMID:Association of plasma homovanillic acid with behavioral symptoms in patients diagnosed with dementia: a preliminary report. 938 53

Previous studies suggest that many untreated schizophrenia patients exhibit motor disturbances. On the basis of these findings, the authors hypothesized that preexisting extrapyramidal movement disorders may increase the risk of developing neuroleptic-induced parkinsonism (NIP). Thirty-five newly medicated psychotic patients underwent pretreatment clinical and instrumental motor and psychiatric assessments. Posttreatment ratings of parkinsonism were conducted at monthly intervals for the first 3 months and every 3 months thereafter. Thirteen patients (37%) developed NIP. Advanced age and pretreatment extrapyramidal disturbances predicted NIP. Life-table survival curves indicated that patients with pretreatment instrumental rigidity developed clinically significant NIP earlier than those without rigidity. These findings suggest that pretreatment motor dysfunction may be a risk factor for drug-induced parkinsonism, especially among older patients.
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PMID:Instrumental motor predictors of neuroleptic-induced parkinsonism in newly medicated schizophrenia patients. 944 97


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