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 relationship between antipsychotic drugs and dyskinesias and other extrapyramidal symptoms (EPS) in schizophrenia is not simple. There is a need to study variables that may influence the occurrence of EPS in schizophrenic patients receiving drugs. The present study examined the relationship of age at onset of illness and treatment to the development of EPS in 122 middle-aged and elderly schizophrenic patients, 84 treated and 38 who had never received antipsychotic drugs. The illness had an early onset (before 45years, EOS) in 68 patients and a late onset (after 45years, LOS) in 54 patients. The patients were evaluated for dyskinesia and parkinsonism using abnormal involuntary movements scale (AIMS) and Simpson-Angus scale. The prevalence of dyskinesia and parkinsonism was similar in all the patient groups. The scores on limb-axial and severity subscales of AIMS were significantly higher in the treated than the untreated patients of the early onset group. This was not so with the late onset patients. The total parkinsonism score was higher among the treated, notably the LOS patients. The development of dyskinesia and parkinsonism in schizophrenia is possibly related to the age at onset of the illness. In late onset forms the ageing of the patient and a possible neurological abnormality related to schizophrenia might enhance the EPS-inducing effect of drugs.
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PMID:Relationship of extrapyramidal symptoms to age at onset and drug treatment in middle-aged and elderly schizophrenic patients. 1116 46

Convulsive therapy was introduced to psychiatric practice in 1934. It was widely hailed as an effective treatment for schizophrenia and quickly recognized as equally effective for the affective disorders. Like other somatic treatments, it was replaced by psychotropic drugs introduced in the 1950s and 1960s. But two decades later, ECT was recalled to treat pharmacotherapy-resistant cases. Avid searches to optimize seizure induction and treatment courses, to reduce risks and fears, to broaden the indications for its use, and to understand its mechanism of action followed. Unlike other medical treatments, however, these searches were severely impeded by a vigorous antipsychiatry movement among the public and within the profession. ECT is effective in the treatment of patients with major depression, delusional depression, bipolar disorder, schizophrenia, catatonia, neuroleptic malignant syndrome, and parkinsonism, and this breadth of action is both remarkable and unique. ECT is a safe treatment. No age or systemic condition bars its use. Its major limitations are the high relapse rates and the occasional profound effects on memory and recall that mar its success. Experiments to sustain its benefits with medications and with continuation ECT are underway. Its mode of action remains a mystery and this puzzle is an unappreciated challenge. The full impact of this intervention is yet to be felt.
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PMID:Convulsive therapy: a review of the first 55 years. 1124 75

Antipsychotic drugs are the most effective treatment for psychotic disorders such as schizophrenia. However, they are known to cause a range of side-effects including acute extrapyramidal symptoms (EPS) that are both distressing and disabling. Mental health nurses play a critical role in both the detection and the management of these symptoms. A review of the literature was conducted to identify strategies for managing acute EPS. Despite a widely held belief that EPS are associated with noncompliance with medication, the data to support this hypothesis are weak. Although akathisia may negatively affect the treatment outcome, there was little evidence to suggest that parkinsonism or dystonia do. Whilst the use of anticholinergic medication may be helpful in treating acute parkinsonism and dystonia they were associated with their own side-effects and the benefit of long-term prophylactic treatment is doubtful. The literature suggests that logical prescribing and rapid detection and management of acute EPS will result in a substantial reduction in the incidence of these disabling side-effects.
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PMID:What can we do about acute extrapyramidal symptoms? 1196 93

Negative symptoms in schizophrenia represent a diagnostic and therapeutic challenge. Diagnostically, they need to be differentiated from depression and treatment-related variables. The latter include akinesia, a part of drug-induced Parkinsonism, sedation, and effects of understimulation, as they have been reported in patients institutionalised for long periods of time. Other patients show negative symptoms as sequelae of positive symptoms: Commanding voices that tell patients to stay in the house or forbid them to speak to other people, or persecutory delusions may result in social withdrawal and alogia. All of the above, often summarised as secondary negative symptoms, have to be distinguished from primary negative symptoms, sometimes also referred to as the deficit state of schizophrenia. These are considered illness inherent problems and usually have an enduring, chronic course. They are often seen in the absence of positive symptoms, as in simple schizophrenia. The chronicity of the disorder, the lack of obviously disturbed and aberrant behavior and the fact that these patients tend to lead secluded lives lead to an underrepresentation of these patients in clinical psychiatry. Next to a description of clinical symptoms a review of means to aid differential diagnosis is provided. Negative symptoms call for sound differential diagnosis provided by a specialist in order to be able to provide optimal management to prevent the negative consequences of a chronic negative syndrome.
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PMID:Negative symptoms in patients with schizophrenia with special reference to the primary versus secondary distinction. 1129 57

We have created a transgenic mouse with a hypomorphic allele of the vesicular monoamine transporter 2 (Vmat2) gene by gene targeting. These mice (KA1) have profound changes in monoamine metabolism and function and survive into adulthood. Specifically, these animals express very low levels of VMAT2, an endogenous protein which sequesters monoamines intracellularly into vesicles, a process that, in addition to being important in normal transmission, may also act to keep intracellular levels of the monoamine neurotransmitters below potentially toxic thresholds. Homozygous mice show large reductions in brain tissue monoamines, motor impairments, enhanced sensitivity to dopamine agonism, and changes in the chemical neuroanatomy of the striatum that are consistent with alterations in the balance of the striatonigral (direct) and striatopallidal (indirect) pathways. The VMAT2-deficient KA1 mice are also more vulnerable to the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in terms of nigral dopamine cell death. We suggest that the mice may be of value in examining, long term, the insidious damaging consequences of abnormal intracellular handling of monoamines. On the basis of our current findings, the mice are likely to prove of immediate interest to aspects of the symptomatology of parkinsonism. They may also, however, be of use in probing other aspects of monoaminergic function and dysfunction in the brain, the latter making important contributions to the pathogenesis of schizophrenia and addiction.
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PMID:Mice with very low expression of the vesicular monoamine transporter 2 gene survive into adulthood: potential mouse model for parkinsonism. 1146 16

Dopamine projections from the midbrain to the striatum and frontal cortex are involved in behavioral reactions controlled by rewards, as inferred from deficits in parkinsonism, schizophrenia, and drug addiction. Recent experiments have shown that dopamine neurons are not directly modulated in relation to movements. Rather, they appear to code the rewarding aspects of environmental stimuli. They show short, phasic increases of activity following primary food and liquid rewards ("unconditioned stimuli") and conditioned, reward-predicting stimuli of visual, auditory, and somatosensory modalities. They also display smaller activation-depression sequences after stimuli resembling rewards and after novel or particularly intense stimuli. Rewards are only reported as far as they occur differently than predicted. According to learning theories, a "prediction error" message may constitute a powerful teaching signal for behavior and learning. The phasic reward message is different from the more tonic enabling function of dopamine that is deficient in Parkinson's disease, indicating that dopamine neurons subserve different functions at different time scales. Neurons in other brain structures, such as the striatum, orbitofrontal cortex, and amygdala, code the quality, quantity, and preference of rewards. The dopamine reward prediction error signal may cooperate with these reward perception signals during the learning and performance of behavioral reactions to motivating environmental stimuli.
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PMID:Reward signaling by dopamine neurons. 1148 95

Open study was performed concerning the efficiency of cerebrolysin in treatment of tardive dyskinesia and parkinsonism. 30 patients of middle (18-41 years) and old (60-82 years) age were examined by means of Extrapyramidal Symptom Rating Scale and Abnormal Involuntary Movement Scale. Cerebrolysin was administered intravenously by drops every other day in a dose of 5-10 ml during 28 days. Significant decrease of the severity of extrapyramidal symptoms (according to the Scales used) was observed by the end of the course of therapy. The number of the responders was 46.6%, of the partial responders--26.6%. Efficiency of cerebrolysin was the same both in the groups of patients with drug-induced parkinsonism (number of the responders--54.5%) and in patients with tardive dyskinesia (the responders' number--60%). The efficiency of cerebrolysin was lower in patients with combination of symptoms of parkinsonism and tardive dyskinesia as well as in ones with pronounced negative schizophrenic disorders in clinical picture. Efficacy of cerebrolysin was also the same in patients of both middle and old age. Its efficiency was equally high independently on the duration of extrapyramidal disorders' existence.
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PMID:[Use of cerebrolysin in the treatment of prolonged extrapyramidal complications of neuroleptic therapy]. 1151 74

N-Acetyl-aspartate (NAA), a marker of neuronal integrity, has been found to be reduced in frontal regions in schizophrenia. However, the impact of antipsychotic drug type on NAA has not been carefully evaluated. We studied outpatients with schizophrenia/schizoaffective disorders chronically treated with haloperidol or clozapine and normal controls with single-voxel 1H-MRS of the caudate nuclei and the left frontal lobe. Concentrations of NAA, choline containing compounds (Cho) and creatine plus phosphocreatine (Cre) were determined and corrected for the proportion of cerebrospinal fluid (CSF) in each voxel. The haloperidol-treated group had significantly lower CSF-uncorrected and CSF-corrected left frontal NAA than the normal controls, with the clozapine group having intermediate concentrations. The haloperidol-treated group had significantly lower CSF-uncorrected caudate NAA than the normal controls, but the three groups did not differ after correcting for CSF fraction. Performance times in the Grooved Pegboard, a measure of motor dexterity and proxy for parkinsonism, were correlated with CSF-uncorrected and CSF-corrected left frontal NAA. Demographic and illness-related variables were not related to NAA. Exposure to haloperidol-like drugs may in part account for the frontal NAA reductions previously reported in schizophrenia. Adjustment for proportion of voxel CSF should be considered in 1H-MRS studies.
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PMID:Effects of chronic haloperidol and clozapine treatments on frontal and caudate neurochemistry in schizophrenia. 1156 30

Both antidepressants and neuroleptics are widely used in psychopharmacological treatment. In view of the often equal efficacy of substances belonging to the same class of drugs, potential side effects have become the most important criteria for the selection of a specific drug. The therapeutic effect of antidepressants is mediated by their inhibition of the reuptake of the neurotransmitters noradrenaline and of serotonin. Significant adverse effects may occur through the interaction of the antidepressants with other receptors believed not to be related to the therapeutic action, most importantly the muscarinic acetylcholine receptor (M), the histamine-1 (H1) receptor and the alpha-1 (alpha 1) adrenergic receptor. In contrast to the classical tricyclic antidepressants, the newly available selective serotonin reuptake inhibitors neither block the M1-, H1- nor the alpha 1 receptors. Although the rate of side effects is considerably lower compared to tricyclic antidepressants, adverse effects may, however, occur through the stimulation of different serotonin receptor subtypes (5-HT2A, 5-HT2B, and 5-HT3), leading to anxiety, sleep disturbances and nausea. Neuroleptics are often administered for years or even decades in the treatment of schizophrenia or schizoaffective disorder. The main adverse effects are extrapyramidal symptoms, including parkinsonism, akathisia, dystonic reactions, and tardive dyskinesias. With the introduction of the atypical neuroleptics (e.g. clozapine, risperidone, olanzapine) it became apparent that the antipsychotic effect and the extrapyramidal unwanted effect are not always and inextricably linked. The evidence for the hypotheses of the pathogenetic mechanisms leading to extrapyramidal side effects is reviewed. Both the dopamine receptor hypersensitivity hypothesis and the hypothesis of mitochondrial respiratory chain inhibition are as yet based on indirect evidence. However, if, as suggested by the analyses of mitochondrial energy metabolism, the antipsychotic effect and the adverse effects are unrelated properties of neuroleptics, new principles should be applied in the development of novel neuroleptics. Neuroleptics might then be developed that are effectively antipsychotic but are less likely to produce limiting extrapyramidal side effects.
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PMID:Cell-mediated side effects of psychopharmacological treatment. 1171 30

The purpose of this study was to investigate the efficacy of cyproheptadine, an antiserotonergic agent, in the treatment of neuroleptic-induced akathisia (NIA), as compared with propranolol, the current gold standard. In a double-blind trial, 30 patients with schizophrenia and NIA received either cyproheptadine 16 mg/day (N = 18) or propranolol 80 mg/day (N = 12) for 4 days, followed by 3 days without any anti-NIA treatment. The Barnes Akahisia Scale, Simpson-Angus Extrapyramidal Effects Rating Scale, and Brief Psychiatric Rating Scale were used to assess the severity of NIA, parkinsonism, and psychosis, respectively. In both groups, the severity of NIA decreased significantly over time (cyproheptadine, -46%; propranolol, -42%), with no significant intergroup difference. The NIA symptoms worsened significantly when cyproheptadine and propranolol were discontinued. We conclude that cyproheptadine 16 mg/day is as effective as propranolol for the treatment of acute NIA. The antiakathisic effect of cyproheptadine may be mostly attributable to its serotonin antagonistic activity.
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PMID:Cyproheptadine versus propranolol for the treatment of acute neuroleptic-induced akathisia: a comparative double-blind study. 1176 11


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