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)

Tardive dyskinesia (TD); abnormal involuntary movements appearing late in neuroleptic treatment) was described shortly after introduction of chlorpromazine and other antipsychotic agents in the 1950s. Consideration of this disorder as a common, progressive, and relentless problem of major public-health and medicolegal concern in the 1970s now appears to have been somewhat exaggerated. Several symptom patterns associated with neuroleptic treatment may or may not appropriately be lumped with the concept of TD (acute and withdrawal-emergent dyskinesias, dystonias, and akathisia, in particular); parkinsonism (with bradykinesia, rigidity, and tremor, including perioral tremor of the "rabbit syndrome") should be differentiated from TD, even though elements of both may occur together. Dyskinesias, more or less similar to TD, can occur in chronically ill neuropsychiatric patients not exposed to neuroleptics. Some may represent stereotyped behaviors of schizophrenia or undiagnosed neurological disorders, but a risk of spontaneous dyskinesias indistinguishable from TD averages about 5% (probably less in young patients). Mean prevalence rates for TD, corrected for spontaneous dyskinesias, average about 15-20% with higher risks at advancing ages. Incidence rates are less certain, but estimates average about 5% a year for at least several years in young patients, with higher rates within the first two years of treatment of elderly patients. Risk factors most clearly defined are advancing age, use of neuroleptic agents at relatively high daily doses for more than six months, and perhaps the diagnosis of a major affective disorder. Female gender and relatively high plasma levels of neuroleptic agents are less significant risk factors and other metabolic or neuroradiological indicators of risk remain unproved. The etiology of TD remains obscure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A summary of current knowledge of tardive dyskinesia. 290 54

In dogs, the influence of chronic administration of the agonist (L-DOPA) and antagonist (haloperidol) of central dopamine processes on functional interrelations of the brain structures was studied by dynamics of evoked potentials. Cortical-subcortical relations during formation of a motor habit are described in intact animals: basic functional regimes of central integration are singled out--sensory and motor one. Change of their equilibrium is the general principle of systemic reconstructions elicited by differently directed interferences in dopamine processes. Against the background of chronic administration of haloperidol, a sensory-motor imbalance is formed due to uniform functioning of the basal ganglia as analyzer of the signal stimulus; simultaneously the utilization of afferentation elicited by the movement is limited. A variant is revealed of intercentral relations corresponding to bradykinesia development. Under chronic administration of L-DOPA, interrelations of sensory and motor regimes become competitive; basal ganglia are provided with nontypical kinds of afferentations. Intercentral relations variant is examined corresponding to development of psycho-motor excitation. The results are discussed in connection with pathogenic and compensatory mechanisms of some symptoms of parkinsonism and schizophrenia.
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PMID:[Principle of reorganizing the functional interrelations of brain structures in action on the dopamine system of dogs]. 343 33

Studies of extrapyramidal motor function in patients with schizophrenia have contributed to our understanding of the phenomenology and therapeutic outcome associated with neuroleptics. An increasing body of literature suggests that extrapyramidal motor abnormalities associated with schizophrenia may be linked to the pathophysiological mechanisms responsible for schizophrenia. Similarly, it has been documented that the extrapyramidal system may be involved in motor abnormalities in patients with Alzheimer's disease (AD). The present study was undertaken to examine motor function in schizophrenia and AD patients with psychosis. Quantitative instrumental procedures were used to examine rigidity, tremor, and bradykinesia in 13 neuroleptic-naive patients with schizophrenia, 13 AD patients with psychosis, and 26 age-comparable controls. Both schizophrenia and AD patients had significantly higher tremor and rigidity scores than did normal subjects. This comparative study of schizophrenia and AD patients with psychosis suggests that the effect of dementia in patients with psychosis is to prolong movement time, whereas abnormal parkinsonian postural tremor tends to be associated with psychosis in the absence of dementia.
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PMID:Extrapyramidal motor abnormalities associated with late-life psychosis. 790 62

The presence of movement disorders was ascertained blind to treatment status in 35 schizophrenic patients. All were on neuroleptics and receiving, or had received earlier during the index episode, adjunctive bilateral electroconvulsive therapy (ECT). None manifested signs of neuroleptic-induced parkinsonism (rigidity, bradykinesia, or abnormal gait). Fine tremor of the hands was noted in two patients, and only one met criteria for probable mild tardive dyskinesia. The implications of these findings for understanding neurological complications associated with schizophrenia and its treatment with ECT are discussed. The hypothesis is proposed that ECT protects against neuroleptic-induced parkinsonism and thereby may reduce the risk for the subsequent development of tardive dyskinesia.
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PMID:Absence of neuroleptic-induced parkinsonism in psychotic patients receiving adjunctive electroconvulsive therapy. 791 62

A major challenge in the clinical assessment of schizophrenia is the differentiation between depressive features, negative symptoms and neuroleptic side effects, including the adverse subjective experiences associated with this medication. The problems include the degree of symptom overlap, and the lack of precise operational definitions, particularly for negative symptoms and the putative, neuroleptic-induced deficit syndrome. The diagnostic process is further confounded by the need to discriminate between primary negative symptoms as persistent, enduring deficits, and social and emotional withdrawal secondary to positive symptoms, or related to depressive features or drug effects such as sedation and the bradykinesia component of parkinsonism. To distinguish between these elements is likely to require careful observation of patients with schizophrenia, over time, by trained raters using appropriate rating scales for depression and negative symptoms that are sensitive to change. Ratings of patients' subjective experiences regarding mood and awareness of behavioural and cognitive deficits should also be included. The associations between the subjective data and the objective ratings of depression, negative symptoms and drug side effects may help with clinical discrimination in these areas of dysfunction and with the refinement of their phenomenological descriptions.
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PMID:How to distinguish between the neuroleptic-induced deficit syndrome, depression and disease-related negative symptoms in schizophrenia. 886 73

Atypical neuroleptics present a unique opportunity to examine confounding by neuroleptic-induced extrapyramidal symptoms (EPS) in the assessment of negative signs of schizophrenia. EPS, such as facial bradykinesia and akinesia, involve some of the same response systems and phenomena as emotional display channels. EPS are attributed to the blockade of dopamine receptors in the striatum by traditional neuroleptics. Newer atypical neuroleptics target primarily mesolimbic and mesocortical areas, and receptors for other transmitters such as serotonin. Olanzapine has been reported as less likely to cause EPS and may improve some negative signs. We investigated the relationship between measures of EPS and negative symptoms in patients with schizophrenia treated with haloperidol or olanzapine. Patients were rated with the Positive and Negative Syndrome Scale (PANSS) and the Simpson-Angus Scale EPS scale. Results show that the two agents have comparable efficacy but different safety outcomes. A positive correlation between EPS and PANSS negative score was detected in the haloperidol group only. Stepwise multiple regression analysis shows that a big proportion of variability in PANSS negative symptoms is predicted by EPS in the haloperidol group, but not in the olanzapine group, even though EPS increased in patients treated with haloperidol but not in olanzapine patients.
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PMID:The relationship between negative symptoms of schizophrenia and extrapyramidal side effects with haloperidol and olanzapine. 956 1

The purpose of this study was to assess the effects of an anticholinergic (trihexyphenidyl) antiparkinsonian medication on the Mini-Mental State Examination (MMSE) and the Cambridge Cognitive Examination (CAMCOG) scores in long-term institutionalized elderly patients with schizophrenia. Seventeen schizophrenic (DSM-III-R) inpatients on long-term medication who had received trihexyphenidyl for at least 6 consecutive months were compared for MMSE scores, CAMCOG scores, and other demographic and clinical variables with 14 patients not receiving any anticholinergic agent for the same time period. Results showed that age, years of education, illness duration, length of current hospital stay, the Manchester Scale scores, and chlorpromazine daily equivalent dose in mg were not different in the two groups compared. Extrapyramidal signs such as tremor, rigidity, and bradykinesia were more frequent in trihexyphenidyl receivers. The scores of MMSE (p < .007) and CAMCOG (p < .005) and CAMCOG subscales of orientation (p < .03), language (p < .01), and memory (p < .002) were significantly lower among trihexyphenidyl receivers, as was the Social and Occupational Functioning Assessment Scale score (p < .05). In addition, the MMSE and CAMCOG scores were significantly lower for patients receiving 10 mg of trihexyphenidyl a day compared with those receiving 5 mg/day and nonusers. It is suggested that trihexyphenidyl in usual clinical doses may impair total MMSE and CAMCOG scores as well as some of the CAMCOG subscales in this patient population. However, only a prospective study, preferably double-blind and controlled, with measures of change will validate this conclusion.
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PMID:Effects of trihexyphenidyl on MMSE and CAMCOG scores of medicated elderly patients with schizophrenia. 962 29

Our experience with atypical antipsychotics in patients with PD is that their motor effects are not predictable. The multiple reports concerning clozapine's beneficial effects on tremor, dystonia, nocturnal akathisia, and dyskinesias all underscore this observation. However, the appearance of even minor degrees of parkinsonism in normal volunteers or schizophrenics should suggest that an antipsychotic will not be well-tolerated in patients with PD. The treatment of PD is probably the most stringent test of a drug's freedom from parkinsonian side effects. The data from trials in schizophrenia concerning parkinsonian effects cannot always be confidently interpreted. Virtually all subjects in these trials have been treated with typical neuroleptics until shortly before study entry. Because the parkinsonian side effects of these drugs may persist for several months, patients may still show declining levels of parkinsonism even when placed on a drug that induces it if this effect is milder than that induced by the pre-study neuroleptic. Depending on the pre-study drug used and the duration of the study, distinguishing placebo from a low-potency neuroleptic may be impossible. Furthermore, the standard measure of parkinsonism in psychiatric studies is the Simpson-Angus scale which is heavily weighted toward rigidity and may underscore bradykinesia, gait, and posture abnormalities. The prolactin response to an antipsychotic drug may turn out to be a good predictor of its freedom from parkinsonian side effects. That would fit with the data presented above of clozapine and quetiapine having less parkinsonian effects, olanzapine having more but variable effects and risperidone being poorly tolerated. With the data presented above, comprising a current review of all reports of the use of atypical antipsychotics in PD that we could locate, we can say little with certainty. The only drug with confirmed benefit without worsening parkinsonism is clozapine. Open-label trials involving over 400 patients and two multicenter, placebo-controlled, double-blind trials have demonstrated that it is effective in treating the psychosis. It improves tremor, does not worsen other motor functions to any significant extent, and is safe at low doses. Limited data provide conflicting information on both risperidone and olanzapine. Quetiapine seems to be well-tolerated with some, but definitely less, worsening of PD motor features than risperidone and olanzapine. Based on the current literature, our personal experience, and anecdotal experience of other PD specialists which we solicited, we will venture our own interpretation and recommendations. We think risperidone is poorly tolerated and should be used only as a last resort; that olanzapine is better than risperidone but will, in a majority of patients with PD, worsen motor function. We are optimistic, but not yet convinced, that quetiapine may prove to be as effective and better tolerated than clozapine. It will not require cumbersome monitoring because it does not induce a blood dyscrasia. We therefore recommend that DP be treated in the following manner. First, the anti-PD medications should be simplified and reduced as much as tolerated. We think, in general, side effects multiply more with increasing numbers of drugs than with drug dose, so that patients are more likely to tolerate a higher dose of levodopa than a lower dose of levodopa combined with other adjunctive anti-PD medications. In reducing anti-PD medications, we recommend tapering and stopping, if necessary, the drugs with the highest risk-to-benefit ratio first. Anticholinergics are stopped first, then selegiline, dopamine agonists, amantadine, and finally COMT inhibitors, which have no psychotomimetic action of their own. Finally, levodopa is reduced. Generally, a point is reached at which the anti-PD medications cannot be reduced without jeopardizing motor function. If psychosis persists at this point, then an antipsychotic is added. (ABS
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PMID:Atypical antipsychotics in the treatment of drug-induced psychosis in Parkinson's disease. 1075 67

Like the striatum, the frontal motor cortices receive dopaminergic fibers from midbrain dopamine cells and contain high levels of dopamine receptors. Among frontal cortical areas, the dorsolateral PFC (PFd1) and the dorsal premotor cortex (PMd) have strong neural connections and play a major role for working memory-guided directional movements. To reveal the role of dopamine in this cognitive motor function, dopamine antagonists (SCH23390 for D1 receptors and sulpiride for D2 receptors) were applied locally or iontophoretically to the PFd1 and PMd in monkeys that performed delayed-response tasks with memory-guided directional movements. Applications of SCH23390, but not sulpiride, to these areas had significant effects at both the behavioral and neuronal levels. In the PFd1 and at the behavioral level, local injections of SCH23390 induced specific errors for memory-guided saccades, whereas it had no effects on visually guided saccades. In the PMd, local injections of SCH23390 induced directional errors and increased reaction time and movement time in memory-guided reaching movements. At the neuron level, iontophoretic applications of SCH23390 attenuated directional tuning of neurons of the PFd1 and PMd, which showed directional activities during the delay-and/or response-period(s). These findings suggest that the activation of D1-dopamine receptors in these frontal cortical areas plays a facilitating role in a series of neuronal processes of working memory-guided directional movements; the working memory process for guiding motor act in the PFd1 and preparation/control of directional manual movements in the PMd. In addition, our findings may provide insight into symptoms of schizophrenia and Parkinson's disease; the dysfunction of D1-dopamine receptors in the PMd1 and PMd may contribute to some symptoms, such as bradyphrenia and bradykinesia, in these disorders.
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PMID:The role of D1-dopamine receptors in working memory-guided movements mediated by frontal cortical areas. 1100 91

It is now known that the blockade of 5-HT2 receptors can ameliorate the negative symptoms of schizophrenia and extrapyramidal side effects (EPS) associated with antipsychotic treatments. Perospirone hydrochloride (perospirone), which was identified as a novel serotonin-dopamine antagonist (SDA)-type antipsychotic agent in 1987 by Sumitomo Pharmaceuticals, possesses high affinities both for dopamine 5-HT2 and D2 receptors. Perospirone, like conventional antipsychotics, significantly inhibited various behaviors induced by dopaminergic hyperactivation. Perospirone also produced a significant improvement in animal models of the negative symptoms and mood disorders, where the conventional antipsychotics were unaffected. In addition, perospirone was weaker than the conventional antipsychotics (e.g., haloperidol) in inducing EPS signs (e.g., catalepsy and bradykinesia), suggesting that the drug has an atypical antipsychotic property. A recent double-blind study with schizophrenia patients demonstrated that perospirone was comparative with haloperidol in improving the positive symptoms, but was significantly superior to haloperidol against the negative symptoms. Furthermore, the extrapyramidal score in patients with perospirone treatment was lower that those with haloperidol treatment. These findings suggested that perospirone acts as an antagonist both for 5-HT2 and D2 receptors and has broader clinical efficacy and lower EPS liability than haloperidol in schizophrenia treatment.
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PMID:[Pharmacological characteristics of perospirone hydrochloride, a novel antipsychotic agent]. 1108 19


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