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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The classification of dopamine receptors and their neuroanatomical distribution is reviewed, including the newly discovered D3, D4 and D5 subtypes. In vivo imaging techniques and methods for quantification are briefly described and PET and SPECT studies of D2 receptors in schizophrenia, under neuroleptic treatment, in aging, Parkinson's disease, Huntington's disease, tardive dyskinesia and multisystem atrophies are reviewed and compared with our own results. A short description is given of imaging studies of D1 receptors.
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PMID:Dopamine receptor classification, neuroanatomical distribution and in vivo imaging. 177 98

Amphetamine (A) (9.2 mg/kg, IP), in combination with iprindole (I) (10.0 mg/kg, IP), caused long-lasting dopamine (DA) depletions in striatum (-49%, 4 weeks) but not in nucleus accumbens following one A/I injection. Striatal DA had recovered by 4 months. DA receptors (DAr) were up-regulated: 1) behavioral responses to a DA receptor agonist (apomorphine) were significantly elevated. These included apomorphine-induced locomotor activity (+103% and +160%, on weeks 3 and 10) and apomorphine-induced stereotypy (day 10). 2) Bmax for [3H]spiroperidol binding to striatal D2 DAr (12 weeks) increased (+53%, week 12). Injection of the DAr neuromodulator cyclo(leucyl-glycyl) (8 mg/kg/day x 4 days, SC) reversed the Bmax increase. Thus toxicity (DA depletion) following high-dose amphetamine appears to induce compensatory changes in DAr. This DAr upregulation may explain the lack of abnormal movements despite enduring DA depletion. Additionally, the A/I paradigm as an animal model of long-lasting DAr up-regulation, could be used to screen neuromodulatory agents, like CLG, that might treat disorders (e.g., tardive dyskinesia and schizophrenia) thought to involve up-regulated DAr.
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PMID:Long-lasting dopamine receptor up-regulation in amphetamine-treated rats following amphetamine neurotoxicity. 181 75

Since the initial observation by Brown (1914) that electrical stimulation applied to the habenular efferent bundle in the chimpanzee evoked a pattern of respiration which closely resembled the act of laughter, the habenular complex has remained a mysterious structure. The anatomy of the habenular complex is well delineated (Jones, 1985) forming a major component of the dorsal diencephalic conduction system. Data derived mainly from animal experimentation over the past decade point to the fact that the habenular complex functions as an important link between the limbic forebrain and the midbrain-extrapyramidal motor system. The elucidation of the functions of the habenular complex may thus significantly increase the current insight into the understanding of the interaction between behavioral and motor functions. Clearly, such information would be of great relevance for further understanding of neuropsychiatric disorders such as schizophrenia, Parkinson's disease, Tardive dyskinesia, and Tourette's syndrome in which behavioral and motor impairments are interfaced. This review summarizes anatomical, functional, and pharmacological aspects of the habenular complex and discusses its potential contribution to the pathophysiology of selected neuropsychiatric and movement disorders.
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PMID:Relevance of the habenular complex to neuropsychiatry: a review and hypothesis. 182 82

Dopamine receptors belong to the family of G protein-coupled receptors. On the basis of the homology between these receptors, three different dopamine receptors (D1, D2, D3) have been cloned. Dopamine receptors are primary targets for drugs used in the treatment of psychomotor disorders such as Parkinson's disease and schizophrenia. In the management of socially withdrawn and treatment-resistant schizophrenics, clozapine is one of the most favoured antipsychotics because it does not cause tardive dyskinesia. Clozapine, however, has dissociation constants for binding to D2 and D3 that are 4 to 30 times the therapeutic free concentration of clozapine in plasma water. This observation suggests the existence of other types of dopamine receptors which are more sensitive to clozapine. Here we report the cloning of a gene that encodes such a receptor (D4). The D4 receptor gene has high homology to the human dopamine D2 and D3 receptor genes. The pharmacological characteristics of this receptor resembles that of the D2 and D3 receptors, but its affinity for clozapine is one order of magnitude higher. Recognition and characterization of this clozapine neuroleptic site may prove useful in the design of new types of drugs.
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PMID:Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. 184 Jun 45

Free radicals are reactive chemical species with an unpaired electron that are produced through a variety of physiologic and pathologic processes. Free radicals have been implicated in a variety of neuropsychiatric conditions, many of which are marked by the gradual development of psychopathologic symptoms and movement disorder. There is evidence that radical-induced damage may be important in Parkinson's disease, tardive dyskinesia, metal intoxication syndromes, and Down's syndrome, and possibly also in schizophrenia, Huntington's disease, and Alzheimer's disease. Although some of this evidence is highly speculative, it may offer an avenue for further understanding and treatment of these conditions.
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PMID:Oxygen radicals and neuropsychiatric illness. Some speculations. 184 28

Investigations aimed at identifying the clinical characteristics that discriminate Tardive dyskinesia (TD) from non-TD patients have yielded disparate findings. A number of studies have suggested that TD may be a feature of negative schizophrenia. In particular, the association of TD with high prevalence of "soft" neurological signs, cognitive deficits, and abnormal brain morphology on CT scan in some patients, have led several investigators to propose that negative schizophrenia may be a risk factor for TD. The neurochemical profile of TD, however, is not consistent with this hypothesis. In the following communication, we present our studies which suggest that TD is specific to and an intergral part of positive schizophrenia. The data suggest that schizophrenic patients with predominant positive symptoms may be at increased risk for the development of TD. In addition, we present evidence linking TD with left cerebral hemispheric dysfunction. By comparison, we provide evidence that negative schizophrenia is related to diencephalic damage, and discuss its relevance to negative schizophrenia and to Parkinsonism. We also provide evidence that negative schizophrenia may be a risk factor for acute drug-induced dystonia. Thus, these findings are consistent with our model that negative schizophrenia is a risk factor for Parkinsonism, whereas positive schizophrenia is related to TD. In analogy with the positive/negative dichotomy of schizophrenia, we propose that TD could be considered a "positive," where Parkinsonism a "negative" movement disorder.
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PMID:The relationship of tardive dyskinesia to positive schizophrenia. 193 27

Oxygen free radicals, any chemical moiety containing an oxygen atom with an unpaired electron in the outer orbital shell, are generated during many normal biochemical reactions in living tissue. The unpaired electron makes these compounds highly reactive and they can initiate disruptive peroxidation reactions with various substrates important to the survival of cells such as proteins, lipids and nucleic acids. A fairly complex defense system has evolved to protect living tissue from free radicals and to minimize the damage they might cause. Neurons are especially vulnerable to free radical attack and impaired defenses or exposure to excess free radicals can lead to neuronal death. Free radicals contribute to neuronal loss in cerebral ischemia and hemorrhage and may be involved in the degeneration of neurons in epilepsy, schizophrenia, tardive dyskinesia, normal aging, Parkinson's Disease and Alzheimer's Disease. The development of drugs that limit or prevent the attack of free radicals on neurons would be an important advance in the treatment of these conditions.
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PMID:Oxygen free radicals and brain dysfunction. 134 20

Computed tomographic (CT) studies have demonstrated structural brain abnormalities including cortical atrophy and enlarged lateral ventricles in a subset of schizophrenic patients including those with abnormal involuntary movements. In the following series of studies, we present our findings pertaining to neuroradiological covariates of drug-induced Parkinsonism and Tardive dyskinesia in schizophrenic patients. In these studies we have explored the relationship of Parkinsonism and Tardive dyskinesia to pineal and choroid plexus calcification. In addition, we also investigated the relationship of pineal calcification to schizophrenia, and specifically to the paranoid and nonparanoid subgroups. In a further series of studies, we investigated the neuroradiological covariates of disorders of gait and posture as well as tremor in schizophrenic patients with drug-induced Parkinsonism. In addition, we explored the relationship of Tardive dyskinesia and its subsyndromes to CT scan measurements of cortical and subcortical atrophy in schizophrenia. Our findings highlight the significance of the pineal gland in the pathophysiology of schizophrenia and drug-induced movement disorders. Furthermore, these studies underscore the heterogeneity of Parkinsonism and Tardive dyskinesia.
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PMID:Neuroradiological covariates of drug-induced parkinsonism and tardive dyskinesia in schizophrenia. 193 76

The use of high doses of neuroleptics (NL) in treatment of chronic psychosis is a controversial subject in the literature. In this context, it is surprising to note the lack of objective data about the prevalence and the consequences concerning this mode of prescription when treating people suffering from severe mental disorders. This study describes the clientele exposed to high doses of NL from an outpatient clinic of a psychiatric hospital. The equivalent of 18 mg or more of haloperidol per day was used as the high dose criterion. Overall, we observed the use of NL in all diagnostic categories and the frequent use of polypharmacy in patients treated with NL. Among the 435 patients receiving NL, 26.4% had high dose prescriptions (two men for every woman). Most of these high dose NL subjects had a diagnosis of schizophrenic disorder (87.9%). Fifty-one of them had been receiving high doses for six months or more and 39 of them agreed to meet our research team. The mean age of these subjects was 37.2 years and the mean dose was 63.5 mg haloperidol equivalent/day. Thirty-five subjects were diagnosed as chronic schizophrenic disorder and four as schizo-affective disorder. Nineteen patients had tardive dyskinesia. In two out of three cases the high dose prescription began during hospitalization and the main reason was presence of severe psychotic symptoms. Significant positive correlations were found between parkinsonian symptoms and negative symptoms of schizophrenia as well as psychosocial dysfunctions on 39 subjects. These findings support the hypothesis that the use of high doses of NL contribute to the negative symptoms and the psychosocial dysfunctions. The implications of these findings relating to assessment and treatment of schizophrenic outpatients are discussed.
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PMID:[Who are the patients treated in an outpatient clinic with high dosage neuroleptics?]. 196 23

The study of eye movement dysfunction in chronic schizophrenics by electronystagmography revealed a significant increase of saccadic dysmetria as well as saccadic intrusions in smooth pursuit in schizophrenic patients with tardive dyskinesia (TD) compared with those without TD and with healthy controls. The pattern of eye movement dysfunction in schizophrenia allows clear discrimination from patients with similar movement disorders due to Huntington's disease. Of several possible explanation's of the schizophrenic eye movement dysfunction the authors favour the hypothesis of a common pathogenetic link between TD and eye movement disorders in schizophrenia, consisting in an underlying dysfunction of regions involved in the regulation of involuntary attention such as the parietal cortex and striatolimbic structures of the right hemisphere. Recent literature supports the assumption of right hemispheric dysfunction in schizophrenia.
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PMID:Association of tardive dyskinesia with increased frequency of eye movement disturbances in chronic schizophrenic patients. A clinical note. 196 45


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