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

Dopamine receptors are classified into D1 and D2 subtypes on the basis of their pharmacological and biochemical characteristics. The D2 dopamine receptor has been implicated in the pathophysiology and treatment of movement disorders, schizophrenia and drug addiction. The D2 dopamine receptor interacts with guanine nucleotide-binding proteins to induce second messenger systems. Other members of the family of receptors that are coupled to G proteins share a significant similarity in primary amino-acid sequence and exhibit an archetypical topology predicted to consist of seven putative transmembrane domains. We have taken advantage of the expected nucleotide sequence similarities among members of this gene family to isolate genes coding for new receptors. Using the hamster beta 2-adrenergic receptor gene as a hybridization probe we have isolated related genes including a cDNA encoding the rat D2 dopamine receptor. This receptor has been characterized on the basis of three criteria: the deduced amino-acid sequence which reveals that it is a member of the family of G-protein-coupled receptors; the tissue distribution of the mRNA which parallels that of the D2 dopamine receptor; and the pharmacological profile of mouse fibroblast cells transfected with the cDNA.
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PMID:Cloning and expression of a rat D2 dopamine receptor cDNA. 253 46

The question of whether schizophrenia is associated with structural or functional abnormalities of the nervous system, or both, has become the principal focus of biological studies of schizophrenia. Computed tomography studies have revealed ventricular enlargement and cortical atrophy in a subgroup of schizophrenic patients. While present from the early stages of the illness, they appear to be most severe in patients with negative symptoms and poor outcome. Quantitative neuropathological studies have tentatively demonstrated decreased volume of specific brain areas, neuronal loss, and other changes in the limbic system, basal ganglia, and frontal cortex. Dopamine (DA) remains the neurotransmitter most likely to be involved in schizophrenia, although there is also evidence for disturbances of serotonin and norepinephrine. Post-mortem and positron emission tomographic studies suggest an increased number of D2 DA receptors in some schizophrenics. Neuroendocrine studies reinforce the role of DA in schizophrenics. Viral infections and autoimmune disturbances may be responsible for some types of schizophrenia, but there is no firm experimental evidence to support either hypothesis. The possibility that mixtures of structural abnormalities and functional changes involving DA occur in the same patients rather than independently as part of two syndromes (Type I, II) seems attractive. Future studies should identify subtypes of schizophrenia based on biological criteria and contribute to identification of specific genetic abnormalities which increase vulnerability to manifest the schizophrenic phenotype.
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PMID:Biological studies in schizophrenia. 360 40

The dopamine hypothesis of schizophrenia claims that increased dopamine activity underlies psychotic behavior. This hypothesis gets major support from the reported d-amphetamine-induced worsening of psychosis, because amphetamine increases dopamine activity in the brain. Dopamine receptor supersensitivity has been shown to be present in animals during the postneuroleptic period. In this study the postulated relationships between psychotic decompensation as observed after d-amphetamine infusion and the dopamine receptor supersensitivity expected to be present during the neuroleptic withdrawal period were examined. Twenty milligrams of d-amphetamine administered intravenously did not cause a stronger psychotogenic effect in 12 schizophrenic patients. One week after discontinuation of pimozide treatment, the d-amphetamine-induced change as indicated by the Brief Psychiatric Rating Scale (BPRS) paranoid disturbance cluster score, was not significantly different from the response to a similar infusion during the drug-free state. Unexpectedly, the increase in the BPRS mannerisms and posturing item and in the pulse rate response to d-amphetamine were decreased. These results raise questions about the role of dopamine in d-amphetamine effects and suggest postneuroleptic dopamine receptor subsensitivity. They challenge a simple dopamine hypothesis of schizophrenia.
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PMID:Lack of behavioral supersensitivity to d-amphetamine after pimozide withdrawal. A trial with schizophrenic patients. 610 56

The dopamine hypothesis of schizophrenia is examined critically. Although the hypothesis is couched in chemical terms, the evidence is primarily pharmacologic. In addition, neuroleptic mechanisms do not fit a simple hyperdopaminergic formulation, and treatment efficacy points to a general psychotic rather than specific schizophrenic role for dopamine. Most compromising to the hypothesis is the therapeutic action of L-dopa when combined with neuroleptics in chronic schizophrenics. Dopamine appears important but cannot be viewed as a simple pathogen.
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PMID:An un-dopamine hypothesis of schizophrenia. 610 5

Schizophrenia shares several genetic features with diseases known to be autoimmune and could therefore be an autoimmune disease itself. Antipsychotic drugs, which are effective in treating the psychotic symptoms of schizophrenia, have one property in common--they block dopamine receptors in the central nervous system. This observation has led to the hypothesis that overactivity of dopaminergic pathways is the cause of the psychotic symptoms, but a seeming anomaly is that the turnover of dopamine is not increased in schizophrenia. Dopamine-receptor-stimulating autoantibodies are postulated to cause the dopaminergic hyperactivity, thereby accounting for the anomaly.
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PMID:Dopamine-receptor-stimulating autoantibodies: a possible cause of schizophrenia. 612 47

The diagnostic criteria for schizophrenia have been extensively changed by the third edition of the Diagnostic and Statistical Manual of Mental Disorders, recently adopted by the American Psychiatric Association (DSM III). To receive this diagnosis, the patient must have onset of illness before age 45 years, have had a chronic course, manifest the presence of characteristic symptoms, such as delusions, hallucinations, or loose associations during a phase of the illness, and have experienced a downhill social and vocational course; affective disorders and organic brain syndrome must be carefully excluded. The utilization of this "narrow" definition has caused a major shift toward increasing the diagnosis of affective disorders and decreasing the diagnosis of schizophrenia in the United States. The etiology of schizophrenia is still uncertain, but recent research has elucidated one subgroup of schizophrenic patients who have subtle indices of neurological damage and a clinical course similar to that found in dementia. Dopamine excess in the mesolimbic system is the predominant inferred cause for the majority of schizophrenia cases, and antipsychotic medications all rely on dopamine receptor blockade for their efficacy. Antipsychotic medications are effective in schizophrenia but are less potent against such negative symptoms as apathy, neglect of personal hygiene, and social withdrawal.
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PMID:Schizophrenia. 613 80

Studies on the treatments for neuroleptic-induced tardive dyskinesia published in the literature are reviewed. The great number of different treatments and the controversial results of most studies show that there is as yet no specific and safe treatment for tardive dyskinesia. Suggestions for well-designed treatment studies are given: Placebo-controlled double-blind design, larger patient populations, clear diagnostic and standard observing and rating conditions using different assessment methods and videotapes, withdrawal of neuroleptics and antiparkinsonian drugs to discover reversible tardive dyskinesia. If this procedure is not feasible, neuroleptics and other drugs should be maintained at a stable dose level. Longer term studies of some months are necessary to study the prolonged efficacy of different drugs. The effect of dopamine-antagonists such as neuroleptics and of dopamine-depleting agents such as reserpine and oxypertine is of limited duration. Dopamine-agonists such as L-Dopa, bromocriptine and amantadine help only few patients and may even aggravate the symptoms of tardive dyskinesia. In some double-blind studies cholinergic drugs such as lecithin and deanol have improved tardive dyskinesia, but further controlled studies are needed. Anticholinergic drugs such as antiparkinsonian agents should not be prescribed because they may aggravate tardive dyskinesia. Some patients respond to GABA-ergic agents such as baclofen, sodium valproate and the benzodiazepines, but further studies are needed before the value of GABA-ergic agents in the treatment of tardive dyskinesia can be properly assessed. After withdrawal of neuroleptics the average of remission rates within a year is 20%-30%. Elderly patients are more likely to have persistent dyskinesias. A progressive stepwise diminution of the neuroleptic dose and of the antiparkinsonian agents is recommended. When a patient's psychosis is exacerbated after withdrawal of the neuroleptics and tardive dyskinesia is also present, small doses of thioridazine, clozapine or tiapride can be administered. If this practice is not successful cholinergic or GABA-ergic agents may be useful. Because no currently available therapeutic agents satisfies the criteria of safety, marked effectiveness and prolonged efficacy in the treatment of tardive dyskinesia, prevention becomes more important. Prolonged use of a neuroleptic medication requires careful evaluation of indications and risks. The doses of neuroleptic drugs during the maintenance treatment of schizophrenia should be as small as possible.
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PMID:[Therapeutic measures in tardive dyskinesia]. 613 57

The neurotransmitter dopamine has biological attributes that make it amenable to study by positron emission tomography, unlike many of the 40 or so neurotransmitters that have been identified in the brain. Dopamine deficiency in the nigrostriatal system is a characteristic of Parkinson's disease, and a disturbance of dopamine metabolism is still widely held to be responsible for the syndrome of schizophrenia. Despite its importance in the regulation of locomotion and mood, it has been impossible to visualize the intracerebral distribution of dopamine and measure its regional metabolism in man. In the first demonstration of the regional distribution of a neurotransmitter in the brain of conscious normal man, we show here that L-3,4-dihydroxyphenylalanine (L-dopa) labelled in the 6-position with the positron-emitting radionuclide fluorine-18, localizes specifically in the dopaminergic pathways of the human brain where its turnover could be measured atraumatically by positron emission tomography.
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PMID:Dopamine visualized in the basal ganglia of living man. 660 27

The dopamine hypothesis of schizophrenia is usually presented in a static, rather than dynamic fashion. We propose that increased dopaminergic activity may represent a stage of a dynamic schizophrenic process rather than its cause. Dopamine, as well as other neurotransmitters, responds in an adaptive fashion to stimuli that perturb the homeostasis of the brain. One such stimulus could be an epileptic focus in the temporal lobe. Other such stimuli undoubtedly also exist.
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PMID:Variability and the dopamine hypothesis of schizophrenia. 662 90

Receptor binding studies with a variety of dopaminergic ligands have confirmed behavioral and biochemical findings that the central nervous system and peripheral nervous system contain several dopamine receptor subtypes. These subtypes can be discriminated on the basis of their agonist-antagonist pharmacological specificities, linkage to adenylate cyclase, cellular location, regulation by guanine neucleotides and ions, and involvement in several human diseases. Although questions remain unanswered, progress is rapidly being made in equating the subgroupings arrived at by these different experimental approaches. Dopamine receptors are regulated by a number of factors. Acutely, guanine nucleotides and some ions regulate agonist but not antagonist binding and are essential for receptor coupling with adenylate cyclase. Chronically, changes in the level of dopaminergic stimulation modulate the number of at least some receptor subtypes, resulting in "up or down regulation." An increase in receptor number appears central to the pathology of Parkinson's disease, tardive dyskinesia, and perhaps schizophrenia. Animal models indicate that it may be possible to exploit inherent capabilities for receptor modulation in clinical therapy. The therapeutic precedents set by the indentification of distinct subtypes of adrenoreceptors. histamine, and cholinergic receptors portends and exciting future for dopamine receptor research.
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PMID:Dopamine receptors: subtypes, localization and regulation. 700 83


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