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)

Numerous homeostatic mechanisms regulate impulse traffic in the neural pathways of the brain. If, for whatever reason, these mechanisms are unable to maintain neural activity within normal levels, the resulting disruption of the balance of impulse traffic produces brain dysfunction such as mental or neurological disorders. Drug treatment of these disorders involves the use of agents that return impulse traffic to homeostatic levels. Such agents have been found only for certain disorders such as Parkinson's Disease, certain affective disorders and some aspects of schizophrenia. The development of therapeutic interventions for currently untreatable conditions such as Huntington's Chorea or Alzheimer's Disease and the design of drugs for the more efficient treatment of psychiatric disorders, would be greatly facilitated by more detailed knowledge of the specific homeostatic mechanisms controlling brain function.
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PMID:Neurochemical psychiatry as a source of hypotheses concerning the role of homeostatic mechanisms in brain function. 615 Sep 4

In Huntington's disease, there is a decrease of the neuropeptides, substance P, enkephalins, and cholecystokinin in the striatonigral system, whereas in Parkinson's disease an increase of substance P is found in the substantia nigra. Several neuropeptides should be involved in Alzheimer's disease: substance P, endorphins, vasopressin, ACTH, somatostatin, vasoactive intestinal peptide, cholecystokinin, neurotensin, delta sleep-inducing peptide. Alterations of substance P, vasoactive intestinal peptide, cholecystokinin, somatostatin, and endorphins may be related to the pathophysiology of schizophrenia. Delta sleep-inducing peptide may interfere in addiction pathology.
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PMID:Putative peptide neurotransmitters in human neuropathology: a review of topography and clinical implications. 618 57

We studied, in a "blind" and quantitative fashion, the density of cerebellar Purkinje cells in 17 adult cases of Huntington's disease (HD), 17 patients with other movement disorders, 17 with schizophrenia, and 23 normal controls. There was a highly significant reduction in Purkinje cell density in HD compared with any of the other three groups. A much smaller difference in neuronal density between patients with other movement disorders and normal controls was barely significant. Eight of the 17 HD patients and only 1 of the other 57 subjects had Purkinje cell density less than 50% of the mean for the normal controls. The low density of Purkinje cells in HD could not be attributed to aging, seizures, or cause of death, nor was it merely a part of a generalized brain atrophy. The loss of large Purkinje cells suggests that the neuronal loss in HD may not be restricted to small and medium-size neurons.
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PMID:Reduced Purkinje cell density in Huntington's disease. 620 75

GABA-ergic systems are involved in all the main functions of the brain. In most brain regions impairment of this system produces epileptic activity. GABA-mediated inhibitory function can be enhanced by drugs of at least seven different types. They act on the metabolism or synaptic release of GABA, or its reuptake into neurones of glia, or on various components of the GABA receptor complex (GABA recognition site, "benzodiazepine" receptor or chloride ionophore). Among such compounds, those which act most specifically and potently on GABA receptors remain primarily research tools. Among compounds in clinical use, valproate, benzodiazepines, and anticonvulsant barbiturates al enhance GABA-mediated inhibition. In the future, new inhibitors of GABA uptake, new GABA agonists and potent inhibitors of GABA-transaminase are likely to become available. Trials of drugs enhancing GABA-ergic function have been made in a wide variety of neurological disorders. In most forms of epilepsy a therapeutic effect is evident. Real benefit from GABA therapies has not been demonstrated in the principal disorders of movement (Huntington's chorea, Parkinson's disease, dystonias), except in so far as they have a myoclonic or paroxysmal component. Among psychiatric disorders the acute symptoms of schizophrenia are exacerbated by enhanced GABA-ergic function. Abstinence syndromes (alcohol, barbiturate or narcotic withdrawal) are ameliorated by drugs enhancing GABA-ergic function, and there is some evidence for a beneficial action in anxiety states and mania. Attempts to relate the molecular neurobiology of GABA with clinical pharmacology are of very recent origin. Improved understanding of the variety of GABA receptor mechanisms will provide the key to the more selective pharmacological manipulations that are required for therapeutic success.
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PMID:Pharmacology of GABA. 621 5

Preclinical data suggest that cholinergic precursors such as choline or lecithin, increase levels of acetylcholine in specific brain structures, and under certain conditions may enhance cholinergic neurotransmission. A variety of neuropsychiatric diseases including tardive dyskinesia. Huntington's chorea, ataxias, Tourette's syndrome, schizophrenia, affective illness, and senile dementia of the Alzheimer type, has been implicated with a general underactivity of central cholinergic mechanisms. Recent studies have investigated the possibility that cholinergic precursor loading strategies may provide viable treatments for these disorders of presumed cholinergic underactivity. Extensive data demonstrate that the symptoms of tardive dyskinesia can be reduced by choline or lecithin, whereas investigations in other disorders have met with mild success, at best, or are still in preliminary stages. Further controlled studies with choline or lecithin using broader dose ranges, longer durations of treatment, and concomitant administration of agents which may increase the release of acetylcholine are warranted.
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PMID:The use of cholinergic precursors in neuropsychiatric diseases. 621 43

1. Introduction of radioligand binding techniques has opened new possibilities in the study of the biological basis of psychiatric disorders. 2. The possible role of CNS receptors in schizophrenia, depression, anxiety, Huntington's disease and Alzheimer's dementia is discussed. 3. Data are presented in a systematic manner starting with the identification of receptors which appear to be the primary locus of action of drugs currently used in the treatment of these disorders. 4. A review of the data on the changes in receptor levels and/or affinity that might be associated with the respective disease follows. 5. Changes in receptor number and/or affinity after chronic drug therapy are outlined and the possible utilization of radioligand binding techniques in drug plasma level determination is discussed.
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PMID:Central nervous system receptors in neuropsychiatric disorders. 621 1

Using Huntington disease, mental retardation, and schizophrenia, it has been shown that two individuals with identical genotypes or phenotypes have different fitnesses because of affected nuclear family members. Such fitness interaction seems to occur because of cultural and social reactions due to the presence of affected individuals, and the interaction has been termed "social selection." Without assuming any specific genetic control for the social behavior, we can study the effect of social behavior on the incidence of a genetic disease.
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PMID:Theories of social selection in human populations. 622 46

In experiments designed to investigate transmission, cerebrospinal fluid (CSF) from patients with schizophrenia and neurological disease (huntington's chorea and multiple sclerosis) which had been found to induce cytopathic effects in human embryonic fibroblast cell culture was injected intracerebrally into mice, hamsters and marmosets (small New World primates). No evidence was obtained of transmission to mice or hamsters. A total of 15 marmosets (Callithrix jacchus) was injected intracerebrally with CSF [8 with samples from 4 patients with schizophrenia. 3 with samples from patients with neurological disease (2 with Huntington's chorea and 1 with multiple sclerosis) and 4 with samples from 3 patients without neurological or psychiatric disease] and was observed over a period of 2 1/2 years. Analysis of variance on data obtained from behavioral observations averaged over 6-month periods revealed that animals injected with CSF from patients with schizophrenia and neurological disease became progressively more inactive when compared with animals injected with CSF from control patients. The change detected by behavioural observation was confirmed as a difference 2 and 2 1/2 years after injection by automated activity monitoring. There was an incidence of reproductive anomalies (including two occipital encephalocoeles) in the females in the experimental group, but the numbers are too small to draw firm conclusions from this observation. Many reported differences in biological samples from schizophrenic patients and normal controls have subsequently been found to be due to factors unrelated to the disease state. This may prove to be the case with the changes observed in this experiment. Nevertheless, the fact that marmosets injected with CSF from patients suffering from neuropsychiatric disease, including schizophrenia, subsequently differed in their behaviour from those injected with control CSF warrants further investigation.
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PMID:An investigation of the effects of intracerebral injection in the marmoset of cytopathic cerebrospinal fluid from patients with schizophrenia or neurological disease. 622 54

The psychiatric manifestations of Huntington's Disease (HD) include dementia, irritability and apathy, a major affective syndrome, and hallucinosis. The theoretical and practical utility of chorea as a focus of research interest in HD is questioned, whereas the data reviewed suggest that assessments of cognition, functional capacity and motor impairment are better correlated neuropathologically, and are better indicators of disease severity and progress than chorea. The high incidence of major affective disorders on modified DSM III criteria among HD patients (41 per cent) may be explained either as a manifestation of genetic heterogeneity within the HD phenotype or on the basis of genetic linkage between HD and manic depressive illness (MDI). This is supported by the high coincidence of HD and MDI (20 out of 23) among secondary cases of HD ascertained through probands having both disorders, indicating a strong familial clustering of the association. This implies that a young adult at risk for HD who has had episodes of severe depression has considerably more than 50 per cent likelihood of progressing to manifest HD. Although auditory hallucinations appear occasionally in patients with HD, most do not meet current criteria for schizophrenia.
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PMID:Psychiatric features of Huntington's disease: recent approaches and findings. 623 7

Swollen, degenerate and fragmented neurons of the septal nuclei and the nucleus ansae peduncularis are commonly found in chronic neurological diseases such as Alzheimer's or Huntington's disease, and rarely found in neurologically normal control patients without mental symptoms. These pathological lipid and pigment laden neurons appear to be a common feature of schizophrenia and have been consistently found in a series of unselected young (mean age 38) schizophrenics.
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PMID:Structural lesions of the brain in young schizophrenics. 626 6


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