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)

According to the dopamine (DA) hypothesis of schizophrenia, there is a functional excess of dopaminergic activity within unspecified areas of the brain in schizophrenic patients. As a clinical test of this hypothesis, we administered metyrosine for three weeks to symptomatic chronic male schizophrenic patients who were maintained on suboptimal doses of neuroleptic agents. Metyrosine inhibits tyrosine hydroxylase, the rate-limiting enzymatic step in the synthesis of DA. No clinical improvement was observed, using the National Institute of Mental Health Inpatient Behavioral Rating Scale or the Brief Psychiatric Rating Scale. Central inhibition of DA synthesis by metyrosine was suggested, however, by (1) the development of extrapyramidal side effects and (2) a significant increase in plasma prolactin concentrations. Plasma chlorpromazine concentrations remained unchanged during metyrosine treatment. There was, nevertheless, a significant improvement on the scores of the Wechsler Adult Intelligence Scale Comprehension subtest, which measures judgment and common sense. This finding suggests that DA may be involved in the regulation of subtle psychological processes. The results are discussed in light of the DA hypothesis of schizophrenia and previous reports suggesting that metyrosine potentiates the antipsychotic effect of neuroleptics in schizophrenia.
Arch Gen Psychiatry 1977 Jun
PMID:Inhibition of dopamine synthesis in chronic schizophrenia. Clinical ineffectiveness of metyrosine. 1 74

The prolactin response to neuroleptics can serve as an index of dopamine blockade in humans. Plasma prolactin increments to single doses of chlorpromazine, and prolactin decrements to single doses of levodopa, were similar in normal and schizophrenic subjects. Antischizophrenic drugs of all chemical classes stimulated prolactin release,while chemically related drugs and other psychotropic agents ineffective in schizophrenia did not. The prolactin response to neuroleptic therapy occurred in all patients, and tolerance did not develop. Within subjects, prolactin responses were graded according to neuroleptic dose, but the upper limit of sensitivity of the response curve was achieved at doses below the therapeutic range. Relative prolactin-stimulating potency in humans of chlorpromazine, thioridazine, trifluoperazine, butaperazine, and haloperidol correlated well with their relative clinical potencies.
Arch Gen Psychiatry 1978 Jan
PMID:Prolactin responses to neuroleptics in normal and schizophrenic subjects. 2 87

In a study of vestibular responses to caloric stimulation that controlled opportunity for fixation and state of alertness, we evaluated previous findings of diminished nystagmus in schizophrenia. We failed to replicate earlier reports in these respects: (1) None of the psychotic patient groups, when compared with normal controls, showed lower response intensity, latency, or culmination time of the nystagmic response. (2) The schizophrenic groups did not manifest a prevalence of clinically significant asymmetry. We did, however, observe that chronic deteriorated schizophrenics and recent schizophrenics have significantly greater dysrhythmic responses. This diminished orderliness of nystagmus may explain previous reports of absent or diminished nystagmus in the schizophrenics. The results are not compatible with peripheral vestibular disease in schizophrenia, but they may reflect state-related phenomena consistent with disturbances in alertness, which are not necessarily voluntary or motivational in origin.
Arch Gen Psychiatry 1978 Aug
PMID:Vestibular responses in schizophrenia. 2 3

This review surveys the therapeutic efficacy of tricyclic antidepressants and monoamine oxidase inhibitors in schizophrenic patients. In general, the use of these drugs alone was found not to be warranted in schizophrenia, except perhaps in the so-called pseudoneurotic subgroup. In most cases, combinations of antidepressants and phenothiazines were not more beneficial than phenothiazines alone. In particular, the conditions of agitated patients and patients with histories of social deviance dating back to childhood were often made worse by the addition of an antidepressant. However, when the patients who demonstrated symptoms of clinical depression other than anergia were isolated from several of these studies, it was found that they constituted a subgroup that was often benefited by use of these combinations. Favorable and unfavorable clinical response patterns are discussed, and recommendations for future research are outlined.
Arch Gen Psychiatry 1978 Nov
PMID:Use of antidepressant drugs in schizophrenia. 3 Apr 29

In an effort to establish correlations between abnormal behaviors characteristic of schizophrenia and simultaneous cerebral electrical activity, EEGs and electro-oculograms (EOGs) were continuously recorded for 2 to 24 hours by radiotelemetry from 40 patients with schizophrenia and 12 normal control subjects. Trained observers recorded specific behavior patterns permitting visual and computer analysis of EEG during hallucinations, stereotypy, catatonia, psychomotor blocking, and other characteristic manifestations of schizophrenia. Electroencephalographic abnormalities consisting of focal slow or spike activity over either temporal region were found in nearly half of the patients so recorded. In contrast to the EEG during ictal episodes of epilepsy, the abnormal wave forms of schizophrenic patients seldom coincided with episodes of blocking, stereotypy, or other abnormal behaviors. Increased extraocular activity or blinking were recorded in a majority of patients, but were not consistently associated with the abnormal behavior or perceptual events.
Arch Gen Psychiatry 1979 Mar
PMID:Telemetered EEG-EOG during psychotic behaviors of schizophrenia. 3 32

We report a double-blind, randomized, placebo-controlled study utilizing a within-subjects design on 20 hospitalized, psychiatric patients who participated in sodium amobarbital interviews to determine if the drug has a specific effect in eliciting clinically useful information. The patients selected had difficulty communicating with their primary therapists during the postadmission, diagnostic interviews. Two raters completed a Hamilton Depression Scale, a New Haven Schizophrenia Index, and a Brief Psychiatric Rating Scale after each interview. Although both the amobarbital and saline interviews were moderately useful in obtaining new information, we found no significant difference in the primary therapists' assessments of clinical usefulness. In addition, the drug interview did not uncover material that would aid in the differential diagnosis between depression and schizophrenia. There was, however, a significant negative correlation between the assessment of general usefulness and the time interval between admission and interviewing. We report our only exception, a case of catatonic schizophrenia, in which the patient responded specifically to the drug.
Arch Gen Psychiatry 1979 Jul
PMID:Clinical usefulness of sodium amobarbital interviewing. 3 65

Enzymes concerned with neurotransmitter metabolism were measured postmortem in 50 regions from the brains of 11 chronic schizophrenics, 2 patients with senile dementia, 1 depressive, and 18 controls. Enzymes studied were tyrosine hydroxylase, dopa decarboxylase, glutamic decarboxylase, choline acetyltransferase (CAT), and acetylcholinesterase. The schizophrenic group had high CAT activities in the hippocampus, caudate, putamen, and nucleus accumbens; the other patients from the same hospital did not. A compensatory response to long- or short-term drug usage is considered, but correlations are hard to establish in the group studied. An alternative hypothesis proposes that the high levels are a compensatory response to defective cholinergic receptors in the affected areas. On this hypothesis, and by analogy with chorea, dopaminergic antagonists would act in schizophrenia by helping to reestablish cholinergic-dopaminergic balance.
Arch Gen Psychiatry 1977 Nov
PMID:Possible changes in striatal and limbic cholinergic systems in schizophrenia. 4 82

Whole blood, plasma, or serum levels of various components were measured in fasting, drug-free control subjects and drug-free schizophrenic patients. Compared to normal controls, chronic schizophrenic patients showed increased alpha2-globulins and decreased plasma cholinesterase activity and ceruloplasmin activity, and acute schizophrenic patients showed decreased alpha2-globulins. Compared to chronic patients, acute schizophrenics showed decreased alpha2-globulins and IgA. Compared to normal controls of similar age, chronic schizophrenic patients weighed less, were shorter, and had smaller body surface area. The acute schizophrenic patients were significantly younger than the normal subjects or chronic schizophrenics but there was no difference in the other physical measurements. The present study indicates no gross disturbances in the blood variables studied. That some differences are statistically significant from controls is of scientific interest, but of no clinical value in the diagnosis of schizophrenia.
Arch Gen Psychiatry 1975 Jun
PMID:Blood protein fraction comparisons of normal and schizophrenic patients. 4 63

Sixty patients meeting the criteria established for schizophrenia who attained a clinical plateau following hospital discharge were randomized to receive for one year either penfluridol, 20 to 160 mg orally once each week, or fluphenazine decanoate, 0.5 to 4 ml every two weeks. The relapse rate for both treatments was low and equal. The rate of recurrence of psychosis for patients receiving penfluridol was 7% and for those receiving fluphenazine decanoate 10%. A retrospective comparison of the penfluridol group was made to a similar group of patients assigned to placebo in an earlier study. Placebo-treated patients had a relapse rate of 68%. Penfluridol patients had statistically fewer psychotic relapses. Questions about the possible carcinogenicity of penfluridol in animals will have to be resolved before it can be widely used. This study demonstrates the feasibility of using an oral, long-acting antipsychotic agent. It would be a useful psychopharmacologic addition in the treatment of outpatient schizophrenics.
Arch Gen Psychiatry 1978 Jul
PMID:Long-acting oral vs injectable antipsychotic drugs in schizophrenics: a one-year double-blind comparison in multiple episode schizophrenics. 9 27

The effect of a treatment program (E) providing inpatient care, a day hospital, community housing, and sheltered work are compared with a program (C) emphasizing rapid discharge. A group of 94 male general psychiatric patients were randomized to the two units. Outcome data collected at 18 months from admission revealed small but significant differences between the total samples in employment, maintenance of treatment contact, use of medication, and social adjustment. More C than E patients were in the hospital after the 14th month. Program effects varied considerably with patient type. Patients with less social disability had somewhat better employment outcomes with the E program, but no differences in use of services. Patients with a better prognosis by measure of psychopathology (Minnesota Multiphasic Personality Inventory cluster and diagnosis of schizophrenia) spent less inpatient time in the E program, but were not helped to better employment outcomes. Patients with greater social handicap were not differentially affected. More E patients than C with a poorer prognosis stayed in outpatient treatment and used antipsychotic medications. Patients in the E group with better previous employment and more social isolation used the E day hospital and community housing more heavily than other E subgroups.
Arch Gen Psychiatry 1977 Nov
PMID:Controlled evaluation of a hospital-originated community transitional system. 12 50


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