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)

The effect of the selective serotonin-2 antagonist ritanserin was investigated in an open study of patients with schizophrenia. The patients were in an acute psychotic state considered to require neuroleptic medication. No neuroleptic drug was allowed during the study or during the last month preceeding the study. Oxazepam or nitrazepam were allowed for sedation or sleep inducement. Safety, tolerability, potential antipsychotic effect, and drug effects on monoamine metabolites in serum and CSF and prolactin in serum were evaluated. Central D2-dopamine receptor occupancy was determined by positron emission tomography. Ten male patients (mean age 32.4) fulfilling DSM-III-R criteria for schizophrenia were included in the study. Nine of these patients completed 4 weeks' treatment with ritanserin 10 mg b.i.d. The clinical effect was evaluated by means of CPRS and SANS and significant improvement was seen after 4 weeks' treatment both in positive and negative symptoms. Ritanserin was well tolerated and no extrapyramidal symptoms or akathisia were seen. Concentrations of monoamine metabolites and prolactin did not change during treatment. Ritanserin did not occupy D2-dopamine receptors. Thus, no indications of any D2-dopamine-antagonistic activity were obtained. All patients had expected ritanserin levels in plasma during the whole study. This first study of a selective serotonin-2 antagonist in the treatment of acute schizophrenic patients demonstrated significant clinical effects. However, the open design of the study does not allow us to conclude with any certainty that the patients' improvement was due to a specific blockade of serotonin-2 receptors or unspecific factors, although a direct D2-dopamine blockade could be ruled out.
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PMID:An open clinical and biochemical study of ritanserin in acute patients with schizophrenia. 784 5

Circadian rhythm abnormalities have been described mostly with respect to manic-depressive illness; little information is available concerning circadian rhythms and schizophrenia or their influence on neuroleptic drugs. We showed previously that the MESOR of dopamine is higher in schizophrenic patients than in healthy subjects and that women who are drug-free schizophrenic have lower prolactin MESORs and lower amplitudes than healthy women. We now report the data of a cosinor analysis of tryptophan, serotonin, melatonin, and pituitary hormones in the blood of 34 healthy subjects, 90 drug-free schizophrenics, and 25 neuroleptic-treated schizophrenic patients. This data indicated a significant phase advance of serum tryptophan, prolactin, and melatonin concentrations, a trend toward a phase advance in serotonin. Thyroid stimulating hormone (TSH), and growth hormone concentrations, and decreases in the TSH MESORs among patients compared to healthy subjects. These results suggest that circadian changes, such as phase advances and alterations in MESOR, are not only present in depression but also in schizophrenia. Although neuroleptic treatment raised the prolactin MESOR and amplitude, it did not elicit any change in circadian rhythmicity among the other parameters.
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PMID:Circadian rhythm of tryptophan, serotonin, melatonin, and pituitary hormones in schizophrenia. 790 93

The incidence of cancer was studied in a cohort of all first admitted 9156 patients in Denmark with a diagnosis of schizophrenia in the period 1970-1987. The overall incidence of cancer was reduced particularly in the males. Adjustment for the smoking habits of psychiatric patients enhanced this risk reduction. Fewer than expected had been diagnosed with cancer prior to the first schizophrenia admission. This tendency was limited to the female patients. The reduced cancer incidence was particularly marked for genital cancers, in particular testicular cancer, and skin cancers including malignant melanoma. Breast cancer risk was not increased, thus not substantiating concerns that neuroleptics would increase breast cancer risk through the elevation of serum prolactin levels. Some available evidence in the literature supports the hypothesis of an antineoplastic effect of neuroleptics as an explanation for the low occurrence of cancer in schizophrenic patients. Further large sample studies including an extension of the follow-up of this cohort are needed to establish the reduced risk of cancer in schizophrenic patients as well as exploring the causes for this reduction.
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PMID:The occurrence of cancer in first admitted schizophrenic patients. 791 30

Prompt and efficient treatment of acute psychotic episodes combined with the prevention of relapses will limit the accrued morbidity of schizophrenia. However, the heterogeneity of schizophrenia makes it difficult to determine which individuals are most likely to relapse. There are three major potential biological predictors of schizophrenic relapse: (1) behavioral response to dopamine agonist stimulation, (2) the presence of tardive dyskinesia, and (3) increases in anterior pituitary hormones. Dopamine agonists and dopamine antagonist provocative tests, using a single dose of medication, can be used to predict outcome in stabilized schizophrenics undergoing maintenance drug therapy. These tests are indicators of increased dopamine activity, which potentially indicates a worse outcome. This article discusses behavioral response to psychostimulant tests and pituitary hormone levels, particularly growth hormone and prolactin response to dopamine antagonist stimulation. As predictors of outcome, these measures may be useful, clinically, when selecting neuroleptic maintenance schedules, dosage, or withdrawal strategies.
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PMID:Prediction of outcome in first-episode schizophrenia. 809 92

Twenty physically healthy men with schizophrenia responded to a 15-item questionnaire inquiring about their usual and their present (on medications) sexual functioning. Two summary measures of present impairment (the average of items 7-13 that detail the patients' specific complaints of impairment, and item 15, the interviewer's global judgment of impairment) were significantly correlated with each other and with the differences between usual and present reported frequencies of erection and masturbation. More severe impairment on these summary measures was significantly associated with greater biological evidence of dopamine blockade (more severe extrapyramidal side effects and higher serum prolactin levels).
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PMID:A pilot study of a structured interview addressing sexual function in men with schizophrenia. 816 1

Serum prolactin levels are determined in 116 schizophrenics and 120 control subjects. Values of prolactin levels of the patients are compared with the values of control of the same sex and age group. There is no significant difference between prolactin levels of controls and those with negative or positive symptoms of schizophrenia. Analysis, taking age into account, also does not show any significant difference between patients with positive or negative symptoms and controls. The relationship between nature of symptoms of schizophrenia and serum prolactin levels varies in different studies. The possible reasons for such variations are discussed.
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PMID:A study on serum prolactin levels in schizophrenia: correlation with positive and negative symptoms. 826 15

Circadian rhythm abnormalities have been described in various psychiatric disorders, but they have not received much attention in studies of schizophrenia and schizophreniform psychosis. The present study used the cosine model to determine the circadian patterns of amino acids, dopamine, and prolactin concentrations, which were analyzed over a 24-hour period in serum of healthy subjects, drug-free schizophrenic patients, and neuroleptic-treated schizophrenic patients. The mesor (the daily mean) of phenylalanine was lower in drug-free schizophrenic women than in healthy women. The mesors of the ratio of phenylalanine or tyrosine to competing amino acids were similar in healthy subjects and patients. The ratio of phenylalanine/competing amino acids showed a phase advance (i.e., earlier onset of the time of highest concentration) in drug-free patients compared with healthy subjects. Schizophrenic patients displayed a higher dopamine mesor than healthy subjects. Female drug-free schizophrenic patients had lower prolactin mesors and lower amplitudes (i.e., half of the total predictable change in rhythm) than healthy women. Compared with healthy subjects, schizophrenic patients showed a phase advance of circadian prolactin concentrations. Neuroleptics raised the prolactin mesor and amplitudes but did not elicit any phase change in amino acids, dopamine, or prolactin. These data confirm the indirect pharmacologic evidence of increased dopaminergic activity in schizophrenic patients that relates to dopamine's precursors and to the neuroendocrine regulation of prolactin.
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PMID:Hyperdopaminergia in schizophreniform psychosis: a chronobiological study. 834 71

The introduction of clozapine has given clinicians a unique agent for treating patients with schizophrenia that is refractory to other neuroleptics. Despite its efficacy, the drug continues to be prescribed with trepidation due to the incidence of agranulocytosis. This article reviews the pharmacokinetic and pharmacological properties of clozapine and the clinical implications for monitoring plasma concentrations. Various assays have been developed for clozapine that include gas-liquid chromatography, radioimmunoassay and high performance liquid chromatography. Only a few studies have examined the pharmacokinetics of clozapine in patients with schizophrenia. These studies have revealed a wide interpatient variability in pharmacokinetic parameters that include: time to reach peak plasma concentrations 1.1 to 3.6h; elimination half-life 9.1 to 17.4h; clearance 8.7 to 53.3 L/h; and a volume of distribution of 1.6 to 7.3 L/kg. Clozapine is metabolised via the hepatic microsomal enzyme system into 2 principle metabolites: demethyl-clozapine and clozapine N-oxide. Urine samples have reported the ratio of clozapine:demethyl:N-oxide to be 1:1:2. The clozapine N-oxide binding affinity with 3H-haloperidol was 4 times lower than clozapine and its conversion back to clozapine is hypothesised. Although the exact pharmacological mechanism of action of clozapine is not fully understood, the drug does possess significant binding affinity for different dopamine receptors, with recent evidence supporting binding to the D4 receptor subtype. Clozapine transiently increases serum prolactin levels with minimal changes in homovanillic acid plasma levels. Limited studies investigating the relationship between clinical response and plasma clozapine concentrations have investigated the range between 100 and 800 micrograms/L. In the treatment of patients with refractory schizophrenia, a minimum concentration of 350 micrograms/L was suggested as needed. The occurrence of agranulocytosis could have a genetic basis and patients should be rigorously monitored during treatment. The incidence of tardive dyskinesia and extrapyramidal side effects is minimal. Clozapine can lower the seizure threshold in a dose- and time-dependent manner. Careful patient selection and monitoring are required when clozapine therapy is used in patients with schizophrenia.
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PMID:Pharmacokinetics and pharmacodynamics of clozapine. 845 23

The neuroendocrine responses to subcutaneous (SC) administration of the dopamine (DA) agonist apomorphine (APO) hydrochloride (0.75 mg) were studied in a large group of subjects: 110 drug-free inpatients with either DSM-III-R schizophrenia (SCZ, n = 46), schizoaffective disorder (SAD, n = 14), or major depressive episode (MDE, n = 50), plus 18 hospitalized controls. Compared to a saline test, APO induced a significant increase of growth hormone (GH), adrenocorticotropin (ACTH), and cortisol (COR) release and a decrease in prolactin (PRL) secretion. No change in thyrotropin (TSH) levels was observed. In the total sample the extents of ACTH, COR and GH responses were correlated, but in the group of 88 subjects who exhibit a normal GH stimulation this correlation disappeared. This discrepancy suggests that APO-induced ACTH and COR stimulation may be mediated by pathways different from those mediating GH stimulation. According to diagnostical categories, we found significant lower ACTH and COR stimulation in the schizophrenic group and in patients with SAD, compared with that among controls or depressed patients. We found also a significant difference between subgroups of schizophrenic patients. These results agree with the hypothesis that different aspects of psychosis might involve different subtypes of DA-receptors with different localizations and sensitivities.
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PMID:Multihormonal responses to apomorphine in mental illness. 853 20

Osteoporosis is a common problem in postmenopausal women. It has been linked to estrogen deficiency, other neuroendocrine processes such as hypercortisolemia and male hypogonadism, nutritional deficiencies, and other mechanisms. Some of these changes have been also reported in male and female patients with mental disorders, especially those receiving psychotropic medications. Therefore, bone mineral density was measured by dual-photon absorptiometry in the lumbar spine and in the femoral neck of 33 female and 35 male consenting psychiatric inpatients admitted consecutively. Patients were diagnosed as having major depressive disorder (N = 21), schizophrenia (N = 33), schizoaffective disorder (N = 7), mania (N = 2), and adjustment disorder (N = 5). Plasma levels of prolactin, estrogen, cortisol, and testosterone were also measured in a subgroup of these patients. It is reported that female patients, but especially male patients, had a highly significant decrease in bone mineral density when compared with age- and sex-matched normal data. It is suggested that psychiatric patients treated with antidepressants or neuroleptics might have decreased bone mineral density than is normal for their age and sex, and may be at an increased risk for fractures. These results may be related to low levels of gonadal hormones, especially in male subjects. Data should be confirmed with a larger number of patients with and without medications to distinguish between diagnosis-related and treatment-related effects.
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PMID:Decreased bone mineral density in medicated psychiatric patients. 855 40


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