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)

Clozapine administration to schizophrenic patients was found to produce dopamine2 (D-2) and serotonin2 (5-HT2) receptor blockade, as evidenced by the ability to block the increases in growth hormone and cortisol secretion produced by apomorphine and MK-212, respectively, direct acting dopamine (DA) and 5-HT2 agonists. Clozapine did not increase plasma prolactin (PRL) levels nor did it block the apomorphine-induced decrease in plasma PRL concentration, as would be expected from a D-2 receptor antagonist. These PRL results are consistent with the observation that clozapine may increase DA release. Clozapine also decreased plasma tryptophan, plasma homovanillac acid (HVA) and basal plasma cortisol levels. Rodent studies suggest clozapine also increases 5-HT release. We hypothesize that antagonism of D-2 and 5-HT2 receptors and enhancement of DA and 5-HT release are critical elements in the action of clozapine to minimize both positive and negative symptoms without producing significant extrapyramidal symptoms or plasma PRL increases. It is proposed that schizophrenia may also involve a dysregulation of 5-HT2- and D-2-mediated neurotransmission, and that a more normal balance in serotonergic and dopaminergic neurotransmission is at least partially restored by clozapine.
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PMID:Clinical studies on the mechanism of action of clozapine: the dopamine-serotonin hypothesis of schizophrenia. 268 29

The benzodiazepine clonazepam was approved for the treatment of epilepsy in 1976. To study its use in acute mania, the author compared clonazepam with lithium in a crossover trial. Clonazepam proved more effective than lithium in controlling the symptoms of mania and caused fewer manifestations of parkinsonism. Associated side effects included ataxia, drowsiness, and behavioral changes. No treatment-emergent depression was observed. Neither clonazepam nor any other benzodiazepine is recommended in schizoaffective or schizophrenic disorders because of the high risk of dependence in those patients, in contrast to manic-depressives. For the maintenance treatment of bipolar disorder, lithium is recommended as the initial agent, with L-tryptophan added if concomitant medication is needed. Clonazepam can then be added as the anticonvulsant, if necessary. In the treatment of acute mania, clonazepam is recommended for the first week of treatment, and lithium is added in the beginning of the second week, thus avoiding the use of neuroleptics.
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PMID:The use of benzodiazepines in the treatment of manic-depressive illness. 290 43

Before and one hour after tryptophan loading laterality differences in the alpha-waves were evaluated from the EEG data obtained from 16 right-handed patients with paranoid hallucinatory schizophrenia and 16 right-handed controls. The alpha wave asymmetry of the patients which was increased and shifted to the right before tryptophan loading may be due to a disturbed relationship between both hemispheres. Particularly in the patients, the pronounced changes in the laterality of alpha-waves after tryptophan loading demonstrate that like psychotic substances tryptophan and its metabolites may bring about changes in subcortical and cortical asymmetries.
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PMID:[Alpha-rhythm asymmetry of schizophrenic patients before and after tryptophan administration]. 343 38

Amino acid transport was studied in vitro in cultured fibroblasts from schizophrenic patients and controls. An isolated decrease in the transport capacity (Vmax) for tyrosine was observed in cells from the patients. The Km for tyrosine transport was unaffected. The kinetic parameters for phenylalanine, tryptophan, leucine and glycine transport did not differ between patients and controls. Competitive inhibition among the amino acids transported by the L-system and its exchange properties were normal in cells from the patients. No differences in intracellular levels of amino acids between patients and controls were observed. The decreased tyrosine transport in the cells from schizophrenic patients appears not to be related to any known amino acid transport system and may reflect a more general defect in plasma membrane function in schizophrenia.
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PMID:Decreased tyrosine transport in fibroblasts from schizophrenic patients. 369 4

Considerable evidence has accrued in the last two decades to support the hypothesis that alterations in serotonergic neuronal function in the central nervous system occur in patients with major depression. These findings include the following: (a) reduced cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA), the major metabolite of serotonin (5-HT) in drug-free depressed patients; (b) reduced concentrations of 5-HT and 5-HIAA in postmortem brain tissue of depressed and (or) suicidal patients; (c) decreased plasma tryptophan concentrations in depressed patients and a profound relapse in remitted depressed patients who have responded to a serotonergic antidepressant when brain tryptophan availability is reduced; (d) in general, all clinically efficacious antidepressants augment 5-HT neurotransmission following chronic treatment; (e) clinically efficacious antidepressant action by all inhibitors of 5-HT uptake; (f) increases in the density of 5-HT2 binding sites in postmortem brain tissue of depressed patients and suicide victims, as well as in platelets of drug-free depressed patients; (g) decreased number of 5-HT transporter (determined with [3H]imipramine or [3H]paroxetine) binding sites in postmortem brain tissue of suicide victims and depressed patients and in platelets of drug-free depressed patients. In our studies, this reduction in platelet 5-HT transporter binding is not due to prior antidepressant treatment of hypercortisolemia and is not observed in mania, Alzheimer disease, schizophrenia, panic disorder, fibromyalgia, or atypical depression. In a pilot study, this deficit predicted treatment response to an experimental antidepressant. These findings support the hypothesis that alterations in 5-HT neurons play a role in the pathophysiology of depression.
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PMID:Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter. 1949 50

Recently, it has been shown that higher plasma serine concentrations are a possible biological marker for psychoses including schizophrenia. The present study was carried out in order to investigate plasma serine levels in 123 depressed subjects (41 minor; 47 simple major; 35 melancholic depressives) and 50 normal controls. It was found that plasma serine concentrations were significantly higher in depressed subjects than in normal controls. There were no significant correlations between plasma serine and postdexamethasone cortisol values. Dexamethasone administration had a significant suppressive effect on plasma serine levels in depression but not in normal controls. In the latter--but not in depressed subjects--there were significant positive correlations between plasma serine and L-tryptophan concentrations.
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PMID:Increased plasma serine concentrations in depression. 770 76

The concentrations of serum tyrosine, phenylalanine and tryptophan have been determined in 23 male neuroleptic-free patients with schizophrenia and 28 male healthy control subjects. Tyrosine was significantly lower in neuroleptic-free patients with an early onset (starting before adulthood) than in healthy control subjects (p < 0.05), and the ratio of tyrosine to phenylalanine was significantly lower in neuroleptic-free patients with an early onset than in those with a late onset (starting at adulthood). No significant differences in these three amino acids were found between the patients with a late onset and healthy control subjects. The present findings suggest that there may be a disturbance of balance between tyrosine and phenylalanine in early-onset patients with schizophrenia.
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PMID:Low concentrations of serum tyrosine in neuroleptic-free schizophrenics with an early onset. 776 38

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

Recent hypotheses and findings indicate that measurements of interactions between cerebrospinal fluid (CSF) biogenic amine systems, rather than measurement of CSF biogenic amine metabolites, better correlate with clinically important findings in schizophrenia. To test hypotheses, we used a recent technological advance in high performance liquid chromatography with electrochemical detection and combined it with multivariate statistical analyses to study biogenic amine concentrations in CSF in schizophrenia. This approach enabled the study of the interactions of several metabolites of each of the three major neurotransmitter pathways (dopaminergic, noradrenergic, and serotonergic) to test existing hypotheses regarding the neurobiochemical basis of schizophrenia. Twenty biogenic amines, their metabolites, and other compounds from 24 medication-free schizophrenic patients and 12 normal control subjects were simultaneously measured using a recently developed technique of gradient high performance liquid chromatography coupled with a 16-channel electrochemical array detector. After covariation for storage time, results of a stepwise discriminant function analysis comparing the control and patient groups identified tryptophan, tryptophol, and epinephrine as discriminating variables. Hotelling's paired T2 test from a subgroup of schizophrenic patients studied while they were and were not receiving neuroleptic treatment did not yield any significant differences between subgroups. A discussion of the findings and a comparison with previous studies of CSF biogenic amines in schizophrenia are presented.
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PMID:A multidimensional approach to analysis of cerebrospinal fluid biogenic amines in schizophrenia: I. Comparisons with healthy control subjects and neuroleptic-treated/unmedicated pairs analyses. 799 18

As part of a multidimensional study of cerebrospinal fluid biogenic amine metabolites in schizophrenia, the relationship between neurochemical measures and psychopathology assessed using the Psychiatric Symptom Assessment Scale (PSAS) was analyzed. In a group of 20 unmedicated patients, 3,4-dihydroxyphenylacetic acid (DOPAC) was a predictor of symptom severity in a stepwise multiple regression model. Values of 3-hydroxykynurenine and metanephrine in the unmedicated state predicted clinical response in a stepwise multiple regression model, as measured by improvement in PSAS mean item score following 6 weeks on a standard dose of neuroleptic. In a subgroup of 14 patients in whom both off- and on-medication concentrations of cerebrospinal fluid biogenic amines and metabolites were measured, change in 3-hydroxykynurenine predicted clinical outcome in a multiple regression model. These findings point toward the need to examine the role of the kynurenine pathway of tryptophan metabolism in the pathophysiology of schizophrenia.
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PMID:A multidimensional approach to analysis of cerebrospinal fluid biogenic amines in schizophrenia: II. Correlations with psychopathology. 799 19


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