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)

Basal serum amino acids (including central monoamine precursors), central monoamines, and hormones were studied in schizophrenic patients (drug-naive; n = 20; drug-withdrawn for 3 or more days, n = 67; neuroleptic-treated, n = 23) and healthy subjects (n = 90) to answer the following questions: (1) Do neuroleptic-withdrawn and neuroleptic-naive patients differ on these serum measures? (2) What are the effects of neuroleptic treatment on these measures? (3) On which variables do drug-free and neuroleptic-treated patients differ? Because serum amino acid, central monoamine, and hormone levels were similar in drug-naive and drug-withdrawn patients, data from these groups ("drug-free") were combined and compared to those of healthy subjects and neuroleptic-treated patients. Asparagine, citrulline, phenylalanine, and cysteine were higher, while tyrosine, tryptophan, and the ratio of tryptophan to competing amino acids were significantly lower in drug-free schizophrenic patients than in healthy subjects. Dopamine was increased, and melatonin and thyroid hormones were decreased in drug-free schizophrenic patients compared to healthy subjects. Norepinephrine, epinephrine, and prolactin were higher in neuroleptic-treated men compared to drug-free male patients or healthy men. These results are consistent with the hypothesis of dopaminergic overactivity in schizophrenia, which might be caused by altered amino acid precursor availability and could be related to the decrease in melatonin and reduction in thyroid hormone levels.
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PMID:Serum amino acids, central monoamines, and hormones in drug-naive, drug-free, and neuroleptic-treated schizophrenic patients and healthy subjects. 198 23

Biological tests may help clarify the relationship of schizoaffective disorder to major depressive disorder (MDD) and schizophrenia (SCZ). Thyrotropin-releasing hormone (TRH), 500 micrograms, was administered intravenously to eight schizoaffective depressed (SD), ten SCZ, 23 MDD patients and 43 healthy controls (HC), all males, ages 20-66 years and drug-free. Research Diagnostic Criteria (RDC) were utilized for establishing diagnoses, Hamilton Rating Scale for Depression (HRSD) total scores were used for assessing depressive symptoms. There were no differences in dmax PRL (post-TRH prolactin peak minus baseline, mean +/- SD) amongst SD, SCZ and HC groups (27.3 +/- 5.2, 28.8 +/- 5.4 and 31.5 +/- 5.6 ng/ml respectively). Mean dmax PRL in MDD was significantly lower than each of the other three groups (17.1 +/- 2.2 ng/ml, P less than 0.05 for all). The essentially normal PRL response to TRH in SD, significantly different from MDD but similar to SCZ parallels our previous observations on the pattern of thyrotropin (TSH) response to TRH in the same diagnostic groups. These biological findings may be taken to indicate that schizoaffective disorder, depressed subtype, is closer to schizophrenia than to major depressive disorder. However, they cannot be considered definitive evidence to that effect since schizoaffective disorders are known to be quite heterogeneous, and since the utilized biological tests lack specificity.
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PMID:Prolactin response to thyrotropin-releasing hormone in schizoaffective depressed compared to depressed and schizophrenic men and healthy controls. 212 54

1. Preclinical studies reveal that long-term treatment with antidepressant drugs induces significant changes in serotonergic (5-HT) receptor sensitivity. Similarly, clinical studies suggest that brain 5-HT function is abnormal in depression. Of the available methodologies for conducting such clinical studies, the pharmacological challenge strategy has proven particularly useful. 2. I.v. L-TRP has emerged as the most frequently used challenge agent in diagnostic and neuropsychopharmacological studies of 5-HT function. I.v. L-TRP increases serum prolactin (PRL) in humans, probably via 5-HT mechanisms. Under carefully standardized conditions, this PRL response to L-TRP appears to be a reasonably sensitive and valid measure of net 5-HT function. 3. The PRL response to L-TRP is blunted in depressed patients compared with healthy controls. Blunting has not been observed in panic disorder, obsessive compulsive disorder, or schizophrenia, although preliminary findings suggest it may occur in bulimia. 4. The PRL response to L-TRP is enhanced by certain classes of thymoleptic drugs (TCAs, MAOIs, 5-HT reuptake inhibitors, lithium) in a differentially time-dependent fashion. So-called "atypical" antidepressants (trazodone, mianserin) and benzodiazepines have no effect. Such findings are generally consistent with preclinical electrophysiological findings. 5. These clinical studies of the PRL response to L-TRP, in conjunction with emerging evidence that experimentally reduced plasma TRP can reverse the therapeutic effects of some antidepressants, suggest that antidepressant drug action may be more accurately conceptualized as 5-HT dependent rather than 5-HT enhancing. The availability of more selective 5-HT-active drugs promises to further clarify 5-HT mechanisms of neuropsychiatric disease and drug action at the clinical level.
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PMID:Clinical studies of 5-HT function using i.v. L-tryptophan. 223 80

Haloperidol was administered IV to 46 male psychotic inpatients and 28 male control subjects. A two-way analysis of covariance, with age as the covariate, revealed that DSM-III schizophrenics (n = 27) had a lower prolactin response to haloperidol than did the controls (n = 28). There were no significant differences between the prolactin responses in schizophrenics, patients with affective disorders (n = 7), and those with other psychoses (n = 12), which included patients with paranoia, schizophreniform, schizoaffective disorder, and atypical psychoses. These findings support the proposition that tuberoinfundibular dopaminergic dysfunction may occur in certain patients with DSM-III schizophrenia.
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PMID:Prolactin response to low-dose haloperidol challenge in schizophrenic, non-schizophrenic psychotic, and control subjects. 225 50

Forty-four male, neuroleptic-free, acutely psychotic patients with at least one diagnosis of schizophrenia among 11 diagnostic systems, and 28 healthy controls, underwent measurement of prolactin (PRL) concentrations before and after intravenous administration of haloperidol (0.5 mg). Basal PRL concentrations were lower in the patients with Research Diagnostic Criteria (RDC) DSM-III, Cloninger, and Taylor and Abrams schizophrenias than in controls. Compared with the controls, the PRL response to haloperidol was lower in the patients with schizophrenia defined by all diagnostic systems except those of Schneider and M. Bleuler. Neither basal nor stimulated PRL concentrations were correlated with positive symptoms, but basal PRL was correlated with the Brief Psychiatric Rating Scale (BPRS) depression-related subscore. This study lends further support for the presence of dopaminergic dysfunction in schizophrenia, and demonstrates the advantages and problems in the use of multidiagnostic psychopathological evaluation to categorize a disorder where there is major disagreement among diagnostic systems.
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PMID:Basal and haloperidol-stimulated prolactin in neuroleptic-free men with schizophrenia defined by 11 diagnostic systems. 235 27

Fifteen acutely ill patients (8 male, 7 female) aged 19 to 63 who met DSM-III criteria for schizophrenic disorder or schizophreniform disorder participated in a 4-week open trial of raclopride. The starting dose of raclopride was 2 mg increasing to 4 mg twice daily in the first week, further increments to 6 mg twice daily at day 14, and 8 mg twice daily at day 21 depending on response. Weekly assessments were made using the BPRS, Montgomery Schizophrenia Scale, Krawiecka-Goldberg Scale and Clinical Global Impression Scale. Extra-pyramidal symptoms and other side-effects were recorded weekly. Four patients failed to complete. Two were withdrawn because of clinical deterioration, and 2 others left hospital against advice after 2 weeks having shown initial improvement. Of the 11 completers, 4 were very much improved and 6 much improved; one was minimally worse. Extra-pyramidal symptoms were infrequent: 3 patients expressed occasional mild akathisia. Six patients complained of mild drowsiness. No major deviations were found in biochemical and physiological safety parameters. Plasma concentrations of raclopride were stable throughout treatment or proportional to dose changes. There was approximately a 6-fold inter-individual difference in steady-state drug concentrations. Plasma levels of prolactin increased transiently after raclopride intake to a maximum of up to 80 and 130 ng/ml in male and female patients respectively.
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PMID:Efficacy, safety and tolerability of raclopride, a specific D2 receptor blocker, in acute schizophrenia: an open trial. 253 73

As some of the pharmacological activities of neuroleptic medication may involve pathophysiological mechanisms underlying schizophrenia and tardive dyskinesia (TD), it is useful to study patients undergoing medication discontinuation. In this study, 19 stable, neuroleptic-maintained patients with persistent TD underwent taper and discontinuation of their neuroleptic medication over a 3-week period, and multiple behavioral and biochemical (plasma HVA, MHPG, and prolactin) measures were obtained. The major finding was that early relapsing patients had lower baseline and a significantly greater increase in plasma HVA levels after discontinuation than nonrelapsing patients. In addition, patients exhibiting withdrawal-exacerbated TD had significantly lower plasma MHPG levels than patients not exhibiting this phenomenon. The clinical and pharmacological implications of these findings are discussed.
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PMID:The effect of neuroleptic discontinuation on psychopathology, involuntary movements, and biochemical measures in patients with persistent tardive dyskinesia. 256 32

Clozapine can produce greater clinical improvement in both positive and negative symptoms than typical antipsychotic drugs in neuroleptic-resistant schizophrenic patients. The clinical response may occur rapidly in some patients but is delayed in others. Clozapine has also been reported to produce fewer parkinsonian symptoms, to involve a lower risk of producing tardive dyskinesia, and to produce no serum prolactin elevations in man. It seems likely that these effects are the result of a common biological mechanism or related mechanisms, rather than unrelated effects. Other atypical antipsychotic drugs, such as melperone and fluperlapine, share at least some of these properties. A relatively low affinity for the D-2 dopamine (DA) receptor and high affinity for the 5-HT2 receptor, producing a high 5-HT2/D-2 ratio, best distinguishes atypical antipsychotics like clozapine from typical antipsychotic drugs. Through its weak antagonist action on D-2DA receptors and a potent inhibitory effect on 5-HT2 receptors, as well as its ability to increase DA and 5-HT2 release, clozapine may be able to permit more normal dopaminergic function in the anterior pituitary, the mesostriatal, mesolimbic and mesocortical regions. The numerous advantages of clozapine over typical neuroleptics are consistent with the primary importance of DA to the pathophysiology of schizophrenia. The secondary but still significant role of 5-HT in the action of clozapine may either be direct or via the effect of 5-HT on dopaminergic mechanisms. Some aspects of schizophrenia could be due to a dysregulation of the interaction between serotonergic and dopaminergic neurotransmission.
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PMID:Clozapine: new research on efficacy and mechanism of action. 256 75

Partial dopamine agonists showing high affinity but low efficacy at D2 receptors can act as dopaminergic "buffers," reducing dopaminergic activity when it is excessive, and promoting it when reduced. This makes them of interest as potential therapeutic agents for the treatment of both positive and negative symptoms in schizophrenia, where they should also result in fewer or less severe motor disturbances than classical neuroleptics. SDZ 208-911 and SDZ 208-912 are amino-ergolines exhibiting partial agonistic properties in the rat, where they inhibit apomorphine-induced stereotypies, are only weakly cataleptogenic, induce varying degrees of circling behavior after unilateral lesioning of the nigrostriatal pathway, and strongly suppress prolactin secretion. The least agonistically acting agent, SDZ 208-912, should be effective against positive symptoms, whereas SDZ 208-911 could be suitable for the treatment of negative symptoms. In addition to possible therapeutic effects, the clinical testing of this class of agent should help to elucidate the status of central dopaminergic function in schizophrenic psychosis.
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PMID:Partial brain dopamine D2 receptor agonists in the treatment of schizophrenia. 257 20

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


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