Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent reports have suggested that high doses of propranolol may be an effective treatment in schizophrenia. To determine whether such treatment has effects on cerebrospinal fluid (CSF) amine metabolites and prolactin similar to the effects of the neuroleptic drugs, we studied CSF from ten patients before and after propanolol therapy. The initial CSF sample was removed after a drug-free period and propranolol dosage was then increased over 1 week to 1000 mg daily in all ten patients. A second CSF sample was removed after 3 weeks of propranolol therapy. Propranolol levels and prolactin in CSF were measured by radioimmunoassay. Homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylethylene glycol were measured by gas chromatography-mass spectrometry. Propranolol had no effect on the prolactin or amine metabolite concentrations. CSF propranolol levels averaged 40 ng/ml (range less than 1--78).
 ...
PMID:The effect of propranolol treatment in shizophrenia on CSF amine metabolites and prolactin. 11 17

The relationships between CSF monoamine metabolites (HVA and 5HIAA), nurses' ratings of clinical symptoms, and telemetered measures of motor movement of ten schizophrenic and ten depressed patients were investigated. There was a significant negative correlation between CSF 5HIAA and both agitation ratings and motor movement in the schizophrenics. CSF HVA correlated positively to anxiety and anger in the depressives. The schizophrenics had a significantly higher CSF HVA than the depressives which appeared unrelated to motor movement. The effects of serotonin turnover and arousal in schizophrenia and the association between CSF metabolite gradients, stress, motor movement, and biogenic amine levels in depression are discussed.
 ...
PMID:CSF amine metabolites, clinical symptoms, and body movement in psychiatric patients. 96 33

1. The efficacy of mianserin as a supplement in treating chronic schizophrenia was tested by monitoring the BPRS and plasma monoamine metabolites. 2. Twenty inpatients with schizophrenia were administered fixed doses of neuroleptics throughout the study. 3. A control BPRS scoring and blood sampling were done before mianserin administration. 4. Fixed doses of 60 mg/day of mianserin for 2 weeks and flexible doses for 4 weeks were given orally in an open study for 6 consecutive weeks, and no treatment followed for 1 additional week. 5. BPRS scoring was carried out once weekly, and blood samples were obtained after mianserin treatment. 6. Both total BPRS scores and scores for negative symptoms were decreased by mianserin treatment as compared with the control values. 7. 5-HIAA concentrations of both responding patients and nonresponding patients to mianserin were increased after medication; however, 5-HIAA values of responding patients were lower than those of nonresponding patients. 8. HVA concentrations of the responding group were slightly increased by mianserin administration. 9. There were no significant changes in MHPG levels between the two groups. 10. These results suggest that the negative symptoms of schizophrenia are partly improved by mianserin treatment.
 ...
PMID:Effects of mianserin in chronic schizophrenia. 164 95

The efficacy of mianserin as a supplement in treating chronic schizophrenia was tested in 20 inpatients with schizophrenia who were receiving fixed doses of neuroleptics. Mianserin was given for six weeks with a starting dose of 60 mg/day. A brief psychiatric rating scale (BPRS) was completed before starting mianserin and thereafter BPRS scoring was carried out once weekly. The total BPRS score and the score for negative symptoms were decreased by mianserin treatment as compared to the pre-treatment values. Plasma 5-HIAA concentrations were increased after medication in both responding patients and nonresponding patients. However, the 5-HIAA values of responders were lower than those of nonresponders. Plasma HVA levels were slightly increased by mianserin in the responders. There were no significant changes in MHPG levels. These results suggest that the negative symptoms of schizophrenia may be improved by mianserin treatment.
 ...
PMID:Effects of mianserin on negative symptoms in schizophrenia. 169 92

Nocturnal sleep data and cerebrospinal fluid (CSF) concentrations of the biogenic amine metabolites were measured in 20 male schizophrenics. Consistent with other reports of a stage 4 sleep deficit in schizophrenia, measures of stage 4 sleep were low relative to normal reference data. Measures of stage 4 sleep in absolute amounts and corrected for total sleep were positively correlated with CSF concentrations of the serotonin metabolite, 5-hydroxyindole acetic acid (5-HIAA). CSF 5-HIAA was also correlated with measures of stage 3 sleep and total sleep time suggesting that serotonin may modulate the amount of slow wave sleep broadly defined and possibly sleep duration. Total stage 4 time was also correlated with the dopamine metabolite HVA; consequently, the specificity of the finding might be limited. Also, in this study, schizophrenia was used as a particular model for stage 4 deficits; however, the association of measures of stage 4 sleep with CSF levels of 5-HIAA is not thought to be specific to schizophrenia.
 ...
PMID:Evidence for the role of serotonin in the regulation of slow wave sleep in schizophrenia. 171 97

It is difficult to come away from review of pharmacologic and metabolite studies without concluding that dopaminergic mechanisms play a significant role in mediating both negative and positive symptoms. Nevertheless, the characteristics of dopaminergic involvement are unclear. Whereas compelling evidence continues to link the mechanism of action of neuroleptic drugs, including therapeutic effects on negative and positive symptoms, to blockade of D2 receptors, neuroleptic-induced alterations in dopaminergic function are time-dependent and may include reductions in variability as well as in net dopamine activity. Moreover, pharmacologic enhancement of dopaminergic function may at least transiently improve symptomatology (negative greater than positive) and levels of CSF HVA appear to be reduced or are negatively correlated with symptoms in some schizophrenic patients. Thus, there is support for both increased and decreased dopamine function in schizophrenia. Functional brain imaging has, after only a few years of application, made significant contributions to our understanding of the pathophysiology of schizophrenia. Studies of cerebral metabolism and regional CBF have shown remarkable consistency in their identification of abnormal function of the frontal cortex in schizophrenia. It should be pointed out, however, that agreement across studies remains largely conceptual with significant discrepancies still existing with regard to the precise localization of dysfunction and its relationship to cognitive activation. Although less well documented than 'hypofrontality' itself, negative symptomatology appears to bear some relationship to this defect. The idea that positive symptoms might be associated with increased subcortical and/or metabolism is less well supported. The recent advances in our understanding of structure and function of CNS dopaminergic systems may help to integrate these two bodies of data into more dynamic models of dopaminergic defects in schizophrenia. For example, the concept that diminished mesocortical coupled with increased subcortical dopaminergic activity might be a 'substrate' for psychosis is compatible with neurochemical evidence suggesting both diminished and enhanced dopaminergic processes as well as with metabolic hypofrontality. Better understanding of the regulatory mechanisms involved in establishing functional balance between cortical and subcortical systems might, therefore, identify new possibilities for biological dysfunction in schizophrenia. The recent study by Weinberger et al. which correlates CSF HVA levels with neuropsychologically induced frontal CBF is an example of how neurochemistry can enhance brain imaging data.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Neurochemical and neural mechanisms of positive and negative symptoms in schizophrenia. 197 Aug 51

The effects of a series of six ECT treatments were observed on the CSF concentrations of HVA, MHPG, and 5-HIAA in 12 patients suffering from schizophrenia. Four patients were previously neuroleptic drug-free, and eight had received only oral neuroleptic drugs at the same dose for more than 4 weeks. A significant increase in the concentration of HVA was observed after the first ECT treatment but not after the final treatment. No significant changes were observed in the concentrations of MHPG and 5-HIAA. The patients improved clinically, and the results suggest that ECT has important effects on dopaminergic systems.
 ...
PMID:The effect of electroconvulsive therapy on CSF amine metabolites in schizophrenic patients. 245 96

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.
 ...
PMID:The effect of neuroleptic discontinuation on psychopathology, involuntary movements, and biochemical measures in patients with persistent tardive dyskinesia. 256 32

Neuroleptic drugs have provided not only the most efficacious form of treatment for schizophrenia but also a unique pharmacologic probe for discerning its pathophysiology. The link between the antipsychotic effects of neuroleptics and dopamine systems continues to be supported by current research. Recent preclinical and clinical studies suggest that time-delayed changes in DA neuronal function may more closely relate to the therapeutic effects of neuroleptics than does their relatively immediate effect of DA receptor blockade. The use of levels of plasma HVA as a noninvasive reflector of DA function provides a research strategy for longitudinal studies of neuroleptic effects in schizophrenia. Preliminary evidence suggests that neuroleptic-induced changes in levels of plasma HVA may be of value as an in vivo marker for neuroleptic antipsychotic effects. The recent identification and characterization of the mesocortical DA system, which links the midbrain to frontal areas of the cerebral cortex, represents a significant development in the neurobiology of CNS DA systems. The behavioral implications of the functional neuroanatomy of the mesocortical system, its relative unresponsiveness to neuroleptic agents, and the possibility of modulatory effects on the mesolimbic DA system render the mesocortical system a particularly important area of research with etiologic and pharmacotherapeutic implications for schizophrenia. The accumulating evidence indicating structural brain abnormalities in a significant number of schizophrenic patients has renewed interest in classical neuropathologic approaches to understanding its etiology. Although current evidence does not uniformly support the hypothesis of two schizophrenia types reflecting DA and non-DA forms of the illness, the postulate is useful as an attempt to integrate recent findings into a conceptual framework. Better understanding of the biochemical basis for heterogeneity of neuroleptic response and systematic data relating this responsivity to morphologic brain changes constitute an important direction for schizophrenia research.
 ...
PMID:Neuroleptics, dopamine, and schizophrenia. 287 Apr 80

Despite the limitations of the dopamine hypothesis, compelling evidence remains that implicates dysfunction of CNS dopamine systems in the pathophysiology of schizophrenia. The longitudinal measurement of levels of plasma HVA has proved a useful tool in studying neuroleptic effects and has highlighted time-dependent effects as a potentially important facet of the mechanism of antipsychotic action of these drugs. Despite the good clinical correlates of plasma HVA levels, caution is needed in interpreting plasma levels of HVA with regard to CNS dopamine activity. The peripheral nervous system significantly contributes to levels of HVA that circulate in plasma. This issue is underscored by the fact that CSF HVA shows different neuroleptic response patterns than that seen in plasma. The administration of a peripherally acting MAO inhibitor to enhance the CNS "signal" in circulating levels of HVA does not resolve the "problem" of different CSF-plasma HVA neuroleptic response patterns. The possibility that mesocortical dopamine activity is reflected by CSF HVA is suggested by indirect evidence from clinical and preclinical studies. Future studies in which attempts are made at using both plasma and CSF HVA to enhance neurochemical and clinical correlates may help to advance our understanding of the contributions of specific CNS dopamine systems to schizophrenia.
 ...
PMID:Plasma homovanillic acid as an index of central dopaminergic activity: studies in schizophrenic patients. 290 83


1 2 3 4 5 Next >>