Serotonin In Schizophrenia Research Articles

Role of Serotonin in Schizophrenia

Norokimyasal degisikliklerin sizofreni etiyolojisindeki rolu cok belirgindir. Bu norokimyasal degisiklikler dort kimyasal iletici ile iliskilendirilmistir. Bunlar, dopaminerjik, serotonerjik, glutamaterjik ve noradrenerjik sistemlerdir. Gunumuzde bozuklugun olusumunun aciklanmasinda en yaygin kabul goren dusunce olan dopamin hipotezine gore sizofreni, dopaminerjik islevlerde bir artisla sonuclanan dopamin iletim ve metabolizmasinin denge bozuklugundan kaynaklanir. Atipik antipsikotikler olarak adlandirilan yeni ilaclarin etki mekanizmalari sizofreni etiyolojisinde serotonerjik sistemin de rol oynadigini gostermistir. Sizofrenide serotonin hipotezinde postsinaptik serotonin reseptorlerindeki duyarlilik artisinin sizofreninin bir kisim belirtilerinden sorumlu oldugunu ileri surulmustur. Bu duyarlilik artisi muhtemelen merkezi serotonin islevindeki azalmayla iliskilidir. Her bir norotransmitter sistemdeki olasi bozukluklarin birbirlerinden bagimsiz olmadiklari, iki sistem arasindaki dinamik etkilesimlerle iliskili olarak dusunulmektedir.

The Effect of Olanzapine Treatment on Monoamine Metabolite Concentrations in the Cerebrospinal Fluid of Schizophrenic Patients

The mechanism of action of both typical antipsychotics and the atypical antipsychotic, clozapine, may be related to the (changing) interaction of dopamine and serotonin in schizophrenia. This study examined the effect of olanzapine in schizophrenic patients on cerebrospinal fluid (CSF) metabolites of dopamine (homovanillic acid, HVA) and serotonin (5-hydroxyindoleacetic acid, 5-HIAA). Twenty-three male schizophrenic patients, who were drug-free for at least 2 weeks (mean drug-free period of 35 days ± 43; median 16 days), underwent a lumbar puncture (LP). Patients were subsequently treated with olanzapine 10 mg/day for 6 weeks, after which the LP was repeated. CSF was assayed for HVA and 5-HIAA concentrations. Psychiatric symptoms were rated once a week. Olanzapine significantly increased HVA concentrations and the HVA/5-HIAA ratio while 5-HIAA concentrations were not altered. These changes did not significantly correlate with treatment response. A negative correlation was found between HVA concentrations and negative symptoms after olanzapine treatment. In conclusion, olanzapine treatment increases HVA concentrations and the HVA/5-HIAA ratio in CSF of schizophrenic patients, but these changes are unrelated to its clinical efficacy.

The Clomipramine Challenge Test in Major Cases of Depression and Schizophrenia

The neuroendocrine challenge test is a useful way of examining the functional integrity of the monoamine pathways that control the secretion of pituitary hormones. The 5-HT uptake inhibitor clomipramine has a considirable use as a 5-HT challenge test. Serotonergic systems in the brain are often disturbed in depressed patients and the role of serotonin in schizophrenia is still unclear. Serotonin is an effective stimulator of prolactine and cortisol release. In this study, we investigated the activity of serotonergic system in depressive and schizophrenic patients via serum plolactin and cortisol levels stimulated by the clomipramine challenge test. While the prolactin /DeltaEmax responses of the depressed and schizophrenia patients to clomipromine tended to be significantly different, the difference between responses of cortisol /DeltaEmax was not statistically significant. We believe that this study gives quite reliable results relating to the serotonergic system; even though the total number of cases was small, the placebo and clomipramine test results of each patient were compared. This study has two important results 1) The cortisol and prolactin responses to clomipramine are more predictive in depression than schizophrenia cases 2) Depressives give more active responses to serotonergic stimulations.

Peripheral indices of dopamine and serotonin in schizophrenia

PRL, and cortisol in normal humans, possibly via a 5-HT2c receptor mechanism. This study investigated the effects of MK-212 on plasma PRL, cortisol, and temperature response in neuroleptic-free schizophrenic patients (60 males, 12 females) and normal controls (32 males, 11 females). The PRL and temperature, but not the cortisol responses to MK212, were significantly blunted in male but not female schizophrenic patients. MK-212 made normals more restless, feel less good overall and strange. These effects were blunted in schizophrenics. There was no difference in the PRL, cortisol or temperature responses between neuroleptic resistant and responsive schizophrenic patients. The PRL and cortisol responses to MK-212 were significantly correlated. The hormone and temperature responses were not correlated with baseline psychopathology. The cortisol and PRL responses in male schizophrenic patients were also positively correlated with ventricular brain ratio and prefrontal sulcal prominence, respectively. The MK-212-induced PRL response was negatively correlated with plasma homovanillic acid (HVA) levels. Clozapine treatment blocked the hormone and temperature responses to MK-212. Improvement in positive and negative symptoms after 6 weeks of clozapine treatment was negatively correlated with the hormone responses to MK-212 in male schizophrenic patients. Further studies are needed to determine the etiology and significance of the diminished response of 5HT2c receptors to serotonergic challenges in schizophrenia.

The role of serotonin in schizophrenia

The hypothesis that the LSD psychosis and by inference schizophrenic psychoses are related to dysfunctions in central serotonergic systems, formulated by Woolley and Shaw in the early 1950s was the first testable theory of modern biological psychiatry. Initially, it did not get the scientific attention it deserved. First, because LSD fell into disrepute and was to all intents and purposes banned from human experimentation. Secondly, the antipsychotics were discovered in the same period, and it became clear that these compounds block dopaminergic transmission and hence for many years thereafter the dopaminergic system occupied center stage in biological schizophrenia research. Presently, interest in the relation between serotonin and schizophrenia has been revived, due to the development of serotonin-blocking agents that appear to exert therapeutic effects in schizophrenia. In this paper the evidence for and against a link between serotonergic defects and schizophrenia psychopathology is critically discussed. The conclusion to be reached is threefold. (1) Interruption of certain serotonergic circuits represents an antipsychotic principle. (2) Tentative evidence suggests the involvement of serotonergic dysfunctions in the pathogenesis of schizophrenic psychoses. (3) It is not yet known whether serotonergic lesions contribute directly to the occurrence of schizophrenic psychopathology or via alterations in the dopaminergic system.

Atypical Antipsychotics Based on the D2/S-HT2 Ratio Hypothesis

Abstract: Medicinal chemistry has played a major role in the improvement of antipsychotic therapy by helping to develop the 02/5-HT2 ratio hypothesis. Early pharmacological insights implicating a role for serotonin in schizophrenia by virtue of its control of the dopamine system have been tested by numerous combined 02/5-HT2 receptor antagonists. Recent work indicates that 5-HT2 receptor blockade can compensate for relatively weaker 02 receptor affinity, lessening the chance of side effects while maintaining antipsychotic efficacy. Many of the newer agents are poised to test the validity of the 02/5-HT2 ratio hypothesis in the clinic.

Serotonin 2 receptor binding in blood platelets of schizophrenic patients

Platelet serotonin 2 (5-HT 2) binding was determined in 47 neuroleptic-free schizophrenic patients and 42 normal control subjects. Although the maximum number of 5-HT 2 binding sites ( B max) was significantly higher in the blood platelets of schizophrenic patients than in those of the normal control subjects, the difference disappeared after correction for age and sex effects. However, the B max of schizophrenic patients who had made suicide attempts was significantly greater than that of schizophrenic patients who had not, as well as that of normal controls. There was no difference in K d between the schizophrenic patients and control subjects, and no relation between K d and suicide attempts. The importance of serotonin in schizophrenia and suicide attempts is discussed.

The role of serotonin in schizophrenia: an overview of the nomenclature, distribution and alterations of serotonin receptors in the central nervous system.

Serotonin is a neurotransmitter that is widely distributed throughout the central nervous system. The role of serotonin in schizophrenia is still unclear. Postmortem studies of serotonin receptor subtypes in schizophrenia have been inconclusive for the most part. The most promising findings involve a reduction in 5-HT2 receptors and 5-HT reuptake sites in the prefrontal cortex of schizophrenic patients. In this paper we review the function, distribution and pharmacological characteristics of serotonin receptors. Postmortem studies are also reviewed, focusing upon the role of these receptors in schizophrenia.

The role of serotonin in schizophrenia.

Studies examining serotonin (5-hydroxytryptamine; 5HT) in schizophrenia show variable and inconsistent findings, which might reflect the heterogeneity of the disease. When these studies are reviewed in the light of Crow's "two-syndrome" paradigm of schizophrenia, a new trend emerges. It appears that 5HT findings may be related to certain features of Type II schizophrenia such as negative symptoms, degenerative brain changes, and chronicity in the following manner: (1) 5HT2 antagonists, which have recently become available, have been shown to have an antipsychotic effect, particularly on the negative symptom cluster. (2) Decreased levels of 5-hydroxyindoleacetic acid in cerebrospinal fluid have been found to be correlated with cortical atrophy or ventricular enlargement in schizophrenic patients. (3) A subgroup of chronic schizophrenic patients has been shown to have elevated levels of platelet or whole blood 5HT. We propose, then, that 5HT dysfunction might be related to Type II, or negative syndrome, schizophrenia, and that the nature of this dysfunction might involve 5HT postsynaptic receptor hypersensitivity. We further suggest that the pharmacotherapy of schizophrenia should include a 5HT-blocking component, as well as a dopamine-blocking component, and we propose that future research should address the role of selective 5HT receptor hypersensitivity in schizophrenia.

Psychotropic drugs and gender as modifiers of the role of plasma tryptophan and serotonin in schizophrenia

Psychotropic drugs and gender as modifiers of the role of plasma tryptophan and serotonin in schizophrenia