engleski

Biological markers in the ethiology and treatment of schizophrenia

Schizophrenia is a severe chronic mental disorder that appears in 1% of the population. The pathophysiology and treatment of schizophrenia could be connected with the alterations in serotonergic system, hypothalamic-pituitary-adrenal (HPA) axis activity and lipids levels. Peripheral biochemical markers studied in schizophrenia include platelet serotonin (5-HT) levels, activity of platelet monoamine oxidase (MAO), plasma cortisol and prolactin (PRL) levels and serum lipids: cholesterol, triglycerides, high density lipoprotein cholesterol (HDL-C) and low density lipoproteins cholesterol (LDL-C) levels. Clinical diagnosis of schizophrenia was made according to the DSM-IV criteria. The efficacy measures included the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI) scale and Hamilton Depression Rating Scale (HAMD). Control group consisted of drug free healthy persons with no personal or family history of psychopathology. Platelet 5-HT, plasma cortisol and PRL concentrations were determined by the spectrofluorimetric, radioimmunoassay and immunoradiometric methods, respectively. Serum lipids levels were determined by enzymatic color test (cholesterol, HDL-C and TG) and by enzymatic clearance assay (LDL-C). Schizophrenic patients had higher values of platelet 5-HT and both hormones, and lower values of cholesterol, HDL-C and LDL-C than healthy controls. A significant correlation was found between platelet 5-HT concentration and plasma levels of cortisol and PRL in healthy, but not in schizophrenic subjects. There was no significant relationship between plasma PRL and cortisol levels in all groups. Age had no influence on biochemical parameters. Our results suggest an altered relationship between 5-HT system, HPA axis activity and PRL secretion in schizophrenia. Antipsychotic olanzapine is a potent antagonist of serotonergic 5-HT2A and dopaminergic D2 receptors. In a naturalistic study the clinical response and safety of olanzapine administration was determined in schizophrenic patients. The long-term (at least 6 months) administration of olanzapine (5-20 mg/day) induced good therapeutic response (improvement in all efficacy measures) with minor side effects and without significant alterations in biochemical parameters. In another, double blind study, clinical efficacy and peripheral biochemical parameters (platelet 5-HT concentration, plasma PRL and cortisol levels) were determined in schizophrenic patients receiving olanzapine (5-20 mg/day) and fluphenazine (6-21 mg/day) over 5 months. After treatment, olanzapine was better than fluphenazine in efficacy measures of PANSS (positive, general psychopathology), BPRS and HAMD (depressive symptoms). No effect of both treatment on the negative simptoms was observed. Platelet 5-HT concentration, although higher in schizophrenic patients than in controls, was not affected by either olanzapine or fluphenazine treatment. There was no correlation between biochemical parameters and clinical efficacy. Treatment with olanzapine, in contrast to fluphenazine, normalized increased plasma cortisol levels observed at baseline in schizophrenic patients. Fluphenazine treatment induced hypercortisolemia, hyperprolactinemia and rigidity. Treatment with olanzapine lacked undesirable neuroendocrine side effects, suggesting that olanzapine was better tolerated than fluphenazine in schizophrenic patients.

platelet serotonin; platelet monoamine oxidase; cortisol; prolactin; serum lipids: cholesterol; triglycerides; HDL; LDL; schizophrenia; pharmacotherapy

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