engleski

Peripheral biological markers and treatment response in schizophrenia

Schizophrenia is a severe, chronic mental disorder that appears in 1% of the population. The abnormal neurotransmission of serotonin (5-hydroxytryptamine, 5-HT), dopamine, noradrenalin, and altered neuroendocrine function are implicated in the pathophysiology of schizophrenia. Peripheral biochemical markers might be used to improve the understanding of the underlying neurobiology of schizophrenia, for the preclinical screening, diagnosis, disease staging, and monitoring of treatment. Since there are striking similarities how both central nervous system and platelets store and metabolize 5-HT, blood platelets have been widely used as a peripheral model for the central serotonergic synaptosomes. The dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity and altered secretion of prolactin (PRL) and plasma lipids levels are frequently found in schizophrenia. Clinical diagnosis of schizophrenia was made according to the DSM-IV criteria. Main outcome measures were scores in Positive and Negative Syndrome Scale, Clinical Global Impression of Severity (CGIS) or Change (CGIC), Hamilton Rating Scale for Depression (HAMD), and HAMD subscale for suicidal behavior. Control group consisted of drug free healthy persons with no personal or family history of psychopathology. Biomarkers studied were: platelet 5-HT concentration, platelet monoamine oxidase (MAO) activity, serum lipids levels: cholesterol, triglycerides, high density lipoprotein cholesterol (HDL-C), low density lipoproteins cholesterol (LDL-C), plasma PRL levels and cortisol levels at baseline and after dexamethasone suppression test (DST). Biomarkers were determined using spectrofluorimetric, radioimmunoassay, immunoradiometric methods, enzymatic color test and enzymatic clearance assay. Schizophrenic patients had higher values of platelet 5-HT, cortisol and PRL, abnormal cortisol response DST, and lower values of cholesterol, HDL-C and LDL-C than healthy controls. Platelet 5-HT concentration was correlated to 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, and abnormal DST response in schizophrenia. The effects of different neuroleptics (fluphenazine, haloperidol) or atypical antipsychotic (olanzapine) on peripheral biochemical markers, clinical response and safety were studied in naturalistic, comparative or double-blind studies in schizophrenic patients. Our data suggest that the evaluation of the peripheral biological markers might improve the characterization of the baseline group characteristics, might be used to predict a suicidal risk, to help to differentiate particular symptoms, or syndromes, and to predict the treatment response in schizophrenia.

biomarkers, platelets, serotonin, monoamine oxidase, cortisol, prolactin, plasma lipid levels, schizophrenia, treatment response

Chapter 15