Evaluation of neuropeptides and amino acids to elucidate the neurobiology of psychiatric diseases

Author(s)

Marina Salviato Balbão Santiago Fonseca

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC)
• Defense date: 2012-09-04

Examining board members

Regina Helena Costa Queiroz; Isarita Martins; Antonio Waldo Zuardi

• Advisor: Regina Helena Costa Queiroz; Jaime Eduardo Cecilio Hallak

Abstract

Neuropsychiatric disorders are among diseases with high incidence, difficult to identify and with varied predictions. Among them stands out schizophrenia, a brain functional disease essentially characterized by fragmentation of the basic structure of thinking processes, accompanied by difficulty to distinguish between internal and external experiences. The present study aims to investigate cardiac risk in schizophrenic patients due to weight gain caused by the use of antipsychotic olanzapine, as well as evaluating the levels of neuropeptides related to energy balance in order to establish the mechanism of action responsible for such weight gain. As the conclusive identification of etiological or pathogenic factors of neuropsychiatric disorders remains unknown, the work also aims to assess the plasma levels of some neurotransmitter amino acids, correlating them with these disorders. For the evaluation of cardiac risk and the possible mechanism of weight gain, a group of 30 patients diagnosed with schizophrenia and at the start of olanzapine therapy underwent anthropometric evaluations and biochemical quantification of serum ghrelin, leptin, and neuropeptide NPY polypeptide YY 12 months. The investigation of the correlation between neuropsychiatric disorders and amino acids was performed in other 150 individuals divided into five groups of 30 persons, patients with schizophrenia, epilepsy, depression and bipolar disorder, which were compared to a control group. The results obtained for the study of cardiac risk were demonstrated by the significant increase in weight, body mass index and waist and hip circumferences. Regarding biochemical parameters, there were no clinically significant changes in cholesterol, triglycerides, LDL-cholesterol, glucose, insulin and cortisol. Concerning neuropeptides, we could observe a significant increase in ghrelin and neuropeptide NPY. Plasma levels of nonessential amino acids, glutamate, aspartate, serine, glycine and arginine, in turn, were significantly altered in neuropsychiatric disorders. Glutamate showed a highly significant increase in all studied neuropsychiatric disorders, showing the close correlation between this amino acid and the aforementioned disorders, as well as the glutamatergic hyperfunction hypothesis at peripheral level, that is, plasma levels. In this context, it was observed that therapy with olanzapine increases cardiac risk due to augmented release of orexigenic hormones, which can compromise the quality of life of patients by promoting metabolic syndrome. Thus, it contributes to elucidation of this striking side effect of olanzapine which is the weight gain. It was also clear that the determination of plasma amino acids, combined with other evaluation techniques in research and development, may serve as biomarkers for neuropsychiatric disorders, as well as preventive measures and the establishment of a new perspective for future targets adjuvant therapy for neuropsychiatric drugs. (AU)

• FAPESP's process: 10/00900-3 - Evaluation of neuropeptides and amino acids to elucidate the neurobiology of psychiatric diseases
• Grantee: Marina Salviato Balbão Santiago Fonseca
• Support Opportunities: Scholarships in Brazil - Doctorate