Biomarcadores de estresse oxidativo na esquizofrenia resistente ao tratamento

Abstract

Schizophrenia is a severe mental disorder affecting around 1% of the world’s population. About a third of the affected population are treatment resistant Schizophrenia (TRS). Several hypotheses were aimed at understanding the neurobiological mechanisms behind TRS, especially the role of oxidative stress; it can worsen the disease and may be a reason of poor response to therapy. Objectives: To evaluate the levels of oxidative stress biomarkers on the schizophrenic patients currently treated at a tertiary healthcare center and to compare to a control group, correlating to psychopathologic, sociodemographic, and clinical characteristics. Methods: Eighty-nine individuals were selected and divided into three groups: 36 healthy control subjects (HC), 26 non-treatment resistant Schizophrenia patients (NTRS) and 27 treatment resistant Schizophrenia patients (TRS). All patients met the criteria for Schizophrenia diagnosis, as proposed by DSM-IV (Diagnostic and Statistical Manual of Mental Disorders). The Kane et al. criteria and IPAP algorithms (International Psychopharmacology Algorithm Project) were also used to determine the presence of TRS. The individuals had peripheral blood drawn for the measurements of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), total glutathione (GSH-t), trolox equivalent antioxidant capacity (TEAC), and levels of lipid peroxidation marker malondialdehyde (MDA), using the methodology of spectrophotometry. Lipid profiles, clinical and sociodemographic data were collected to compare and correlate biomarkers. Positive and Negative Syndrome Scale (PANSS) was applied for Psychopathology assessment. The statistical analysis employed the chi-square test, Fisher’s exact test, Mann-Whitney test, Kruskal-Wallis test and Spearman’s correlation. Results: NTRS and TRS groups had significantly decreased activity of SOD and increased levels of MDA than HC group; while CAT, GPx, GSH-t and TEAC levels remained similar among all groups. NTRS and TRS groups had similar levels of biomarkers; however, TRS group had decreased all of them. There was statistical significance, in the TRS group, in positive correlation between CAT with PANSS positive scale and ziprasidone, GSH-t with glucose and risperidone, MDA with HDL and negative correlation between GPx with patients age, SOD with BMI, CAT with CHO and chlorpromazine, GSH-t with VLDL and TG. NTRS group had positive correlation between GPx with VLDL and TG and negative correlation between CAT with PANSS positive scale. Conclusion: Decreased levels of SOD and higher levels of MDA are associated with Schizophrenia. Decreased levels of all biomarkers in TRS group, compared to NTRS, although without significant difference, suggests a tendency to decrease biomarkers in treatment resistant Schizophrenia. CAT can be considered an indicator of severity of psychopathology. Correlations between oxidative stress biomarkers, metabolic profile and antipsychotics suggests that oxidative stress in treatment resistant Schizophrenia is associated to treatment and should be better evaluated in further longitudinal design studies.