RESUMO
Brain-derived neurotrophic factor (BDNF) and the immune-inflammatory response system (IRS) have been implicated in the pathophysiology of schizophrenia. However, no research examined the associations between BDNF and immune activation both before and after treatment in antipsychotic-naïve first episode psychosis (AN-FEP). This study aims to examine serum BDNF levels and their association with IRS and the compensatory immune-regulatory reflex system (CIRS) in AN-FEP before and after risperidone treatment. We included 31 AN-FEP and 22 healthy controls. AN-FEP showed reduced levels of BDNF as compared to controls, and BDNF levels normalized after treatment with risperidone. BDNF levels were inversely correlated with a greater IRS response. Higher levels of IRS/CIRS biomarkers were associated with lower levels of BDNF including M1 macrophage, T-helper (Th)-1, Th-2, and Th-17, and T-regulatory (Treg) cell responses. Our findings indicate that AN-FEP is characterized by decreased levels of BDNF, which are normalized after treatment with risperidone. BDNF levels were inversely associated with activated immune-inflammatory pathways. The findings support the hypothesis that, increased IRS is linked to neurotoxicity, and that a decrease in BDNF may be part of the IRS/CIRS responses in FEP and, thus, be involved in the development of psychosis.
Assuntos
Antipsicóticos , Transtornos Psicóticos , Esquizofrenia , Antipsicóticos/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo , Humanos , Transtornos Psicóticos/tratamento farmacológico , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológicoRESUMO
Psychotic disorders are accompanied by activation of the immune inflammatory response system (IRS). The compensatory immune-regulatory system (CIRS) is a regulatory immune response that is induced by the IRS but exerts negative feedback through increased levels of anti-inflammatory cytokines such as interleukin (IL)-4, IL-13 and IL-10. This study aims to examine the IRS and CIRS components, including macrophagic M1, T-helper (Th)-1, Th-2, Th-17 and T-regulatory (Treg) phenotypes, in antipsychotic-naïve first episode psychosis (AN-FEP) before and after risperidone treatment. We included 31 AN-FEP and 22 healthy controls. AN-FEP showed increments in M1, Th-1, Th-2, Th-17 and Treg phenotypes and a relatively greater IRS response (especially granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6 and IL-12) as compared with the CIRS response. Inflammatory markers, especially IL-6 and IL-8, were significantly correlated with negative, psychotic, affective and excitation symptom dimensions. Treatment with risperidone significantly suppressed the IRS and CIRS. Baseline levels of CIRS biomarkers, especially higher soluble tumor necrosis factor receptor-1 and IL-10 predicted clinical improvement after treatment. Our findings indicate that AN-FEP is characterized by robust IRS (M1â¯+â¯Th-1â¯+â¯Th-17) and CIRS responses, suggesting that monocytes, macrophages, Th-1, Th-2, Th-17 and Treg cells are activated. The findings indicate that (a) FEP patients are prone to the detrimental effects of M1, Th-1, Th-17 and Th-2 cells, which may contribute to long-lasting abnormalities in brain circuitry; and (b) in FEP, the CIRS may contribute to recovery from the acute phase of illness. Enhancing the CIRS might be a new drug target to treat FEP.
Assuntos
Antipsicóticos/uso terapêutico , Citocinas/metabolismo , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/imunologia , Risperidona/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Receptores de Citocinas/metabolismo , Adulto JovemRESUMO
BACKGROUND: Schizophrenia is accompanied by increased lipid peroxidation and nitric oxide (NO) levels and by lowered antioxidant levels. However, the effect of antipsychotic agents on these processes remains unclear. The objective of this study is to determine the oxidative stress (OS) status in drug naïve first-episode psychotic patients (FEP) compared to healthy controls and to delineate the effects of risperidone on these biomarkers. METHODS: 51 drug naive FEP patients and 61 healthy controls were enrolled; FEP patients were reassessed 11 weeks after risperidone treatment. Three OS biomarkers, i.e. lipid hydroperoxides - LOOH, NO metabolites - NOx, and advanced oxidation protein products - AOPP, and two antioxidant biomarkers, i.e. total radical-trapping antioxidant parameter - TRAP, and paraoxonase 1 - PON1, were measured. The Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS) were used to measure symptoms severity. RESULTS: Significantly lower PON1 activity and increased TRAP values were found in FEP patients. There were no significant associations between any of the OS/antioxidant biomarkers and clinical data. Risperidone treatment significantly increased PON1 activity and decreased LOOH levels. These effects of risperidone were not significantly associated with the clinical response and risperidone dosage. DISCUSSION: Changes in antioxidant profile, but not in lipid or protein oxidation or increased NO production, were found in drug-naive FEP. Risperidone may have antioxidant effects by lowering lipid peroxidation and increasing the antioxidant defenses against lipid peroxidation related to PON1. None of the biomarkers predicted treatment outcome.
Assuntos
Antioxidantes/farmacologia , Antipsicóticos/farmacologia , Peroxidação de Lipídeos , Estresse Oxidativo , Transtornos Psicóticos , Risperidona/farmacologia , Esquizofrenia , Antioxidantes/administração & dosagem , Antipsicóticos/administração & dosagem , Biomarcadores/sangue , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Transtornos Psicóticos/sangue , Transtornos Psicóticos/tratamento farmacológico , Risperidona/administração & dosagem , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Resultado do TratamentoRESUMO
Bipolar disorder (BD) usually follows a neurobiological progression pathway, but a relatively long interval between the first symptoms of the disorder and the correct diagnosis and treatment takes place in most patients. Strategies used to recognize BD at an early stage and even prior to the first manic episode could help identify the risk and modifying factors that influence the onset and course of disease, and improve outcomes. Drawing on current research results, this article presents considerations on risk factors for the development of BD, including genetic/familial risk, endophenotypes and clinical characteristics. Taken together, this article provides a framework and tools for research on the BD prodrome, as well as for the early recognition and timely treatment of patients prior to and immediately after the emergence of BD.