Associação entre neurotrofinas, estresse oxidativo e marcadores inflamatórios e psicopatologia na infância

• Ano de defesa: 2016
• Autor(a) principal: Asevedo, Graccielle Rodrigues da Cunha [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Inflammation; Psychopathology; Childhood; Neurotrophyns; Inflamação; Psicopatologia; Infância; Neurotrofinas; Estresse oxidativo
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=3805913; http://repositorio.unifesp.br/handle/11600/47036

The first manifestations of mental disorders (MD) usually occur in childhood and adolescence. Recently, MD have been characterized as neurodevelopmental disorders. The course and clinical presentation of MD are influenced by risk and protective factors in different ways in specific developmental windows. Several biomarkers related to neurotrophism, oxidative stress and inflammation have been investigated among the factors that potentially influence underlying pathophysiological processes in psychiatric disorders. This dissertation will include a review of the literature contextualizing the study of neuroplasticity biomarkers for mental disorders in childhood and an original article exploring the relationship between neuroplasticity biomarkers and child psychopathology. Neuroplasticity is a broad term that encompasses a variety of structural and functional mechanisms involved in the brain?s perception and adaptation in the face of external and internal stimuli. Several molecules and proteins are involved in these processes, among them neurotrophins, and oxidative stress and inflammation mediators. Neurotrophins, of which the brainHderived neurotrophic factor (BDNF) is a major representative, are a class of proteins known as growth factors directly involved in the processes of differentiation, proliferation and survival of neurons. Oxidative stress is a process of imbalance between production of ROS, reactive oxygen species generated by cells oxygen metabolism, and their consumption by antioxidant molecules. Inflammation is a process by which a body reacts to aggression and it is mediated by various molecules including cytokines. Overall, there were no marked associations between the concentration of BDNF and child psychopathology. High levels of BDNF were found in women, particularly in children with a diagnosed psychiatric disorder. This result reinforces findings that the influence of BDNF in mental disorders may be mediated by gender and that BDNF changes can be found late in the development of mental disorders. High levels of oxidative stress markers were particularly associated with externalizing symptoms, especially aggression and defiant behavior in children with a psychiatric diagnosis and in the total sample. 101 In children with a psychiatric diagnosis, we found serum levels of ILH6 increased significantly only in internalizing symptoms such as anxiety and depression. However, there was an association between ILH6 and different groups of symptoms in CBCL in typical children, pointing to a possible involvement of this interleukin in other underlying aspects of psychopathology, even in the absence of depression. High levels of sTNFR2 were negatively associated with overall scores in CBCL as well as with various subgroups of symptoms, possibly featuring a neuroprotective action of this receptor, indicating a new target in studies of resiliency mechanisms. This is the first study to examine the relationship between a wide range of peripheral biomarkers of neuroplasticity and inflammatory activity and measures of general psychopathology in both clinical and nonHclinical populations. These results reinforce the findings that there is an association between biomarkers of neuroplasticity and general psychopathology in children even in the absence of specific MD. Additional research on the significance of these associations can provide new perspectives in this field. The followHup of this cohort will provide data on the potential predictive role of these biomarkers and can clarify some of the issues raised by the current findings.