Evolução das alterações no metabolismo energético cerebral ao longo dos diferentes estágios do transtorno bipolar

• Ano de defesa: 2015
• Autor(a) principal: Mansur, Rodrigo Barbachan [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: bipolar disorder; clinical stages; metabolism; obesity; diabetes mellitus; insulin resistance; adipokines; stress; copeptin; oxidative stress; transtorno bipolar; metabolismo; obesidade; síndrome metabólica; estadiamento
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=2693730; https://repositorio.unifesp.br/handle/11600/46329

Metabolic comorbidities are frequent in individuals with bipolar disorder (BD), including a high prevalence of diabetes mellitus and metabolic syndrome in this population. Several biological systems related to energy metabolism have been shown to be altered in BD, but the pathophysiology of metabolic changes in BD remains largely unknown. Recent theories postulate that the brain prioritizes its own energy supply, modulating the peripheral metabolism through the regulation of allocation and nutrient intake ("selfish brain? theory). The studies that compose this thesis were based on the hypothesis that the metabolic changes observed in BD are the result of an inefficient regulation of brain energy supply and its compensatory responses. The aim was to investigate the relationship between energy metabolism and clinical and biological characteristics of BD over the course of the illness. Towards this aim we conducted a casecontrol study comparing three groups: 30 patients with BD in the early stages (defined as less than 5 episodes of mania or depression), 30 patients with BD in late stages (defined as more than 5 episodes of mania or depression) and 30 healthy volunteers. All subjects were submitted to standardized psychiatric interview and blood sampling for analysis of markers of glucose metabolism, oxidative stress, stress response, lipids and regulatory hormones. The results demonstrate that the presence of metabolic comorbidities moderate clinical and biological features of the disease. Patients in the late stages of BD had a higher prevalence of metabolic comorbidities, when compared to patients in the early stages and healthy controls. Conversely, the presence of metabolic abnormalities (e.g. insulin resistance and dyslipidemia) was associated with an unfavorable course of BD, characterized by a higher number of previous mood episodes and poor psychosocial functioning. Furthermore, the stages of BD and the presence of impaired glucose metabolism or diabetes mellitus impacted the activity levels of the antioxidant enzymes 17 glutathione peroxidase and superoxide dismutase. Finally, it was also documented that in patients with BD, broad changes in energy metabolism, such as abnormalities in glucose metabolism, leptin levels and activity of antioxidant enzymes were associated with activation of the stress response system, assessed by levels of the biomarker copeptin. All results described herein were independent of keys confounders such as socio-demographic characteristics, smoking and use of psychotropic medications. In conclusion, not only BD is frequently associated with metabolic comorbidities, but they also affect several different domains of the illness, as demonstrated by the results of the studies that comprise this thesis. The differences in course, psychosocial functioning and pathophysiological substrates observed among patients with BD in the late and early stages, as well as between patients and controls, indicate that metabolic systems are, in fact, prominently involved in BD pathophysiology and are therefore promising targets for the development of future clinical and therapeutic investigations.