Aerobic Exercise Does Not Predict Brain Derived Neurotrophic Factor And Cortisol Alterations in Depressed Patients Murilo Khede Lamego, Antonio Marcos de Souza Moura, Flávia Paes, Nuno Barbosa Ferreira Rocha, Alberto Souza de Sá Filho, Eduardo Lattari, Ridson Rimes, João Manochio, Henning Budde, Mirko Wegner, Gioia Mura, Oscar Arias-Carrión, Ti-Fei Yuan, Antonio Egidio Nardi and Sergio Machado Abstract: The pathophysiology of depression is related to neurobiological changes that occur in the monoamine system, hypothalamic-pituitary-adrenal axis, neurogenesis system and the neuroimmune system. In recent years, there has been a growing interest in the research of the effects of exercise on brain function, with a special focus on its effects on brainderived neurotrophic factor (BDNF), cortisol and other biomarkers. Thus, the aim of this study is to present a review investigating the acute and chronic effects of aerobic exercise on BDNF and cortisol levels in individuals with depression. It was not possible to establish an interaction between aerobic exercise and concentration of BDNF and cortisol, which may actually be the result of the divergence of methods, such as type of exercises, duration of the sessions, and prescribed intensity and frequency of sessions. Keywords: Aerobic exercise, biomarkers, brain derived neurotrophic factor, cognition, cortisol, depression. INTRODUCTION Depression is related to several neurobiological changes [1, 2]. Research on the possible molecular pathways of depression demonstrated that the increased cell dysfunction in cortical and limbic areas of the brain can be observed in individuals suffering from depression [3, 4] and is strongly related to the decrease in neurotrophic activity [5]. Therefore, the investigation of biomarkers, such as brainderived neurotrophic factor (BDNF), has attracted great interest, in order to clarify its role in the pathophysiology of depression [6]. BDNF is a protein expressed mainly in the central nervous system (CNS), and it has an important role in the survival and maintenance of neuronal function [7]. In fact, a low neurotrophic activity is associated with reduced numbers of cells in the prefrontal cortex [8], amygdala [9, 10] and a decrease in hippocampal volume [11, 12], indicating that the growth nerve factors, and more specifically, the changes in BDNF may play an important role in the development of depression [3, 4, 13-15]. Furthermore, the dysfunction of the hypothalamuspituitary-adrenal (HPA) axis has been the most valid neurobiological theory to explain the pathophysiology of depression. The HPA axis is the interaction between the hypothalamus, pituitary gland, and the adrenal cortex, and is a major part of the neuroendocrine system that controls reactions to stress [16]. The clinical manifestation of its dysfunction in depression includes basal hypercortisolemia [17], elevated cortisol secretion in the dexamethasone suppression test [18], and increased cortisol release in the combined dexamethasone suppression-corticotropine releasing hormone stimulation test [19, 20]. The first line of treatment for depression is the use of antidepressants [21]. However, the remission rate with selective serotonin reuptake inhibitor (SSRI), which is currently the first- line treatment for depression, is only 60% [22]. Exercise is a readily available therapeutic option, effective as a treatment in mild to moderate depression [23] Regular exercise may bring