Seite - (000133) - in Biomedical Chemistry: Current Trends and Developments

Ma-Li Wong, Martin Lewis and Julio Licinio* 2.2 Translational Research in Endocrinology and Neuroimmunology Applied to Depression 2.2.1 Major Depressive Disorder Major depressive disorder (MDD) is a complex chronic illness of gene environment-interactions with enormous medical, social and economic impact. It affects 1.4 million Australians yearly, having the highest non- fatal disease burden and being the nation’s leading cause of disability (Tempier, 2009). MDD is a major cause of suicide, which accounts for the third highest fatal disease burden in Australian men (Tempier, 2009). MDD has considerable morbidity and mortality (Wong & Licinio, 2001, 2004). Currently, the point prevalence of this disorder ranges around 4−7% and the lifetime prevalence estimate is about 15-20% (Kessler, 2005; Kessler, 1994). In Australia, depression is the most common mood disorder, affecting 6.2% of the population (Lohoff, 2010), it is the largest single cause of nonfatal disease burden and the leading cause of disability (Vos, 2004). By the year 2020, MDD will become the second most important contributor to the global burden of disease (Lopez & Murray, 1998). However, MDD has been one of the oldest medical mysteries, described since Hippocrates (460-37 BC) as melancholia (μελαγɛολια). It has been extensively studied in the past forty years; however, we continue to understand little about its fundamental biology (Kessler, 2005; Kessler, 1994; Licinio & Wong, 2011) and the genetic factors conferring susceptibility to this disorder (Sullivan, 2012). The following findings provide persuasive evidence for a role of the stress system in the pathophysiology of MDD: a) antidepressants directly down regulate the hypothalamic-pituitary-adrenal (HPA) axis function; b) antagonism of corticotropin-releasing hormone (CRH) reduces neuroendocrine, autonomic, and behavioural responses to stress in primates, and c) increased cerebrospinal fluid (CSF) concentrations of noradrenaline are increased around the clock, including in sleep, which