Major depressive disorder afflicts ~16% of the population and is a leading cause of disability worldwide. Classical antidepressants take weeks-to-months for clinical efficacy and only a sub-population of patients responds to treatment, highlighting the need for the development of novel rapid-acting and effective pharmacotherapies. Hypogonadism, the decrease in the production of gonadal hormones occurring due to ageing or several other medical conditions, has been associated with an increased risk for development of mood disorders, including depression. Accumulating evidence suggests that epigenetic changes induced by stress or other environmental factors might also contribute to the development of depression; however, the reciprocal interactions between hypogonadism, stress, epigenetic modifications and depression has received limited attention. During this project, my in-depth knowledge in studying the role of gonadal hormones in the pathophysiology of mood disorders will be combined with expertise of the Host lab in assessing epigenetic mechanisms of disease, to identify novel associations between hypogonadism and epigenetic modifications underpinning and/or predicting susceptibility for depression development. In particular, EstroGen proposes an interdisciplinary approach to investigate the combinatorial effect of hypogonadism/stress on epigenome and their role in depression, using preclinical models. In addition, this project aims to identify hypogonadism-related epigenetic biomarkers to predict subsequent development of depression. Importantly, this fellowship will propel my academic career and help me become a scientific leader at the interface of epigenetics, gonadal hormones and mood disorders, by acting as a stepping stone towards securing future research funding and acquiring a tenure track position in Europe.
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