Neurobiology of Mood Disorders

Mood disorders, including bipolar disorder and major depressive disorders, are frequent and severe psychiatric conditions with a complex diathesis. The search for intrinsic, biological causes has permeated the research on mood disorders in the last decades. Indeed, recent years have seen a tremendous advancement in the comprehension of some of the neurobiological underpinnings of mood disorders, including their genetic architecture, the role of environmental risk factors through modulation of the epigenetic machinery, as well as of the contribution of alterations in the composition of the gut microbiota. In this chapter, an overview on the most recent developments in the field of mood disorders is provided, starting from phenotypic definition and molecular genetics, including results from genome-wide association studies and meta-analyses. Furthermore, results from pharmacogenomic, geneenvironment, epigenomic, metabolomic, gut microbiota, and neuroimaging studies are summarized. The last sections give an overview of cellular and molecular pathogenetic mechanisms, with a focus on transmitter systems, intracellular signal transduction pathways, and neurotrophic factors. The causes and mechanisms of mood disorders are beginning to be investigated at multiple levels of analysis. Research in humans and animal models is clarifying the roles of altered neuromodulator and neuroendocrine systems, and discovering the involvement of intracellular signaling cascades, nerve growth factors, risk genes and their interactions with specific adverse environments, metabolomic signatures, and gut microbiota in the pathogenesis of major depressive and bipolar disorders.