Major depressive disorder : Neurobiology and neural circuitry of depression


By Rosa Villanueva

Abstract

We survey studies which relate abnormal neurogenesis to major depressive disorder. Clinically, descriptive gene and protein expression analysis and genetic and functional studies revised here show that individual alterations of a complex signaling network, which includes the hypothalamic-pituitary-adrenal axis; the production of neurotrophins and growth factors; the expression of miRNAs; the production of proinflammatory cytokines; and, even, the abnormal delivery of gastrointestinal signaling peptides, are able to induce major mood alterations. Furthermore, all of these factors modulate neurogenesis in brain regions involved in MDD, and are functionally interconnected in such a fashion that initial alteration in one of them results in abnormalities in the others. We highlight data of potential diagnostic significance and the relevance of this information to develop new therapeutic approaches. Controversial issues, such as whether neurogenesis is the basis of the disease or whether it is a response induced by antidepressant treatments, are also discussed.


Introduction

Major depressive disorder (MDD) is one of the most common psychiatric diseases. MDD is not only characterized by profound dysregulation of affect and mood but is also associated with other abnormalities including cognitive dysfunction, sleep and appetite disturbance, fatigue, and many other metabolic, endocrine, or inflammatory alterations ...

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