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.
Highlights
Major depressive disorder (MDD) is one of the most common psychiatric diseases
Assays to evaluate HPA dysfunction, such as the dexamethasone suppression test or the dexamethasone/corticotropin releasing hormone test, have been useful to establish objective parameters in the diagnosis of endogenous mood disorders and to predict response to antidepressant treatment [57,58,59]. Regardless of whether these alterations are at the origin (i.e., Cushing disease) or are a consequence of MDD, it is important to remark that the elevated levels of stress and glucocorticoid hormones interfere with normal hippocampal neurogenesis [60] contributing to the development of the disease
The evidence surveyed in this review supports a primary involvement of disturbed adult neurogenesis and altered synaptic connectivity in the origin of MDD
Summary
Major depressive disorder (MDD) is one of the most common psychiatric diseases. MDD is characterized by profound dysregulation of affect and mood but is associated with other abnormalities including cognitive dysfunction, sleep and appetite disturbance, fatigue, and many other metabolic, endocrine, or inflammatory alterations (see [1, 2]). MDD is often termed unipolar depressive disorder to be distinguished from depression which alternates with episodes of mania which is termed bipolar depression The latter is potentially distinguishable by functional neuroimaging approaches [3]. The purpose of this review is to summarize information accumulated in the last two decades concerning gene and protein expression changes in MDD [4]. These data suggest that the pathophysiology of this disease is related to disturbed adult neurogenesis [5, 6] and, without doubt, will help develop new therapeutic and diagnostic tools in the near future [2, 7]. These factors may influence both overall risk of illness and the sensitivity of individuals to the environmental adversities
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