New therapeutic strategy for mood disorders

The development of new treatments for mood disorders, as anxiety and depression, is based on identification of neural substrates and the mechanisms underlying their etiology and pathophysiology. The heterogeneity of mood disorders indicates that its origin may lie in dysfunction of multiple brain regions (amygdala, nucleus accumbens, hippocampus, prefrontal cortex and cingulate cortex). The hippocampus of patients with depression show signs of atrophy and neuronal loss. This suggests the contribute of new neurons to the biology of mood disorders that is still under debate. The production of new neurons, referred to as neurogenesis, occurs throughout life in discrete brain areas such as the dentate gyrus (DG) of the hippocampus and the subventricular zone/olfactory bulb. Findings describing that neurogenesis process in DG is increased by antidepressants, like fluoxetine, and it is required for the behavioral effect of antidepressants, lead to a new strategy and drugs for the treatment of mood disorders. As many patients display poor response to therapy, research on depression and antidepressant drugs is necessary. In this regard, focusing on neurogenesis and neuroplasticity processes in experimental models is particularly interesting for the understanding of the pathophysiology of mood disorders and should define the role of adult-born neurons in hippocampal physiology. Different classes of drugs are currently prescribed for the treatment of mood disorders. Among them selective serotonin reuptake (SSRIs), monoamine oxidase inhibitors (MAOIs), specific norepinephrine reuptake inhibitors (SNRIs) and tricyclic acids (TCA) alleviate symptoms of mood disorders. Here we review different strategies that may be adopted for impairing mood disorders and that may be further developed for innovative therapeutic approaches.