During decades, both aetiology and treatment in Depressive Disorders relied on neurotransmitters' physiopathology or on abnormalities in their receptors function. However, recently evidences from research on neurobiological grounds suggest that there are multiple and complex systems involved in the pathophysiology of Depressive Disorders. Several neurobiological structures, such as the neural, immune and endocrine systems seems to interact among themselves and to influence on clinical

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... ions of illness. Moreover, dysregulations on lower levels, such as intracellular and genetic systems might cause anomalies in protein expression, and in consequence might modulate receptors' disfunction and disturbances at the intramolecular level of signal transmission. The above disturbances at different levels of complexity are finally integrated within the frame of most recent theoretical approaches to Depressive Disorders. Specifically, recent theories implicating neuronal plasticity and survival-death cell mechanisms are described. The aim of this review is to integrate recent evidence on pathophysiological mechanisms of Depressive Disorders. New lines of treatment based upon these 'new pathophysiology' of depression will be wellcome.