Still unknown and in many aspects controversial the etiology and subsequent psychopathology of depression appears to result from a complex interaction between psychosocial and biological factors.

The aim is to conduct a review of the literature on the neurobiological mechanisms and its relation to the psychopathologic manifestations of depressive disorder.

A literature search was carried out, selecting articles published between 2000 and 2013.

From a biological point of view, the first conceptual hypothesis considered the decrease of brain monoaminergic neurotransmitters as responsible for the occurrence of depressive symptoms. However, subsequent investigation led to models that suggest the existence of more complex neuroregulatory mechanisms. Neuroendocrine systems, specific molecular processes and different brain structures and neural circuits were implicated in mood regulation and stress response. Furthermore, a correlation between the distinct cerebral regions affected and specific depressive symptoms was found.

The current theories attempt to integrate the various etiologic aspects of depression. Although there are still no definitive conclusions, recent research has emphasized the importance of the association between genetic vulnerability, neurodevelopmental factors, environmental events and epigenetic modifications, that lead to neurochemical, neuroendocrine, neurostructural and neurofunctional changes in several brain areas, which in turn are reflected in the psychopathology of depressive disorders.