Depression is an illness in which the reaction to stress and genetic vulnerability come together in such a way that the emotional tone and evaluation of information becomes biased in a negative direction. The pathophysiology lying behind these changes involves monoamine systems as well as the hypothalamus-pituitary-adrenal (HPA) axis and leads to changes in neuronal plasticity, as reflected by decreased levels of neurotrophins, decreased proliferation of neuronal precursors and, most importantly, changes in synaptic structure and function. These concepts are based on indirect evidence from human studies and have been confirmed by animal studies, allowing assessment of behavior as well as detailed functional and structural analyses. Several animal models, namely stress models and genetic models, have demonstrated a good validity for human depression and provided evidence for synaptic pathology in depression.

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