Figure 1.

Interaction between the components involved in the neurobiology of MDD. Vulnerability factors can lead to development of MDD due to induction of changes in the central nervous system including the neuroendocrine homeostasis, neurochemical alterations, and neuroplasticity impairment. The core response to stress is the HPA axis activation resulting in high circulating levels of glucocorticoids. This endocrine response leads to neuroimmune activation, inhibition of monoaminergic and facilitation of glutamatergic neurotransmissions. These systems interact, and the overall result is impairment of the neuroplasticity in cortical and limbic structures. Neuroplasticity alterations include decreased levels of neurotrophic factors (e.g., BDNF), dendritic atrophy, diminished neurogenesis and synaptogenesis and glial cells dysfunction. Impaired neuroplasticity further contributes to neurochemical imbalances. Green arrows indicate stimulation while red arrows represent inhibition. White arrow with green border means that a stimulating action was blocked. HPA: hypothalamic-pituitary-adrenal; BDNF: brain-derived neurotrophic factor.