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Depression is a heterogeneous group of syndromes comprised of numerous diseases of distinct causes and pathophysiologies. Recently, several promising hypotheses of depression and antidepressant action have been formulated. These hypotheses are largely based on dysregulation of neural plasticity, CREB, BDNF, corticotropin－releasing factor, glucocorticoid, hypothalamicpituitary adrenal axis and cytokines. Recent work has revealed that several brain regions such as hippocampus, prefrontal cortex, amygdala, nucleus accumbens, and other hypothalamic nuclei are involved in the neural circuit of depression. The brain regions are critical in regulating memory, mood, motivation, sleep, eating, circadian rhythm and responses to rewarding and adverse stimuli, which are all abnormal in depressed patients. The neurobiological understanding of depression will fundamentally improve the treatment and prevention of that illness.
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