I. Effects of depression on the brain: (a) Compared with healthy individuals, depressed patients have decreased gray matter volume in some brain regions. The gray matter density in the hippocampus, amygdala, and dorsomedial prefrontal cortex of the brain was significantly decreased in depressed patients. Frodl TS et al. Arch Gen Psychiatry. 2008;65(10):1156-1165. (ii) Depression severity and brain-derived neurotrophic factor (BDNF) are negatively correlated. That is, the more severe the depression, the less brain-derived neurotrophic factor. Second, depression: what prevents patients from getting a better treatment outcome? The key to depression treatment: timely and thorough (a) The dangers of untimely and delayed treatment of depression: delayed treatment is associated with hippocampal volume reduction and predicts ineffectiveness of subsequent antidepressant treatment. That is, untimely treatment of depression may lead to a reduction in the bilateral hippocampal gray matter volume of the patient’s brain; and a reduction in hippocampal volume means that future antidepressant treatment is ineffective or inefficient. (B) The hazards of incomplete treatment of depression and failure to achieve clinical cure: 1. Significant decrease in gray matter density in some brain regions: anterior cingulate cortex dorsomedial prefrontal cortex dorsolateral prefrontal cortex Effective treatment can restore the normal function of prefrontal and limbic loops and minimize the risk of future structural brain changes. 2. Increased risk of recurrence and shorter time to recurrence. Any residual symptoms of depression may be a reflection of the active state of the disease and can increase the risk of relapse. Timely and effective treatment of depression and elimination of all residual symptoms can reduce the chances of relapse.