The project is a multi-center, prospective cohort study. The study's total targeted enrollment is 400 first-episode patients with major depressive disorder (MDD) and 400 healthy controls.

Four hundred patients with a primary diagnosis of depression and HAMD-17 scores ≥14 at baseline visit are to be assigned to one of the second-generation antidepressant drugs, including escitalopram, duloxetine, mirtazapine, paroxetine, sertraline, etc based on investigators' clinical practice. Initial treatment consists of a 8-week course with one of these monotherapies. Patients who meet criteria for full remission are followed for a 22-month follow-up phase to monitor for depression recurrence. Patients who do not remit are offered another 8 weeks of acute treatment, including combination therapy or switching to other antidepressant based on investigators' clinical practice. The clinical assessment (Hamilton Depression Rating Scale(HAMD)/ Clinical general impression (CGI) /the Positive and Negative Affect Schedule (PANAS) /subtypes of depression, Dimensional Anhedonia Rating Scale (DARS) , etc), early life stress, neuropsychological test, and biological examination (MRI, genetics, neurochemistry, and immunology) were conducted to identify the biomarkers associated with diagnosis, treatment efficacy prediction of depression. Among the 400 patients, about 100 patients receive MRI scans at baseline and after treatment.

Inclusion Criteria:

1. Patients with depression

• The inclusion criteria for depressed patients were: male or female outpatients aged between 18 and 55 years old
• Currently in acute depressive episode
• Total HAMD-17 score≥14 at baseline visit.
• The diagnosis of depression was confirmed by a trained psychiatrists using the Mini-International Neuropsychiatric Interview (MINI).
• The patients participating in imaging scans should additionally satisfy: not taking psychiatric drugs within last two weeks (except for benzodiazepine) or fluoxetine last one month
• Not receiving ECT within last 6 months.

Exclusion Criteria:

• Unable to complete the questionnaire and psychological assessment independently
• Significant cognitive impairments determined by system mental examination and inability to sign an informed consent form
• Past or presently suffering from other psychiatric disorders, alcohol and drug dependence
• Suffering from major physical diseases, such as cardiovascular and cerebrovascular diseases, respiratory diseases, kidney disease, cancer and so on; personality disorder
• Intellectual disabilities
• Suicidal behavior
• Being participating in other studies.

Patients with major depressive disorder