Study participants

The inclusion criteria for the patient with TRD were as follows [24]: (1) 18–65 years old; (2) recent diagnosis of depression by ICD-10 criteria for a mood disorder and depressive episode; (3) diagnosis of antidepressant resistance: recurrent attacks in recent 3 years after two or more depressants treatment; (4) no history of taking any other drugs; and (5) the total score of the Hamilton Depression Scale (HAM-D) was higher than 17, indicating mild to moderate depression. Before treatment, the patients were re-evaluated with HAM-D. At the same time, blood samples were collected simultaneously with symptom self-evaluation and before treatment. Subjects in the healthy control group matched the age of patients with depression; they (1) had no history of depression, (2) had a HAM-D score of 0-4 for more than 8 weeks, and (3) exclude any of the conditions described in the criteria. Participants (healthy controls and depressed patients) were excluded from the study if they had severe personality disorders, risk of suicide, pregnancy, thyroid disease, use of any psychotherapy, and participation in any other psychiatric intervention study.

This study was approved by the Nanjing First Hospital Organization evaluation committee, showed in supplementary information. All eight participants provided informed consent before signing up.