The purpose of this observational study is discovering potential biomarkers to predict antidepressant treatment response in patients with major depressive disorder (MDD) while comparing the transcriptomic changes between patients with MDD and healthy controls as well as before and after antidepressant treatment.

Eligible patients will be assessed at Week 1, Week 2, Week 4 and Week 8 while healthy normal volunteers will only be evaluated at baseline. Assessments will include the following: an interview about mental and physical health, a physical examination including drawing of venous blood samples and several psychiatric rating scales.

This study is focusing on evaluating the peripheral immune system of major depressive disorder (MDD) and the impact of antidepressants treatment. Single-cell RNA sequencing and single-cell VDJ sequencing will be performed on peripheral blood mononuclear cells to collect transcriptome information and immune repertoire of peripheral blood in patients with MDD. Bulk RNA sequencing and flow cytometry will be used to validate the clinical value of results.

This is a biomarker study (antidepressants); treatment will be carried out according to physicians' orders.

Inclusion Criteria:

1. Age 18-65 years old, regardless of gender;
2. The subject is an outpatient/inpatient and meets DSM-5 diagnostic criteria of current or past major depressive disorder;
3. SSRIs or SNRIs monotherapy;
4. HAMD-17 total score ≥ 18 at baseline;
5. The subject can read and write and is capable of giving informed consent.

Exclusion Criteria:

1. Patients with mental illness other than MDD;
2. Patients with liver and kidney diseases, cardiovascular system diseases, cancer, diabetes, thyroid diseases or other serious or unstable conditions;
3. Previous organic brain disease, traumatic brain injury or other diseases that can cause structural brain changes;
4. Serious abnormalities indicated by laboratory tests or electrocardiograms;
5. Alcohol or drug addiction;
6. Suffering from systemic lupus erythematosus, multiple sclerosis or other autoimmune diseases;
7. Patients who are taking drugs that directly impact on the immune system such as anti-inflammatory drugs or immunosuppressants;
8. Patients who have taken antidepressants or other antipsychotics within 2 weeks before enrollment;
9. Patients who have received MECT or systematic psychotherapy within 3 months before enrollment;
10. Patients at high risk of suicide, or reporting a HAMD-17 item 3 (suicide item) score >3 at baseline;
11. Subjects who are pregnant or lactating;
12. Other conditions that are considered not suitable for participating in the research.

Outpatients/inpatients who meet DSM-5 diagnostic criteria of current or past major depressive disorder and are going to receive SSRIs or SNRIs monotherapy.

There is no plan to share IPD.