Association of Peripheral Immune Cells With Antidepressant Treatment Response

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.

• Mental assessments (Diagnostic test), also known as Psychiatric rating scales: Patients will receive psychiatric rating scales evaluation every visit.

Primary outcomes

• Change of HAMD-17 (Hamilton Depression Rating Scale) total score [From baseline to Week 8]: The overall score of HAMD-17 (Hamilton Depression Rating Scale) is 68 points. Primary outcome measures the change of HAMD-17 total score between baseline and week 8. Larger reduction in HAMD-17 represents better antidepressant treatment response.

Secondary outcomes

• Effective rate measured by HAMD-17 (Hamilton Depression Rating Scale) [From baseline to Week 8]: A reduction of 50% or more in the HAMD-17 (Hamilton Depression Rating Scale) total score. More patients with a reduction of 50% or more indicates better effectiveness. Minimun value of HAMD-17 is 0 and maximum value of HAMD-17 is 68 points.
• MADRS Effective rate measured by MADRS (Montgomery-Åsberg depression rating scale) [From baseline to Week 8]: A reduction of 50% or more in the MADRS (Montgomery-Åsberg depression rating scale) total score. More patients with a reduction of 50% or more indicates better effectiveness. Minimun value of MADRS is 0 and maximum value of MADRS is 60 points.
• Remission rate measured by HAMD-17 (Hamilton Depression Rating Scale) [From baseline to Week 8]: HAMD-17 (Hamilton Depression Rating Scale) total score ≤10 at week8. Lower total score of HAMD-17 at week 8 indicates better outcome. Minimun value of HAMD-17 is 0 and maximum value of HAMD-17 is 68 points.
• MADRS Remission rate measured by MADRS (Montgomery-Åsberg depression rating scale) [From baseline to Week 8]: MADRS (Montgomery-Åsberg depression rating scale) total score ≤7 at week8. Lower total score of HAMD-17 at week 8 indicates better outcome. Minimun value of MADRS is 0 and maximum value of MADRS is 60 points.

Other outcomes

• HAMD-17 (Hamilton Depression Rating Scale) total score [Baseline, Week 2, Week 4 and Week 8.]: Minimun value of HAMD-17 (Hamilton Depression Rating Scale) is 0 and maximum value of HAMD-17 is 68 points. Higher scores implies higher severity.
• MADRS (Montgomery-Åsberg depression rating scale) total score [Baseline, Week 2, Week 4 and Week 8.]: Minimun value of MADRS (Montgomery-Åsberg depression rating scale) is 0 and maximum value of MADRS is 60 points. Higher scores implies higher severity.
• CGI-S (Clinical Gloabl Impression-Severity) score [Baseline, Week 2, Week 4 and Week 8.]: Minimun value of CGI-S (Clinical Gloabl Impression-Severity) is 0 and maximum value of CGI-S is 7 points. Higher scores implies higher severity.
• CGI-I (Clinical Gloabl Impression-Improvement) score [Baseline, Week 2, Week 4 and Week 8.]: Minimun value of CGI-I (Clinical Gloabl Impression-Improvement) is 1 points and maximum value of CGI-I is 7 points. Higher scores implies worse outcome.

Sex: All, ages: 18 Years to 65 Years, accepts healthy volunteers

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.

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• Shen He, Study director, Shanghai Mental Health Center