Integrated Single‐Cell RNA‐seq and ATAC‐seq Reveals Heterogeneous Differentiation of CD4 + Naive T Cell Subsets is Associated with Response to Antidepressant Treatment in Major Depressive Disorder
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Abstract The mechanism involved in major depressive disorder (MDD) is well‐studied but the mechanistic origin of the heterogeneous antidepressant effect remains largely unknown. Single‐cell RNA‐sequencing (scRNA‐seq) and assay for transposase‐accessible chromatin using sequencing (ATAC‐seq) on peripheral blood mononuclear cells from 8 healthy individuals and 8 MDD patients before or after 12 weeks of antidepressant treatment is performed. scRNA‐seq analysis reveals a lower proportion of naive T cells, particularly CD4 + naive T cells, in MDD patients compared to controls, and in nonresponders versus responders at the baseline. Flow cytometry data analysis of an independent cohort of 35 patients and 40 healthy individuals confirms the findings. Enrichment analysis of differentially expressed genes indicated obvious immune activation in responders. A specific activated CD4 + naive T population in responders characterized by enhanced mitogen‐activated protein kinases (MAPK) pathway is identified. E‐twenty six (ETS) is proposed as an upstream regulator of the MAPK pathway and heterogeneous differentiation in activated CD4 + naive T population is associated with the response to antidepressant treatment in MDD patients. A distinct immune feature manifested by CD4 + naive T cells during antidepressant treatment in MDD is identified. Collectively, this proposes the molecular mechanism that underlies the heterogeneous antidepressant outcomes for MDD.
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- [53]J. Niu, Y. Huang, L. Zhang, Int. J. Clin. Exp. Pathol. 2015, 8, 6255. 26261502 PMC4525836
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- Authors
- Sun, Z., Zhang, B., Zhou, J., Luo, Y., Zhu, X., Wang, Y., He, Y., Zheng, P., Zhang, L., Yang, J., & Wang, G.
- Affiliations
- Capital Medical University (CN)
- Beijing Normal University (CN)
- The Affiliated Yongchuan Hospital of Chongqing Medical University (CN)
- Corresponding author
- Yang, Jian
- Wang, Gang
- ORCID
- Venue
- Advanced Science
- Publisher
- Wiley
- Published
- 2024-06-13
- Volume
- 11
- Issue
- 30
- Pages
- e2308393-e2308393
- ISSN
- 2198-3844 (ISSN-L)
- PMC
- PMC11321657
- OpenAlex
- W4399647845
- Cited by
- 20
- References
- 58
- Citations by year
- 2026: 13 · 2025: 5 · 2024: 2
- FWCI
- 5.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Advanced Science (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (82171526, 82171525)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- major depressive disorder, antidepressant response, naive CD4+ T cells, T cell differentiation, immune activation, MAPK signaling, ETS transcription factors, peripheral blood mononuclear cells, single-cell transcriptomics, chromatin accessibility
- MeSH terms
- RNA-Seq, Single-Cell Gene Expression Analysis, Adult, Antidepressive Agents, Cell Differentiation, Major Depressive Disorder, Female, Humans, Male, Middle Aged, CD4-Positive T-Lymphocytes, T-Lymphocyte Subsets, Sequence Analysis, RNA, Single-Cell Analysis
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