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Cellular immune phenotype of major depressive disorder - findings from the EMBARC study
Cherise R Chin Fatt1, Srividya Vasu1, Nabila Haque1
1Center for Depression Research and Clinical Care, Peter O'Donnell Jr. Brain Institute and Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Insights
Major depressive disorder (MDD) is linked to immune dysfunction. This study found lower levels of cytotoxic T, NK, NK T, and Naïve B cells in moderate/severe MDD, indicating immune cell alterations.
Area of Science:
- Immunology
- Psychiatry
- Computational Biology
Background:
- Major depressive disorder (MDD) is frequently associated with immune system dysfunction.
- Understanding the specific cellular immunophenotypes involved in MDD-related immune dysregulation is crucial for developing targeted therapies.
Purpose of the Study:
- To characterize cellular immunophenotypes associated with immune dysregulation in individuals with Major Depressive Disorder (MDD).
- To compare immune cell abundance and marker expression between mild and moderate/severe MDD patient groups.
Main Methods:
- Utilized mass cytometry on peripheral blood mononuclear cells (PBMC) from MDD participants in the EMBARC study.
- Employed Uniform Manifold Approximation and Projection for Dimension Reduction (UMAP), FlowSOM clustering, and Significance Analysis of Microarrays (SAM) for data analysis.
- Analyzed a panel of 33 antibodies to assess immune cell populations and surface marker expression.
Main Results:
- FlowSOM identified 8 distinct immune cell clusters.
- Participants with moderate/severe MDD exhibited significantly lower abundance of cytotoxic T cells, NK cells, NK T cells, and Naïve B cells compared to those with mild MDD.
- NKT cells in moderate/severe MDD patients showed significantly reduced CD56 and CD16 expression.
Conclusions:
- The study provides evidence of altered abundance and cell surface marker expression in B, NKT, and NK cells in moderate/severe MDD.
- These findings highlight potential immune cell dysfunction contributing to the severity of depression.
- Further research is warranted to explore immune cell dysfunction in moderate/severe MDD.
Objectives:
Major depressive disorder (MDD) is associated with immune dysfunction. This study aimed to characterize the cellular immunophenotypes that may underpin immune dysregulation in MDD.
Methods:
Peripheral blood mononuclear cell (PBMC) samples at baseline from participants with MDD from the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study were included. A panel of 33 antibodies was analyzed using mass cytometry to compare the immune cell abundance and marker expression profiles between participants with mild and moderate/severe depression. Mass cytometry data were investigated using (1) Uniform Manifold Approximation and Projection for Dimension Reduction (UMAP), (2) FlowSOM (self-organizing maps) for clustering, and (3) Significance Analysis of Microarrays (SAM) for statistical analyzes.
Results:
FlowSOM identified 8 clusters of distinct cell types. The abundance of cytotoxic T, NK, NK T, and Naïve B cells was significantly lower in participants with moderate/severe depression compared to mild depression. NKT cells had significantly lower CD56 and CD16 expression in patients with moderate/severe depression compared to patients with mild depression.
Conclusion:
Our observations provide evidence for alterations in B, NKT, and NK cell abundance and their cell surface markers in moderate/severe depression. Further investigations into immune cell dysfunction in moderate/severe depression are necessary.
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