Talks
Investigating the Association between Choroid Plexus Volume by Neuroimaging and Inflammatory Cytokines in Major Depressive Disorder
Presenting Author Academic/Professional Position
Medical Student
Academic Level (Author 1)
Medical Student
Academic Level (Author 2)
Other
Discipline/Specialty (Author 2)
Psychiatry
Academic Level (Author 3)
Other
Discipline/Specialty (Author 3)
Psychiatry
Academic Level (Author 4)
Other
Discipline/Specialty (Author 4)
Population Health and Biostatistics
Academic Level (Author 5)
Medical Student
Presentation Type
Oral Presentation
Discipline Track
Translational Science
Abstract Type
Research/Clinical
Abstract
Background: Major depressive disorder (MDD) is a prevalent psychiatric condition characterized by depressed mood, diminished interests, and cognitive dysfunction. MDD has a multifactorial etiology including genetic, environmental, and epigenetic factors, with heritability estimated at 35%. Recent research has linked neuroinflammatory processes to MDD pathophysiology, with changes to choroid plexus (CP) volume and elevated inflammatory cytokines identified as potential biomarkers. Increased CP volumes have been observed in MDD and bipolar disorder, correlating with neuroinflammation markers and circulating cytokine levels. The Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study was designed to explore biological markers associated with treatment response in MDD. This study aimed to build upon these findings by investigating the relationship between CP volumes, inflammatory cytokines, and treatment outcomes in MDD, providing insights into potential neuroinflammatory mechanisms and biomarkers for personalized therapeutic approaches.
Methods: This study analyzed data from 222 MDD patients in the EMBARC cohort. Participants underwent structural MRI for CP volume quantification, serum biomarker analysis using a 40-plex immunoassay, and clinical assessment with the Hamilton Depression Rating Scale (HAMD-17). CP volumes were adjusted for age and brain volume. A 40-plex panel of cytokines and chemokines, including IL-10, Macrophage migration inhibitory factor (MIF), and Fractalkine, was reduced to three factors using principal components analysis (PCA) with parallel analysis. Spearman and Pearson correlation analyses assessed relationships between CP volumes and cytokine levels, with adjustments for age and brain volume. Mixed-effects models evaluated changes in HAMD-17 scores over eight weeks of treatment in relation to cytokine factors. False discovery rate (FDR) corrections were applied to account for multiple comparisons.
Results: CP volumes showed significant correlations with specific cytokines. Right CP volume was positively associated with MIF (FDR-adjusted p=0.0039), IL-10 (p=0.0325), and Fractalkine (p=0.0325), while left CP volume showed weaker associations with IL-10, MCP-3, and Eotaxin (FDR-adjusted p-values >0.1287). PCA revealed three cytokine factors, with Factor 1 (dominated by IL-10, IL-6, and IFN-γ) significantly predicting HAMD-17 score changes (p=0.0045). Larger CP volumes and elevated Factor 1 cytokines were associated with poorer treatment outcomes, supporting a link between neuroinflammation and treatment resistance. Notably, no significant correlations were observed between IL-17a levels and CP volumes after adjustment for confounders.
Conclusion: This study highlights the role of neuroinflammation in MDD, with CP volumes and inflammatory cytokines serving as potential biomarkers for treatment response. The findings underscore the importance of IL-10, MIF, and Fractalkine in MDD pathophysiology and suggest that CP volume may reflect neuroinflammatory processes influencing treatment outcomes. Future research should explore longitudinal changes in CP volume and cytokine levels to establish causality and develop targeted therapies for treatment-resistant depression. These results advance our understanding of MDD and provide a foundation for personalized treatment approaches guided by neuroinflammatory biomarkers.
Recommended Citation
Arellano Villanueva, Elias; Trivedi, Madhukar; Ayvaci, Rabia; Carmody, Thomas; Torres, Tyler; Gaddis, John; Torres, Juan; Baker, Kelsey; and Gadad, Bharathi, "Investigating the Association between Choroid Plexus Volume by Neuroimaging and Inflammatory Cytokines in Major Depressive Disorder" (2025). Research Symposium. 12.
https://scholarworks.utrgv.edu/somrs/2025/talks/12
Investigating the Association between Choroid Plexus Volume by Neuroimaging and Inflammatory Cytokines in Major Depressive Disorder
Background: Major depressive disorder (MDD) is a prevalent psychiatric condition characterized by depressed mood, diminished interests, and cognitive dysfunction. MDD has a multifactorial etiology including genetic, environmental, and epigenetic factors, with heritability estimated at 35%. Recent research has linked neuroinflammatory processes to MDD pathophysiology, with changes to choroid plexus (CP) volume and elevated inflammatory cytokines identified as potential biomarkers. Increased CP volumes have been observed in MDD and bipolar disorder, correlating with neuroinflammation markers and circulating cytokine levels. The Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study was designed to explore biological markers associated with treatment response in MDD. This study aimed to build upon these findings by investigating the relationship between CP volumes, inflammatory cytokines, and treatment outcomes in MDD, providing insights into potential neuroinflammatory mechanisms and biomarkers for personalized therapeutic approaches.
Methods: This study analyzed data from 222 MDD patients in the EMBARC cohort. Participants underwent structural MRI for CP volume quantification, serum biomarker analysis using a 40-plex immunoassay, and clinical assessment with the Hamilton Depression Rating Scale (HAMD-17). CP volumes were adjusted for age and brain volume. A 40-plex panel of cytokines and chemokines, including IL-10, Macrophage migration inhibitory factor (MIF), and Fractalkine, was reduced to three factors using principal components analysis (PCA) with parallel analysis. Spearman and Pearson correlation analyses assessed relationships between CP volumes and cytokine levels, with adjustments for age and brain volume. Mixed-effects models evaluated changes in HAMD-17 scores over eight weeks of treatment in relation to cytokine factors. False discovery rate (FDR) corrections were applied to account for multiple comparisons.
Results: CP volumes showed significant correlations with specific cytokines. Right CP volume was positively associated with MIF (FDR-adjusted p=0.0039), IL-10 (p=0.0325), and Fractalkine (p=0.0325), while left CP volume showed weaker associations with IL-10, MCP-3, and Eotaxin (FDR-adjusted p-values >0.1287). PCA revealed three cytokine factors, with Factor 1 (dominated by IL-10, IL-6, and IFN-γ) significantly predicting HAMD-17 score changes (p=0.0045). Larger CP volumes and elevated Factor 1 cytokines were associated with poorer treatment outcomes, supporting a link between neuroinflammation and treatment resistance. Notably, no significant correlations were observed between IL-17a levels and CP volumes after adjustment for confounders.
Conclusion: This study highlights the role of neuroinflammation in MDD, with CP volumes and inflammatory cytokines serving as potential biomarkers for treatment response. The findings underscore the importance of IL-10, MIF, and Fractalkine in MDD pathophysiology and suggest that CP volume may reflect neuroinflammatory processes influencing treatment outcomes. Future research should explore longitudinal changes in CP volume and cytokine levels to establish causality and develop targeted therapies for treatment-resistant depression. These results advance our understanding of MDD and provide a foundation for personalized treatment approaches guided by neuroinflammatory biomarkers.
