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Association between peripheral inflammation and free-water imaging in Major Depressive Disorder before and after
Mina Langhein1, Johanna Seitz-Holland2, Amanda E Lyall2
1Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Psychiatry Neuroimaging Branch, Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Background:
Alterations in the peripheral inflammatory profile and white matter (WM) deterioration are frequent in Major Depressive Disorder (MDD). The present study applies free-water imaging to investigate the relationship between altered peripheral inflammation and WM microstructure and their predictive value in determining response to ketamine treatment in MDD.
Methods:
Ten individuals with MDD underwent diffusion-weighted magnetic resonance imaging and a blood-draw before and 24 h after ketamine infusion. We utilized MANCOVAs and ANCOVAs to compare tissue-specific fractional anisotropy (FAT) and free-water (FW) of the forceps and cingulum, and the ratio of pro-inflammatory interleukin(IL)-8/anti-inflammatory IL-10 between individuals with MDD and 15 healthy controls at baseline. Next, we compared all baseline measures between ketamine responders (6) and non-responders (4) and analyzed changes in imaging and blood data after ketamine infusion.
Results:
The MDD group exhibited an increased IL-8/IL-10 ratio compared to controls at baseline (p = .040), which positively correlated with average FW across regions of interest (p = .013). Ketamine responders demonstrated higher baseline FAT in the left cingulum than non-responders (p = .023). Ketamine infusion did not influence WM microstructure but decreased the IL-8/IL-10 ratio (p = .043).
Limitations:
The small sample size and short follow-up period limit the conclusion regarding the longer-term effects of ketamine in MDD.
Conclusions:
This pilot study provides evidence for the role of inflammation in MDD by illustrating an association between peripheral inflammation and WM microstructure. Additionally, we demonstrate that free-water diffusion-weighted imaging might be a valuable tool to determine which individuals with MDD benefit from the anti-inflammatory mediated effects of ketamine treatment.
Insights
This study found that Major Depressive Disorder (MDD) patients have higher inflammation and altered white matter (WM) which predicts ketamine treatment response. Free-water imaging may identify patients who benefit from ketamine
Area of Science:
- Neuroimaging
- Neuroinflammation
- Psychiatry
Background:
- Major Depressive Disorder (MDD) is frequently associated with peripheral inflammation and white matter (WM) damage.
- Investigating the interplay between inflammation and WM integrity is crucial for understanding MDD pathophysiology.
- Ketamine shows promise as a treatment for MDD, potentially through anti-inflammatory mechanisms.
Purpose of the Study:
- To explore the relationship between peripheral inflammation and WM microstructure in MDD using free-water imaging.
- To determine if these factors predict response to ketamine treatment in individuals with MDD.
- To assess the impact of ketamine infusion on peripheral inflammation and WM microstructure.
Main Methods:
- Diffusion-weighted magnetic resonance imaging and blood draws were performed on 10 MDD patients before and 24 hours after ketamine infusion.
- Tissue-specific fractional anisotropy (FA ) and free-water (FW) measures were compared between MDD patients and 15 healthy controls.
- The ratio of pro-inflammatory interleukin-8 (IL-8) to anti-inflammatory IL-10 was analyzed, along with changes post-ketamine.
Main Results:
- MDD patients exhibited a higher IL-8/IL-10 ratio at baseline, correlating positively with increased FW.
- Ketamine responders showed significantly higher baseline FA in the left cingulum compared to non-responders.
- Ketamine infusion reduced the IL-8/IL-10 ratio but did not alter WM microstructure.
Conclusions:
- This pilot study suggests a link between peripheral inflammation and WM alterations in MDD.
- Free-water imaging may serve as a biomarker to predict ketamine treatment efficacy in MDD.
- The findings support the role of anti-inflammatory effects in ketamine's therapeutic action for MDD.
