Association between peripheral inflammation and free-water imaging in Major Depressive Disorder before and after ketamine treatment - A pilot study

Mina Langhein; Johanna Seitz-Holland; Amanda E Lyall; Ofer Pasternak; Natalia Chunga; Suheyla Cetin-Karayumak; Antoni Kubicki; Christoph Mulert; Randall T Espinoza; Katherine L Narr; Marek Kubicki

doi:10.1016/j.jad.2022.06.043

Association between peripheral inflammation and free-water imaging in Major Depressive Disorder before and after ketamine treatment - A pilot study

J Affect Disord. 2022 Oct 1:314:78-85. doi: 10.1016/j.jad.2022.06.043. Epub 2022 Jun 30.

Authors

Affiliations

¹ Psychiatry 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.
² Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
³ Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁴ Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁵ Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
⁶ Centre for Psychiatry, Justus-Liebig-University, Giessen, Germany.
⁷ Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
⁸ Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at the University of California, Los Angeles, CA, USA; Jane and Terry Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
⁹ Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: kubicki@bwh.harvard.edu.

PMID: 35779673
DOI: 10.1016/j.jad.2022.06.043

Abstract

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 (FA_T) 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 FA_T 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.

Keywords: Diffusion tensor imaging; Magnetic resonance imaging; Neuroinflammation; Treatment response; Treatment-resistant depression; White matter.

Publication types

Clinical Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Depressive Disorder, Major* / diagnostic imaging
Depressive Disorder, Major* / drug therapy
Depressive Disorder, Major* / pathology
Humans
Inflammation / diagnostic imaging
Inflammation / drug therapy
Inflammation / pathology
Interleukin-10
Interleukin-8
Ketamine* / therapeutic use
Pilot Projects
Water
White Matter* / pathology

Substances

Interleukin-8
Water
Interleukin-10
Ketamine

Abstract

Publication types

MeSH terms

Substances

Grants and funding