Elevated Systemic Inflammation Is Associated with Reduced Corticolimbic White Matter Integrity in Depression - PubMed (original) (raw)

doi: 10.3390/life12010043.

Jonathan Savitz 1 2, Ye Zhang 3, Kaiping Burrows 1, Ryan Smith 1, Leandra Figueroa-Hall 1, Rayus Kuplicki 1, Sahib S Khalsa 1, Yasuyuki Taki 3 4 5, Tracy Kent Teague 6 7 8, Michael R Irwin 9 10 11, Fang-Cheng Yeh 12, Martin P Paulus 1 2, Haixia Zheng 1, On Behalf Of Tulsa Investigators

Affiliations

Elevated Systemic Inflammation Is Associated with Reduced Corticolimbic White Matter Integrity in Depression

MacGregor Thomas et al. Life (Basel). 2021.

Abstract

(1) Background: Growing evidence indicates that inflammation can induce neural circuit dysfunction and plays a vital role in the pathogenesis of major depressive disorder (MDD). Nevertheless, whether inflammation affects the integrity of white matter pathways is only beginning to be explored. (2) Methods: We computed quantitative anisotropy (QA) from diffusion magnetic resonance imaging as an index of white matter integrity and regressed QA on C-reactive protein (CRP), controlling for age, sex, and BMI, in 176 participants with MDD. (3) Results: The QA values of several white matter tracts were negatively correlated with CRP concentration (standardized beta coefficient = -0.22, 95%CI = -0.38--0.06, FDR < 0.05). These tracts included the bilateral cortico-striatal tracts, thalamic radiations, inferior longitudinal fasciculi, corpus callosum (the forceps minor portion and the tapetum portion), cingulum bundles, and the left superior longitudinal fasciculus III. Importantly, the association remained robust after regressing up to twelve potential confounders. The bilateral fornix and a small portion of the thalamic radiation showed a positive association with CRP levels, but these associations did not remain significant after adjusting for confounders. (4) Conclusions: Peripheral inflammation may contribute to the etiology of MDD by impacting the microstructural integrity of brain corticolimbic white matter pathways.

Keywords: CRP; MDD; connectometry analysis; diffusion MRI; quantitative anisotropy; white matter integrity.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1

Figure 1

White matter tracts with QA values significantly correlated with log-transformed CRP value. (A) Tracts showing a negative association with log-transformed CRP value. (B) Tracts showing a positive association with log-transformed CRP value.

Figure 2

Figure 2

White matter tracts positively and negatively associated with the CRP concentration. (A) Illustration of white matter tracts positively (red) and negatively (blue) associated with the CRP concentration. (B) Scatter plot of mean QA extracted from the negatively associated tracts (blue tracts) and the CRP concentration. (C) Scatter plot of mean QA extracted from the positively associated tracts (red tracts) and the CRP concentration. The mean QA value in (B,C) regressed out age, sex, and BMI.

References

    1. Dantzer R., O’Connor J.C., Freund G.G., Johnson R.W., Kelley K.W. From inflammation to sickness and depression: When the immune system subjugates the brain. Nat. Rev. Neurosci. 2008;9:46–56. doi: 10.1038/nrn2297. -DOI -PMC -PubMed
    1. Dantzer R. Neuroimmune Interactions: From the Brain to the Immune System and Vice Versa. Physiol. Rev. 2018;98:477–504. doi: 10.1152/physrev.00039.2016. -DOI -PMC -PubMed
    1. Miller A.H., Raison C.L. The role of inflammation in depression: From evolutionary imperative to modern treatment target. Nat. Rev. Immunol. 2016;16:22–34. doi: 10.1038/nri.2015.5. -DOI -PMC -PubMed
    1. Han K.M., Ham B.J. How Inflammation Affects the Brain in Depression: A Review of Functional and Structural MRI Studies. J. Clin. Neurol. 2021;17:503–515. doi: 10.3988/jcn.2021.17.4.503. -DOI -PMC -PubMed
    1. Ironside M., Admon R., Maddox S.A., Mehta M., Douglas S., Olson D.P., Pizzagalli D.A. Inflammation and depressive phenotypes: Evidence from medical records from over 12,000 patients and brain morphology. Psychol. Med. 2020;50:2790–2798. doi: 10.1017/S0033291719002940. -DOI -PMC -PubMed

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