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

Macgregor Thomas,Sahib S Khalsa,Ye Zhang,Fang-Cheng Yeh,Rayus Kuplicki,Leandra Figueroa-Hall,Martin P Paulus,Haixia Zheng,Tracy Kent Teague,Kaiping Burrows,Ryan Smith,Yasuyuki Taki,Jonathan Savitz,Michael R Irwin

doi:10.3390/life12010043

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.

Highlights

An increasing number of human and animal studies indicate that systemic inflammation can induce corticolimbic circuit dysfunction and may contribute to the onset and maintenance of major depressive disorder (MDD) [1,2,3,4,5,6]
In one study that pooled MDD and healthy control participants (n = 590), the results indicate that methylation-based measures of C-reactive protein (CRP) were associated with widespread reductions in fractional anisotropy (FA), and the strongest relationships were found in the external capsule and the anterior limb of the internal capsule [29]
We found that the quantitative anisotropy (QA) values in the bilateral cortico-striatal tracts, thalamic radiations, inferior longitudinal fasciculi, corpora callosum, cingulum bundles, and the left superior longitudinal fasciculus III showed a robust negative correlation with CRP concentration

Summary

Introduction

An increasing number of human and animal studies indicate that systemic inflammation can induce corticolimbic circuit dysfunction and may contribute to the onset and maintenance of major depressive disorder (MDD) [1,2,3,4,5,6]. The relationship between systemic inflammation and the integrity of white matter pathways is only beginning to be explored.

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