Relationship between white matter integrity and serum inflammatory cytokine levels in drug-naive patients with major depressive disorder: diffusion tensor imaging study using tract-based spatial statistics

Koichiro Sugimoto,Natsuki Igata,Yukunori Korogi,Issei Ueda,Keita Watanabe,Shingo Kakeda,Asuka Katsuki,Osamu Abe,Ryohei Igata,Reiji Yoshimura

doi:10.1038/s41398-018-0174-y

Abstract

Recently, accumulated evidence has indicated a role of inflammation in the pathogenesis of major depressive disorder (MDD). Therefore, we evaluated the relationship between white matter integrity and serum cytokine levels during the first depressive episode in drug-naive MDD patients, using a tract-based spatial statistics (TBSS) method. A total of 35 drug-naive MDD patients with a first depressive episode and 35 healthy subjects (HS) underwent diffusion tensor imaging, and an analysis was conducted using TBSS. We measured serum cytokine levels (interleukin [IL]-1β, IL-6, interferon-γ, and tumor necrosis factor-α). Fractional anisotropy (FA) values of the bilateral inferior fronto-occipital fasciculus (IFOF) and genu of the corpus callosum in MDD patients were decreased significantly to the HS (p < 0.05 with family-wise error [FWE] correction) and were significantly inversely correlated with the IL-1β levels (p < 0.05, with FWE correction). No regions showed a correlation between FA values and other serum cytokine levels. Our results suggested that the microstructural changes in IFOF and genu of the corpus callosum are associated with the high IL-1β levels in the early stage of MDD.

Highlights

Introduction Quantitative measures byDiffusion tensor imaging (DTI) such as fractional anisotropy (FA) values are useful markers for microstructural changes in white matter (WM)
Some studies have detected higher levels of inflammation in major depressive disorder (MDD) patients than in healthy subjects (HS), the strength of the evidence varies according to the type of inflammatory marker that is examined
There were no significant differences in age or sex between the HS and MDD patients

Summary

Introduction

Diffusion tensor imaging (DTI) such as fractional anisotropy (FA) values are useful markers for microstructural changes in white matter (WM). Reduced FA values are thought to reflect reduced organization of the WM, reduced axonal density, and/or reduced myelination[1,2]. Many previous DTI studies have reported alterations (i.e., reduced FA values) in various WM fiber tracts among major depressive disorder (MDD) patients[3–11]. The pathogenesis of WM alteration in MDD is only partly understood. Accumulated evidence has indicated a role of inflammation in the pathogenesis of MDD. Some studies have detected higher levels of inflammation in MDD patients than in healthy subjects (HS), the strength of the evidence varies according to the type of inflammatory marker (cytokine) that is examined

Methods

Results

Conclusion