White Matter Alterations Associated with Pro-inflammatory Cytokines in Patients with Major Depressive Disorder

Lim, Jaehwa; Sohn, Hoyoung; Kwon, Min Soo; Kim, Borah

doi:10.9758/cpn.2021.19.3.449

Cited by 25 publications

(26 citation statements)

References 71 publications

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“…Another study compared 22 patients with MDD and 22 healthy subjects. They reported similar findings, showing that peripheral concentrations of TNF were negatively correlated with FA in several white matter regions, including the corpus callosum and both the left anterior and superior corona radiata [28]. In one study that pooled MDD and healthy control participants (n = 590), the results indicate that methylation-based measures of CRP were associated with widespread reductions in FA, and the strongest relationships were found in the external capsule and the anterior limb of the internal capsule [29].…”

Section: Introductionsupporting

confidence: 54%

“…These findings bear some similarity to results attained by other studies, but also shed new light on the relationship between systemic inflammation and white matter integrity in depression. Previous studies have reported inverse associations between proinflammatory cytokines in the periphery (i.e., IL-1β and TNF) and corpus callosum integrity (indexed by FA value) [27,28]. The corpus callosum is the most prominent forebrain commissure connecting the left and right hemispheres, and is only found in placental mammals [56,57].…”

Section: Discussionmentioning

confidence: 99%

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

Thomas

Savitz

Zhang

et al. 2021

Life

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(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.

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Section: Introductionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

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

Thomas

Savitz

Zhang

et al. 2021

Life

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“…Another probable reason might be group-related differences between depression participants. There is only one study with the voxelwise approach that showed a connection between TNF-a and FA in depression [33], which, however, differs from the results of the current study and the study cited above [29]. To speculate, individual differences could account for the different outcomes, i.e., macrophages, for example, produce cytokines, IL-1b and TNF-a, which have an inflammatory effect [61].…”

Section: (Running Title: Fractional Anisotropy and Inflammation In De...contrasting

confidence: 78%

“…In a volumetric MRI study by Frodl et al, participants with depression who were not drug-naïve showed smaller hippocampal volumes but higher IL-6 concentrations [34]. Two further DTI studies showed negative correlations between the FA values of various WM fiber tracts and peripheral inflammatory cytokines (i.e., and TNF-⍺) in patients with a first episode or drug-naïve depressed patients [29,33].…”

Section: Introductionmentioning

confidence: 98%

“…A meta-analysis by Howren et al showed positive correlations between depression and the cytokines IL-1 and IL-6 in patients with depression [32]. In addition, recent studies have shown significant correlations in depressive episodes between WM structures and peripheral inflammation [10,29,33]. In a volumetric MRI study by Frodl et al, participants with depression who were not drug-naïve showed smaller hippocampal volumes but higher IL-6 concentrations [34].…”

Section: Introductionmentioning

confidence: 99%

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Fractional anisotropy and peripheral cytokine concentrations in outpatients with depressive episode: a diffusion tensor imaging observational study

Sammer

Neumann

Blecker

et al. 2022

Preprint

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Background: Over the past few years, evidence of a positive relationship between inflammation and depression has grown steadily. The aim of the current study was to investigate whether such depression-related inflammation could also be associated with altered microstructural changes in the white matter. Methods: FA and serum cytokines (IL-1𝛽, IL-6, TNF-𝛼, and IFN-𝛾) were measured in 25 patients with depression (DE) and 24 healthy controls (HC). Diffusion tensor imaging was performed. Fractional anisotropy (FA) was calculated using the FSL pipeline for TBSS. Both voxelwise and mean whole-brain FA were analyzed using general linear models (GLM). Results: Higher concentrations of IL-1𝛽 were associated with lower fractional anisotropy of the whole brain, especially in people with depression. TNF-𝛼 shares some of the variance with IL-1𝛽, and therefore higher TNF-𝛼 concentrations also showed a negative relationship with FA. In detail, the voxelwise analysis showed that the regression slopes of IL-1𝛽 on FA were more negative in the DE group than in the HC group, mainly in the corpus callosum. Similar effects were not found for the other remaining cytokines. Conclusions: This study clearly demonstrated an association between peripherally measured IL-1𝛽 and white matter integrity in depression as assessed by DTI. The results suggest that microstructural changes in the corpus callosum are associated with increased peripheral IL-1𝛽 concentrations in depression.

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Correlation of White Matter Microstructure MRI and Inflammatory Cytokine Alterations With Symptom Severity in Premenstrual Syndrome

Duan,

Qin,

Lai

et al. 2024

Magnetic Resonance Imaging

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BackgroundWomen with premenstrual syndrome (PMS) are at increased risk for depression throughout their lives. White matter (WM) microstructure and inflammatory cytokine alterations have been proposed in its etiology.PurposeTo investigate whether WM, assessed using diffusion tensor imaging (DTI), and inflammatory cytokine levels are altered in PMS, and to examine the relationships between WM microstructure, inflammatory cytokines, and symptom severity.Study TypeProspective.SubjectsForty‐two PMS patients and 58 healthy controls (HCs), categorized according to the daily record of severity of problems (DRSP).Field Strength/Sequence3‐T, echo planar imaging DTI.AssessmentFractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured by using tract‐based spatial statistics (TBSS). Venous blood was collected to measure cytokines, including interleukin‐1β (IL‐1β) and tumor necrosis factor‐α (TNF‐α). Symptoms were assessed by using the DRSP.Statistical TestsTwo‐sample t test or Mann–Whitney U test were used to compare the DRSP and cytokines. Abnormal DTI metrics in WM were extracted and the differences between groups were analyzed by using two sample t‐tests. Spearman's correlation (r) was used to assess the relationship between DTI metrics, cytokines, and DRSP. A P‐value <0.05 with FDR correction was considered statistically significant.ResultsCompared with HCs, PMS patients showed significantly lower FA in the corpus callosum and corona radiata, and significantly higher MD, AD, and RD in the corticospinal tract (CST), and significantly higher MD and RD in the anterior thalamic radiation (ATR). These differential metrics were significantly correlated with DRSP. Patients showed significantly higher IL‐1β and TNF‐α than HCs. Moreover, TNF‐α correlated positively with MD, AD, and RD in both groups (r range, 0.256–0.315).Data ConclusionAlterations of WM microstructure and IL‐1β and TNF‐α may be associated with PMS symptom severity, and TNF‐α may correlate with DTI metrics of CST and ATR pathways.Evidence Level1Technical EfficacyStage 2

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White Matter Alterations Associated with Pro-inflammatory Cytokines in Patients with Major Depressive Disorder

Cited by 25 publications

References 71 publications

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

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

Fractional anisotropy and peripheral cytokine concentrations in outpatients with depressive episode: a diffusion tensor imaging observational study

Correlation of White Matter Microstructure MRI and Inflammatory Cytokine Alterations With Symptom Severity in Premenstrual Syndrome

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