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

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

The British Journal of Psychiatry ◽

10.1192/bjp.bp.114.155689 ◽

2016 ◽

Vol 208 (6) ◽

pp. 585-590 ◽

Cited By ~ 23

Author(s):

Xiaodan Liu ◽

Keita Watanabe ◽

Shingo Kakeda ◽

Reiji Yoshimura ◽

Osamu Abe ◽

...

Keyword(s):

Major Depressive Disorder ◽

White Matter ◽

Diffusion Tensor ◽

Serum Cortisol ◽

White Matter Integrity ◽

Uncinate Fasciculus ◽

Major Depressive ◽

Drug Naïve ◽

Cortisol Levels ◽

Anterior Thalamic Radiation

BackgroundHigher daytime cortisol levels because of a hyperactive hypothalamic–pituitary–adrenal axis have been reported in patients with major depressive disorder (MDD). The elevated glucocorticoids inhibit the proliferation of the oligodendrocytes that are responsible for myelinating the axons of white matter fibre tracts.AimsTo evaluate the relationship between white matter integrity and serum cortisol levels during a first depressive episode in drug-naive patients with MDD (MDD group) using a tract-based spatial statistics (TBSS) method.MethodThe MDD group (n = 29) and a healthy control group (n = 47) underwent diffusion tensor imaging (DTI) scans and an analysis was conducted using TBSS. Morning blood samples were obtained from both groups for cortisol measurement.ResultsCompared with the controls, the MDD group had significantly reduced fractional anisotropy values (P<0.05, family-wise error (FWE)-corrected) in the inferior fronto-occipital fasciculus, uncinate fasciculus and anterior thalamic radiation. The fractional anisotropy values of the inferior fronto-occipital fasciculus, uncinate fasciculus and anterior thalamic radiation had significantly negative correlations with the serum cortisol levels in the MDD group (P<0.05, FWE-corrected).ConclusionsOur findings indicate that the elevated cortisol levels in the MDD group may injure the white matter integrity in the frontal–subcortical and frontal–limbic circuits.

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P.0718 High levels of peripheral neuroinflammatory markers are associated with disruption of white matter integrity in patients with major depressive disorder

European Neuropsychopharmacology ◽

10.1016/j.euroneuro.2021.10.788 ◽

2021 ◽

Vol 53 ◽

pp. S525-S526

Author(s):

C. Di Pasquasio ◽

E. Mazza ◽

C. Lorenzi ◽

R. Zanardi ◽

S. Poletti ◽

...

Keyword(s):

Major Depressive Disorder ◽

White Matter ◽

Depressive Disorder ◽

White Matter Integrity ◽

Major Depressive

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Elevated serum neurofilament levels in young first-episode and medication-naïve major depressive disorder patients with alterative white matter integrity

Psychiatry Research Neuroimaging ◽

10.1016/j.pscychresns.2021.111351 ◽

2021 ◽

pp. 111351

Author(s):

Linling Jiang ◽

Zonglin Shen ◽

Yuqi Cheng ◽

Jin Lu ◽

Bo He ◽

...

Keyword(s):

Major Depressive Disorder ◽

White Matter ◽

Depressive Disorder ◽

Elevated Serum ◽

White Matter Integrity ◽

First Episode ◽

Major Depressive

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Microstructural degeneration underlies executive dysfunction after stroke

10.1101/2020.02.03.20020131 ◽

2020 ◽

Author(s):

Michele Veldsman ◽

Emilio Werden ◽

Natalia Egorova ◽

Mohamed Salah Khlif ◽

Amy Brodtmann

Keyword(s):

Executive Function ◽

White Matter ◽

Structural Equation ◽

Executive Dysfunction ◽

White Matter Integrity ◽

Stroke Severity ◽

Lesion Volume ◽

Stroke Patients ◽

Cerebrovascular Risk ◽

Microstructural Integrity

ABSTRACTObjectiveExecutive dysfunction affects 40% of stroke patients and is associated with poor quality of life. Stroke severity and lesion volume rarely predict whether a patient will have executive dysfunction. Stroke typically occurs on a background of cerebrovascular burden, which impacts cognition and brain network structural integrity. We investigated whether measures of white matter microstructural integrity and cerebrovascular risk factors better explain executive dysfunction than markers of stroke severity.MethodsWe used structural equation modelling to examine multivariate relationships between cerebrovascular risk, white matter microstructural integrity (fractional anisotropy and mean diffusivity), stroke characteristics and executive dysfunction in 126 stroke patients (mean age 68.4 years), three months post-stroke, and compared to 40 age- and sex-matched control participants. Executive function was measured using the Trail Making Tests, Clock Drawing task and Rey Complex Figure copy task. Microstructural integrity was estimated using a standard pipeline to process diffusion weighted images.ResultsExecutive function was below what would be expected for age and education level in stroke patients (t-test compared to controls t(79)=5.75, p<0.001). A multivariate structural equation model illustrated the complex relationship between executive function, white matter integrity, stroke characteristics and cerebrovascular risk. Pearson’s correlations confirmed a stronger relationship between executive dysfunction and white matter integrity, than executive dysfunction and stroke severity. Mediation analysis showed the relationship between executive function and white matter integrity is mediated by cerebrovascular burden.InterpretationWhite matter microstructural degeneration of the superior longitudinal fasciculus in the executive control network better explains executive dysfunction than markers of stroke severity.

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