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

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.

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

“…This literature shows that peripheral inflammation and changes in WM microstructure are associated with depression 28 , 34 , 38 . It would be interesting to see this in drug-naïve first-episode depression and in people in outpatient treatment to define endophenotypes in depression 40 .…”

“…Post-mortem and animal studies have demonstrated that peripheral inflammation is associated with WM injury 26 , 27 . Moreover, other experimental studies have also shown that psychological stress could cause the downregulation of the claudin-5, promoting the entrance of peripheral pro-inflammatory cytokines into the central nervous system and damaging the white matter integrity 28 – 30 . In addition, many studies have highlighted in the past decade the in vivo relationship between depression and peripheral inflammation 31 – 35 .…”

“…IL-1β and TNF-⍺), as well as with acute-phase inflammatory proteins (i.e. CRP) in patients with a first episode or drug-naïve depressed patients 28 , 34 , 38 .…”

Serum Inflammatory Markers and Their Associations with the Integrity of the Cingulum Bundle in Schizophrenia, from Prodromal Stages to Chronic Psychosis

“…For example, our previous study showed correlations between reduced integrity of the corpus callosum and increased levels of IFN-γ in SCH and IL-6 in HC [ 33 ]. Recently, Thomas et al [ 34 ] showed that systemic inflammation is associated with reduced white matter integrity of the CB in patients with depression. Correlations between the integrity of various brain regions, including the CB, and levels of peripheral inflammatory cytokines were also observed in patients with bipolar disorder [ 35 ].…”

Imagens de tensores de difusão em mulheres com queixas cognitivas persistentes após quimioterapia para câncer de mama

“…É possível que a falha no mecanismo de recuperação da resposta inflamatória possa ser responsável pela manutenção das queixas cognitivas em algumas mulheres, dada a variabilidade da resposta inflamatória entre os indivíduos -esta inclusive é a nossa crença. Recentemente, pesquisadores associaram altos índices de inflamação periférica com queda em índices de difusividade no cérebro de pacientes com depressão maior em áreas cortico-limbicas, (161) corroborando com o relatado aumento de sintomas depressivos durante inflamação. (162) Este também é um mecanismo biológico explorado para entender o quadro de fadiga relacionada ao câncer, (40) com a ação inflamatória por via do eixo hipotálamo-adrenal, ou por sua influência no sistema imune.…”