Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT:

Objective

Regarding the neuroinflammatory theory of major depressive disorder (MDD), little is known about the effect of pro-inflammatory cytokines on white matter (WM) changes in MDD. We aimed to investigate the relationship between pro-inflammatory cytokines and WM alterations in patients with MDD.

Methods

Twenty-two patients with MDD and 22 healthy controls (HC) were evaluated for brain imaging and pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8, interferon-γ and tumor necrosis factor (TNF)-α. Tract-based spatial statistics and FreeSurfer were used for brain image analysis.

Results

The levels of TNF-α and IL-8 were significantly higher in the MDD group than in HC. Compared to HC, lower fractional anisotropy (FA), and higher median diffusivity (MD) and radial diffusivity (RD) values were found in the MDD group for several WM regions. Voxel-wise correlation analysis showed that the level of TNF-α was negatively correlated with FA, and positively correlated with MD and RD in the left body and genu of the corpus callosum, left anterior corona radiata, and left superior corona radiata.

Conclusion

Our findings suggest that TNF-α may play an important role in the WM alterations in depression, possibly through demyelination.

SUBMITTER: Lim J

PROVIDER: S-EPMC8316659 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

A potential role for pro-inflammatory cytokines in regulating synaptic plasticity in major depressive disorder.

Project description:A growing body of data suggests that hyperactivation of the immune system has been implicated in the pathophysiology of major depressive disorder (MDD). Several pro-inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) have been found to be significantly increased in patients with MDD. This review focuses on these two cytokines based on multiple lines of evidence from genetic, animal behaviour, and clinical studies showing that altered levels of serum TNF-alpha and IL-1 are associated with increased risk of depression, cognitive impairments, and reduced responsiveness to treatment. In addition, recent findings have shown that centrally expressed TNF-alpha and IL-1 play a dual role in the regulation of synaptic plasticity. In this paper, we review and critically appraise the mechanisms by which cytokines regulate synaptic and neural plasticity, and their implications for the pathophysiology and treatment of MDD. Finally, we discuss the therapeutic potential of anti-inflammatory-based approaches for treating patients with severe mood disorders. This is a promising field for increasing our understanding of the mechanistic interaction between the immune system, synaptic plasticity, and antidepressants, and for the ultimate development of novel and improved therapeutics for severe mood disorders.

| S-EPMC2771334 | biostudies-literature

Dvl3 polymorphism interacts with life events and pro-inflammatory cytokines to influence major depressive disorder susceptibility.

Project description:The purpose of this study is to explore Dvl3 variants and their interaction with negative life events on MDD susceptibility in a Chinese Han population. Additionally, we also attempted to identify whether there is an association between Dvl3 variants and pro-inflammatory cytokines. A total of 1102 participants, consisting of 550 patients with MDD and 552 healthy subjects, were recruited for genotyping by TaqMan allelic discrimination assay. Pro-inflammatory cytokine mRNA levels in peripheral blood were measured by QPCR. After the assessment of negative life events by the Life Events Scale, the Dvl3 gene-environment interaction (G?×?E) and risk factors were evaluated using generalized multifactor dimensionality reduction method (GMDR) and logistic regression analysis, respectively. This study is the first to reveal the interaction between Dvl3 allelic variations and negative life events as well as pro-inflammatory cytokines on MDD susceptibility in a Chinese Han population.

| S-EPMC6155061 | biostudies-literature

Brain grey matter volume alterations associated with antidepressant response in major depressive disorder.

Project description:Not all patients with major depressive disorder respond to adequate pharmacological therapy. Psychoradiological studies have reported that antidepressant responders and nonresponders show different alterations in brain grey matter, but the findings are inconsistent. The present study reports a meta-analysis of voxel-based morphometric studies of patients with major depressive disorder, both antidepressant responders and nonresponders, using the anisotropic effect size version of Seed-based D Mapping to identify brain regions correlated to clinical response. A systematic search was conducted up to June 2016 to identify studies focussing on antidepressant response. In responders across 9 datasets grey matter volume (GMV) was significantly higher in the left inferior frontal gyrus and insula, while GMV was significantly lower in the bilateral anterior cingulate cortex (ACC) and the right superior frontal gyrus (SFG). In nonresponders across 5 datasets GMV was significantly lower in the bilateral ACC, median cingulate cortex (MCC) and right SFG. Conjunction analysis confirmed significant differences in the bilateral ACC and right SFG, where GMV was significantly lower in nonresponders but higher in responders. The current study adds to psychoradiology, an evolving subspecialty of radiology mainly for psychiatry and clinical psychology.

| S-EPMC5585337 | biostudies-literature

White Matter Network Disruption Is Associated With Melancholic Features in Major Depressive Disorder.

Project description:BackgroundThe efficacy and prognosis of major depressive disorder (MDD) are limited by its heterogeneity. MDD with melancholic features is an important subtype of MDD. The present study aimed to reveal the white matter (WM) network changes in melancholic depression.Materials and methodsTwenty-three first-onset, untreated melancholic MDD, 59 non-melancholic MDD patients and 63 health controls underwent diffusion tensor imaging (DTI) scans. WM network analysis based on graph theory and support vector machine (SVM) were used for image data analysis.ResultsCompared with HC, small-worldness was reduced and abnormal node attributes were in the right orbital inferior frontal gyrus, left orbital superior frontal gyrus, right caudate nucleus, right orbital superior frontal gyrus, right orbital middle frontal gyrus, left rectus gyrus, and left median cingulate and paracingulate gyrus of MDD patients. Compared with non-melancholic MDD, small-worldness was reduced and abnormal node attributes were in right orbital inferior frontal gyrus, left orbital superior frontal gyrus and right caudate nucleus of melancholic MDD. For correlation analysis, the 7th item score of the HRSD-17 (work and interest) was positively associated with increased node betweenness centrality (aBC) values in right orbital inferior frontal gyrus, while negatively associated with the decreased aBC in left orbital superior frontal gyrus. SVM analysis results showed that abnormal aBC in right orbital inferior frontal gyrus and left orbital superior frontal gyrus showed the highest accuracy of 81.0% (69/83), the sensitivity of 66.3%, and specificity of 85.2% for discriminating MDD patients with or without melancholic features.ConclusionThere is a significant difference in WM network changes between MDD patients with and without melancholic features.

| S-EPMC9046786 | biostudies-literature

Pro-inflammatory Monocyte Phenotype and Cell-Specific Steroid Signaling Alterations in Unmedicated Patients With Major Depressive Disorder.

Project description:Several lines of evidence have strongly implicated inflammatory processes in the pathobiology of major depressive disorder (MDD). However, the cellular origin of inflammatory signals and their specificity remain unclear. We examined the phenotype and glucocorticoid signaling in key cell populations of the innate immune system (monocytes) vs. adaptive immunity (T cells) in a sample of 35 well-characterized, antidepressant-free patients with MDD and 35 healthy controls individually matched for age, sex, smoking status and body mass index. Monocyte and T cell phenotype was assessed by flow cytometry. Cell-specific steroid signaling was determined by mRNA expression of pre-receptor regulation (11β-hydroxysteroid dehydrogenase type 1; 11β -HSD1), steroid receptor expression [glucocorticoid receptor (GR) and mineralocorticoid receptor (MR)], and the downstream target glucocorticoid-induced leucine-zipper (GILZ). We also collected salivary cortisol samples (8:00 a.m. and 10:00 p.m.) on two consecutive days. Patients showed a shift toward a pro-inflammatory phenotype characterized by higher frequency and higher absolute numbers of non-classical monocytes. No group differences were observed in major T cell subset frequencies and phenotype. Correspondingly, gene expression indicative of steroid resistance (i.e., lower expression of GR and GILZ) in patients with MDD was specific to monocytes and not observed in T cells. Monocyte phenotype and steroid receptor expression was not related to cortisol levels or serum levels of IL-6, IL-1β, or TNF-α. Our results thus suggest that in MDD, cells of the innate and adaptive immune system are differentially affected with shifts in monocyte subsets and lower expression of steroid signaling related genes.

| S-EPMC6265986 | biostudies-literature

Reconciling variable findings of white matter integrity in major depressive disorder.

Project description:Diffusion tensor imaging (DTI) has been used to evaluate white matter (WM) integrity in major depressive disorder (MDD), with several studies reporting differences between depressed patients and controls. However, these findings are variable and taken from relatively small studies often using suboptimal analytic approaches. The presented DTI study examined WM integrity in large samples of medication-free MDD patients (n=134) and healthy controls (n=54) using voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) approaches, and rigorous statistical thresholds. Compared with health control subjects, MDD patients show no significant differences in fractional anisotropy, radial diffusivity, mean diffusivity, and axonal diffusivity with either the VBM or the TBSS approach. Our findings suggest that disrupted WM integrity does not have a major role in the neurobiology of MDD in this relatively large study using optimal imaging acquisition and analysis; however, this does not eliminate the possibility that certain patient subgroups show WM disruption associated with depression.

| S-EPMC3988550 | biostudies-literature

White Matter Tracts Associated With Deep Brain Stimulation Targets in Major Depressive Disorder: A Systematic Review.

Project description:BackgroundDeep brain stimulation (DBS) has been proposed as a last-resort treatment for major depressive disorder (MDD) and has shown potential antidepressant effects in multiple clinical trials. However, the clinical effects of DBS for MDD are inconsistent and suboptimal, with 30-70% responder rates. The currently used DBS targets for MDD are not individualized, which may account for suboptimal effect.ObjectiveWe aim to review and summarize currently used DBS targets for MDD and relevant diffusion tensor imaging (DTI) studies.MethodsA literature search of the currently used DBS targets for MDD, including clinical trials, case reports and anatomy, was performed. We also performed a literature search on DTI studies in MDD.ResultsA total of 95 studies are eligible for our review, including 51 DBS studies, and 44 DTI studies. There are 7 brain structures targeted for MDD DBS, and 9 white matter tracts with microstructural abnormalities reported in MDD. These DBS targets modulate different brain regions implicated in distinguished dysfunctional brain circuits, consistent with DTI findings in MDD.ConclusionsIn this review, we propose a taxonomy of DBS targets for MDD. These results imply that clinical characteristics and white matter tracts abnormalities may serve as valuable supplements in future personalized DBS for MDD.

| S-EPMC9095936 | biostudies-literature

A COMPREHENSIVE EXAMINATION OF WHITE MATTER TRACTS AND CONNECTOMETRY IN MAJOR DEPRESSIVE DISORDER.

Project description:BackgroundMajor depressive disorder (MDD) is a debilitating disorder characterized by widespread brain abnormalities. The literature is mixed as to whether or not white matter abnormalities are associated with MDD. This study sought to examine fractional anisotropy (FA) in white matter tracts in individuals with MDD using diffusion tensor imaging (DTI).Methods139 participants with MDD and 39 healthy controls (HC) in a multisite study were included. DTI scans were acquired in 64 directions and FA was determined in the brain using four methods: region of interest (ROI), tract-based spatial statistics (TBSS), and diffusion tractography. Diffusion connectometry was used to identify white matter pathways associated with MDD.ResultsThere were no significant differences when comparing FA in MDD and HC groups using any method. In the MDD group, there was a significant relationship between depression severity and FA in the right medial orbitofrontal cortex, and between age of onset of MDD and FA in the right caudal anterior cingulate cortex using the ROI method. There was a significant relationship between age of onset and connectivity in the thalamocortical radiation, inferior longitudinal fasciculus, and cerebellar tracts using diffusion connectometry.ConclusionsThe lack of group differences in FA and connectometry analysis may result from the clinically heterogenous nature of MDD. However, the relationship between FA and depression severity may suggest a state biomarker of depression that should be investigated as a potential indicator of response. Age of onset may also be a significant clinical feature to pursue when studying white matter tracts.

| S-EPMC4701622 | biostudies-literature

White matter abnormalities and cognitive function in euthymic patients with bipolar disorder and major depressive disorder.

Project description:ObjectivesIn recent years, a growing number of diffusion tensor imaging (DTI) studies have compared white matter integrity between patients with major depressive disorder (MDD) and bipolar disorder (BD). However, few studies have examined the pathophysiological significance of different degrees of white matter abnormalities between the two disorders. The present study comprehensively assessed white matter integrity among healthy controls (HC) and euthymic patients with MDD and BD using whole-brain tractography and examined associations between white matter integrity and cognitive functioning.MethodsWe performed neurocognitive examinations and DTI with 30 HCs, 30 patients with MDD, and 30 patients with BD. We statistically evaluated white matter integrity and cognitive function differences across the three groups, assessing associations between white matter integrities and cognitive function.ResultsThe BD group showed lower fractional anisotropy (FA) for the corpus callosum body, as well as lower, sustained attention and set-shifting scores compared to the other groups. FA for the left body of the corpus callosum was correlated with sustained attention in patients with BD.ConclusionsThe significant reduction of white matter integrity in the corpus callosum in BD, compared to MDD, was associated with an impairment of sustained attention. This result promotes the understanding of the significance of white matter integrity in mood disorders.

| S-EPMC7749556 | biostudies-literature

Relationship between serum inflammatory cytokines and suicide risk in patients with major depressive disorder.

Project description:BackgroundStudies have shown that increased inflammatory cytokines are associated with suicide risk, but the relationship between suicide risk and inflammatory cytokines is not clear. This study aimed to investigate the relationship between specific inflammatory markers and suicide risk in patients with MDD.MethodsThis is a cross-sectional study. Firstly, we measured and compared psychological characteristics and 10 peripheral inflammatory cytokines in 130 MDD patients and 130 healthy controls(HC). Secondly, MDD patients were divided into 4 groups according to the severity of suicide risk for comparison between groups. Finally, multiple linear regression analysis was used to explore the predictors of suicide risk.ResultsWe found that the group with higher suicide risk had higher levels of IL-6, CRP, TNF-α, CXCL-2, and IFN-γ, and lower levels of IL-2 and IL-8 (all p<0.01). However, we found no difference in CRP between MIS and LS groups (p=0.337). Regression models were well-fitted. IL-2,IL-8 negatively predicted suicide risk (all p<0.05),IL-6,CRP,TNF-α,CXCL-2, and IFN-γ can positively predict the risk of suicide (all p<0.05).LimitationsThis study employed a self-assessment scale.ConclusionsThe higher the levels of IL-6, CRP, TNF-α, CXCL-2, and IFN-γ and the lower the levels of IL-2 and IL-8 of MDD patients, the higher the risk of suicide.

| S-EPMC11236750 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data