Inflammation Links to Functional Connectivity and White Matter Changes in Chronic Depression
Poster No:
664
Submission Type:
Abstract Submission
Authors:
Jungho Cha1, Divyaansh Raj2, Ki Sueng Choi1, Justin Rajendra3, Boadie Dunlop4, Edward Craighead4, Helen Mayberg1
Institutions:
1Icahn School of Medicine at Mount Sinai, New York, NY, 2Johns Hopkins University of School of Medicine, Baltimore, MD, 3National Institutes of Health, Bethesda, MD, 4Emory University School of Medicine, Atlanta, GA
First Author:
Co-Author(s):
Introduction:
There is increasing evidence for the role of inflammation in major depressive disorder (MDD)[1]. Notably, disease chronicity has garnered attention as a predictor of poor long-term outcomes [2]. However, a comprehensive understanding of the complex relationship between inflammation, changes in functional connectivity, and white matter (WM) microstructure in patients with chronic depression remains unclear.
Methods:
344 never treated MDD patients from the Emory PReDICT study a randomized controlled study of CBT and medication to biomarkers for never-treated MDD patients [3], 209 had usable DWI scans, and 132 had usable fMRI scans. We assessed inflammatory status by measuring CRP levels in blood samples. Chronicity was categorized based on current depression episodes lasting over 2 years. Imaging processing was performed using FMRIB Software Library (FSL)[4] and Analysis of Functional NeuroImages (AFNI)[5]. We conducted Tract-Based Spatial Statistics (TBSS) analyses [6] using fractional anisotropy (FA) values and explored whole-brain resting-state functional connectivity (RSFC) using seed regions from four brain networks, including default mode network (DMN), salience network (SN), affective network (AN), and control network (CN). To examine the impact of CRP levels on FA or RSFC and how these relationships differ between chronic and non-chronic patients, linear regression models with interaction terms for CRP and patient chronicity were utilized for FA and RSFC analyses, respectively. Significance was set at FWE-corrected p < 0.05. Correlation analyses were conducted to assess the connection between effects on gray matter and white matter. Furthermore, mediation analyses were conducted to explore the potential mediation relationships among CRP, RSFC, and FA, investigating the effects of CRP on RSFC and the role of FA changes in mediating this association.
Results:
Significant interaction effects (chronicity x CRP) were observed for FA in the external capsule area including association pathway and cingulum tracts (Fig1 A). Additionally, significant interaction effects were noted in the RSFC between the posterior cingulate cortex (PCC) and dorsal anterior cingulate cortex (dACC) (i.e. within the DMN) (Fig1 B) and between the anterior insula (ant.INS) and anterior paracingulate (i.e. within the SN) (Fig1 C). Specifically, higher CRP levels were associated with lower FA values and increased FC patterns in chronic depression patients. Notably, these relationships were not observed in the nonchronic depression group. Furthermore, mediation analyses showed both direct and FA-mediated effects of CRP on the ant.INS-paracingulate RSFC (Figure 2A). Additionally, PCC-dACC RSFC was negatively correlated with FA across all patients, but there were no mediation effects (Figure 2B).
Conclusions:
Our findings showed that CRP was associated with decreased FA and increased RSFC, specifically in chronic MDD patients. The relationship between PCC RSFC and FA was observed across all patient groups, indicating a common phenomenon shared among all depressed patients. Moreover, mediation analyses indicated both direct and FA-mediated effects of CRP on ant.INS-paracingulate RSFC in chronic patients. The result suggests that alterations in white matter microstructure may, at least partially, explain the relationship between CRP levels and changes in RSFC in this specific region and the direction of changes suggesting a specific compensatory change in function in the salience network in MDD.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Physiology, Metabolism and Neurotransmission :
Physiology, Metabolism and Neurotransmission Other 2
Keywords:
FUNCTIONAL MRI
Psychiatric Disorders
White Matter
Other - inflammation
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