NODDI-derived white matter changes after ECT in treatment-resistant depression
Poster No:
49
Submission Type:
Abstract Submission
Authors:
Artemis Zavaliangos-Petropulu1, Yeun Kim1, Paloma Pfeiffer1, Brandon Taraku1, Randall Espinoza2, Katherine Narr2,1, Jennifer Kruse2
Institutions:
1Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at UCLA, Los Angeles, CA, 2Semel Institute for Neuroscience and Human Behavior, Geffen School of Medicine at UCLA, Los Angeles, CA
First Author:
Artemis Zavaliangos-Petropulu
Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at UCLA
Los Angeles, CA
Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at UCLA
Los Angeles, CA
Co-Author(s):
Yeun Kim
Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at UCLA
Los Angeles, CA
Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at UCLA
Los Angeles, CA
Paloma Pfeiffer
Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at UCLA
Los Angeles, CA
Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at UCLA
Los Angeles, CA
Brandon Taraku
Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at UCLA
Los Angeles, CA
Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at UCLA
Los Angeles, CA
Randall Espinoza
Semel Institute for Neuroscience and Human Behavior, Geffen School of Medicine at UCLA
Los Angeles, CA
Semel Institute for Neuroscience and Human Behavior, Geffen School of Medicine at UCLA
Los Angeles, CA
Katherine Narr
Semel Institute for Neuroscience and Human Behavior, Geffen School of Medicine at UCLA|Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at UCLA
Los Angeles, CA|Los Angeles, CA
Semel Institute for Neuroscience and Human Behavior, Geffen School of Medicine at UCLA|Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, Geffen School of Medicine at UCLA
Los Angeles, CA|Los Angeles, CA
Jennifer Kruse, MD
Semel Institute for Neuroscience and Human Behavior, Geffen School of Medicine at UCLA
Los Angeles, CA
Semel Institute for Neuroscience and Human Behavior, Geffen School of Medicine at UCLA
Los Angeles, CA
Introduction:
Electroconvulsive therapy (ECT) is a highly effective, rapidly-acting intervention for treatment-resistant depression (TRD). Evidence also suggests that a course of ECT can reduce inflammation(Espinoza & Kellner, 2022), which is often elevated in patients with depression. Previous studies have utilized diffusion MRI (dMRI) with tensor-based models to explore alterations in white matter microstructure(Belge et al., 2022; Repple et al., 2020) and associations with inflammatory biomarkers following ECT(Andreou et al., 2022). However, more advanced multi-compartment diffusion imaging methods as applied in this study may better reveal how ECT influences white matter microstructure in relation to clinical and inflammatory response.
Methods:
Patients with TRD (N=30; age=36.90±14.06; 12F/18M) received dMRI scans, clinical assessments using the 17-item Hamilton Depression Rating Scale (HDRS)(Hamilton, 1960) and blood draws for measuring interleukin 6 (IL6) at baseline (BL) and post-ECT index (PI; ~13 ECT sessions)(Fig1A). IL-6 levels were measured using a Meso Scale Discovery (MSD) electrochemiluminescence assay and log transformed for analysis. Human Connectome Project (HCP) acquisition protocols were used to collect structural (T1/T2, voxel size (VS): 0.8 mm³) and dMRI (VS: 1.5 mm³, b=1500, 3000 s/mm²) on a Siemens 3T Prisma. Imaging data were preprocessed using the HCP minimal pipeline(Glasser et al., 2013). Processed dMRI in T1 space was used to generate orientation dispersion index (ODI), neurite density (NDI), and cerebrospinal fluid volume fraction (FISO) maps via the NODDI Matlab Toolbox(Zhang et al., 2012), and fractional anisotropy (FA) and mean diffusivity (MD) were generated using FSL's DTIFIT. Longitudinal tract-based spatial statistics (TBSS)(Engvig et al., 2012) was used to extract white matter in 46 tract regions of interest (ROI) of the Johns Hopkins University atlas(Mori et al. 2006). Mixed effect models assessed the impact of ECT on HDRS-17, IL6, and WM diffusion metrics, adjusting for age, sex, and participant (random effect), with FDR correction. Linear regressions examined correlations between percent changes in WM metrics with HDRS and IL6, adjusting for age and sex.
·Figure 1
Results:
Significant improvements in HDRS (p=2.6e-4, d=-1.6) and decreases in IL6 levels (p=0.01, d=-1.0) were observed at PI (Fig1B-C). Significant changes in WM were observed in 9 ROIs for NDI, 4 for ODI, and 9 for FISO (Fig2A-F). Significant decreases in NDI and FISO were observed in several tracts, overlapping only in the right cingulum, while decreased FISO and ODI were found in the right superior corona radiata, and decreased NDI and ODI in the right uncinate fasciculus. Greater increase in right hippocampal cingulum NDI significantly correlated with improvements in HDRS (p=0.002, d=1.4). Correlations were observed between change in IL6 and left posterior corona radiata NDI (p=0.04, d=0.9), right superior fronto-occipital fasciculus ODI (p=0.03, d=0.9), and left fornix (crus)/stria terminalis FA (p=0.02, d=1.0) but did not pass FDR correction (Fig2G-J).
·Figure 2
Conclusions:
ECT significantly improved depressive symptoms and reduced circulating inflammatory biomarker IL-6. Significant alterations in white matter microstructure were observed following ECT. Decreased NDI findings distinct from FISO change suggest that ECT induces changes in white matter connectivity in distinct neural pathways, potentially reflecting microstructural reorganization. Decreased FISO distinct from NDI may reflect the anti-inflammatory properties of ECT. While decreases in NDI were mostly observed, increased NDI in the right hippocampal cingulum correlated with clinical improvements, suggesting alterations in the microstructure of this region may play a key role in ECT's antidepressant effects. Nominal correlations between changes in white matter microstructure and inflammation suggest potential for circulating anti-inflammatory mechanisms of ECT biomarkers, but further investigation is needed.
Brain Stimulation:
Non-Invasive Stimulation Methods Other 1
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia)
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis 2
Keywords:
White Matter
Other - Electroconvulsive Therapy; Major Depressive Disorder; Diffusion MRI; NODDI; Treatment Resistant Depression
1|2Indicates the priority used for review
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Provide references using APA citation style.
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