Abstract
White matter (WM) abnormalities have long been suspected in major depressive disorder (MDD). Tract-based spatial statistics (TBSS) studies have detected abnormalities in fractional anisotropy (FA) in MDD, but the available evidence has been inconsistent. We performed a quantitative meta-analysis of TBSS studies contrasting MDD patients with healthy control subjects (HCS). A total of 17 studies with 18 datasets that included 641 MDD patients and 581 HCS were identified. Anisotropic effect size-signed differential mapping (AES-SDM) meta-analysis was performed to assess FA alterations in MDD patients compared to HCS. FA reductions were identified in the genu of the corpus callosum (CC) extending to the body of the CC and left anterior limb of the internal capsule (ALIC) in MDD patients relative to HCS. Descriptive analysis of quartiles, sensitivity analysis and subgroup analysis further confirmed these findings. Meta-regression analysis revealed that individuals with more severe MDD were significantly more likely to have FA reductions in the genu of the CC. This study provides a thorough profile of WM abnormalities in MDD and evidence that interhemispheric connections and frontal-striatal-thalamic pathways are the most convergent circuits affected in MDD.
Highlights
In contrast to conventional T1-weighted structural images of WM in the brain, diffusion tensor imaging (DTI), a noninvasive magnetic resonance method based on the diffusion characteristics of water, can be used to quantify the fibre orientation and integrity of WM pathways within neural networks14,15
They did not find the association between the symptom severity evaluated by Hamilton Depression Rating Scale (HAMD) and neuroimaging alterations because only 7 tract-based spatial statistics (TBSS) datasets reporting HAMD scores were included in Wise's research while according to Radua et al.30, the meta-regression analysis is invalid if data is available for fewer than 9 datasets
The present voxel-wise meta-analysis using anisotropic effect size-signed differential mapping (AES-SDM) primarily revealed that patients with Major depressive disorder (MDD) have fractional anisotropy (FA) reductions in the genu of the corpus callosum (CC) extending to the body of the CC and left anterior limb of the internal capsule (ALIC)
Summary
In contrast to conventional T1-weighted structural images of WM in the brain, diffusion tensor imaging (DTI), a noninvasive magnetic resonance method based on the diffusion characteristics of water, can be used to quantify the fibre orientation and integrity of WM pathways within neural networks. In the study conducted by Wise et al., only 10 DTI studies with TBSS were included, and other confounding factors, such as medication status, were not considered They did not find the association between the symptom severity evaluated by Hamilton Depression Rating Scale (HAMD) and neuroimaging alterations because only 7 TBSS datasets reporting HAMD scores were included in Wise's research while according to Radua et al., the meta-regression analysis is invalid if data is available for fewer than 9 datasets. The goals of this study were threefold: first, we conducted an updated quantitative summary of 17 TBSS studies (14 TBSS datasets reported HAMD scores) concerning FA abnormalities in MDD using anisotropic effect size-signed differential mapping (AES-SDM), a newly developed meta-analytic technique with the potential to quantify the reproducibility of neuroimaging findings and to generate insights that are difficult to obtain from an individual study; second, we performed subgroup meta-analyses to compare first-episode, treatment-naive/ medication-free MDD patients with HCS to avoid the potential confounding effects of medication; third, we used a meta-regression method to examine the potentially moderating effects of symptom severity and other relevant variables on the reported WM abnormalities
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