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Gray and White matter microstructural alterations in major depressive disorder: a multi-center diffusion imaging
Kento Takahashi1, Taro Suwa1, Yujiro Yoshihara1
1Department of Psychiatry, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan.
Abstract:
Diffusion imaging techniques have been widely used to investigate alterations in brain microstructure associated with major depressive disorder (MDD). Due to its technical limitations, diffusion tensor imaging (DTI)-based studies have often been restricted to evaluating white matter (WM), and analyses of gray matter (GM) microstructural changes using advanced diffusion models remain insufficient. Additionally, many of these studies concentrate on region-specific associations with symptoms rather than a comprehensive assessment of broader microstructural changes. In this study, we employed neurite orientation dispersion and density imaging (NODDI) and DTI to investigate GM and WM microstructural changes at both whole-brain and regional levels. Data were collected from 159 MDD patients and 112 healthy controls across multiple centers. Our findings revealed significantly increased mean free water fraction (FWF) in GM, elevated mean orientation dispersion index (ODI) in WM, and decreased fractional anisotropy (FA) in WM among MDD patients compared to healthy controls. Furthermore, the mean FA of WM exhibited a negative correlation, and the mean ODI of WM showed a positive correlation with illness duration. No significant correlations were observed between diffusion indices and Hamilton Depression Rating Scale (HAMD-17) scores. Gray matter-based spatial statistics demonstrated increased FWF in several GM regions, including the frontal lobes, temporal lobes, and limbic system. Tract-based spatial statistics revealed widespread reductions in FA across WM in MDD patients. These findings suggest that microstructural tissue disorganization may underlie the pathophysiology of MDD, emphasizing the need for future research to link neuroimaging findings with underlying biological mechanisms.
Insights
Major depressive disorder (MDD) is linked to brain microstructural changes. Advanced diffusion imaging reveals gray matter water content increases and white matter disorganization in MDD patients, correlating with illness duration.
Area of Science:
- Neuroimaging
- Neuroscience
- Psychiatry
Background:
- Diffusion imaging, including diffusion tensor imaging (DTI), is crucial for studying brain microstructure in major depressive disorder (MDD).
- Previous DTI studies often focused on white matter (WM) and region-specific changes, with limited analysis of gray matter (GM) microstructural alterations using advanced models.
- A comprehensive assessment of widespread microstructural changes in MDD is needed.
Purpose of the Study:
- To investigate gray matter (GM) and white matter (WM) microstructural changes in MDD patients using neurite orientation dispersion and density imaging (NODDI) and DTI.
- To examine both whole-brain and regional microstructural alterations.
- To explore correlations between diffusion indices and clinical variables like illness duration and depression severity.
Main Methods:
- Employed NODDI and DTI techniques on data from 159 MDD patients and 112 healthy controls across multiple centers.
- Utilized gray matter-based spatial statistics (GMS) and tract-based spatial statistics (TBSS) for regional analyses.
- Assessed diffusion indices including free water fraction (FWF), orientation dispersion index (ODI), and fractional anisotropy (FA).
Main Results:
- MDD patients showed significantly increased FWF in GM, elevated ODI in WM, and decreased FA in WM compared to controls.
- WM FA negatively correlated with illness duration, while WM ODI positively correlated with illness duration.
- GMS identified increased FWF in frontal, temporal, and limbic regions; TBSS revealed widespread FA reductions in WM.
Conclusions:
- Microstructural tissue disorganization, characterized by increased GM water and altered WM integrity, may be integral to MDD pathophysiology.
- Diffusion imaging findings suggest widespread GM and WM alterations in MDD, extending beyond previously studied regions.
- Further research is required to elucidate the biological mechanisms underlying these neuroimaging findings in MDD.
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