White Matter Abnormalities in Major Depression: A Tract-Based Spatial Statistics and Rumination Study

Abstract

Increasing evidence indicates that major depressive disorder (MDD) is usually accompanied by altered white matter in the prefrontal cortex, the parietal lobe and the limbic system. As a behavioral abnormity of MDD, rumination has been believed to be a substantial indicator of the mental state of the depressive state. So far, however, no report that we are aware of has evaluated the relationship between white matter alterations and the ruminative state. In this study, we first explored the altered white matter using a tract-based spatial statistics (TBSS) method based on diffusion tensor imaging of 19 healthy and 16 depressive subjects. We then investigated correlations between the altered white matter microstructure in the identified altered regions and the severity of ruminations measured by the ruminative response scale. Our results demonstrated altered white matter microstructure in circuits connecting the prefrontal lobe, the parietal lobe and the limbic system (p<0.005, uncorrected), findings which support previous research. More importantly, the result also indicated that a greater alteration in the white matter is associated with a more ruminative state (p<0.05, Bonferroni corrected). The detected abnormalities in the white matter should be interpreted cautiously because of the small sample size in this study. This finding supports the psychometric significance of white matter deficits in MDD.

Microstructural brain abnormalities in medication-free patients with major depressive disorder: a systematic review and meta-analysis of diffusion tensor imaging

“…21 Results from whole-brain studies have suggested widespread white matter abnormalities in MDD in regions such as the frontal gyrus, 15,22,23 cerebellum, 22,24,25 right thalamus, 24,25 right parietal lobe, 22,23 corpus callosum (CC) 26,27 and superior longitudinal fasciculus (SLF). [28][29][30] However, these results are not consistent, probably owing to small or heterogeneous study samples and methodological differences. A whole-brain meta-analysis detecting common regions of white matter abnormality from DTI studies of patients with MDD is therefore of particular importance.…”

“…The search strategy identified 4046 studies, 15 of which met our inclusion criteria, 13,15,[22][23][24][25][26][27][28][29][30][41][42][43][44] with 1 study reporting a significant difference in age between the MDD and control groups. 44 They included a combined total of 434 medicationfree patients with MDD (183 men and 251 women with a mean age of 34 [range 18-67] yr) and 429 controls (196 men and 233 women with a mean age of 33 [range 18-67] yr).…”

“…The medication washout subgroup analysis included 8 data sets 13,22,24,25,27,30,41,44 that compared 260 patients with MDD and 272 healthy controls. Fractional anisotropy reductions were identified in the white matter of the right cerebellum hemispheric lobule, body of the CC, bilateral SLF III and the long segment of the arcuate network (Table 3 and Appendix 1, Fig.…”

“…13,15,25,43 Furthermore, studies have shown that MDD is associated with significant disturbances in cognitive functioning, including executive functions, attention, memory and psychomotor speed. 13,30,43,71 Some investigations have provided evidence for the hypothesis that the cerebellum is an essential node in the distributed neural circuitry subserving cognitive and affective functions. [72][73][74] Further, a range of remarkable tasks associated with cerebellar activation have been designed to assess attention, executive control, language, working memory, emotion and addiction, generating compelling support for the view that the cerebro-cerebellar circuitry provides the cerebellum with the anatomic substrate to influence the control of movement and cognition.…”

“…Nevertheless, to our knowledge no such meta-analysis has been published to date despite the increase in published DTI studies on medication-free patients with MDD. 13,15,[22][23][24][25][26][27][28][29][30][41][42][43][44] To this end, the aim of the present meta-analysis is to provide an updated quantitative summary of studies investigating white matter abnormalities in medication-free patients with MDD and the effects of demographics and clinical characteristics on white matter microstructure in individuals with MDD. Differences between the findings of current and previous metaanalyses would provide a clearer picture of the white matter alterations directly related to the illness and those potentially influenced by current antidepressant treatment.…”