Reconciling Variable Findings of White Matter Integrity in Major Depressive Disorder

Abstract

Diffusion tensor imaging (DTI) has been used to evaluate white matter (WM) integrity in major depressive disorder (MDD), with several studies reporting differences between depressed patients and controls. However, these findings are variable and taken from relatively small studies often using suboptimal analytic approaches. The presented DTI study examined WM integrity in large samples of medication-free MDD patients (n ¼ 134) and healthy controls (n ¼ 54) using voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) approaches, and rigorous statistical thresholds. Compared with health control subjects, MDD patients show no significant differences in fractional anisotropy, radial diffusivity, mean diffusivity, and axonal diffusivity with either the VBM or the TBSS approach. Our findings suggest that disrupted WM integrity does not have a major role in the neurobiology of MDD in this relatively large study using optimal imaging acquisition and analysis; however, this does not eliminate the possibility that certain patient subgroups show WM disruption associated with depression.

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

“…The subgroup analysis of studies with corrected results included 10 data sets 13,22,[25][26][27][28][41][42][43][44] comprising 344 patients with MDD and 338 healthy controls. These results were consistent with the pooled meta-analysis (Table 3), showing few effects of uncorrected results on the overall conclusions.…”

“…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.…”

“…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.…”

The neuroscience of depression: Implications for assessment and intervention

“…Using DTI, investigators have documented abnormalities in MDD in white matter tracts that connect portions of the PFC to subcortical structures (Liao et al, 2013), suggesting that MDD is a syndrome of white matter disconnection. Researchers have also reported lower levels of white matter integrity in the limbic system, DLPFC, thalamic projection fibers, corpus callosum, and other association fibers in depressed than in nondepressed individuals (but see also Choi et al, 2013). …”