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when investigating 23 single‑episode, medication‑naive the anterior cingulum, forceps minor, and left SLF in
MDD subjects relative to 21 healthy controls. patients receiving ECT compared to healthy controls.
The authors also reported significant reductions in
Lower FA values in the bilateral medial frontal gyri, radial and mean diffusivity of the anterior thalamic
right subgyral frontal and temporal lobes, left middle radiation related to therapeutic response in MDD
frontal, and cingulate gyri have been reported by patients. In another DTI study, Taylor et al. [98] suggested
Ouyang et al. [91] in 18 MDD patients compared to 18 that 74 subjects who were responders to Sertraline
controls. reported higher FA values in the superior frontal gyri
and anterior cingulate cortices bilaterally; however,
Abnormalities of WM integrity, especially within there is no significant association between apparent
cortical‑subcortical neural circuits, have been suggested diffusion coefficient measures and remission.
to play a key role in the pathophysiology of MDD.
Reduced FA values in the left WM anterior limb of the Furthermore, Nobuhara et al. reported improvements
[99]
internal capsule (ALIC), right parahippocampal gyrus, of WM integrity in frontal brain regions after ECT
and left posterior cingulate cortex in 25 first‑episode, treatment in 8 late‑life depressed patients with
treatment‑naive young adult MDD patients compared significant frontal and temporal FA reductions
with 25 healthy controls have been reported by compared with 12 healthy age‑matched controls.
Zhu et al. [92] Interestingly, the severity of depressive
symptoms was negatively correlated with the reduced In another report, Wang et al. [33] suggested a significant
FA values of the left ALIC suggesting a crucial role of reduction of the 17‑item Hamilton depression rating
this brain region in the pathogenesis of MDD. scale in 21 depressed patients after 4‑week guided
imagery psychotherapy. Significantly increased FA
Lamar et al. [93] reported an association between WM in the right thalamus was reported in depressed
damage and endorsed depressive symptoms in 79 individuals compared to healthy controls. Changes
euthymic older adults whereas Zou et al. [94] observed in WM have been also described after left repetitive
a significant decrease in FA of the left hemisphere, transcranial magnetic stimulation by Kozel et al. [100] A
including the left ALIC and inferior parietal portion mean (although not significant) increase was found in
of the SLF in 45 patients with MDD compared with the left prefrontal WM in 8 depressed patients.
45 healthy controls. Finally, lower FA of the rostral/
dorsal anterior cingulate, dorsolateral prefrontal cortex, Recently, Hoogenboom et al. [28] found that failure to
genu of the corpus callosum, WM adjacent to the achieve remission was associated with lower medial
hippocampus, multiple posterior cingulate cortex body of the fornix FA among 92 MDD patients (of
regions, and insular WM, neostriatum and midbrain which 29 were nonremitters, 26 partial‑remitters, and
together with temporal and parietal regions were found 37 full‑remitters).
in 23 individuals who failed to remit compared to
25 patients who recovered from depression. [95] Not all studies supported the existence of WM alterations
as assessed using DTI techniques in MDD patients. Choi
Meta‑analytic evidence of DTI studies also confirmed et al. [30] found no significant differences in FA, radial
[96]
the association between WM integrity abnormalities diffusivity, mean diffusivity, and axonal diffusivity
and MDD. Reduced FA in the WM fascicles connecting using voxel‑based morphometry or tract‑based spatial
the prefrontal cortex within cortical (frontal, temporal statistics approach in 134 medication‑free MDD patients
and occipital lobes) and subcortical areas (amygdala compared to 54 healthy controls.
and hippocampus) supported the involvement of
these brain areas in the pathogenesis of MDD. Similar Moreover, Bezerra et al. [101] reported no significant
findings were reported in a previous meta‑analysis when differences among FA or mean diffusivity values between
Murphy and Frodl [97] found reduced WM FA values in depressed and non‑depressed elderly individuals
SLF and increased FA values in the fronto‑occipital with or without mild/moderate MDD. Abe et al. [102]
fasciculus in depressed patients compared to controls. also suggested no significant difference between 21
right‑handed patients and 42 age‑ and gender‑matched
There are also DTI studies demonstrating the positive controls for FA and whole WM volume. Only a trend
effect of treatments on WM integrity in patients with of negative correlation between FA and total days in
MDD. Lyden et al. suggested that WM microstructure the right anterior cingulate and left frontal WM was
[27]
abnormalities in frontal and limbic regions of reported in this study.
20 MDD patients are modulated by electroconvulsive
therapy (ECT). They found significant FA increases Similarly, Kieseppä et al. [103] investigated 16 MDD
of the dorsal fronto‑limbic circuits encompassing patients and found only a trend for lower values of FA

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