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authors reported that altered connectivity for the Depression total scores were negatively correlated with
cingulum part of the cingulate and stria terminalis mean‑FA of these brain regions.
tracts significantly predicted remission. Hayakawa
et al. [31] reported a positive correlation between Center Structural abnormalities of cortico‑cortical WM motor
for Epidemiologic Studies Depression Scale (CES‑D) pathways have been also suggested in 2012 by Bracht
scale score and radial diffusivity in the right anterior et al. [26] in a study of 21 MDD patients relative to 21
cingulum of 21 subclinically depressed women healthy controls. They observed that patients had
compared with 21 matched controls. lower activity levels and showed increased mean
diffusivity in pathways linking left presupplementary
Another recent report [12] suggested that in 95 MDD motor area and supplementary motor area, and right
outpatients compared to 102 matched control subjects supplementary motor area and primary motor cortex.
structural connectivity alterations between nodes of Notably, a negative association between activity level
the default mode network and frontal‑thalamo‑caudate and mean diffusivity of the left dorsolateral prefrontal
areas (having an important role in emotional and cortex‑pre‑supplementary motor area connection was
cognitive processing) may play a critical role in the observed only in MDD patients with low activity levels.
pathophysiology of MDD.
In addition, Osoba et al. [32] reported significant FA
Structural connectivity alterations were also observed deficits in the right parietal WM of 20 MDD patients
in the brainstem and the amygdala in 95 MDD patients whereas severity of depression has been associated
compared to 34 gender‑matched controls [14] whereas with increased thalamic FA in centromedian tracts
lower FA values in the body of the corpus callosum, and decreased FA in mediodorsal and dorsolateral
increased radial and mean diffusivity were found after prefrontal cortex tracts. Lower activity levels in frontal
whole‑brain analysis. In addition, higher FA values in WM regions and posterior cingulum when compared
the uncinate fasciculus together with increased axial with 21 matched healthy controls were also found by
diffusivity, reduced radial diffusivity were reported Walther et al. [86] in a cohort of 21 medicated patients
after region‑of‑interest analysis by Aghajani et al. [84] with MDD. Depressed subjects also reported negative
associations of FA and activity levels below the left
A preliminary report [24] on 17 MDD adolescents primary motor cortex and left parahippocampal gyrus
suggested decreased WM integrity in the anterior WM.
cingulum and anterior corona radiata compared to
[87]
16 matched controls. Depression severity has been In 2012, Cole et al. reported that MDD was associated
correlated with reduced WM integrity in the genu with widespread reductions in WM integrity of the
of corpus callosum, anterior thalamic radiation, corpus callosum, SLF and anterior corona radiate in
anterior cingulum, and sagittal stratum. Similarly, 66 patients with recurrent major depression compared
Bessette et al. [20] reported significantly lower FA of the to 66 controls. The authors suggested that WM integrity
frontal lobe, bilateral anterior/posterior limbs of the of the corpus callosum was negatively correlated with
internal capsules, left external capsule, right thalamic increasing symptom severity.
radiation and left inferior longitudinal fasciculus in
31 MDD adolescents when compared with 31 healthy Using a 3T scanner DTI, Colloby et al. [88] investigated
volunteers. A first DTI study [85] found altered WM 68 subjects (30 healthy individuals, and 38 depressed
microstructure in frontolimbic neural pathways of 14 individuals) and found a loss of WM integrity within
MDD adolescents compared with 14 healthy controls. the frontal, temporal and midbrain fibers. Patients with
LOD demonstrated significant lower FA compared with
Furthermore, Tha et al. [22] reported clusters of FA older healthy subjects due to the possible disruption
decrease in several brain regions (e.g. the bilateral of limbic‑orbitofrontal networks. However, after
frontal WM, anterior limbs of internal capsule, conducting regression analyses, the authors did not
cerebellum, left putamen and right thalamus) in a find a significant association between DTI parameters
limited cohort of nine patients with MDD who are not and current depressive symptoms.
taking antidepressant medications.
Moreover, Korgaonkar et al. [89] reported the presence
Interesting findings were also found in melancholic of WM integrity deficits in 11 melancholic MDD
subtype of MDD. [25] The authors suggested that MDD subjects relative to 39 healthy controls postulating the
melancholic patients (n = 12) had lower mean FA in the existence of a pattern of reduced myelination or other
right ventral tegmental area‑lateral orbitofrontal cortex degenerative changes whereas Wu et al. [90] reported
and ventral tegmental area‑dorsolateral orbitofrontal a significantly lower FA in the right SLF within the
cortex connections compared to 21 healthy controls. frontal lobe, right middle frontal and left parietal WM

204 Neuroimmunol Neuroinflammation | Volume 2 | Issue 4 | October 15, 2015