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Gender differences in WM disease of patients with MDD showed greater WMHs in the superior longitudinal
in late life have been recently described by Dotson et al. fasciculus (SLF), fronto‑occipital fasciculus,
[48]
The authors reported that depressive symptoms predicted uncinate fasciculus, extreme capsule, and inferior
increased WMHs rates in men but not in women. A higher longitudinal fasciculus that were associated with both
rate of WMHs was commonly reported in individuals cognitive (e.g. episodic memory, processing speed, and
with late‑onset depression (LOD) when compared with executive functions) and emotional functions when
healthy elderly controls and subjects with early‑onset compared with 32 healthy controls.
depression (EOD). [49‑52] Salloway et al. reported that
[53]
both deep WMHs and periventricular WMHs were Finally, there are also few studies reporting the
significantly more severe in the LOD group than EOD association between WMHs and suicidal behavior in
group. More recently, Gunning‑Dixon et al. found that MDD patients. In 2012, Serafini et al. [71] reported that
[54]
22 patients who did not remit following escitalopram among 85 adult outpatients with chronic headache,
treatment had significantly greater WMHs on MRI than patients with periventricular WMHs were 1.06 times
20 remitted patients and 25 elderly controls. In addition, more likely to report fewer depressive symptoms
Takahashi et al. [55] reported that patients with LOD than patients without PWMHs suggesting that WMH
showed a higher rate of deep WMHs and more severe lesions were associated with less depression severity.
pathological changes especially in the bilateral frontal However, no association between WMHs and suicidal
areas and left parieto‑occipital area compared with behavior was found. Interestingly, in a meta‑analysis
EOD. Compelling evidence suggested that deep WMHs including four MRI studies, a significantly higher
are more severe in LOD than in healthy controls. [50,56,57] number of suicide attempters was reported to have
WMHs compared to non‑attempters. [72] Specifically,
The frontal lobes have mutual fiber communications unipolar depressed patients who had attempted
with subcortical nuclei, such as the thalamus, basal suicide were 1.9 and 2.1 times, respectively, more
ganglia, and amygdala via WM projections mediating likely to have deep WMHs and periventricular WMHs
emotional processing of information and regulation of than nonattempters.
emotional states. It has been suggested that dysfunctions
of the frontal lobes may be caused by subcortical WM In addition, in a cohort of 99 unipolar/bipolar patients,
lesions triggering the emergence and maintenance of Pompili et al. [73] reported after logistic regression
mood disorders. [58] analyses that periventricular WMHs were robustly
associated with suicidal behaviors after controlling
There are also studies suggesting that the presence of for age. Importantly, the same research group had
[9]
WM lesions may be associated with clinical severity previously found in a smaller (n = 65) cohort of
and treatment responsiveness. In 12‑week, randomized unipolar/bipolar inpatients an higher WMHs prevalence
clinical trial comparing Sertraline with Nortriptyline, in subjects with past suicide attempts than in those
Sneed et al. [59] also tested the hypothesis that remission without.
from geriatric depression may depend on lesion volume
[8]
by region of interest and found that patients with higher In 2005, Ehrlich et al. suggested a higher prevalence
deep WMHs were 7.14 times more likely to not remit of periventricular WMHs in subjects with past suicide
after antidepressant treatment compared to patients attempts among a cohort of 102 young psychiatric
with lower deep WMHs. The authors also suggested inpatients with MDD. Furthermore, a significant
that those having higher periventricular VMHs and association between WMHs and higher prevalence
total volumes may be 4.17 and 5.00 times more likely of past suicide attempts in 48 unipolar depression
[7]
to not remit, respectively. group had been previously reported. The same
research group found that youths with deep WMHs
[6]
Increased severity of WM lesions is also associated mainly located in the parietal and frontal lobes have a
with a more chronic outcome, [46,60‑62] poorer response significantly higher prevalence of reported past suicide
to antidepressant medications, [63‑65] and long‑term attempts.
disability [66] in depressed patients. WMHs are also
generally associated with cognitive decline in various WMHs have been commonly reported in both patients
domains, particularly executive skills, attention, and with MDD and suicidal behavior; however, the
mental speed. [63,67‑69] clinical significance of these lesions is still poorly
understood as they may be also found in non‑depressed
In addition, Sheline et al. [70] suggested the critical individuals with cerebrovascular risk factors such as
and strategic importance of WMHs location in LOD. hypertension, [56,57,67] diabetes, myocardial infarction or
The authors reported that 83 depressed subjects coronary artery disease, and smoking. [57,74]

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