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factors may help to recognize those depressed or To date, the association between microstructural WM
nondepressed individuals who are at increased high risk abnormalities, affective temperaments, and suicidal
for suicide, the mechanisms underlying this complex behavior in patients with MDD is poorly understood.
[3]
behavior as well as the link with psychopathology are Therefore, this paper aims to critically review the
still poorly understood. current literature about this association.

White matter hyperintensities (WMHs) appear Studies investigating the presence and significance
as hyperintense signals on T2‑weighted magnetic of WM abnormalities and their link with affective
resonance imaging (MRI) and represent ependymal temperaments in patients with major depression
loss and differing degrees of myelination in the and suicidal behavior were retrieved from Medline
brain. [4,5] WMHs, depending on their localization, may databases. The reference lists of these publications were
be classified as periventricular WMHs and deep WMHs, further investigated to find additional relevant studies.
with the latter usually having a vascular etiology. An extensive search was carried out for research
Degenerative changes in brain white matter (WM) published between January 1980 and October 2014
have been associated with both mood disorders and using the following search terms: (“major depressive
suicidal behavior in children as well as young adults, [6‑9] disorder” OR “MDD” OR “Major depression”)
however they seem to be not specific of patients with AND (“Affective temperaments”) AND (“White matter
first‑episode psychotic disorders. [10] hyperintensities” OR “microstructural white matter
lesions” OR “white matter abnormalities” OR “white
Diffusion tensor imaging (DTI) studies can identify matter changes signals”) AND (“MRI” OR “magnetic
microstructural WM abnormalities with high special resonance imaging”) AND (“Diffusion Tensor Imaging”)
resolution enabling the characterization of WM tracts OR (“DTI”). Only studies published in English were
that relate to critical brain regions implicated in mood included. We did not analyze in the present overview
regulation. According to the current literature, there studies including patients with bipolar depression nor
are many recent DTI studies examining WM networks patients with treatment‑resistant major depression.
abnormalities in patients with MDD [11‑14] as well as in
those with suicidal behavior. [15‑18] Specifically, some THE ROLE OF MICROSTRUCTURAL WM
DTI studies reported the existence of frontolimbic BRAIN ABNORMALITIES AS ASSESSED BY
WM abnormalities in treatment‑naive first‑episode MRI IN PATIENTS WITH UNIPOLAR MAJOR
MDD individuals [19‑22] and adolescents with MDD [23‑24] DEPRESSION
whereas other studies investigated the role of WM
microstructural alterations in patients with melancholic Microstructural brain lesions, especially in the context
MDD characteristics [25,26] or the effect of treatments on of WM integrity, may be frequently found in patients
WM integrity in subjects with MDD. [27‑30] Further, DTI with unipolar major depression. [45] Based on their
studies also investigated the impact of WM abnormalities systematic review and meta‑analysis, cross‑sectional
during the different illness phases (e.g. subclinical subgroup analyses showed that deep WMHs resulted
depression, throughout the acute MDD episode, at the significantly associated with major depression whereas
end of therapy and subsequent follow‑up). [31‑33] periventricular and overall WMHs did not. In addition,
according to longitudinal subgroup analyses, overall
Taylor et al. [34] hypothesized that patients with WM WMHs were significantly associated with major
lesions may be at higher risk for developing mood depression but deep WMHs did not.
disorders and suicide due to possible disruption of
neuroanatomical pathways. Mood regulation depends Microstructural WM brain alterations are neuropathologically
on the complex extensive connections between the characterized by decreased oligodendrocyte density,
prefrontal cortex, amygdala‑hippocampus complex, molecular changes in intercellular cell adhesion molecule
[35]
thalamus and basal ganglia. Mood disorders range from expression levels and possible ischemia. [46]
subthreshold affective temperamental traits as measured
by the Temperament Evaluation of Memphis, Pisa, Paris In another meta‑analysis, Kempton et al. reported that
[47]
and San Diego‑auto‑questionnaire (TEMPS‑A) [36] up MDD was associated with lateral ventricle enlargement;
to mood disorders (of minor and major severity) and larger cerebrospinal fluid volume; smaller volumes of
severe affective psychosis. [37‑40] Affective temperaments the basal ganglia, thalamus, hippocampus, frontal lobe,
may significantly influence the psychopathological orbitofrontal cortex, and gyrus rectus compared with
characteristics of mood disorders, in particular, the structures of the healthy brain. Furthermore, during
the clinical trajectory of episodes and polarity, depressive episodes patients reported significantly
symptomatology, long‑term course, suicidality, and smaller hippocampal volume than patients during
medication adherence. [37,38,40‑44] remission.

Neuroimmunol Neuroinflammation | Volume 2 | Issue 4 | October 15, 2015 201