White-matter tract integrity in late-life depression: associations with severity and cognition

Abstract

Background Although significant changes in both gray and white matter have been noted in late-life depression (LLD), the pathophysiology of implicated white-matter tracts has not been fully described. In this study we examined the integrity of specific white-matter tracts in LLD versus healthy controls (HC). Method Participants aged ≥60 years were recruited from the community. The sample included 23 clinically diagnosed individuals with LLD and 23 HC. White-matter integrity metrics [fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD)] were calculated in the bilateral cingulum and uncinate fasciculus. Depression severity was measured using the Center for Epidemiological Studies Depression Scale (CESD). Composite scores for learning and memory and executive function were created using standardized neuropsychological assessments. Results White-matter integrity was lower in LLD versus HC in the bilateral cingulum and right uncinate fasciculus (p≤0.05). In the whole sample, depression severity correlated with integrity in the bilateral cingulum and right uncinate fasciculus (p ≤0.05). In patients, depression severity correlated with the integrity of the left uncinate fasciculus (p=0.03); this tract also correlated with executive function (p=0.02). Among HC, tract integrity did not correlate with depression scores; however, learning and memory correlated with integrity of the bilateral uncinate fasciculus and bilateral cingulum; executive function correlated with the right uncinate and left cingulum (p ≤0.05). Conclusions White-matter tract integrity was lower in LLD than in HC and was associated with depression severity across all participants. Tract integrity was associated with cognition in both groups but more robustly among HC.

Neuroanatomical correlates of apathy in late-life depression and antidepressant treatment response

“…We did observe lower FA in bilateral uncinate fasciculi of the depressed patient group compared to controls, however this difference failed to reach statistical significance. Work by others demonstrated lower FA of right uncinate fasciculi in depressed compared to healthy controls (Charlton et al, 2013) and less white matter hyperintensities in left uncinate fasciculi of depressed compared to healthy controls (Sheline et al, 2008). It is possible that our study was not adequately powered to identify this as a significant difference between depressed and control groups.…”

Limbic white matter microstructure plasticity reflects recovery from depression

“…We investigated the slMFB, CB, UF, parahippocampal cingulum (PHC) and the fornix. In all of these pathways white matter microstructure alterations have been reported during depressive episodes (Aghajani et al, 2013;Bracht et al, 2014c;Charlton et al, 2014;Kieseppa et al, 2010;Korgaonkar et al, 2011;Zhang et al, 2012;Zhu et al, 2011). White matter microstructure of the slMFB and the CB may be related to hedonic tone (Bracht et al, 2014a, Keedwell et al, 2012 and to anhedonia in depression (Bracht et al, 2014c;Coenen et al, 2012;Schlaepfer et al, 2013), while the UF microstructure may mediate impaired emotion regulation in depression (Aghajani et al, 2013;Zhang et al, 2012).…”

Impaired Frontolimbic Connectivity and Depressive Symptoms in Patients with Alzheimer's Disease

“…The UF connects the anterior temporal lobe (including the amygdala and hippocampus) with the ventral, medial and orbital parts of the prefrontal cortex. Both CB and UF mediate anatomical connectivity of the frontal lobe and limbic structures and are thought to be associated with emotion processing, learning and memory, and executive function [6,31]. Many studies have reported microstructural changes in these fiber tracts during the course of AD.…”

“…We found significantly increased MD and RD in the bilateral CB and right UF, and additionally increased AxD in the right UF in dep-AD patients compared to nondep-AD patients, which is similar to the results of some depressive disorder studies. One study using DTI tractography found that compared with healthy controls, patients with late-life depression demonstrated lower WM integrity with increased MD, AxD, and RD in the bilateral CB and right UF [31]. Another study using TBSS reported that regional differences in the CB and UF were largely driven by increased RD in late-life depression [49].…”