Cingulum bundle white matter lesions influence antidepressant response in late-life depression: A pilot study

Abstract

Background Late-life depression is associated with white matter hyperintense lesions (WMLs) occurring in specific fiber tracts. In this study, we sought to determine if greater WML severity in the cingulum bundle or uncinate fasciculus was associated with poor short-term antidepressant response. Methods Eleven depressed elders completed a baseline cranial 3T MRI and received antidepressant treatment following a medication algorithm. MRIs were analyzed to measure the fraction of each fiber tract’s volume occupied by WMLs. Statistical analyses examined the effect of dichotomized fiber tract WML severity on three- and six-month depression severity after controlling for age and baseline depression severity. Results Greater WML severity in the left hemispheric cingulum bundle adjacent to the hippocampus was associated with greater post-treatment depression severity at three- (F1,7=6.42, p=0.0390) and six-month assessments (F1,5=9.62, p=0.0268). Other fiber tract WML measures were not significantly associated with outcomes. Limitations The study had a small sample size and analyses were limited to only a priori fiber tracts. Conclusions This pilot study supports the hypothesis that focal damage to the cingulum bundle may contribute to poor short-term antidepressant response. These findings warrant further investigation with a larger, more definitive study.

Imaging predictors of remission to anti-depressant medications in major depressive disorder

“…The two highest-powered studies thus far have supported a predictive value of the fractional anisotropy of the left cingulum bundle for ADM treatment remission/non-remission (Korgaonkar et al, 2015;Korgaonkar et al, 2014b). Indirectly supportive of this finding, Taylor et al (2014) showed, in a small population of 11 elderly MDD patients, a relationship between a higher density of white matter lesions in the left cingulum bundle and worse treatment response (Taylor et al, 2014).…”

White Matter Hyperintensity Accumulation During Treatment of Late-Life Depression

“…Therefore, one possible interpretation of the association between WMH accumulation and non-remission is that the former represents further degradation of these neural pathways, which are critical to patient recovery. This hypothesis arises from a number of previous studies, which demonstrate that WMHs and microstructural abnormalities in specific frontostriatal circuit structures are associated with treatment outcomes in LLD (Alexopoulos et al, 2002(Alexopoulos et al, , 2008(Alexopoulos et al, , 2010Taylor et al, 2014). It is also a distinct possibility that this effect is bidirectional.…”

“…Furthermore, one of the most salient models of depression in older adults is the vascular depression hypothesis, which suggests that cerebrovascular ischemic damage promotes depressive symptoms Butters et al, 2008). The relationship between WMHs and the vascular depression hypothesis is further strengthened by studies demonstrating that WMHs are associated with treatment outcomes (Aizenstein et al, 2011;Firbank et al, 2007;Heiden et al, 2005;Taylor et al, 2014). However, as several other studies have failed to find the association between WMHs and depression, the vascular depression hypothesis is not universally accepted (Aizenstein et al, 2011;Dotson et al, 2013).…”

Longitudinal Cognitive Outcomes of Clinical Phenotypes of Late-Life Depression

“…20 Damage to such circuits may predispose individuals to depression and diminish the ability of antidepressants to modify brain function and connectivity, resulting in poorer clinical response. 21 Thus clinically relevant depressive symptoms in context of mild cognitive symptoms may be an early marker of brain pathology. Second, a “depression neurotoxicity” hypothesis proposes that repeated depressive episodes contribute to pathological brain aging and cognitive decline.…”