Treatment Course With Antidepressant Therapy in Late-Life Depression

Abstract

Objective In order to assess the effect of gray matter volumes and cortical thickness on antidepressant treatment response in late-life depression, the authors examined the relationship between brain regions identified a priori and Montgomery-Åsberg Depression Rating Scale (MADRS) scores over the course of an antidepressant treatment trial. Method In a nonrandomized prospective trial, 168 patients who were at least 60 years of age and met DSM-IV criteria for major depression underwent MRI and were enrolled in a 12-week treatment study. Exclusion criteria included cognitive impairment or severe medical disorders. The volumes or cortical thicknesses of regions of interest that differed between the depressed group and a comparison group (N=50) were determined. These regions of interest were used in analyses of the depressed group to predict antide-pressant treatment outcome. Mixed-model analyses adjusting for age, education, age at depression onset, race, baseline MADRS score, scanner, and interaction with time examined predictors of MADRS scores over time. Results Smaller hippocampal volumes predicted a slower response to treatment. With the inclusion of white matter hyperintensity severity and neuropsychological factor scores, the best model included hippocampal volume and cognitive processing speed to predict rate of response over time. A secondary analysis showed that hippocampal volume and frontal pole thickness differed between patients who achieved remission and those who did not. Conclusions These data expand our understanding of the prediction of treatment course in late-life depression. The authors propose that the primary variables of hippocampal volume and cognitive processing speed, subsuming other contributing variables (episodic memory, executive function, language processing) predict antidepressant response.

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

“…It appears also likely that regional volume differences exist between patients who remit and do not remit to ADM, particularly in the cortical and limbic areas. In this review, 3 studies (2 late-life depression, 1 non-geriatric MDD) have correlated larger hippocampal volumes with an increased likelihood of remission, and a fourth only established this relationship for the right hippocampus in females (Hsieh et al, 2002;MacQueen et al, 2008;Sheline et al, 2012;Vakili et al, 2000). One of these studies however observed that the size of the left hippocampus did not influence treatment outcome.…”

Repeated restraint stress-induced atrophy of glutamatergic pyramidal neurons and decreases in glutamatergic efflux in the rat amygdala are prevented by the antidepressant agomelatine

“…For example, initial reports from Sheline and coworkers reported that amygdalar volumes were decreased in recurrent depressive illness patients, structural deficits that were observed in the absence of changes in total cerebral volumes (Sheline et al, 1998(Sheline et al, , 1999. These same investigators reported that amygdalar volumes were decreased in late-life depressive illness patients and that these volumetric reductions were predictive of treatment responsiveness (Sheline et al, 2012). Additional studies reported similar decreases in amygdalar volumes in late-life depressive illness patients (Andreescu et al, 2008;Burke et al, 2011), while other studies suggested that late-life depression was associated with changes in amygdalar shape (Tamburo et al, 2009).…”

“…Beyond these alterations in mood and physiology, depressive illness patients also exhibit neuroanatomical alterations in limbic structures such as the amygdala. For example, imaging studies have revealed that amygdala volumes may be increased (Frodl et al, 2002(Frodl et al, , 2003Lange and Irle, 2004;Weniger et al, 2006), decreased (Sheline et al, 1998(Sheline et al, , 1999von Gunten et al, 2000;Hastings et al, 2004;Andreescu et al, 2008;Burke et al, 2011;Sheline et al, 2012) or unchanged (Bremner et al, 2000;Caetano et al, 2004;Frodl et al, 2004) in MDD patients. While these discrepancies may be related to a variety of factors including illness duration, the number of depressive illness episodes, gender and therapeutic interventions (Campbell et al, 2004), the results demonstrate that the amygdala is a site for neuroanatomical alterations in depressive illness.…”

Association of Depressive Symptoms with Hippocampal Volume in 1936 Adults

“…Third, hippocampal volume may be associated with treatment response in MDD. Smaller hippocampal volume appears to be associated with a poorer response to antidepressants (Hsieh et al, 2002;Sheline et al, 2012;Vakili et al, 2000).…”