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 antidepressant 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 hyper-intensity 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.

FIGURE 1. Model of Treatment Response in Late-Life Depression^a

^a In this model, the predictor variables for late-life depression are shown as stress and genetics, with resilience as a protective factor, modified by Framingham vascular risk factors and white matter hyperintensity severity. This is not meant to be an exclusive list; other factors, such as baseline depression severity, clearly influence antidepressant response. Furthermore, in some samples, late-life depression can be confounded by dementia. Not shown are the covariates in the model—age, age at onset, education, gender, depression severity, and race. Late-life depression is associated with smaller hippocampal volumes and slower cognitive processing speed. Within cognitive processing speed are subsumed executive function, episodic memory, and language processing. Together, smaller hippocampal volume and slower cognitive processing speed predict a slower rate of response to antidepressant treatment.

FIGURE 2. Box Plots of Hippocampal Volume and Cognitive Processing Speed in Patients With Late-Life Depression Who Did or Did Not Achieve Remission With Antidepressant Treatment and in Comparison Subjects^a

^a In panel A, hippocampal volumes are from Table 1 (comparison group) and Table 4 (patients with late-life depression who did or did not achieve remission). In panel B, cognitive processing speed data are from Sheline et al. (21). Box plots show group median, 25%, and 75%. Error bars indicate standard deviations.