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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 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.

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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 1185 - 1193
PubMed: 23534057

History

Received: 24 January 2012
Revision received: 11 May 2012
Revision received: 6 June 2012
Accepted: 21 June 2012
Published online: 1 November 2012
Published in print: November 2012

Authors

Affiliations

Yvette I. Sheline, M.D.
From the Departments of Psychiatry, Neurology, Radiology, Psychology, Biostatics, and Internal Medicine–Geriatrics, Washington University School of Medicine, St. Louis, Mo.; and the Departments of Psychiatry and Behavioral Sciences, Biostatistics and Bioinformatics, Radiology, and Biomedical Engineering, Duke University School of Medicine, Durham, N.C.
Brianne M. Disabato, M.D.
From the Departments of Psychiatry, Neurology, Radiology, Psychology, Biostatics, and Internal Medicine–Geriatrics, Washington University School of Medicine, St. Louis, Mo.; and the Departments of Psychiatry and Behavioral Sciences, Biostatistics and Bioinformatics, Radiology, and Biomedical Engineering, Duke University School of Medicine, Durham, N.C.
Jennifer Hranilovich
From the Departments of Psychiatry, Neurology, Radiology, Psychology, Biostatics, and Internal Medicine–Geriatrics, Washington University School of Medicine, St. Louis, Mo.; and the Departments of Psychiatry and Behavioral Sciences, Biostatistics and Bioinformatics, Radiology, and Biomedical Engineering, Duke University School of Medicine, Durham, N.C.
Carrie Morris
From the Departments of Psychiatry, Neurology, Radiology, Psychology, Biostatics, and Internal Medicine–Geriatrics, Washington University School of Medicine, St. Louis, Mo.; and the Departments of Psychiatry and Behavioral Sciences, Biostatistics and Bioinformatics, Radiology, and Biomedical Engineering, Duke University School of Medicine, Durham, N.C.
Gina D’Angelo, Ph.D.
From the Departments of Psychiatry, Neurology, Radiology, Psychology, Biostatics, and Internal Medicine–Geriatrics, Washington University School of Medicine, St. Louis, Mo.; and the Departments of Psychiatry and Behavioral Sciences, Biostatistics and Bioinformatics, Radiology, and Biomedical Engineering, Duke University School of Medicine, Durham, N.C.
Carl Pieper, Dr.P.H.
From the Departments of Psychiatry, Neurology, Radiology, Psychology, Biostatics, and Internal Medicine–Geriatrics, Washington University School of Medicine, St. Louis, Mo.; and the Departments of Psychiatry and Behavioral Sciences, Biostatistics and Bioinformatics, Radiology, and Biomedical Engineering, Duke University School of Medicine, Durham, N.C.
Tommaso Toffanin, M.D.
From the Departments of Psychiatry, Neurology, Radiology, Psychology, Biostatics, and Internal Medicine–Geriatrics, Washington University School of Medicine, St. Louis, Mo.; and the Departments of Psychiatry and Behavioral Sciences, Biostatistics and Bioinformatics, Radiology, and Biomedical Engineering, Duke University School of Medicine, Durham, N.C.
Warren D. Taylor, M.D.
From the Departments of Psychiatry, Neurology, Radiology, Psychology, Biostatics, and Internal Medicine–Geriatrics, Washington University School of Medicine, St. Louis, Mo.; and the Departments of Psychiatry and Behavioral Sciences, Biostatistics and Bioinformatics, Radiology, and Biomedical Engineering, Duke University School of Medicine, Durham, N.C.
James R. MacFall, Ph.D.
From the Departments of Psychiatry, Neurology, Radiology, Psychology, Biostatics, and Internal Medicine–Geriatrics, Washington University School of Medicine, St. Louis, Mo.; and the Departments of Psychiatry and Behavioral Sciences, Biostatistics and Bioinformatics, Radiology, and Biomedical Engineering, Duke University School of Medicine, Durham, N.C.
Consuelo Wilkins, M.D.
From the Departments of Psychiatry, Neurology, Radiology, Psychology, Biostatics, and Internal Medicine–Geriatrics, Washington University School of Medicine, St. Louis, Mo.; and the Departments of Psychiatry and Behavioral Sciences, Biostatistics and Bioinformatics, Radiology, and Biomedical Engineering, Duke University School of Medicine, Durham, N.C.
Deanna M. Barch, Ph.D.
From the Departments of Psychiatry, Neurology, Radiology, Psychology, Biostatics, and Internal Medicine–Geriatrics, Washington University School of Medicine, St. Louis, Mo.; and the Departments of Psychiatry and Behavioral Sciences, Biostatistics and Bioinformatics, Radiology, and Biomedical Engineering, Duke University School of Medicine, Durham, N.C.
Kathleen A. Welsh-Bohmer, Ph.D.
From the Departments of Psychiatry, Neurology, Radiology, Psychology, Biostatics, and Internal Medicine–Geriatrics, Washington University School of Medicine, St. Louis, Mo.; and the Departments of Psychiatry and Behavioral Sciences, Biostatistics and Bioinformatics, Radiology, and Biomedical Engineering, Duke University School of Medicine, Durham, N.C.
David C. Steffens, M.D.
From the Departments of Psychiatry, Neurology, Radiology, Psychology, Biostatics, and Internal Medicine–Geriatrics, Washington University School of Medicine, St. Louis, Mo.; and the Departments of Psychiatry and Behavioral Sciences, Biostatistics and Bioinformatics, Radiology, and Biomedical Engineering, Duke University School of Medicine, Durham, N.C.
Ranga R. Krishnan, M.D.
From the Departments of Psychiatry, Neurology, Radiology, Psychology, Biostatics, and Internal Medicine–Geriatrics, Washington University School of Medicine, St. Louis, Mo.; and the Departments of Psychiatry and Behavioral Sciences, Biostatistics and Bioinformatics, Radiology, and Biomedical Engineering, Duke University School of Medicine, Durham, N.C.
P. Murali Doraiswamy, M.D.
From the Departments of Psychiatry, Neurology, Radiology, Psychology, Biostatics, and Internal Medicine–Geriatrics, Washington University School of Medicine, St. Louis, Mo.; and the Departments of Psychiatry and Behavioral Sciences, Biostatistics and Bioinformatics, Radiology, and Biomedical Engineering, Duke University School of Medicine, Durham, N.C.

Notes

Address correspondence to Dr. Sheline ([email protected]).

Funding Information

Dr. D’Angelo has received support from the National Institute on Aging. Dr. Welsh-Bohmer has served on an advisory panel for Takeda and has received grant funding from Takeda and Zinfandel. Dr. Krishnan holds equity in Orexigen and has indirect holdings in CeneRx, and he is a coinventor on a patent that is licensed to Cypress Biosciences. Dr. Doraiswamy has received research support or honoraria from Angelini, Bristol-Myers Squibb, Janssen, Lilly, Lundbeck, NIH, and Pfizer. The other authors report no financial relationships with commercial interests.
Supplementary Material
Supported by a Collaborative R01 for Clinical Studies of Mental Disorders grant MH60697 to Dr. Sheline and grant MH62158 to Dr. Doraiswamy; by grant RR00036 to the Washington University School of Medicine’s General Clinical Research Center; and by a grant from Pfizer to cover drug costs. Dr. Sheline also receives support from NIMH grant K24 MH79510-09.

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