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Original Research

Depressive Symptoms in Healthy Apolipoprotein E ε4 Carriers and Noncarriers: A Longitudinal Study

Dona E. C. Locke, PhD; Amylou C. Dueck, PhD; Cynthia M. Stonnington, MD; David S. Knopman, MD; Yonas E. Geda, MD, MSc; and Richard J. Caselli, MD

Published: December 15, 2013

Article Abstract

Objective: To determine if symptoms of depression accelerate in cognitively normal apolipoprotein E (APOE) ε4 carriers as compared to noncarriers.

Method: Six hundred thirty-three cognitively and functionally normal members of the Arizona APOE Cohort aged 21-86 years underwent neuropsychological testing every 1 to 2 years that included the Hamilton Depression Rating Scale, the Beck Depression Inventory, the Geriatric Depression Scale, and the Personality Assessment Inventory. We estimated the longitudinal change on these measures using mixed models that simultaneously modeled cross-sectional and longitudinal effects of age on depression scores by APOE status and the interaction between the two. We also estimated incident depression on the basis of accepted clinical cut-scores on depression measures and use of depression medications.

Results: The mean length of follow-up was 7.7 years. Comparing APOE ε4 carriers with noncarriers revealed no significant longitudinal difference in the rate of change or slope of change on any depression scale or subscale. There was also no difference in incident depression or antidepressant drug use between the carrier and noncarrier groups.

Conclusions: These data fail to support a relationship between APOE genotype and longitudinal change in depression symptoms, suggesting that depression symptoms may not be intrinsic to the early preclinical phase of Alzheimer’s disease.

J Clin Psychiatry 2013;74(12):1256-1261

Submitted: May 2, 2013; accepted June 14, 2013 (doi:10.4088/JCP.13m08564).

Corresponding author: Dona E .C. Locke, PhD, Department of Psychiatry and Psychology, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ 85259 (

Volume: 74

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