Biol Psychiatry. 2015 Nov 15;78(10):730-6.

A 9-year prospective population-based study on the association between the APOE*E4 allele and late-life depression in Sweden.

Abstract

BACKGROUND: It is well established that there is an association between the apolipoprotein E (APOE) ε4 allele (APOE*E4) and Alzheimer’s disease. It is less clear whether there is also an association with geriatric depression. We examined the relationship between APOE*E4 and 5-year incidence of depression in a Swedish population-based sample of older adults without dementia and excluding older adults who developed dementia within 4 years after the diagnosis of depression.

METHODS: In 2000-2001, 839 women and men (age range, 70-92 years; mean age, 73.8 years) free from dementia and depression underwent neuropsychiatric and neuropsychological examinations and genotyping of the APOE*E4 allele. Follow-up evaluations were conducted in 2005 and 2009.The association between APOE*E4 allele and 5-year incidence of depression was examined, while avoiding possible confounding effects of clinical or preclinical dementia by excluding participants who had dementia at study entry, subsequently developed dementia during the 9-year follow-up period, or had a decline in Mini-Mental State Examination score of ≥5 points.

RESULTS: Among subjects without depression at study entry and without dementia or significant cognitive decline during the subsequent 9 years, APOE*E4 was prospectively associated with more severe depressive symptoms (b = 1.56, p = .007), incident minor depression (odds ratio = 1.99 [confidence interval = 1.11-3.55], p = .020), and any depression (odds ratio = 1.75 [confidence interval = 1.01-3.03], p = .048).

CONCLUSIONS: The presence of the APOE*E4 allele predicted future depression in this Swedish population study, even after excluding depressed individuals who later developed dementia, suggesting that the APOE*E4 allele could potentially identify people at high risk for clinically significant depression.

KEYWORDS: Apolipoprotein E ε4 (APOE*E4) allele; Dementia; Depression; Older adults; Population-based study; Prospective

PMID: 25708227

Supplements

The gene apolipoprotein ε4 is one of the most important biomarkers in neuropsychiatry. This gene variant has an association with Alzheimer`s disease. This gene variant is also associated with arteriosclerosis and other cardiovascular diseases. Up until today, the association between the Apolipoprotein (APOE) ε4 allele and depression has been debated. We therefore examined the relationship between APOE ε4 and depression in a population-based sample of older Swedish adults. The study participants were followed after 5 years and after 9 years to exclude participants who developed dementia. In our study, the presence of the APOE ε4 was related to future depression. Our study is the first longitudinal study to even show an association between the APOE ε4 and future depression, even after controlling for dementia.

Contact:

Silke Kern, MD, PhD

Neuropsychiatric Epidemiology Unit,

Department of Psychiatry and Neurochemistry

Institute of Neuroscience and Physiology

Sahlgrenska Academy at the University of Gothenburg

Gothenburg, Sweden.

Phone: 0046 31 342 2164

E-mail:silke.kern@neuro.gu.se