Apolipoprotein E genotype and subcortical vascular lesions in older depressed patients and control subjects

Background: Several studies have linked geriatric depression with cerebrovascular disease. The apolipoprotein E gene (APOE) epsilon4 allele has been associated with a variety of late-life neuropsychiatric disorders, including Alzheimer's disease, vascular dementia, and depression. Methods: The sample consisted of 145 elderly depressive individuals and 100 nondepressed elderly control subjects. After a standardized clinical assessment, all subjects underwent a magnetic resonance imaging brain scan. Volumes of subcortical white and gray matter lesions were determined using a semi-automated method. Apolipoprotein E genotype was determined on blood sample using a standard protocol. A series of linear regression models were developed to assess the relationships between APOE genotype and white and gray matter lesion volumes. Results: Older age, lower Mini-Mental State Examination score, and having any APOE epsilon4 allele were each correlated with gray-matter lesion volume in depressed patients. Apolipoprotein E genotype was not associated with any lesion volume among control subjects. In a subsequent linear regression model, gray matter lesion volume was associated with older age, having at least one APOE epsilon4 allele, and white matter lesion volume among depressed patients. Conclusions: These results are consistent with previous reports linking cerebrovascular disease and APOE genotype. Further studies are needed to replicate this finding in elderly depressive individuals and to explain the relationship between the APOE locus and development of central nervous system vascular pathology. (C) 2003 Society of Biological Psychiatry.