Orbitofrontal cortex volume in late life depression: influence of hyperintense lesions and genetic polymorphisms

Orbitofrontal cortex (OFC) volumetric differences have been reported in depression, but in relatively small samples. Factors associated with these differences are not well described. We examined OFC volumes in a large sample of elderly depressed and non-depressed subjects, exploring the relationship between OFC volume, 5HTTLPR genotype, apolipoprotein E (APOE) genotype and hyperintense lesion volume. We hypothesized that smaller OFC volume would be associated with depression, greater hyperintense lesion volume and severity, and APOE epsilon4 or 5HTTLPR short allele carriers.

A total of 226 depressed and 144 non-depressed older subjects completed 1.5 T magnetic resonance imaging (MRI) and genotyping. OFC volumes and lesion volumes were measured using standardized methods. Lesion severity was additionally rated using the Coffey rating scale. Differences between groups were compared while controlling for age, sex and total cerebral volume; separate models added lesion measures and genetic polymorphisms.

Depressed subjects exhibited smaller OFC volumes. There was a trend for a negative association between white-matter lesion volume and OFC volume; however, rated white-matter lesion severity was significantly negatively associated with OFC volume. There was no association between gray-matter lesion measures or 5HTTLPR genotype and OFC volume. Contrary to our hypothesis, subjects who were APOE epsilon4 allele positive exhibited larger OFC volumes; in secondary analyses, this finding was limited to the non-depressed group.

Reduced OFC volumes are seen in depression and associated with greater severity of white-matter lesions. Healthy subjects who are APOE epsilon4 allele positive exhibited larger OFC volumes. This finding should be examined in other populations.