Structural Imaging in Late-Life Depression: Association with Mood and Cognitive Responses to Antidepressant Treatment

Objectives Recent positron emission tomography studies of cerebral glucose metabolism have identified the functional neural circuitry associated with mood and cognitive responses to antidepressant treatment in late life depression (LLD). The structural alterations in these networks are not well understood. The present study used magnetic resonance (MR) imaging and voxel-based morphometry to evaluate the association between gray matter volumes and changes in mood symptoms and cognitive function with treatment with the antidepressant citalopram. Design Open-label trial with baseline brain MR scan. Mood and cognitive assessments performed at baseline and during citalopram treatment. Setting Outpatient clinics of an academic medical center. Participants 17 previously unmedicated patients age 55 years or older with a major depressive episode and 17 non-depressed comparison subjects. Intervention 12-week trial of flexibly dosed citalopram. Measurements Gray matter volumes, Hamilton Depression Rating Scale, California Verbal Learning Test, Delis–Kaplan Executive Function System. Results In LLD, higher gray matter volumes in the cingulate gyrus, superior and middle frontal gyri, middle temporal gyrus, and precuneus was associated with greater mood improvement. Higher gray matter volumes in primarily frontal areas were associated with greater improvement in verbal memory and verbal fluency performance. Conclusions Associations with antidepressant induced improvements in mood and cognition were observed in several brain regions previously correlated with normalization of glucose metabolism after citalopram treatment in LLD. Future studies will investigate molecular mechanisms underlying these associations (e.g., beta-amyloid, inflammation, glutamate).