Ventromedial Prefrontal Cortex Processing During Emotional Evaluation in Late-Life Depression: A Longitudinal Functional Magnetic Resonance Imaging Study

Abstract

Functional imaging studies using emotional stimuli have suggested a role for the ventromedial prefrontal cortex (vmPFC) in the pathophysiology of midlife depression. In contrast, the neural correlates of late-life depression (LLD), a highly prevalent but under-recognized clinical entity in which age-related brain changes might influence disease mechanisms, have not been studied in great detail. With an emotional evaluation task, we conducted a longitudinal study of vmPFC functioning in a homogeneous sample of elderly antidepressant naive female outpatients with isolated, first diagnosed mild to moderate depressive symptoms. Neural responses of the vmPFC to the emotional evaluation of positive, negative, and neutral words were measured with functional magnetic resonance imaging (fMRI) in LLD (n = 13) and healthy older subjects (n = 13). All patients were rescanned after approximately 7 months. Although there were no performance differences, compared with healthy volunteers, LLD patients showed a decreased response to negative compared with positive stimuli in the vmPFC. This altered pattern was positively correlated with symptom severity. At follow-up, the attenuated neural response in the vmPFC had "normalized," accompanied by a significant improvement in symptoms. These findings indicate vmPFC dysfunction as a biological state marker of geriatric depression. Furthermore, our data underline the pathological significance of mild to moderate LLD and highlight the usefulness of functional neuroimaging for evaluating remission processes in this specific depression subtype.