Depression in late-life is strongly associated with personality changes, social withdrawal, and suicide. Most elderly suicide victims visit their primary care provider within a month prior to their death, but depression often goes unrecognized. In older persons, the presenting complaints are often only somatic and cognitive, and not emotional. Many individuals with subsyndromal depression experience nondysphoric depression (e.g., absence of reported sadness, loss of pleasure), making depression without sadness difficult to detect and an often severe mental health condition. Because of the elusive nature of this disorder, improved methods of assessment, prevention, and treatment are needed. While the mechanisms of nondysphoric depression are not known, structural neuroimaging studies suggest a connection between late-life depression and ischemic cerebrovascular lesions. Based on the role ventral and medial frontal lobe play in self-awareness of emotional states, we propose that nondysphoric depression is associated with greater white matter lesions in ventral and medial frontal regions. In addition, because white matter lesions (irrespective of their location) impair frontal lobe function, the relationship between overall white matter ischemic lesions and the hemodynamic response in the ventral and medial frontal lobe in nondysphoric depression will be examined.
1. To examine the functional neuroanatomy of nondysphoric late-life depression using affective probes and fMRI.
2. To examine the regional and global density of white matter lesions in nondysphoric depression with automated methods using fluid-attenuated inversion recovery (FLAIR) MRI.
3. To examine the extent to which ischemic disease of the cerebral microvasculature, measured as global white matter ischemic lesions, influences the hemodynamic response function in ventral and medial frontal lobe regions in nondysphoric depression.
Sixty older adults will be studied. In a semi-structured interview, patients with dysphoric and non-dysphoric depression must endorse an appropriate subset of the DMS-IV criteria for depression. Controls will be included based on negative screening for these criteria.
Functional and structural neuroimaging will be conducted. A fast event-related fMRI paradigm has been designed to allow tracking of the shape of the hemodynamic response curve, which has been shown to be sensitive to aging and a putative marker for arteriolar narrowing and stiffening.
To achieve our first goal, an emotion recognition task has been developed using faintly morphed emotional facial expressions. Morphed images allow testing perception of faint levels of emotion more routinely encountered in everyday life.
To achieve our second goal, an automated method will be used to measure severity of white matter ischemic lesions. This automated method will provide an objective and quantitative assessment of white matter lesions.
To achieve our third goal, the degree to which global white matter ischemic burden predicts BOLD and ASL responses in the ventral and medial prefrontal regions will be examined.