Objective: There has been considerable speculation that vascular abnormalities play an etiological role in the development and progression of late-onset major depression. This presentation will summarize the state of knowledge in this area. New findings will be presented from a longitudinal study of patients with late-onset major depression and healthy volunteers, matched to cerebrovascular risk factors.
Design: PET imaging techniques included fully quantified high resolution measurements of regional cerebral blood flow (rCBF) at rest and under hypercapnia, and regional cerebral metabolic rate for glucose (rCMR) at rest. PET measurements were taken after a 3 week medication washout, at least 8 weeks of treatment with sertraline, and at two year follow-up (after a 4 week medication washout; rCBF measurements only). MRI assessments (5 sequences) were conducted at baseline and 2-year follow-up.
Results: At baseline, the depressed patient sample had regional reductions in both resting rCBF and rCMR. The rCBF abnormalities were more extensive and severe than the rCMR abnormalities, and only the rCBF abnormalities involved prefrontal cortex. This mismatch between rCBF and rCMR may represent the first breakdown in autoregulation in a psychiatric illness and supports the notion of a primary vascular etiology, even when controls are matched for CVD risk factors. However, antidepressant treatment produced a profound change in both rCBF and rCMR among patients who responded to treatment, while nonresponders showed no change. The majority of the variance in symptom change over the treatment course was associated with change in a single network of brain areas, highly concordant between rCBF and rCMR. Prefrontal regions were prominent in the areas of change linked to positive clinical outcome and showed reduced rCBF and rCMR.
Conclusion: The findings suggest dissociation between the process that lead to late-onset depression and those that result in symptomatic improvement. While a vascular disturbance may be responsible for manifesting late-onset major depression, symptomatic improvement was produced through independent mechanisms. The tight concordance between the physiological indices of rCBF and rCMR indicated that the changes associated with symptomatic improvement are metabolically driven and, as such, are unlikely to impact on the vascular disturbance observed at baseline.
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