Tissue-Specific Differences in Brain Phosphodiesters in Late-Life Major Depression

Objective: Late-life depression has been hypothesized to have a neurodegenerative component that leads to impaired executive function and increases in subcortical white matter hyperintensities. Phosphorus magnetic resonance spectroscopy (MRS) can quantify several important phosphorus metabolites in the brain, particularly the anabolic precursors and catabolic metabolites of the constituents of cell membranes, which could be altered by neurodegenerative activity. Methods: Ten patients with late-life major depression who were medication free at time of study and 11 aged normal comparison subjects were studied using P-31 MRS three-dimensional chemical shift imaging at 4 Tesla. Phosphatidylcholine and phosphatidylethanolamine comprise 90% of cell membranes in brain but cannot be quantified precisely with 31P MRS. We measured phosphocholine and phosphoethanolamine, which are anabolic precursors, as well as glycerophosphocholine and glycerophosphoethanolamine, which are catabolic metabolites of phosphatidylcholine and phosphatidylethanolamine. Results: In accordance with our hypotheses, glycerophosphoethanolamine was elevated in white matter of depressed subjects, suggesting enhanced breakdown of cell membranes in these subjects. Glycerophosphocholine did not show any significant difference between comparison and depressed subjects but both showed an enhancement in white matter compared with gray matter. Contrary to our hypotheses, neither phosphocholine nor phosphoethanolamine showed evidence for reduction in late-life depression. Conclusion: These findings support the hypothesis that neurodegenerative processes occur in white matter in patients with late-life depression more than in the normal elderly population.