Plasma polyunsaturated fatty acids and regional cerebral glucose metabolism in major depression

Abstract

Deficiencies in polyunsaturated essential fatty acids (PUFA) are implicated in mood disorders, although mechanisms of action and regional specificity in the brain are unknown. We hypothesized that plasma phospholipid PUFA levels are correlated with regionally specific relative cerebral metabolic rates of glucose (rCMRglu). Medication-free depressed subjects (N=29) were studied using [(18)F]-fluoro-2-deoxyglucose positron emission tomography. Docosahexaenoic acid (22:6n-3), arachidonic acid (20:4n-6), and eicosapentaenoic acid (20:5n-3) were assessed as a percentage of total phospholipid PUFA (DHA%, AA%, and EPA%, respectively). DHA% and AA% correlated positively with rCMRglu in temporoparietal cortex. In addition, DHA% correlated negatively with rCMRglu in prefrontal cortex and anterior cingulate. No correlations were seen with EPA%. Thus, under conditions of low plasma DHA, rCMRglu was higher in temporoparietal cortex and lower in anterior cingulate/prefrontal cortex. Opposing effects of DHA on these regions is a hypothesis that could be addressed in future prospective studies with n-3 supplementation. This pilot study is the first to demonstrate fatty acid and regionally specific correlations in the brain between plasma PUFA and rCMRglu in humans.

Figures

Figure 1. Statistical parametric maps of regional cerebral metabolic rates of glucose metabolism correlated with plasma polyunsaturated fatty acid levels

Regional cerebral metabolic rates of glucose metabolism (rCMRglu) are shown correlated with plasma phospholipid docosahexaenoate and arachidonate as a percentage (DHA%, EPA%) of total phospholipid polyunsaturated fatty acids (PUFA). All analyses have been corrected for global cerebral rates of glucose metabolism, age, diagnosis (Major Depressive or Bipolar Disorder), and sex. A. Correlations are shown in orthogonal views in a ‘glass brain’ format (left panels) and also as superimposed on relevant MRI slices (right panels). Color scales indicate the strength (t score) of the correlations. B. Correlations are graphed at the cluster global maxima for DHA% (positive, r = 0.77, p = 0.0005; negative, r = −0.77, p < 0.0000) and AA% (positive, r = 0.75, p < 0.0000).