Decreased brain PME/PDE ratio in bipolar disorder: A preliminary ³¹P magnetic resonance spectroscopy study

Objectives: The aim of the present study was to measure brain phosphorus-31 magnetic resonance spectroscopy (³¹P MRS) metabolite levels and the creatine kinase reaction forward rate constant (k_f) in subjects with bipolar disorder (BD). Methods: Subjects with bipolar euthymia (n = 14) or depression (n = 11) were recruited. Healthy comparison subjects (HC) (n = 23) were recruited and matched to subjects with BD on age, gender, and educational level. All studies were performed on a 3-Tesla clinical magnetic resonance imaging system using a ³¹P/¹H double-tuned volume head coil. ³¹P spectra were acquired without ¹H-decoupling using magnetization-transfer image-selected in vivo spectroscopy. Metabolite ratios from a brain region that includes the frontal lobe, corpus callosum, thalamus, and occipital lobe are expressed as a percentage of the total phosphorus (TP) signal. Brain pH was also investigated. Results: Beta-nucleoside-triphosphate (β-NTP/TP) in subjects with bipolar depression was positively correlated with k_f (p = 0.039, r² = 0.39); similar correlations were not observed in bipolar euthymia or HC. In addition, no differences in k_f and brain pH were observed among the three diagnostic groups. A decrease in the ratio of phosphomonoesters to phosphodiesters (PME/PDE) was observed in subjects with bipolar depression relative to HC (p = 0.032). We also observed a trend toward an inverse correlation in bipolar depression characterized by decreased phosphocreatine and increased depression severity. Conclusions: In our sample, k_f was not altered in the euthymic or depressed mood state in BD. However, decreased PME/PDE in subjects with bipolar depression was consistent with differences in membrane turnover. These data provide preliminary support for alterations in phospholipid metabolism and mitochondrial function in bipolar depression.