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

Xian Feng Shi, Paul J. Carlson, Young Hoon Sung, Kristen K. Fiedler, Lauren N. Forrest, Tracy L. Hellem, Rebekah S. Huber, Seong Eun Kim, Chun Zuo, Eun Kee Jeong, Perry F. Renshaw, Douglas G. Kondo

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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 (kf) 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 kf (p = 0.039, r2 = 0.39); similar correlations were not observed in bipolar euthymia or HC. In addition, no differences in kf 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, kf 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.

Original languageEnglish (US)
Pages (from-to)743-752
Number of pages10
JournalBipolar Disorders
Issue number7
StatePublished - Nov 2015

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Biological Psychiatry


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