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

Bipolar Disord. 2015 Nov;17(7):743-52. doi: 10.1111/bdi.12339. Epub 2015 Oct 19.


Objectives: The aim of the present study was to measure brain phosphorus-31 magnetic resonance spectroscopy ((31) P 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 (31) P/(1) H double-tuned volume head coil. (31) P spectra were acquired without (1) H-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, r(2) = 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.

Keywords: 31P MRS; bipolar disorder; magnetization transfer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Bipolar Disorder* / diagnosis
  • Bipolar Disorder* / metabolism
  • Bipolar Disorder* / psychology
  • Corpus Callosum / metabolism*
  • Depression / diagnosis
  • Depression / metabolism*
  • Female
  • Frontal Lobe / metabolism*
  • Humans
  • Magnetic Resonance Imaging / methods
  • Magnetic Resonance Spectroscopy / methods
  • Male
  • Mitochondria / metabolism
  • Phosphocreatine / metabolism*
  • Phospholipids / metabolism
  • Phosphorus Isotopes / pharmacology
  • Psychiatric Status Rating Scales
  • Thalamus / metabolism*


  • Phospholipids
  • Phosphorus Isotopes
  • Phosphocreatine