Frontal lobe bioenergetic metabolism in depressed adolescents with bipolar disorder: a phosphorus-31 magnetic resonance spectroscopy study

Bipolar Disord. 2012 Sep;14(6):607-17. doi: 10.1111/j.1399-5618.2012.01040.x. Epub 2012 Jul 20.


Objectives: To compare the concentrations of high-energy phosphorus metabolites associated with mitochondrial function in the frontal lobe of depressed adolescents with bipolar disorder (BD) and healthy controls (HC).

Methods: We used in vivo phosphorus-31 magnetic resonance spectroscopy ((31) P-MRS) at 3 Tesla to measure phosphocreatine (PCr), beta-nucleoside triphosphate (β-NTP), inorganic phosphate (Pi), and other neurometabolites in the frontal lobe of eight unmedicated and six medicated adolescents with bipolar depression and 24 adolescent HCs.

Results: Analysis of covariance, including age as a covariate, revealed differences in PCr (p=0.037), Pi (p=0.017), and PCr/Pi (p=0.002) between participant groups. Percentage neurochemical differences were calculated with respect to mean metabolite concentrations in the HC group. Post-hoc Tukey-Kramer analysis showed that unmedicated BD participants had decreased Pi compared with both HC (17%; p=0.038) and medicated BD (24%; p=0.022). The unmedicated BD group had increased PCr compared with medicated BD (11%; p=0.032). The PCr/Pi ratio was increased in unmedicated BD compared with HC (24%; p=0.013) and with medicated BD (39%; p=0.002). No differences in β-NTP or pH were observed.

Conclusions: Our results support the view that frontal lobe mitochondrial function is altered in adolescent BD and may have implications for the use of Pi as a biomarker. These findings join volumetric studies of the amygdala, and proton MRS studies of n-acetyl aspartate in pointing to potential differences in neurobiology between pediatric and adult BD.

Publication types

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

MeSH terms

  • Adolescent
  • Bipolar Disorder / complications
  • Bipolar Disorder / metabolism*
  • Bipolar Disorder / physiopathology
  • Case-Control Studies
  • Depression / etiology
  • Depression / metabolism*
  • Depression / physiopathology
  • Energy Metabolism
  • Female
  • Frontal Lobe / metabolism*
  • Frontal Lobe / physiopathology
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Spectroscopy
  • Male
  • Mitochondria / metabolism
  • Phosphates / metabolism
  • Phosphocreatine / metabolism
  • Phosphorus Isotopes
  • Polyphosphates / metabolism


  • Phosphates
  • Phosphorus Isotopes
  • Polyphosphates
  • Phosphocreatine