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

Shi X‐F, Kondo DG, Sung Y‐H, Hellem TL, Fiedler KK, Jeong E‐K, Huber RS, Renshaw PF. Frontal lobe bioenergetic metabolism in depressed adolescents with bipolar disorder: a phosphorus‐31 magnetic resonance spectroscopy study. Bipolar Disord 2012: 14: 607–617. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. 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.