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

Abstract

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.

Fig. 1

Voxel placement (left), axial slice location (top, right), and a representative phosphorus-31 magnetic resonance spectroscopy (³¹P-MRS) spectrum (bottom, right). PME = phosphomonoester; Pi = inorganic phosphate; PDE = phosphodiester; PCr = phosphocreatine; NTP = nucleoside triphosphate.

Fig. 2

Bar graphs depicting frontal lobe phosphorus metabolite levels and post-hoc Tukey–Kramer pairwise comparisons: (A) PCr/TP; (B) Pi/TP; (C) PCr/Pi; and (D) beta-NTP/TP. Error bars represent 95% confidence intervals. HC = healthy controls; BD-MED = medicated bipolar disorder; BD-UNMED = unmedicated bipolar disorder; PCr = phosphocreatine; TP = total phosphate; Pi = inorganic phosphate; NTP = nucleoside triphosphate. The values in parentheses refer to the percentage difference of metabolites with respect to mean metabolite concentrations in the HC group.

Fig. 3

The volume percentage of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) in the region of interest. Error bars represent 95% confidence intervals. HC = healthy controls; BD-MED = medicated bipolar disorder; BD-UNMED = unmedicated bipolar disorder.