Abnormalities in High-Energy Phosphate Metabolism in First-Episode Bipolar Disorder Measured Using 31P-Magnetic Resonance Spectroscopy

Abstract

Background: Brain energy metabolism is critical for supporting synaptic function and information processing. A growing body of evidence suggests abnormalities in brain bioenergetics in psychiatric disorders, including both bipolar disorder (BD) and schizophrenia. ³¹P magnetic resonance spectroscopy provides a noninvasive window into these processes in vivo. Using this approach, we previously showed that patients with BD show normal adenosine triphosphate (ATP) and phosphocreatine levels at rest but cannot maintain normal ATP levels in the visual cortex during times of high energy demand (photic stimulation). Because ATP is replenished from phosphocreatine via the creatine kinase reaction, we have now measured the creatine kinase forward reaction rate constant in BD.

Methods: We studied 20 patients experiencing a first episode of BD and 28 healthy control participants at 4T and quantified creatine kinase forward reaction rate constant using ³¹P magnetization transfer magnetic resonance spectroscopy as described previously.

Results: We found a significant reduction in creatine kinase forward reaction rate constant in the BD group (F = 4.692, p = .036), whereas brain ATP and phosphocreatine concentrations, as well as brain parenchymal pH, were normal.

Conclusions: These results pinpoint a specific molecular mechanism underlying our previous observation of an inability to replenish brain ATP during times of high energy demand in BD.

Keywords: ATP; Bioenergetics; Imaging; MRS; Mania; Mitochondria.

Figure 1

(a) ³¹P surface coil placed over forehead and its sensitivity profile (6 × 6 × 4 cm³). (b) In vivo ³¹P spectra obtained from a representative healthy volunteer in the absence (upper tracing) and presence of γ-ATP saturation (middle and bottom tracings, with saturation time of 6.6s and 12.3s, respectively). The reduction of PCr resonance magnitude during γ- ATP saturation indicates transfer of high energy phosphates from PCr to ATP catalyzed by CK enzyme.