A pilot study of alterations in high energy phosphoryl compounds and intracellular pH in unmedicated adolescents with bipolar disorder

Abstract

Background: Several lines of evidence suggest that mitochondrial dysfunction underlies the pathophysiology of bipolar disorder, including prior studies indicating abnormalities in phosphometabolites. We examined abnormalities in biomarkers of cellular metabolism including adenosine triphosphate and adenosine diphosphate as well as the pH levels in the anterior cingulate (ACC) and left ventrolateral prefrontal cortices (VLPFC) of adolescents with bipolar disorder.

Method: Nineteen unmedicated manic and 14 unmedicated euthymic bipolar adolescents as well as 20 healthy adolescents underwent (1)H and (31)P magnetic resonance spectroscopy scans. Intracellular pH levels and concentrations of phosphometabolites were compared among groups.

Results: A significant reduction in pHi was found in the ACC of manic adolescents compared to healthy subjects (p=0.03) but not in the left VLPFC. There was no difference in concentration of adenosine triphosphate in the ACC or the left VLPFC among groups. However, compared to healthy subjects, adenosine diphosphate was significantly lower in manic subjects in the ACC (p=0.01) and in euthymic subjects in the left VLPFC (p=0.02).

Limitations: This was a cross-sectional study with a modest sample size. A longitudinal study of a larger number of bipolar adolescents who are treatment naïve would clarify the impact of mood state on metabolic function.

Conclusion: These results are suggestive of abnormal cellular metabolism and mitochondrial dysfunction in the pathophysiology of bipolar disorder.

Keywords: Adenosine diphosphate; Adenosine triphosphate; Adolescent; Bipolar disorder; Phosphorus; pH.