Abstract
Background
With Bipolar Disorder (BD) having a lifetime prevalence of 4.4% and a significant portion of patients being chronically burdened by symptoms, there has been an increased focus on uncovering new targets for intervention in BD. One area that has shown early promise is the mitochondrial hypothesis, with supporting evidence in the form of mtDNA copy number, SNPs, ETC complex activity in peripheral cells, postmortem analyses of ETC function, and iPSC-derived biomarkers, among others. Despite this compelling evidence, at the time of this publication no studies have utilized PET imaging to assess mitochondrial function in the setting of BD.
Case Presentation
Our participant is a 58 year old male with a past medical history notable for alcohol use disorder and bipolar disorder (unspecified type) who, while enrolled as a control for a separate trial, underwent PET imaging with the mitochondrial complex 1 PET ligand 18F-BCPP-EF. Those images were compared to normal controls which demonstrated significant overlap between areas of dysfunction identified with the 18F-BCPP-EF PET ligand and areas of dysfunction previously identified in the setting of BD with fMRI techniques. That overlap was seen in both affective and cognitive circuits, with mitochondrial dysfunction in the fronto-limbic, ventral affective, and dorsal cognitive circuits showing particularly significant differences.
Conclusions
Despite mounting evidence implicating mitochondria in BD, this study represents the first PET imaging study to investigate this mechanistic connection. There were key limitations in the form of comorbid alcohol use disorder, limited statistical power inherent to a case study, no sex matched controls, and the absence of a comprehensive psychiatric history. However, even with these limitations in mind, the significant overlap between areas of dysfunction previously demonstrated on fMRI and this 18F-BCPP-EF PET ligand imaging provides compelling preliminary evidence that strengthens the mechanistic link between mitochondrial dysfunction and Bipolar Disorder and warrants further investigation.