Impaired mitochondrial function in bipolar disorder and alcohol use disorder: a case study using 18F-BCPP-EF PET imaging of mitochondrial Complex I.

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. However, at the time of publication no studies have utilized positron emission tomography (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 BD (unspecified type) who underwent PET imaging with the mitochondrial complex I PET ligand ¹⁸F-BCPP-EF. The resulting images demonstrated significant overlap between areas of dysfunction identified with the ¹⁸F-BCPP-EF PET ligand and prior functional magnetic resonance imaging (MRI) techniques in the setting of BD. 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 dysfunction previously demonstrated on functional MRI and this imaging provides compelling preliminary evidence that strengthens the mechanistic link between mitochondrial dysfunction and BD.