Exploring the interplay between mitochondrial dysfunction, early life adversity and bipolar disorder

Objective: Mitochondria are essential for energy production and reactive oxygen species (ROS) generation, with changes in ROS levels or energy demands affecting mitochondrial DNA (mtDNA) copy numbers, indicating mitochondrial function. Early life adversity (ELA) affects mitochondrial dynamics, influencing long-term health. Both ELA and mitochondrial abnormalities have been independently associated with bipolar disorder (BD). This study aims to explore the complex interplay between mitochondrial dysfunction, ELA, and BD. Methods: The study included 60 participants diagnosed with BD and 66 healthy controls (HCs). Data were collected using the Childhood Trauma Questionnaire (CTQ), and leukocyte mtDNA copy number (MCN) was determined from blood samples. Results: The results indicated the CTQ sum scores were significantly higher in the BD group, reflecting greater exposure to ELA. In HCs, a marginally significant nonlinear relationship between the square of the CTQ sum score and MCN was found. Further analysis demonstrated a significant interaction between ELA and BD on MCN (p = 0.023), highlighting a critical connection between ELA and mitochondrial dysfunction in BD and reinforcing its biological underpinnings. Conclusions: Future treatments for BD might target mitochondrial dysfunctions related to chronic stress, with potential pharmaceuticals designed to address these issues and mitigate the negative effects of chronic stress.