Bipolar disorder (BD) is a psychiatric illness marked by fluctuating mood states and substantial systemic consequences, including dysregulated bioenergetics, immune modulations and significant metabolic dysfunction. Although BD affects males and females at comparable rates, the literature indicates that the symptomatology and course of the disorder can differ between sexes. Females with BD are more likely to exhibit rapid cycling and depressive symptoms, whereas males are frequently associated with reckless behaviour and hallucinations. A plausible mechanism for these symptomatology differences may be marked by the estrogen – mitochondria axis, which reflects the bioenergetic consequences of fluctuating estrogen levels on mitochondrial biogenesis. Estrogen constitutes a family of steroid hormones that have critical regulatory roles in many physiological processes, including reproduction, metabolism, and immune regulation. Within the context of bioenergetics, estrogen supports mitochondrial function in neural tissue by promoting oxidative phosphorylation, reducing oxidative stress, and regulating mitochondrial biogenesis. In this literature review, we examine evidence linking estrogen fluctuation to periods of psychiatric vulnerability across the lifespan in females with BD. There is a particular focus on the mechanistic role of estrogen modulating mitochondrial biogenesis, the existing experimental and pre-clinical evidence underlying this mechanism and the evaluation of current pharmacological and nutraceutical therapeutics that have the potential to modulate this axis. Finally, this review discusses the clinical and future therapeutic implications for behavioural symptomatology across the lifespan of females with bipolar disorder. While this review focuses solely on literature in BD, the plausibility of investigating this mechanism extends to other mood disorders and psychiatric diseases.
Zachos et al. (Sun,) studied this question.