Brain bioenergetics and the menopause in bipolar disorder (MENO-BD)

Bipolar disorder (BD) is a common and severe mental illness affecting at least 1 in 100 people. The perimenopause is a time of risk for new onset or relapse of BD, but mechanisms are unclear. Key to this proposal is the novel idea that disrupted brain bioenergetics represent a point of pathophysiological convergence of BD and menopause, specifically, reduced brain energy (adenosine triphosphate (ATP)) reserve, driven by mitochondrial dysfunction. My overarching hypothesis is that brain bioenergetic changes during the menopause drive mental health symptoms in women with BD. This is a co-designed observational study incorporating menopause as a “natural experiment”: prospective clinical cohort study in healthy people and people with BD who are pre, peri, post menopause (n= 75 per group, total n = 150), assessed at baseline and 12 months. Aims a) Quantify brain bioenergetics (phosphocreatine/ATP ratio, lactate) across menopausal stages using Magnetic Resonance Spectroscopy. b) Test associations of brain bioenergetics with perimenopausal mental health symptoms (cognition, mood), and c) Explore putative compensatory mechanisms by quantifying metabolomic changes across menopausal stages. This innovative approach to understanding metabolic mechanisms of relapse in women with BD represents a novel potential avenue for intervention in a highly morbid but currently under-served patient group.