Mitochondrial Dysfunction as a Biomarker of Illness State in Bipolar Disorder: A Critical Review

Mitochondria are organelles involved in different cellular functions, especially energy production. A relationship between mitochondrial dysfunction and mood disorders, especially bipolar disorder (BD), has been reported in the scientific literature, which suggests altered energy production and higher levels of oxidative stress compared to healthy controls. Specifically, in BD, the hypothesis of a biphasic pattern of energy availability has been postulated according to mood states. Current evidence highlights the presence of mitochondrial dysfunction in BD and variations between the manic, depressive, and euthymic phases. These findings need to be confirmed in future studies to identify biomarkers that may lead to individualized management of patients with BD and also to identify profiles with a higher risk of presenting an unfavorable course of illness, which would enable the design of preventive and therapeutic strategies in determined subpopulations of patients with BD. The limitations of this review include the non-systematic methodology, variety of mitochondrial-related functions associated with BD, heterogeneous study designs, preliminary evidence for specific findings, and limited recommendations regarding the use of mitochondrial modulators in BD.