Lactate: A Theranostic Biomarker for Metabolic Psychiatry?

Abstract

Alterations in neurometabolism and mitochondria are implicated in the pathophysiology of psychiatric conditions such as mood disorders and schizophrenia. Thus, developing objective biomarkers related to brain mitochondrial function is crucial for the development of interventions, such as central nervous system penetrating agents that target brain health. Lactate, a major circulatory fuel source that can be produced and utilized by the brain and body, is presented as a theranostic biomarker for neurometabolic dysfunction in psychiatric conditions. This concept is based on three key properties of lactate that make it an intriguing metabolic intermediate with implications for this field: Firstly, the lactate response to various stimuli, including physiological or psychological stress, represents a quantifiable and dynamic marker that reflects metabolic and mitochondrial health. Second, lactate concentration in the brain is tightly regulated according to the sleep–wake cycle, the dysregulation of which is implicated in both metabolic and mood disorders. Third, lactate universally integrates arousal behaviours, pH, cellular metabolism, redox states, oxidative stress, and inflammation, and can signal and encode this information via intra- and extracellular pathways in the brain. In this review, we expand on the above properties of lactate and discuss the methodological developments and rationale for the use of functional magnetic resonance spectroscopy for in vivo monitoring of brain lactate. We conclude that accurate and dynamic assessment of brain lactate responses might contribute to the development of novel and personalized therapies that improve mitochondrial health in psychiatric disorders and other conditions associated with neurometabolic dysfunction.