AGEING RESEARCH REVIEWS (ARR-D-24-01334R1) Metabolic dysfunction contributes to mood disorders after traumatic brain injury.

Traumatic brain injury (TBI) presents significant risks concerning mortality and morbidity. Individuals who suffer from TBI may exhibit mood disorders, including anxiety and depression. Both preclinical and clinical research have established correlations between TBI and disturbances in the metabolism of amino acids, lipids, iron, zinc, and copper, which are implicated in the emergence of mood disorders post-TBI. The purpose of this review is to elucidate the impact of metabolic dysfunction on mood disorders following TBI and to explore potential strategies for mitigating anxiety and depression symptoms. We researched the PubMed and Web of Science databases to delineate the mechanisms by which metabolic dysfunction contributes to mood disorders in the context of TBI. Particular emphasis was placed on the roles of glutamate, kynurenine, lipids, iron, zinc, and copper metabolism. Metabolic dysfunction is linked to mood disorders post-TBI through multiple pathways, encompassing the glutamatergic system, the kynurenine pathway, endocannabinoids, iron deposition, iron-related ferroptosis, zinc deficiency, and copper dysregulation. Furthermore, this review addresses the influence of metabolic dysfunction on mood disorders in the elderly demographic following TBI. Targeting metabolic dysfunction for therapeutic intervention appears promising in alleviating symptoms of anxiety and depression that arise after TBI. While further investigation is warranted to delineate the underlying pathophysiologic mechanisms of mood disorders post-TBI, current evidence underscores the potential contribution of metabolic dysfunction to these conditions. Therefore, rectifying metabolic dysfunction represents a viable and strategic approach to addressing mood disorders following TBI.