Immunometabolic reprogramming of central and peripheral immune cells in mental disorders: mechanisms and therapeutic implications

Immune cells are those involved in or related to immune responses, found throughout immune organs and the body. The discipline of immunometabolism, which merges immunology with metabolism, has gained significant attention in recent years. This emerging field focuses on the metabolic processes and mechanisms of various immune cells, aiming to uncover how these cells’ metabolism influences disease onset and progression. Research in immunometabolism spans several diseases, including chronic inflammatory conditions, infectious diseases, cardiovascular disorders, and cancer, highlighting the critical role of immune cell metabolism in these diseases. Mental illnesses, characterized by brain function abnormalities due to biological, psychological, and environmental factors, lead to impairments in cognitive, emotional, volitional, and behavioral functions. Conditions such as schizophrenia, neurodegenerative diseases (Alzheimer’s disease AD, Parkinson’s disease PD), anxiety, and depression are associated with significant metabolic changes. The intersection of neuroimmunology and immunometabolism has become a focal point for understanding the regulation of mental illnesses by immune cells’ metabolic alterations. This review systematically examines how metabolic reprogramming of central and peripheral immune cells contributes to the pathogenesis of mental disorders, and critically evaluates emerging therapeutic strategies targeting these immunometabolic pathways—including pharmacological modulators (HK2 inhibitors, kynurenine pathway modulators, CD38 checkpoint targeting), lifestyle interventions (ketogenic diet, exercise), and their translational challenges. By integrating mechanistic insights with therapeutic perspectives, this review aims to provide fresh insights into disease mechanisms and inform the development of precision diagnostic and therapeutic approaches for mental disorders.