Beyond comorbidities: metabolic dysfunction as a root cause of neuropsychiatric disorders

SUMMARY Metabolic dysfunction has been long associated with severe mental illness (SMI), often viewed as a comorbidity to be managed. However, emerging evidence suggests that metabolic dysfunction, particularly at the mitochondrial level, may be a foundational element in the pathophysiology of neuropsychiatric disorders. This commentary expands on the current understanding by exploring the brain energy theory of mental illness, which posits that mitochondrial dysfunction is central to both metabolic and psychiatric conditions. The roles of insulin resistance, chronic stress and environmental factors are highlighted as shared biopsychosocial determinants that contribute to deterioration in both metabolic and mental health. The therapeutic potential of the ketogenic diet is discussed, particularly its ability to improve mitochondrial function and alleviate psychiatric symptoms. This shift in perspective, from viewing metabolic dysfunction as a secondary concern to recognising it as a root cause of SMI, has significant implications for clinical practice and research. By focusing on bioenergetic deficits and mitochondrial health, psychiatry may advance towards more effective, integrated treatment approaches that target the underlying cellular dysfunctions driving both metabolic and mental illnesses.