Purpose of review: To synthesize recent evidence on the role of immunometabolism in the pathophysiology and treatment of mood disorders; highlighting the interplay between inflammation, metabolic dysfunction (obesity, insulin resistance, mitochondrial changes), and clinical outcomes.

Recent findings: Mood disorders are increasingly recognized as systemic illnesses involving bidirectional links with metabolic disturbances and chronic low-grade inflammation. Elevated BMI, insulin resistance, and specific inflammatory markers (e.g., CRP, IL-6, TNF-α) are associated with increased risk, specific symptom profiles (atypical depression, anhedonia), cognitive deficits, and poorer treatment outcomes, particularly for conventional antidepressants. Mechanistic insights involve neuroinflammation (microglial/astrocyte activation, kynurenine pathway), altered brain insulin signaling, mitochondrial dysfunction, and changes in reward/cognitive control circuits. Metabolic interventions (ketogenic diets, GLP-1 agonists, metformin, exercise) show promise but require more rigorous investigation, with ongoing debate regarding efficacy and safety profiles (e.g., GLP-1 suicide risk). The "immunometabolic depression" construct aims to identify patient subtypes that could potentially benefit from individualized therapy.

Summary: Integrating immunometabolism into psychiatry offers a paradigm shift for understanding and managing mood disorders. Targeting metabolic dysfunction and inflammation presents novel therapeutic avenues. Future research must focus on validating biomarkers for patient stratification, elucidating mechanisms, conducting robust RCTs for metabolic interventions, and developing integrated care models incorporating lifestyle and metabolic health monitoring.