[Immunometabolic mechanisms in atypical depression]

Atypical depression (AD) is a subtype of unipolar depression characterized by mood reactivity, hypersomnia, hyperphagia and interpersonal sensitivity. The concept of immunometabolic depression (IMD) describes a subgroup with additional metabolic and inflammatory abnormalities, such as obesity, insulin resistance and elevated C‑reactive protein (CRP) levels.

To summarize current evidence on AD, its overlap with immunometabolic mechanisms and therapeutic implications.

Narrative review based on a PubMed search using the terms "atypical depression" and "immunometabolic depression" (IMD), supplemented by relevant review articles.

Atypical depressive syndromes are associated with increased systemic inflammation and metabolic dysregulation. There is evidence suggesting specific efficacy of bupropion and monoamine oxidase (MAO) inhibitors, although overall evidence remains limited. In patients with immunometabolic abnormalities (e.g., elevated C-reactive protein), anti-inflammatory agents (e.g., infliximab) and metabolically active medications (e.g., oral antidiabetic drugs) are discussed as potential treatment options; however, statins have not shown consistent antidepressant effects to date. Physical activity and dietary interventions appear additionally beneficial.

The concept of IMD could enable stratified treatment approaches in the future. At present the evidence is inconclusive and no specifically approved treatment is available. Moreover, frequent fluctuation between atypical and melancholic syndromes complicates clinical differentiation.