Distinguishing clinical features of paediatric autoimmune Addison’s disease and polyendocrine syndromes: a 15-year single-centre observational study from Baghdad, Iraq.

Patients with major depressive disorder (MDD) have higher mean levels of blood inflammatory markers compared to non-MDD controls (). Several studies suggest that low-grade inflammation is more common in an MDD subgroup with certain depressive symptoms such as sleep disturbance, fatigue and abnormal appetite (; ; ; ). This has led to the hypothesis that, in a subgroup of patients with MDD, chronic low-grade inflammation may contribute to the development of depressive symptoms – a proposed subtype often referred to as “inflammatory depression”. Evidence suggests that this profile may characterize approximately one-third of patients with MDD (). Potential treatments targeting inflammatory depressive symptoms include both non-pharmacological interventions, such as dietary treatments and exercise, as well as anti-inflammatory medications (; ). Although several studies suggest that patients with more pronounced inflammatory depressive symptoms and elevated inflammatory markers may have a preferential effect of such treatments, the current evidence is insufficiently robust to support precision treatment of anti-inflammatory interventions in MDD (). Improved understanding of the biological processes underlying inflammatory depression would allow for better enrichment strategies and the selection of outcome measures more closely aligned with these mechanisms in future treatment studies, which could advance precision psychiatry. So far, most studies investigating biomarkers of depressive symptoms tentatively linked to inflammation have typically assayed a limited number of proteins such as C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Employing a broader proteomic approach has been proposed as a means to gain greater mechanistic insights and identify new biomarkers of the inflammatory depression subtype (; ). Assuming homogeneity in complex and multifactorial psychiatric disorders such as MDD can be detrimental for research that strives to understand underlying pathophysiological mechanisms (). Proteomic studies have not found any disease-specific pathways, and using larger and more well-defined clinical samples ( investigating specific symptom profiles) has been proposed as a way to detect separation between phenotypes (). In this study, we investigated the relationship between inflammatory depressive symptoms and a broad panel of immunometabolic biomarkers assessed using proteomics.