Major Depressive Disorder
An estimated of 322 million people worldwide are affected with major depressive disorder. Many studies want to unravel the molecular mechanism to identify biomarkers as possible targets of treatments. The challenge in this lies in the heterogeneity of MDD. Patients with the same MDD diagnoses endorse different symptom profiles and thus may have different underlying biological dysregulations. Marije van Haeringen, Rick Jansen, Brenda Penninx, Yuri Milaneschi, and Femke Lamers hypothesized that networks of biomarkers capture the interactions of underlying biological alterations better than single biomarkers.
Pathways involved in inflammation and metabolism
The data originated from the Netherlands Study of Depression and Anxiety (NESDA), with a sample of 1621 subjects. The proteomic assay with 171 markers that quantify serum proteins involved in hormonal, immunological, and metabolic pathways was used. Using these proteins, the research group investigated which clusters are most strongly associated with MDD and which depressive symptoms are the drivers of these associations. They identified six clusters of which one was significantly associated with current MDD. The cluster was enriched with pathways involved in inflammation and metabolism, including C-reactive protein (CRP), leptin, and insulin. The cluster was associated with ten symptoms of which five are energy-related.
Immune-metabolic form of depression
CRP, leptin, and insulin are known to be altered in MDD and are distinct in patients with an immune-metabolic form of depression (IMD). Their findings show that in MDD, there are alterations in a network of proteins involved in inflammatory and metabolic processes. More specifically, their results suggest that CRP, leptin, and insulin play an important role in the biological process underlying IMD and may provide a tool for patient stratification compared to single biomarkers.
Read the article in Psychological Medicine: Dissection of depression heterogeneity using proteomic clusters