Evidence for two distinct immune phenotypes in subjects with depression and comorbid kidney disease

Abstract

Evidence suggests that inflammation may characterize a biologically distinct subgroup of patients with Major Depressive Disorder (MDD) and comorbid medical illness. In Chronic Kidney Disease (CKD) depression is common and increases morbidity and mortality. We examined baseline immune function in 27 adults with non-dialysis, stage 3–5 CKD and MDD, enrolled in the CKD Antidepressant Sertraline Trial (CAST), using RNA Sequencing of whole blood. Subjects completed the Quick Inventory of Depression Symptomatology (QIDS) to quantify depression severity. We analyzed co-expression of hyper-variable genes, performing hierarchical cluster analysis according to correlation with QIDS score. Subjects empirically divided into two clusters: (1) 18 subjects in whom depression severity inversely correlated with expression of interferon signaling genes (correlation coefficient 0.95), and (2) 9 subjects without correlation to the interferon cluster but whose depression was significantly correlated with ribosomal gene expression (cc = 0.83) (both p 0.001). Using a significance threshold of p 0.001, we analyzed genes within each group for correlation with clinical parameters. In group 2, STAT3 pathway expression was associated with fatigue and expression of interferon and insulin like growth factor signaling genes were correlated with mental and physical function, respectively. Our results suggest the existence of different depression immune phenotypes; further exploration of these types will provide an opportunity to develop personalized depression treatment in patients with comorbid depression and CKD.