Comparison of Immune and Systemic Inflammation Parameters in Patients with a Depressive Episode in Bipolar Disorder and Major Depressive Disorder: A Scoping Review.

Background: Many studies have aimed to investigate and compare immune system and systemic inflammation parameters in patients with bipolar disorder (BD) and major depressive disorder (MDD) suffering from a depressive episode. However, no systematic review of the results has been conducted so far.

Aim: The aim of this study was to conduct a scoping review of research studies comparing immune and systemic inflammation parameters in patients with BD and MDD during a depressive episode.

Methods: The search for studies was conducted in the Medline and eLIBRARY databases for the period from January 1994 to December 2022. Open-access articles written in English and Russian were selected. The review included original studies that compared groups of patients with BD and MDD (diagnosed based on the DSM-IV, DSM-5, or ICD-10 criterion) by immune and systemic inflammation parameters (such as the counts, ratio, and functions of blood cells, erythrocyte sedimentation rate, concentrations of immunoglobulins, cytokines, acute phase proteins, complement components, and autoantibodies).

Results: The review included 24 studies. Current depressive episodes in patients with BD were associated with higher concentrations of chemokines (C-C motif chemokine ligand 3 (CCL3), CCL4, CCL5, CCL11), platelet-derived growth factor B, and interleukin 9 (IL-9) (two studies in each case), whereas patients with MDD tended to have higher concentrations of soluble tumor necrosis factor receptor 1 and immunoglobulin G to oxidized low-density lipoproteins (two studies each). Patients with BD and MDD had comparable concentrations of IL-8 (five studies); IL-2 and IL-10 (four studies each); IL-13 and gamma interferon (three studies each); IL-17, IL-1Rα, the vascular endothelial growth factor, as well as white blood cells, monocyte, and platelet counts (two studies each). Contradictory results were obtained for the levels of tumor necrosis factor-α (the concentrations did not differ in five studies, were elevated in BD patients in five studies, were elevated in MDD patients in two studies), IL-6 (the concentrations did not differ in eight studies and were elevated in BD patients in four studies), C-reactive protein (the concentrations did not differ in six studies, were elevated in BD patients in two studies), IL-4 (the concentrations did not differ in three studies and were elevated in MDD patients in two studies), IL-1β and the neutrophil count (the levels did not differ in one study each and were elevated in BD patients in two studies). Several studies have demonstrated an association between immune and systemic inflammation parameters and the severity of depressive and anxiety symptoms, melancholic depression, age of mood disorder onset, body mass index, and imipramine equivalent.

Conclusion: Some immune and systemic inflammation parameters are associated with a current depressive episode in patients with MDD or BD. These parameters may be considered as potential biomarkers for a differential diagnosis of these disorders.