Immune Cell Ratios Are Higher in Bipolar Affective than Unipolar Depressive Disorder and Modulated by Mood Episode: A Retrospective, Cross-Sectional Study

Abstract

Immune dysregulation is implicated in the pathophysiology of both bipolar and major depressive disorder, while immune cell ratios (IRCs) have recently been proposed as clinically applicable immune biomarkers. We investigated IRCs differences in affective disorders and their association with current mood episodes and clinical features. This retrospective cohort study analyzed neutrophil–lymphocyte (NLR), monocyte–lymphocyte (MLR), and platelet–lymphocyte (PLR) ratios upon admission in 135 affective disorder in-patients with mania (MA, n = 36), bipolar depression (BiD, n = 38), and unipolar depression (MDD, n = 61). Demographic, clinical, and immune data were extracted from medical records. Monocyte count was significantly higher in BiD compared to MDD (p < 0.001). Multivariable regression models suggested higher NLR in MA compared to MDD (p = 0.039), higher MLR in both MA and BiD compared to MDD (p < 0.001 and p = 0.004 respectively), while we found neither group differences in PLR nor an effect of type and duration of hospitalization, current psychotic, or suicidal features and psychiatric history on IRCs. Here, we show that IRCs are elevated in bipolar disorder versus MDD and affected by mood episode, while MLR could be especially valuable in the differential diagnosis between bipolar and unipolar depression. IRCs represent inexpensive, routinely accessible and clinically applicable biomarkers with diagnostic validity in affective disorders that could be easily implemented as illness activity indicators, to better follow the course of illness and eventually predict relapse or treatment response and, thus, guide therapeutic targeting.

Association Between Mood Disorder Severity, Treatment Response and Systemic Inflammatory Markers: Exploring the Role of NLR, PLR, MLR, and SII

“…Currently, research on the relationship between different stages of affective disorders and inflammatory ratios yields slightly disparate results. Since Koureta et al 20 found that NLR values were significantly higher only in bipolar manic episodes and MLR values were significantly higher in both stages of bipolar disorder compared to MDD, Mazza et al 8 found that manic patients had higher NLR and MLR compared to patients with unipolar and bipolar depression, with no significant difference between unipolar and bipolar depression. In clinical practice, distinguishing between bipolar and unipolar depression can be difficult.…”

“…Although a few studies found significantly higher NLR or MLR values in bipolar depression than in unipolar depression, most studies observed no significant difference, which is consistent with previous findings. 20 , 21 …”

Neutrophil-to-lymphocyte ratio as a predictive biomarker for early diagnosis of depression: A narrative review

“…Furthermore, it has been demonstrated that as compared to individuals with unipolar depression, bipolar manic patients exhibited a higher level of inflammation as measured by the NLR index. Additionally, it has been reported that the manic phase in BD was characterized by a higher inflammation activation, reflected by the NLR index, than the depression phase ( Dionisie et al, 2021 ; Koureta et al, 2023 ). Since neutrophils are the first line of defense for the innate immune system and lymphocytes are predominantly involved in the adaptive immunological response, elevated NLR in BD (hypo) manic episodes may indicate an imbalance in favor of innate immunity.…”

Transient splenial lesion syndrome in bipolar-II disorder: a case report highlighting reversible brain changes during hypomanic episodes

“…Serum levels of these inflammatory biomarkers may increase or decrease with different mood episode. Meanwhile, another study ( 12 ) suggests that psychiatric disorders may have the potential to function as inducers of a wide range of immune responses, leading to a dysregulation of the inflammatory status and the cell-mediated immunity. Therefore, we speculate that these inflammatory responses may link RESLES and BD from a pathophysiological perspective.…”