Association of the neutrophil to lymphocyte ratio and white blood cell count with response to pharmacotherapy in unipolar psychotic depression: An exploratory analysis

Abstract

Background Low-grade inflammation occurs in a subgroup of patients with Major Depressive Disorder (MDD) and may be associated with response to antidepressant medications. The Neutrophil to Lymphocyte Ratio (NLR) and total White Blood cell Count (WBC) are markers of systemic inflammation which have not been investigated as predictors for outcome to pharmacotherapy in unipolar depression yet. Moreover, the association between inflammation and treatment response has not been studied in unipolar Psychotic Depression (PD). We conducted an exploratory analysis to examine the prognostic significance of NLR and WBC in pharmacotherapy of PD. Methods Baseline NLR and WBC were examined in their association with response to seven weeks of treatment with antidepressants (venlafaxine or imipramine) and the combination of an antidepressant with an antipsychotic (venlafaxine plus quetiapine) in 87 patients with PD. Logistic regression models were adjusted for age, gender, Body Mass Index (BMI), depression severity, duration of the current episode and number of previous depressive episodes. Secondary outcomes were remission of depression and disappearance of psychotic symptoms. Results Higher NLR was associated with increased response to pharmacotherapy (Exp(B) 1.66, 95 ​% CI 1.03–2.66, p ​= ​0.036), but not with remission of depression or disappearance of psychotic symptoms. WBC was not associated with any of the outcome measures. Conclusion NLR may be a novel, inexpensive and widely available biomarker associated with response to pharmacotherapy in PD. The association between white blood cell measures and treatment outcome should be further investigated for different types of antidepressants in PD and in non-psychotic MDD.

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

“…Studies that examine the connection between NLR and major depression are available ( Table 1 ). It appears that major depressive patients had higher levels of NLR than the control group ( Demircan et al, 2016 ; Vos et al, 2021 ). However, meta-analyses on depression and inflammation suggest a large heterogeneity across studies ( Dowlati et al, 2010 ; Chai et al, 1999 ).…”

“… Llorca-Bofí et al (2021) 6 PD NLR may be a novel, inexpensive and widely available biomarker associated with response to pharmacotherapy in PD. Vos et al (2021) 7 PD Elevated NLR may reflect a transdiagnostic pathological process occurring in a subpopulation of psychiatric patients. Brinn and Stone (2020a) 8 BD Higher neutrophil-lymphocyte ratios in bipolar manic episodes was found, suggesting that inflammatory changes occur especially during acute episodes of mania.…”

Inflammatory Hematological Ratios in Adolescents with Mental Disorders: A Scoping Review

“…On the one hand, higher values of the SII index and SIRI (systemic inflammatory response index) have been demonstrated in non-responders compared with responders in bipolar depression [ 86 , 87 ]. On the other hand, elevated IHRs have been shown to be associated with higher treatment efficacy in psychotic depression [ 88 , 89 ] and schizophrenia [ 90 , 91 ].…”

“…Although the results of 2 studies included in our review indicate an association between IHRs and self-harm/suicidal behaviors [ 53 , 54 ], the retrospective cross-sectional design of both studies excludes the possibility of using calculated cut-off values to predict the risk of future suicide attempts or non-suicidal self-injury. In the absence of studies linking IHRs to treatment response and metabolic syndrome, one can speculate on a possible use of IHRs for predicting the treatment response or assessing metabolic risks in adolescents solely on the grounds of the studies conducted in young adults and adults [ 88 , 89 , 90 , 91 , 92 ].…”

Differences in white blood cell proportions between schizophrenia cases and controls are influenced by medication and variations in time of day

“…In the present study, we use DNA methylation data from whole blood to estimate WBC proportions in SCZ cases and healthy controls and examine the influence of time of day when blood was drawn. We further our investigation of the time of day effect by evaluating the neutrophil-to-lymphocyte (NLR) ratio, previously shown to detect inflammatory activation related to SCZ, related psychoses [ 11 – 13 ], and psychotropic treatment response [ 13 , 14 ]. We compare these results with those of a sub-group of medication-free SCZ cases to estimate the impact of polypharmacy on WBC.…”