Blood Cell Count Ratios at Baseline are Associated with Initial Clinical Response to Clozapine in Treatment-Resistant, Clozapine-Naïve, Schizophrenia-Spectrum Disorder

Abstract

Background Clozapine is the recommended treatment for managing treatment-resistant schizophrenia (TRS), and immunological mechanisms may be involved in its unique antipsychotic efficacy. This study investigated whether baseline immune abnormalities measured with blood cell count ratios can predict the clinical response after initiating treatment with clozapine in patients with clozapine naïve TRS. Methods A longitudinal design was developed, involving 32 patients diagnosed with treatment-resistant, clozapine-naïve schizophrenia-spectrum disorder. Patients were evaluated at baseline before clozapine starting and 8 weeks of follow-up. Psychopathological status and immune abnormalities (blood cell count ratios: neutrophil-lymphocyte ratio [NLR], monocyte-lymphocyte ratio [MLR], platelet-lymphocyte ratio [PLR] and basophil-lymphocyte ratio [BLR]) were evaluated in each visit. Results Baseline NLR (b=− 0.364; p=0.041) and MLR (b =− 0.400; p=0.023) predicted the change in positive symptoms over the 8-week period. Patients who exhibited a clinical response showed higher baseline NLR (2.38±0.96 vs. 1.75±0.83; p=0.040) and MLR (0.21±0.06 vs. 0.17±0.02; p=0.044) compared to non-responders. In the ROC analysis, the threshold points to distinguish between responders and non-responders were approximately 1.62 for NLR and 0.144 for MLR, yielding AUC values of 0.714 and 0.712, respectively. No statistically significant differences were observed in the blood cell count ratios from baseline to the 8-week follow-up. Conclusion Our study emphasizes the potential clinical significance of baseline NLR and MLR levels as predictors of initial clozapine treatment response in patients with TRS. Future studies with larger sample sizes and longer follow-up periods should replicate our findings.

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 ].…”