Peripheral Inflammatory Profiles in Acute Schizophrenia Relapse: Associations with 6-month Antipsychotic Treatment Coverage

Abstract Objectives Peripheral inflammatory markers are frequently elevated in schizophrenia, but the extent to which inflammatory indices at acute relapse are associated with preceding antipsychotic treatment coverage remains unclear. We examined whether 6-month treatment coverage patterns—long-acting injectable (LAI) monotherapy, regular oral monotherapy, or no antipsychotic treatment—were associated with peripheral inflammatory indices measured at hospitalization for acute relapse. Methods We retrospectively evaluated 127 adults hospitalized for acute psychosis. Laboratory values obtained within 24 hours of admission and PANSS scores were extracted. Inflammatory indices (NLR, PLR, MLR, MHR, and CRP/albumin ratio) were calculated. Patients were categorized by treatment pattern in the preceding six months. Results The no-treatment group had higher PANSS scores than treated groups. In adjusted models, LAI treatment was associated with lower NLR (β = 0.75; p = 0.004), whereas regular oral treatment did not differ from no treatment. Similar patterns were observed for PLR (β = 0.78; p = 0.003) and MLR (β = 0.74; p = 0.004). When the reference was set to regular oral treatment, LAI remained associated with lower NLR (β = 0.804; p = 0.008). In treated-only overlap analyses additionally adjusting for molecule category and dose, LAI remained associated with lower NLR compared with oral treatment (p = 0.037). Discussion Schizophrenia involves a chronic inflammatory component shaped by treatment patterns. Findings suggest regular antipsychotic exposure, particularly via LAI, is associated with a lower peripheral inflammatory burden during relapse. Conclusion Preceding LAI treatment coverage was consistently associated with lower peripheral inflammatory ratios at acute relapse compared with no treatment and regular oral treatment, even after adjustment for symptom severity and metabolic covariates.