Inflammation-HDL axis indices differentiate drug-naïve first-episode mania and recurrent mania from healthy controls:...

Bipolar disorder (BD) is associated with immune dysregulation and cardiometabolic risk, yet low-cost biomarkers reflecting immune-lipid interactions across illness stages are not well defined.

We compared 168 individuals with BD (69 drug-naive first-episode mania; 99 with a history of recurrent mania who were euthymic at assessment) and 60 controls (18-65 years). Diagnoses were established using SCID-5 and manic symptoms were assessed with the Young Mania Rating Scale (YMRS). Morning blood samples were used to compute the systemic inflammation response index (SIRI), neutrophil-to-high-density lipoprotein cholesterol ratio (NHR), monocyte-to-HDL ratio (MHR), low-density lipoprotein to HDL ratio (LHR), and the atherogenic index of plasma (AIP). Group differences were tested with general linear models adjusted for age, sex, and body mass index, applying false discovery rate correction across 12 indices.

YMRS was higher in first-episode mania than in euthymic recurrent patients (28.12 ± 3.10 vs 1.08 ± 1.18; p<0.001). After adjustment, SIRI, NHR, and MHR showed robust group effects; both BD groups had higher SIRI and NHR than controls, and MHR was elevated in both patient groups. LHR was higher in first-episode mania, whereas AIP was higher in the recurrent group compared with controls.

Inflammation-HDL axis markers (SIRI, NHR, MHR) distinguish BD from controls independent of covariates, supporting immune-metabolic dysregulation and warranting prospective validation for risk stratification.