ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Mood Disorders
This article is part of the Research TopicBipolar Disorder: Where are we now? Treatment Response, Neural Correlates and PersonalityView all 5 articles
Inflammation–HDL Axis Indices Differentiate Bipolar Disorder From Healthy Controls: A Comparison of Drug-Naive First-Episode Mania and Euthymic Recurrent Patients
Provisionally accepted
- 1Department of Psychiatry, School of Medicine, Selcuk University, Konya, Türkiye
- 2Department of Child and Adolescence Psychiatry, School of Medicine, Selcuk University, Konya, Türkiye
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Abstract Background: 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. Methods: 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. Results: 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. Conclusion: 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.
Keywords: Atherogenic index of plasma, Bipolar Disorder, Cardiometabolic risk, First-episode mania, HDL, Inflammation, monocyte/HDL ratio, neutrophil/HDL ratio
Received: 04 Jan 2026; Accepted: 10 Feb 2026.
Copyright: © 2026 Ekici, Tekdemir, Bayırlı, Çınar and Tezcan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Fatih Ekici
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