Villegas García Lourdes, Patró Esther, Barbero Juan David, Esteve-Valverde Enrique, Palao Diego J, Soria Virginia, Labad Javier, Cobo Jesús
Universitat Autònoma de Barcelona, Bellaterra, Spain.
Institut d'Investigació i Innovació Parc Taulí (I3PT-CERCA), Sabadell, Barcelona, Spain; Unitat de Neurociència Traslacional, Barcelona, Spain; Mental Health Department, Consorci Corporació Sanitària Parc Taulí, Sabadell, Barcelona, Spain.
Psychoneuroendocrinology. 2025 Jan;171:107209. doi: 10.1016/j.psyneuen.2024.107209. Epub 2024 Oct 15.
The purpose of this research was to investigate peripheral inflammation by analyzing lymphocyte and lipoprotein-derived inflammatory ratios in patients with bipolar disorder type I (BD-I) and healthy controls (HCs), considering mood stabilizer drug treatments, sex and clinical trajectories.
This was a cross-sectional case-control study of BD-I patients (n=252) and healthy controls (n=62). We investigated peripheral inflammation biomarkers through blood count values (CBCs), lipoproteins and a complex panel of inflammatory ratios, including the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), neutrophil-to-HDL ratio (NHR), monocyte-to-HDL ratio (MHR), platelet-to-HDL ratio (PHR) and lymphocyte-to-HDL ratio (LHR). Furthermore, we examined the effects of sex, drug treatment and clinical outcome on the inflammatory profile.
We found that the monocyte-to-lymphocyte ratio (MLR) and lipoprotein-derived inflammatory ratio (NHR, MHR, PHR, and LHR) were significantly greater in BD-I patients than in control individuals. The monocyte-to-HDL ratio (MHR) showed acceptable accuracy as a disease predictor. Logistic regression analysis adjusted for sex, age and BMI indicated that the risk of having a BD-I diagnosis was greater for participants with MHR levels in quartiles 3 (OR= 5.2, p=0.001) and 4 (OR=13, p<0.001). There was a strong association between lithium treatment and increased inflammation represented by elevated lymphocyte-derived inflammatory ratios (NLR, MLR, PLR, SII, and SIRI) in lithium-treated BD-I patients compared to those in lithium-free or lithium treatment-naïve BD-I patients. The main limitations are the cross-sectional nature of the study and limited sample size of HCs.
Several CBCs, lipoproteins, and a complex panel of inflammatory ratios, including lymphocyte-derived inflammatory ratios (NLR, MLR, PLR, SII, and SIRI) and lipoprotein-derived inflammatory ratios (NHR, MHR, PHR, and LHR), are altered in individuals diagnosed with BD-I. The monocyte-to-HDL ratio (MHR) emerged as a disease predictor in our BD-I sample. A remarkable finding is the association of lithium and valproate treatment with the inflammatory state. Considering the study limitations, our results underscore the importance of pharmacological treatments when researching inflammation markers in mood disorders. Lymphocyte-derived and lipoprotein-derived inflammatory ratios are easy-to-implement and relevant biomarkers in BD-I patients.
本研究旨在通过分析I型双相情感障碍（BD-I）患者和健康对照者（HCs）的淋巴细胞及脂蛋白衍生的炎症比率，同时考虑心境稳定剂药物治疗、性别和临床病程，来研究外周炎症。
这是一项针对BD-I患者（n = 252）和健康对照者（n = 62）的横断面病例对照研究。我们通过血细胞计数（CBC）、脂蛋白和一组复杂的炎症比率指标来研究外周炎症生物标志物，这些指标包括中性粒细胞与淋巴细胞比率（NLR）、单核细胞与淋巴细胞比率（MLR）、血小板与淋巴细胞比率（PLR）、全身免疫炎症指数（SII）、全身炎症反应指数（SIRI）、中性粒细胞与高密度脂蛋白比率（NHR）、单核细胞与高密度脂蛋白比率（MHR）、血小板与高密度脂蛋白比率（PHR）以及淋巴细胞与高密度脂蛋白比率（LHR）。此外，我们还研究了性别、药物治疗和临床结局对炎症特征的影响。
我们发现，BD-I患者的单核细胞与淋巴细胞比率（MLR）以及脂蛋白衍生的炎症比率（NHR、MHR、PHR和LHR）显著高于对照个体。单核细胞与高密度脂蛋白比率（MHR）作为疾病预测指标显示出可接受的准确性。经性别、年龄和体重指数调整的逻辑回归分析表明，MHR水平处于第3四分位数（OR = 5.2，p = 0.001）和第4四分位数（OR = 13，p < 0.001）的参与者被诊断为BD-I的风险更高。与未服用锂盐或初治的BD-I患者相比，服用锂盐治疗的BD-I患者中，锂盐治疗与淋巴细胞衍生的炎症比率（NLR、MLR、PLR、SII和SIRI）升高所代表的炎症增加之间存在强烈关联。主要局限性在于研究的横断面性质以及健康对照者样本量有限。
在被诊断为BD-I的个体中，几种血细胞计数指标、脂蛋白以及一组复杂的炎症比率指标发生了改变，这些指标包括淋巴细胞衍生的炎症比率（NLR、MLR、PLR、SII和SIRI）和脂蛋白衍生的炎症比率（NHR、MHR、PHR和LHR）。单核细胞与高密度脂蛋白比率（MHR）在我们的BD-I样本中成为一种疾病预测指标。一个显著的发现是锂盐和丙戊酸盐治疗与炎症状态之间的关联。考虑到研究的局限性，我们的结果强调了在研究心境障碍炎症标志物时药物治疗的重要性。淋巴细胞衍生和脂蛋白衍生的炎症比率是BD-I患者中易于实施且相关的生物标志物。
