炎症标志物谱与精神分裂症患者和非精神病对照受试者神经认知功能的相关性。
Associations between inflammatory marker profiles and neurocognitive functioning in people with schizophrenia and non-psychiatric comparison subjects.
机构信息
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA; Sam and Rose Stein Institute for Research on Aging, University of California San Diego, La Jolla, CA, USA; VA San Diego Healthcare System, San Diego, CA, USA.
出版信息
J Psychiatr Res. 2022 May;149:106-113. doi: 10.1016/j.jpsychires.2022.02.029. Epub 2022 Mar 2.
BACKGROUND
Cognitive dysfunction in schizophrenia is the key predictor of functional disability and drives economic burden. Inflammation has been increasingly implicated in the pathogenesis of schizophrenia, yet its role in cognitive decline has not been evaluated. This study explores the association between inflammation and cognitive functioning in persons with schizophrenia.
METHODS
Participants included 143 persons with schizophrenia (PwS) and 139 non-psychiatric comparison subjects (NCs) from an ongoing study of aging. Cognitive assessments included validated measures for executive functioning, processing speed, and visuospatial skills. Plasma levels of nine biomarkers associated with inflammation (high sensitivity C-reactive protein, intercellular adhesion molecule 1, serum amyloid A, interleukin-6, interleukin-8, interferon gamma-induced protein-10, monocyte chemotactic protein-1, fractalkine, and brain-derived neurotrophic factor) were quantified using commercially available, enzyme-linked immunosorbent assays. Partial least squares regression was used to develop a composite "inflammatory profile" to maximize correlations with the cognitive outcomes. We then constructed a best-fit model using these composites and their interactions with diagnosis and sex as the predictors, controlling for covariates.
RESULTS
The biomarker composite, which best correlated with scores on cognitive testing, included high sensitivity C-reactive protein, intercellular adhesion molecule 1, serum amyloid A, interleukin-6, and brain-derived neurotrophic factor, for a 5-biomarker "inflammatory profile." The best-fit model showed a significant biomarker composite by diagnosis by sex three-way interaction, for executive function and processing speed, but not visuospatial skill.
CONCLUSIONS
This approach to building an "inflammatory profile" may provide insight into inflammatory pathways affecting brain function and potential targets for anti-inflammatory interventions to improve cognition in schizophrenia.
背景
精神分裂症患者的认知功能障碍是导致功能障碍和经济负担的关键预测因素。炎症在精神分裂症的发病机制中的作用越来越受到关注，但它在认知能力下降中的作用尚未得到评估。本研究探讨了精神分裂症患者炎症与认知功能之间的关系。
方法
参与者包括来自一项正在进行的衰老研究的 143 名精神分裂症患者（PwS）和 139 名非精神病对照受试者（NCs）。认知评估包括用于执行功能、处理速度和视空间技能的验证性测量。使用商业上可用的酶联免疫吸附测定法来量化与炎症相关的九种生物标志物（高敏 C 反应蛋白、细胞间黏附分子 1、血清淀粉样蛋白 A、白细胞介素 6、白细胞介素 8、干扰素γ诱导蛋白 10、单核细胞趋化蛋白 1、 fractalkine 和脑源性神经营养因子）的血浆水平。使用偏最小二乘回归来开发一个综合的“炎症谱”，以最大限度地与认知结果相关。然后，我们使用这些综合指标及其与诊断和性别之间的相互作用作为预测因子，构建了一个最佳拟合模型，同时控制了协变量。
结果
与认知测试得分相关性最好的生物标志物综合指标包括高敏 C 反应蛋白、细胞间黏附分子 1、血清淀粉样蛋白 A、白细胞介素 6 和脑源性神经营养因子，这是一个 5 种生物标志物的“炎症谱”。最佳拟合模型显示，在执行功能和处理速度方面，诊断与性别之间存在显著的生物标志物综合指标三因素相互作用，但在视空间技能方面没有这种作用。
结论
这种构建“炎症谱”的方法可能为影响大脑功能的炎症途径提供深入了解，并为改善精神分裂症认知的抗炎干预提供潜在靶点。
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