Catalán Ana, Aymerich Claudia, Rodríguez-Sánchez José Manuel, Pedruzo Borja, Salazar de Pablo Gonzalo, Gil Patxi, Aguayo Francisco, Acasuso Garazi, Collado-Pérez Alvaro, Goena Javier, Ibarretxe Olatz, Zorrilla Iñaki, González-Pinto Ana, Erkoreka Leire, Alonso-Alconada Daniel, Fusar-Poli Paolo, González-Torres Miguel Angel
Department of Neuroscience, University of the Basque Country UPV/EHU, Leioa, Spain.
Department of Psychiatry, Basurto University Hospital, OSI Bilbao-Basurto, Bilbao, Spain.
Eur Psychiatry. 2025 Jul 10;68(1):e95. doi: 10.1192/j.eurpsy.2025.10063.
Cognitive deficits and immune system dysregulation are core features of psychotic disorders. Among inflammatory markers, interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) have been linked to both psychosis pathophysiology and related cognitive impairments.
We investigated associations among IL-6, TNF-α, and neurocognitive performance in 107 participants: individuals at clinical high risk for psychosis (CHR-P, = 35), first-episode psychosis (FEP, = 39), and healthy controls (HC, = 33). Assessments included memory, processing speed, executive function, and social cognition. Cytokines were measured from fasting serum samples. Analyses included ANOVA, correlations, and multivariate regressions controlling for age, sex, IQ, group, and symptom severity.
TNF-α levels were significantly elevated in FEP compared to CHR-P ( = 0.0251); IL-6 differences were non-significant. FEP showed poorer performance in multiple cognitive domains, especially social cognition. CHR-P individuals exhibited intermediate profiles between FEP and HC in cognition. In adjusted regression models, IL-6 was significantly associated with undermentalization on the MASC task ( = 0.28, = 0.0337) and showed a trend-level association with slower processing speed ( = 0.98, = 0.075). TNF-α levels predicted poorer facial emotion recognition ( = -1.37, = 0.0022). IQ and group were significant covariates in most models.
Our findings suggest that peripheral inflammation, particularly IL-6 and TNF-α, may selectively impact social cognitive functioning in early psychosis. Though modest, these associations highlight potential inflammatory contributions to functional impairment and support further investigation of immunological targets in early intervention.
认知缺陷和免疫系统失调是精神障碍的核心特征。在炎症标志物中，白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）与精神病病理生理学及相关认知障碍均有关联。
我们调查了107名参与者中IL-6、TNF-α与神经认知表现之间的关联，这些参与者包括临床高危精神病个体（CHR-P，n = 35）、首发精神病患者（FEP，n = 39）和健康对照者（HC，n = 33）。评估内容包括记忆、处理速度、执行功能和社会认知。从空腹血清样本中检测细胞因子。分析包括方差分析、相关性分析以及控制年龄、性别、智商、组别和症状严重程度的多元回归分析。
与CHR-P相比，FEP中的TNF-α水平显著升高（p = 0.0251）；IL-6差异不显著。FEP在多个认知领域表现较差，尤其是社会认知。CHR-P个体在认知方面表现出介于FEP和HC之间的中间特征。在调整后的回归模型中，IL-6与MASC任务中的心理化不足显著相关（β = 0.28，p = 0.0337），并与处理速度较慢呈趋势性关联（β = 0.98，p = 0.075）。TNF-α水平可预测较差的面部情绪识别能力（β = -1.37，p = 0.0022）。智商和组别在大多数模型中是显著的协变量。
我们的研究结果表明，外周炎症，特别是IL-6和TNF-α，可能在早期精神病中选择性地影响社会认知功能。尽管这些关联程度不大，但它们凸显了炎症对功能损害的潜在作用，并支持在早期干预中进一步研究免疫靶点。
