人们对于患有精神分裂症（PwS）的认知变化的评估具有挑战性，但这对我们的理解非常重要。先前的研究在年龄范围和后续跟踪方面存在局限性，易受练习效应影响。在一个成熟的队列中控制练习效应，我们研究了执行功能发展轨迹及其与炎症生物标志物的关联，假设与非精神疾病对照组（NCs）相比，PwS的执行功能在时间上会变差，并且可以通过更高的基线炎症水平来预测，而且在PwS中的关联关系更强。我们对350名参与者（n = 186的PwS，164名NCs）在12至16个月的间隔（0至7次随访访视）中进行了执行功能评估。基线的炎症生物标志物包括高敏感性C-反应蛋白（hs-CRP），干扰素-γ，肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6，-8和-10。采用线性混合效应模型估计了诊断组之间的执行功能发展轨迹，同时控制了年龄、性别、种族/族裔和教育水平，另外的模型用于评估基线炎症的预测能力。平均随访时间为4.4年，PwS和年龄较大的参与者的执行功能改善有所减弱。控制练习效应消除了改善效果，揭示了受教育程度高的参与者的下降趋势，而不论其诊断结果如何。更高的基线hs-CRP仅预测了NCs的较差的执行功能，而TNF-α在控制练习效应后预测了所有参与者的变化。在多重比较调整后，只有hs-CRP对执行功能的主要影响是显著的。其他的炎症生物标志物都没有预测研究参与者的执行功能或表现轨迹。基线炎症生物标志物水平所反映的全身性炎症没有预测执行功能的长期下降。进一步研究PwS中炎症和认知的时序动态将有助于进一步澄清它们之间的关系和相关机制。 版权所有Ⓒ2023年。Elsevier Inc.出版。

Cognitive change in people with schizophrenia (PwS) is challenging to assess, but important to understand. Previous studies with limited age ranges and follow-up were subject to practice effects. Controlling for practice effects in a well-established cohort, we examined executive functioning trajectories and their association with inflammatory biomarkers, hypothesizing that PwS will have worsening executive functioning over time compared to non-psychiatric comparison participants (NCs), predicted by higher baseline inflammation with a stronger relationship in PwS than NCs.Executive functioning was assessed in 350 participants (n = 186 PwS, 164 NCs) at 12-16-month intervals (0 to 7 follow-up visits). Inflammatory biomarkers at baseline included high sensitivity C-Reactive Protein (hs-CRP), Interferon-gamma, Tumor Necrosis Factor (TNF)-alpha, and Interleukin(IL)-6, -8, and - 10. Executive functioning trajectories across diagnostic groups were estimated using a linear mixed-effects model controlling for age, sex, race/ethnicity, and education level, with additional models to assess prediction by baseline inflammation.Over 4.4 years average follow-up, improvements in executive functioning were attenuated in PwS and older participants. Controlling for practice effects negated improvements, revealing declines among highly educated participants regardless of diagnosis. Higher baseline hs-CRP predicted worse executive functioning only among NCs, while TNF-alpha was predictive of change in all participants only after controlling for practice effects. Only the main effect of hs-CRP on executive function was significant after adjusting for multiple comparisons. None of the other inflammatory biomarkers predicted executive functioning or trajectories of performance among study participants.Systemic inflammation as reflected by baseline inflammatory biomarker levels did not predict longitudinal declines in executive functioning. Additional studies examining the temporal dynamics of inflammation and cognition in PwS will help further clarify their relationship and associated mechanisms.Copyright © 2023. Published by Elsevier Inc.