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端粒生物学及其在精神分裂症谱系障碍中的维持:探索与认知的联系。

Telomere biology and its maintenance in schizophrenia spectrum disorders: Exploring links to cognition.

机构信息

Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Department of Medical Genetics, Oslo University Hospital, Oslo, Norway; Centre for Precision Psychiatry, Division of Mental Health and Addiction, University of Oslo, Norway.

出版信息

Schizophr Res. 2024 Oct;272:89-95. doi: 10.1016/j.schres.2024.08.011. Epub 2024 Aug 28.

Abstract

OBJECTIVE

Contemporary research suggests reduced telomere length in schizophrenia spectrum disorders (SZ) compared to age-adjusted non-affected individuals. However, the role of telomere maintenance and telomere repair in SZ is poorly understood as well as the involvement of telomere biology in cognitive abnormalities in SZ.

METHODS

The study consisted of 758 participants (SZ [n = 357] and healthy controls, HC [n = 401]) collected as part of the Norwegian TOP study. Participants were assessed with standardized neuropsychological tests measuring five cognitive domains. Leucocyte telomere length (TL) was measured via blood and determined by quantitative real-time Polymerase Chain Reaction (qPCR) providing a telomere to single copy ratio (T/S ratio), used to estimate the mean telomere length. Telomerase activity was assessed by the expression levels of the Telomerase Reverse Transcriptase (TERT) and Telomerase RNA Component (TERC) genes. To assess telomere maintenance and telomere repair we calculated the telomerase expression to TL ratio (TERT/TL and TERC/TL respectively).

RESULTS

Patients had reduced TERT (F = 5.03, p = 0.03), but not TERC expression (F = 1.04, p = 0.31), and higher TERT/TL (F = 6.68, p = 0.01) and TERC/TL (F = 6.71, p = 0.01), adjusted for age, sex, and ethnicity. No statistically significant association was observed between any of the telomere biology markers and the cognitive domains (p > 0.05).

CONCLUSION

Our study shows changes in TERT expression and telomere maintenance and telomere repair in SZ compared HC. However, the role of telomere biology in the mechanism underlying cognitive impairment in psychosis seems limited.

摘要

目的

当代研究表明,与年龄匹配的未受影响个体相比,精神分裂症谱系障碍(SZ)患者的端粒长度缩短。然而,SZ 中端粒体维持和端粒修复的作用以及端粒生物学在 SZ 认知异常中的作用仍知之甚少。

方法

该研究包括作为挪威 TOP 研究的一部分收集的 758 名参与者(SZ [n=357]和健康对照,HC [n=401])。参与者接受了五项认知领域的标准化神经心理学测试。通过血液测量白细胞端粒长度(TL),并通过定量实时聚合酶链反应(qPCR)确定端粒到单拷贝比(T/S 比),用于估计平均端粒长度。通过端粒酶逆转录酶(TERT)和端粒酶 RNA 成分(TERC)基因的表达水平评估端粒酶活性。为了评估端粒维持和端粒修复,我们计算了端粒酶表达与 TL 的比值(TERT/TL 和 TERC/TL 分别)。

结果

患者的 TERT 表达减少(F=5.03,p=0.03),但 TERC 表达没有减少(F=1.04,p=0.31),TERT/TL 较高(F=6.68,p=0.01)和 TERC/TL(F=6.71,p=0.01),调整年龄、性别和种族后。任何一种端粒生物学标志物与认知域之间均无统计学显著关联(p>0.05)。

结论

我们的研究表明,与 HC 相比,SZ 中 TERT 表达以及端粒维持和端粒修复发生变化。然而,端粒生物学在精神病认知障碍的发病机制中的作用似乎有限。

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