Psychiatric Genetics Department, Poznań University of Medical Sciences, Poznań, Poland; Children and Adolescent Treatment Center, Zabór, Zielona Góra, Poland.
Psychiatric Genetics Department, Poznań University of Medical Sciences, Poznań, Poland.
Behav Brain Res. 2022 Feb 15;419:113706. doi: 10.1016/j.bbr.2021.113706. Epub 2021 Dec 4.
Cognitive deficits are the core factors impacting quality of life among patients diagnosed with schizophrenia. Effective method of treatment for this domain of symptoms remains lacking. Recent evidence suggests the link between impaired cognition and aberrant inflammatory response. Severity of symptoms might be linked to individual genetic predispositions and single-nucleotide polymorphisms (SNPs) in genes encoding interleukins and their receptors. Current genetic association studies include anti-inflammatory interleukins, such as IL10. Functional polymorphisms of IL10 (rs1800871, rs18008729) have been indicated to affect information processing in schizophrenia.
In this study, we analyzed the potential impact of 27 functional SNPs in 8 cytokine genes on cognitive parameters measured by Wisconsin card-sorting test (WCST) in schizophrenia group (n = 150) and healthy controls (n = 152).
We found significant associations of two functional polymorphisms of IL10 (rs1800871, rs1800872) and WCST results. Allele A carriers in rs1800871 performed significantly better in Percent of Conceptual Level Responses (CLR%). Allele A carriers in rs1800871 and allele T carriers in rs1800872 obtained better results in Completed Categories (CC). The impact of illness duration was observed, with better performance of recent-onset patients.
Results of this study indicate that genetic variants of inflammatory response are associated with cognitive deficits in schizophrenia. The role of cytokines in schizophrenia need to be investigated in the aspect of pro-/anti-inflammatory imbalance. Altered inflammatory response promote chronic mild inflammation in the brain and aberrant synaptic plasticity.
认知缺陷是影响精神分裂症患者生活质量的核心因素。针对这一症状领域,目前仍缺乏有效的治疗方法。最近的证据表明,认知障碍与异常的炎症反应之间存在关联。症状的严重程度可能与个体的遗传倾向和编码白细胞介素及其受体的基因中的单核苷酸多态性(SNPs)有关。目前的遗传关联研究包括抗炎性白细胞介素,如 IL10。IL10 的功能性多态性(rs1800871、rs18008729)已被表明会影响精神分裂症患者的信息处理能力。
在这项研究中,我们分析了 8 个细胞因子基因中的 27 个功能性 SNP 对精神分裂症组(n=150)和健康对照组(n=152)的威斯康星卡片分类测试(WCST)测量的认知参数的潜在影响。
我们发现 IL10 的两个功能性多态性(rs1800871、rs1800872)和 WCST 结果之间存在显著关联。rs1800871 的等位基因 A 携带者在概念水平反应百分比(CLR%)上的表现明显更好。rs1800871 的等位基因 A 携带者和 rs1800872 的等位基因 T 携带者在完成类别(CC)上的表现更好。观察到疾病持续时间的影响,新发病例患者的表现更好。
这项研究的结果表明,炎症反应的遗传变异与精神分裂症的认知缺陷有关。细胞因子在精神分裂症中的作用需要在促炎/抗炎失衡方面进行研究。炎症反应的改变会导致大脑中慢性轻度炎症和异常的突触可塑性。