背景:认知障碍是精神分裂症的核心症状。代谢异常影响认知,尽管血脂对认知的影响已被证明,目前还不清楚。我们进行了一项小型横断面研究,以调查稳定期精神分裂症患者血脂与认知之间的关系。使用Olink蛋白质组学,我们从炎症角度探讨了血脂影响认知的潜在机制.
方法:严格纳入107例稳定期精神分裂症合并认知障碍患者。全面的数据收集包括基本患者信息,血糖,血脂,和体重指数。使用蒙特利尔认知评估(MoCA)和MATRICS共识认知量表(MCCB)评估认知功能。在控制了混杂因素后,我们确定了轻度和重度认知障碍患者的代谢指标差异,并进行了相关和回归分析.此外,我们对两个脂质代谢异常患者的小样本组进行匹配,并使用Olink蛋白质组学分析炎症相关差异蛋白,旨在进一步探讨脂质代谢异常与认知功能的关系。
结果:重度认知障碍(SCI)患者的比例为34.58%。与轻度认知障碍(MCI)患者相比,SCI患者在注意力/警觉性(t=2.668,p=0.009)和工作记忆(t=2.496,p=0.014)认知维度表现较差。血脂代谢指标与认知功能相关,具体显示较高的TG水平(r=-0.447,p<0.001),TC(r=-0.307,p=0.002),LDL-C(r=-0.607,p<0.001)与较差的整体认知功能相关。进一步回归分析显示TG(OR=5.578,P=0.003)和LDL-C(OR=5.425,P=0.001)可能是加重稳定期精神分裂症患者认知功能损害的危险因素。蛋白质组学分析显示,与稳定期精神分裂症和正常脂质代谢的个体相比,高脂血症患者血浆中10种炎症蛋白水平升高,2种炎症蛋白水平降低,这些变化与认知功能有关。差异蛋白主要参与细胞因子-细胞因子受体相互作用等途径。趋化因子信号通路,和IL-17信号通路。
结论:稳定期精神分裂症患者的血脂与认知功能相关,TG水平较高,TC,和LDL-C与较差的整体认知能力相关。TG和LDL-C可能是加重这些患者认知障碍的危险因素。从炎症的角度来看,脂质代谢异常可能通过激活或下调相关蛋白来影响认知,或通过细胞因子-细胞因子受体相互作用等途径,趋化因子信号通路,和IL-17信号通路。
BACKGROUND: Cognitive impairment is a core symptom of schizophrenia. Metabolic abnormalities impact cognition, and although the influence of blood lipids on cognition has been documented, it remains unclear. We conducted a small cross-sectional study to investigate the relationship between blood lipids and cognition in patients with stable-phase schizophrenia. Using
Olink proteomics, we explored the potential mechanisms through which blood lipids might affect cognition from an inflammatory perspective.
METHODS: A total of 107 patients with stable-phase schizophrenia and cognitive impairment were strictly included. Comprehensive data collection included basic patient information, blood glucose, blood lipids, and body mass index. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and the MATRICS Consensus Cognitive Battery (MCCB). After controlling for confounding factors, we identified differential metabolic indicators between patients with mild and severe cognitive impairment and conducted correlation and regression analyses. Furthermore, we matched two small sample groups of patients with lipid metabolism abnormalities and used
Olink proteomics to analyze inflammation-related differential proteins, aiming to further explore the association between lipid metabolism abnormalities and cognition.
RESULTS: The proportion of patients with severe cognitive impairment (SCI) was 34.58%. Compared to patients with mild cognitive impairment (MCI), those with SCI performed worse in the Attention/Alertness (t = 2.668, p = 0.009) and Working Memory (t = 2.496, p = 0.014) cognitive dimensions. Blood lipid metabolism indicators were correlated with cognitive function, specifically showing that higher levels of TG (r = -0.447, p < 0.001), TC (r = -0.307, p = 0.002), and LDL-C (r = -0.607, p < 0.001) were associated with poorer overall cognitive function. Further regression analysis indicated that TG (OR = 5.578, P = 0.003) and LDL-C (OR = 5.425, P = 0.001) may be risk factors for exacerbating cognitive impairment in individuals with stable-phase schizophrenia. Proteomics analysis revealed that, compared to individuals with stable-phase schizophrenia and normal lipid metabolism, those with hyperlipidemia had elevated levels of 10 inflammatory proteins and decreased levels of 2 inflammatory proteins in plasma, with these changes correlating with cognitive function. The differential proteins were primarily involved in pathways such as cytokine-cytokine receptor interaction, chemokine signaling pathway, and IL-17 signaling pathway.
CONCLUSIONS: Blood lipids are associated with cognitive function in individuals with stable-phase schizophrenia, with higher levels of TG, TC, and LDL-C correlating with poorer overall cognitive performance. TG and LDL-C may be risk factors for exacerbating cognitive impairment in these patients. From an inflammatory perspective, lipid metabolism abnormalities might influence cognition by activating or downregulating related proteins, or through pathways such as cytokine-cytokine receptor interaction, chemokine signaling pathway, and IL-17 signaling pathway.