Department of Psychiatry, McGill University, Montreal, QC, Canada; Douglas Centre for Sleep and Biological Rhythms, Douglas Mental Health University Institute, 6875 LaSalle Boulevard, H4H 1R3, Montreal, QC, Canada; Department of Public Health Solutions, Mental Health Unit, Finnish Institute for Health and Welfare, P.O. Box 30, FI-00271, Helsinki, Finland.
Sleep Well Research Program, Faculty of Medicine, P.O. Box 21, FI-00014, University of Helsinki, Finland; Neuroscience Center, Helsinki Institute of Life Science HiLIFE, P.O. Box 21, FI-00014, University of Helsinki, Finland.
J Psychiatr Res. 2021 May;137:383-392. doi: 10.1016/j.jpsychires.2021.03.013. Epub 2021 Mar 16.
he excess availability of glucose and lipids can also have an impact on the dynamics of activation and regulation of peripheral immune cellsWe aimed at understanding the correlations between peripheral metabolic state and immune system during the first year in first-episode psychosis (FEP). Patients with FEP (n = 67) and matched controls (n = 38), aged 18-40 years, were met at baseline, 2 and 12 months. Fasting peripheral blood samples were collected. We applied the NanoString nCounter in-solution hybridization technology to determine gene expression levels of 178 candidate genes reflecting activation of the immune system. Serum triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL) cholesterol and insulin and plasma glucose (fP-Gluc) were measured. We applied Ingenuity Pathway Analysis (IPA) to visualize enrichment of genes to functional classes. Strength of positive or negative regulation of the disease and functional pathways was deduced from IPA activation Z-score at the three evaluation points. We correlated gene expression with plasma glucose, triglycerids and HDL and LDL, and used hierarchical clustering of the pairwise correlations to identify groups of genes with similar correlation patterns with metabolic markers. In patients, initially, genes associated with the innate immune system response pathways were upregulated, which decreased by 12 months. Furthermore, genes associated with apoptosis and T cell death were downregulated, and genes associated with lipid metabolism were increasingly downregulated by 12 months. The immune activation was thus an acute phase during illness onset. At baseline, after controlling for multiple testing, 31/178 genes correlated positively with fasting glucose levels, and 54/178 genes negatively with triglycerides in patients only. The gene clusters showed patterns of correlations with metabolic markers over time. The results suggest a functional link between peripheral immune system and metabolic state in FEP. Metabolic factors may have had an influence on the initial activation of the innate immune system. Future work is necessary to understand the role of metabolic state in the regulation of immune response in the early phases of psychosis.
葡萄糖和脂质的过度供应也会影响外周免疫细胞的激活和调节动态。我们旨在了解首发精神分裂症（FEP）第一年期间外周代谢状态和免疫系统之间的相关性。将 67 例 FEP 患者和 38 例匹配的对照者（年龄 18-40 岁）在基线、2 个月和 12 个月时进行了评估。采集空腹外周血样本。我们应用 NanoString nCounter 溶液杂交技术来确定 178 个候选基因的表达水平，这些基因反映了免疫系统的激活。测定血清甘油三酯、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）胆固醇和胰岛素以及血浆葡萄糖（fP-Gluc）。应用 IPA 对基因进行功能分类富集可视化。从三个评估点的 IPA 激活 Z 分数推断疾病和功能途径的正向或负向调节的强度。我们将基因表达与血浆葡萄糖、甘油三酯和 HDL 和 LDL 进行了相关性分析，并使用代谢标志物的相似相关性模式的基因进行了层次聚类。在患者中，最初与固有免疫反应途径相关的基因上调，到 12 个月时下调。此外，与细胞凋亡和 T 细胞死亡相关的基因下调，与脂质代谢相关的基因在 12 个月时下调。因此，免疫激活是疾病发作时的急性阶段。在基线时，在控制多重检验后，患者中有 31/178 个基因与空腹血糖水平呈正相关，54/178 个基因与甘油三酯呈负相关。基因簇随时间表现出与代谢标志物的相关性模式。结果提示在 FEP 中，外周免疫系统与代谢状态之间存在功能联系。代谢因素可能对固有免疫系统的初始激活有影响。未来的工作有必要了解代谢状态在精神病早期免疫反应调节中的作用。
