Complement pathway changes at age 12 are associated with psychotic experiences at age 18 in a longitudinal population-based study: evidence for a role of stress
Complement pathway changes at age 12 are associated with psychotic experiences at age 18 in a longitudinal population-based study: evidence for a role of stress
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DOI：
10.1038/s41380-018-0306-z
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发表时间：
2021-02-01
影响因子：
11
通讯作者：
Cotter, David R.
中科院分区：
文献类型：
--
作者：
Focking, Melanie;Sabherwal, Sophie;Cotter, David R.
补体级联是免疫防御感染的主要组成部分，越来越多的证据表明补体失调在主要精神疾病中的作用。我们使用数据独立采集对补体信号通路（n = 29个蛋白）进行了定向蛋白质组学分析。参与者从英国雅芳父母和儿童纵向研究（ALSPAC）队列中招募，他们在12岁和18岁时参加了精神评估访谈。在18岁报告有精神病经历（PEs）的个体（n = 64）中，12岁时的蛋白质表达水平与年龄匹配的对照组（n = 67）进行了比较。29个靶向补体蛋白或蛋白亚组分中有6个在多重比较校正后显著上调（VTN向上箭头、C1RL向上箭头、C8B向上箭头、C8A向上箭头、CFH向上箭头和C5向上箭头）。然后，我们对暴露于慢性社会压力下的小鼠进行了无偏倚的血浆蛋白质组学分析，观察到11种补体蛋白的失调，其中3种补体蛋白在PE个体中发生了相同方向的改变（C1R向上箭头，CFH向上箭头和C5向上箭头）。我们的研究结果表明，血液中补体蛋白通路的失调与精神病经历的发生率有关，这些变化可能反映了暴露于压力下。
The complement cascade is a major component of the immune defence against infection, and there is increasing evidence for a role of dysregulated complement in major psychiatric disorders. We undertook a directed proteomic analysis of the complement signalling pathway (n = 29 proteins) using data-independent acquisition. Participants were recruited from the UK avon longitudinal study of parents and children (ALSPAC) cohort who participated in psychiatric assessment interviews at ages 12 and 18. Protein expression levels at age 12 among individuals who reported psychotic experiences (PEs) at age 18 (n = 64) were compared with age-matched controls (n = 67). Six out of the 29 targeted complement proteins or protein subcomponents were significantly upregulated following correction for multiple comparisons (VTN up arrow, C1RL up arrow, C8B up arrow, C8A up arrow, CFH up arrow, and C5 up arrow). We then undertook an unbiased plasma proteomic analysis of mice exposed to chronic social stress and observed dysregulation of 11 complement proteins, including three that were altered in the same direction in individuals with PE (C1R up arrow, CFH up arrow, and C5 up arrow). Our findings indicate that dysregulation of the complement protein pathway in blood is associated with incidence of psychotic experiences and that these changes may reflect exposure to stress.