从风险到慢性:精神分裂症患者自发脑活动演变模式的遗传和神经影像学见解。

IF 5.5 2区 医学 Q1 PSYCHIATRY
Yijing Zhang, He Wang, Mengjing Cai, Wei Wang, Jin Qiao, Xinyu Wang, Yue Wu, Qian Wu, Zhihui Zhang, Minghuan Lei, Qi An, Wenjie Cai, Haolin Wang, Fengtan Li, Yingying Xie, Feng Liu, Lining Guo
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引用次数: 0

摘要

背景:精神分裂症的进展经历高危期、首发期和慢性期,每一个阶段都伴有自发性脑活动的改变。静息状态功能MRI研究强调了这些变化,但不一致仍然存在,遗传基础仍不清楚。方法:进行神经影像学荟萃分析,以评估每个精神分裂症阶段的自发脑活动改变。使用最大的全基因组关联研究(GWAS)对精神分裂症(N = 53386例,77258例对照)进行汇总统计,随后使用基因组注释(H-MAGMA)的hi -c偶联多标记分析来鉴定精神分裂症相关基因。进行转录组-神经成像关联和基因优先级分析,以确定与大脑活动改变一致的基因。通过功能富集探索生物学相关性。结果:52项研究符合纳入标准,包括高危期(n高危= 409,Ncontrol = 475)、首发期(Ncase = 1842, Ncontrol = 1735)和慢性期(Ncase = 1242, Ncontrol = 1300)。高危期右侧中扣带和副扣带脑回活动减少。首发阶段显示右侧壳核活动增加,左侧直回和右侧中央后回活动减少。慢性期表现为右侧额下回活动增强,枕上回和右侧中央后回活动减弱。在所有阶段,199个基因始终与大脑活动变化有关,涉及神经系统发育、突触传递和突触可塑性等生物过程。结论:不同精神分裂症阶段的大脑活动变化和与这些变化一致的基因突出了它们作为精神分裂症通用生物标志物和治疗靶点的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
From risk to chronicity: genetic and neuroimaging insights into the evolving patterns of spontaneous brain activity in schizophrenia.

Background: Schizophrenia progresses through high-risk, first-episode, and chronic stages, each associated with altered spontaneous brain activity. Resting state functional MRI studies highlight these changes, but inconsistencies persist, and the genetic basis remains unclear.

Methods: A neuroimaging meta-analysis was conducted to assess spontaneous brain activity alterations in each schizophrenia stage. The largest available genome-wide association study (GWAS) summary statistics for schizophrenia (N = 53,386 cases, 77,258 controls) were used, followed by Hi-C-coupled multimarker analysis of genomic annotation (H-MAGMA) to identify schizophrenia-associated genes. Transcriptome-neuroimaging association and gene prioritization analyses were performed to identify genes consistently linked to brain activity alterations. Biological relevance was explored by functional enrichment.

Results: Fifty-two studies met the inclusion criteria, covering the high-risk (Nhigh-risk = 409, Ncontrol = 475), first-episode (Ncase = 1842, Ncontrol = 1735), and chronic (Ncase = 1242, Ncontrol = 1300) stages. High-risk stage showed reduced brain activity in the right median cingulate and paracingulate gyri. First-episode stage revealed increased activity in the right putamen and decreased activity in the left gyrus rectus and right postcentral gyrus. Chronic stage showed heightened activity in the right inferior frontal gyrus and reduced activity in the superior occipital gyrus and right postcentral gyrus. Across all stages, 199 genes were consistently linked to brain activity changes, involved in biological processes such as nervous system development, synaptic transmission, and synaptic plasticity.

Conclusions: Brain activity alterations across schizophrenia stages and genes consistently associated with these changes highlight their potential as universal biomarkers and therapeutic targets for schizophrenia.

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来源期刊
Psychological Medicine
Psychological Medicine 医学-精神病学
CiteScore
11.30
自引率
4.30%
发文量
711
审稿时长
3-6 weeks
期刊介绍: Now in its fifth decade of publication, Psychological Medicine is a leading international journal in the fields of psychiatry, related aspects of psychology and basic sciences. From 2014, there are 16 issues a year, each featuring original articles reporting key research being undertaken worldwide, together with shorter editorials by distinguished scholars and an important book review section. The journal''s success is clearly demonstrated by a consistently high impact factor.
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