BACKGROUND To explore the domain-general risk factor of early-life social stress in mental illness, rearing rodents in persistent postweaning social isolation has been established as a widely used animal model with translational relevance for neurodevelopmental psychiatric disorders such as schizophrenia. Although changes in resting-state brain connectivity are a transdiagnostic key finding in neurodevelopmental diseases, a characterization of imaging correlates elicited by early-life social stress is lacking. METHODS We performed resting-state functional magnetic resonance imaging of postweaning social isolation rats (N = 23) 9 weeks after isolation. Addressing well-established transdiagnostic connectivity changes of psychiatric disorders, we focused on altered frontal and posterior connectivity using a seed-based approach. Then, we examined changes in regional network architecture and global topology using graph theoretical analysis. RESULTS Seed-based analyses demonstrated reduced functional connectivity in frontal brain regions and increased functional connectivity in posterior brain regions of postweaning social isolation rats. Graph analyses revealed a shift of the regional architecture, characterized by loss of dominance of frontal regions and emergence of nonfrontal regions, correlating to our behavioral results, and a reduced modularity in isolation-reared rats. CONCLUSIONS Our result of functional connectivity alterations in the frontal brain supports previous investigations postulating social neural circuits, including prefrontal brain regions, as key pathways for risk for mental disorders arising through social stressors. We extend this knowledge by demonstrating more widespread changes of brain network organization elicited by early-life social stress, namely a shift of hubness and dysmodularity. Our results highly resemble core alterations in neurodevelopmental psychiatric disorders such as schizophrenia, autism, and attention-deficit/hyperactivity disorder in humans.

中文翻译：

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早期社会压力作为严重精神疾病发育危险因素的神经机制

背景 为了探索精神疾病早期社会压力的领域一般风险因素，在断奶后持续社交隔离中饲养啮齿动物已被建立为广泛使用的动物模型，其与神经发育性精神疾病（如精神分裂症）具有转化相关性。尽管静息状态大脑连接的变化是神经发育疾病的跨诊断关键发现，但缺乏对早期社会压力引起的成像相关性的表征。方法 我们在隔离后 9 周对断奶后社会隔离大鼠 (N = 23) 进行静息状态功能磁共振成像。针对精神疾病的行之有效的跨诊断连通性变化，我们使用基于种子的方法专注于改变前部和后部连通性。然后，我们使用图论分析检查了区域网络架构和全局拓扑的变化。结果 基于种子的分析表明，断奶后社交孤立大鼠额脑区的功能连通性降低，而后脑区的功能连通性增加。图形分析揭示了区域结构的转变，其特征是额叶区域的优势丧失和非额叶区域的出现，与我们的行为结果相关，以及隔离饲养大鼠的模块性降低。结论我们的额叶脑功能连接改变的结果支持先前的研究，假设社会神经回路，包括前额叶脑区，是通过社会压力源引起精神障碍风险的关键途径。我们通过展示早期社会压力引起的大脑网络组织更广泛的变化来扩展这一知识，即中心性和功能障碍的转变。我们的结果非常类似于人类精神分裂症、自闭症和注意力缺陷/多动障碍等神经发育性精神疾病的核心改变。