Research Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany; Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
Research Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
Biol Psychiatry. 2018 Jul 15;84(2):116-128. doi: 10.1016/j.biopsych.2017.12.010. Epub 2017 Dec 28.
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.
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.
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.
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.
为了探究精神疾病中早期社会应激的一般领域风险因素，持续的新生后社会隔离饲养啮齿动物已被确立为一种具有转化相关性的动物模型，可用于神经发育性精神障碍，如精神分裂症。尽管静息态脑连接的变化是神经发育性疾病的一个跨诊断关键发现，但早期社会应激引起的影像学相关性特征尚不清楚。
我们对新生后社会隔离的大鼠（N=23）进行了静息态功能磁共振成像，这些大鼠在隔离 9 周后进行了成像。针对精神障碍的既定跨诊断连接变化，我们使用基于种子的方法重点研究了额叶和后部连接的改变。然后，我们使用图论分析检查了区域网络结构和全局拓扑的变化。
基于种子的分析表明，新生后社会隔离大鼠的额叶脑区功能连接减少，而后部脑区功能连接增加。图分析显示，区域结构发生了转变，特征是额叶区域的主导地位丧失，非额叶区域出现，与我们的行为结果相关，并且隔离饲养的大鼠的模块性降低。
我们对额叶大脑中功能连接改变的研究结果支持了先前的研究假设，即社会神经回路，包括前额叶大脑区域，作为通过社会应激因素引发精神障碍的风险的关键途径。我们通过证明早期社会应激引起的大脑网络组织的更广泛变化来扩展这一知识，即枢纽性和失调性的转变。我们的研究结果与人类神经发育性精神障碍，如精神分裂症、自闭症和注意缺陷多动障碍的核心改变高度相似。
