The pathophysiology of restricted repetitive behavior.
The pathophysiology of restricted repetitive behavior.
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DOI：
10.1007/s11689-009-9019-6
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发表时间：
2009-06
影响因子：
4.9
通讯作者：
Kim, Soo-Jeong
中科院分区：
文献类型：
--
作者：
Lewis, Mark;Kim, Soo-Jeong
限制性重复行为（RRB）是异质性的，从刻板的身体动作到仪式，再到有限的兴趣。RRB与自闭症密切相关，但在许多其他临床疾病以及典型发育中也会发生。似乎没有一个类别的RRB是独特的或特定的自闭症和RRB似乎并不强烈相关的特定的认知，感觉或运动异常自闭症。尽管其临床意义，很少有人知道RRB的病理生理。临床和动物模型研究都将重复行为与基因突变联系起来，并且许多特定的遗传综合征具有RRB作为临床表型的一部分。遗传风险因素可能与经验因素相互作用，导致自闭症特征的极端重复行为表型表达。很少有自闭症患者的研究将MRI结果与RRB联系起来，也没有尝试将RRB与死后组织结果联系起来。然而，现有的临床和动物模型数据表明，在RRB表达中，皮质-基底神经节回路的功能和结构改变。我们自己的研究指出，在动物模型中，间接基底神经节通路的活性降低与高水平的重复行为有关。这些发现如果可以推广，就提出了具体的治疗靶点。这些，也许还有其他的，对皮质基底神经节回路的扰动是由特定的分子机制介导的（例如，基因表达改变），导致长期的、依赖经验的神经适应，从而启动和维持重复行为。需要更多的研究来揭示这种机制。在物质滥用、强迫症、图雷特综合征、帕金森病和痴呆等领域的工作有望为确定自闭症中与RRB相关的神经生物学机制提供关键的发现。此外，鸟鸣、习惯形成和程序学习等领域的基础研究可能会提供更多急需的线索。了解重复行为的病理生理学对于确定自闭症患者的新治疗靶点和策略至关重要。
Restricted, repetitive behaviors (RRBs) are heterogeneous ranging from stereotypic body movements to rituals to restricted interests. RRBs are most strongly associated with autism but occur in a number of other clinical disorders as well as in typical development. There does not seem to be a category of RRB that is unique or specific to autism and RRB does not seem to be robustly correlated with specific cognitive, sensory or motor abnormalities in autism. Despite its clinical significance, little is known about the pathophysiology of RRB. Both clinical and animal models studies link repetitive behaviors to genetic mutations and a number of specific genetic syndromes have RRBs as part of the clinical phenotype. Genetic risk factors may interact with experiential factors resulting in the extremes in repetitive behavior phenotypic expression that characterize autism. Few studies of individuals with autism have correlated MRI findings and RRBs and no attempt has been made to associate RRB and post-mortem tissue findings. Available clinical and animal models data indicate functional and structural alterations in cortical-basal ganglia circuitry in the expression of RRB, however. Our own studies point to reduced activity of the indirect basal ganglia pathway being associated with high levels of repetitive behavior in an animal model. These findings, if generalizable, suggest specific therapeutic targets. These, and perhaps other, perturbations to cortical basal ganglia circuitry are mediated by specific molecular mechanisms (e.g., altered gene expression) that result in long-term, experience-dependent neuroadaptations that initiate and maintain repetitive behavior. A great deal more research is needed to uncover such mechanisms. Work in areas such as substance abuse, OCD, Tourette syndrome, Parkinson’s disease, and dementias promise to provide findings critical for identifying neurobiological mechanisms relevant to RRB in autism. Moreover, basic research in areas such as birdsong, habit formation, and procedural learning may provide additional, much needed clues. Understanding the pathophysioloy of repetitive behavior will be critical to identifying novel therapeutic targets and strategies for individuals with autism.
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