School of Arts and Sciences, Health Psychology Program, Massachusetts College of Pharmacy and Health Sciences, Boston, MA, USA.
University of Massachusetts Boston, Boston, MA, USA.
Curr Top Behav Neurosci. 2023;63:241-289. doi: 10.1007/7854_2022_389.
Schizophrenia is a complex neurodevelopmental disorder with as-yet no identified cause. The use of animals has been critical to teasing apart the potential individual and intersecting roles of genetic and environmental risk factors in the development of schizophrenia. One way to recreate in animals the cognitive impairments seen in people with schizophrenia is to disrupt the prenatal or neonatal environment of laboratory rodent offspring. This approach can result in congruent perturbations in brain physiology, learning, memory, attention, and sensorimotor domains. Experimental designs utilizing such animal models have led to a greatly improved understanding of the biological mechanisms that could underlie the etiology and symptomology of schizophrenia, although there is still more to be discovered. The implementation of the Research and Domain Criterion (RDoC) has been critical in taking a more comprehensive approach to determining neural mechanisms underlying abnormal behavior in people with schizophrenia through its transdiagnostic approach toward targeting mechanisms rather than focusing on symptoms. Here, we describe several neurodevelopmental animal models of schizophrenia using an RDoC perspective approach. The implementation of animal models, combined with an RDoC framework, will bolster schizophrenia research leading to more targeted and likely effective therapeutic interventions resulting in better patient outcomes.
精神分裂症是一种复杂的神经发育障碍,目前尚未确定其病因。动物的使用对于揭示遗传和环境风险因素在精神分裂症发展中的潜在个体和相互交叉作用至关重要。一种在动物身上重现精神分裂症患者认知障碍的方法是破坏实验室啮齿动物后代的产前或新生儿环境。这种方法会导致大脑生理学、学习、记忆、注意力和感觉运动领域的一致干扰。利用这种动物模型的实验设计导致了对潜在精神分裂症病因和症状生物学机制的极大改善理解,尽管仍有更多需要发现。通过采用跨诊断方法针对机制而不是关注症状,来确定精神分裂症患者异常行为背后的神经机制,研究和领域标准 (RDoC) 的实施至关重要。在这里,我们使用 RDoC 视角方法描述了几种精神分裂症的神经发育动物模型。动物模型的实施与 RDoC 框架相结合,将增强精神分裂症研究,从而导致更有针对性且可能有效的治疗干预措施,最终改善患者预后。