Institute of Biotechnology, University of Cambridge, Cambridge, UK.
Expert Rev Mol Diagn. 2011 Sep;11(7):721-33. doi: 10.1586/erm.11.61.
Schizophrenia and major depressive disorder are severe mental illnesses, which are diagnosed based on patient interviews. Despite many years of extensive research, scientists have not yet fully deciphered how genetic and environmental factors interact to cause these illnesses. Biomarker tests that can confirm diagnoses of schizophrenia or depression are only now beginning to emerge, and could result in a paradigm shift in this field. These tests will help to evaluate the validity of animal models of psychiatric disorders, which are currently characterized based on behavioral measures. In this article, we explore the utility of translating both behavioral and molecular phenotypes of such models to the corresponding human disorders. This approach may help to provide construct validity to animal models and could lead to the identification of models corresponding to defined subtypes of neuropsychiatric disorders based on molecular profiles. Here, we review the molecular and biological pathway alterations that have been found in animal models of schizophrenia and depression and focus on those that are mirrored by similar abnormalities in human patients. Such parallels may provide insight into the validity of specific animal models and therefore help to provide more valuable and accurate tools for the discovery and development of improved psychiatric medications.
精神分裂症和重度抑郁症是严重的精神疾病,其诊断基于患者访谈。尽管经过多年的广泛研究,科学家仍未完全破解遗传和环境因素如何相互作用导致这些疾病。目前,能够确认精神分裂症或抑郁症诊断的生物标志物测试才刚刚开始出现,这可能会彻底改变这一领域。这些测试将有助于评估精神障碍动物模型的有效性,这些模型目前主要基于行为测量来进行特征描述。在本文中,我们探讨了将这些模型的行为和分子表型转化为相应的人类疾病的效用。这种方法可能有助于为动物模型提供结构有效性,并可能导致根据分子谱识别与特定神经精神障碍亚型相对应的模型。在这里,我们回顾了在精神分裂症和抑郁症动物模型中发现的分子和生物学途径改变,并重点关注了那些在人类患者中存在类似异常的改变。这些相似之处可能为特定动物模型的有效性提供一些见解,并有助于为发现和开发更好的精神药物提供更有价值和准确的工具。