BACKGROUND The study of depression in humans depends on animal models that attempt to mimic specific features of the human syndrome. Most studies focus on one or a few behavioral domains, with time and practical considerations prohibiting a comprehensive evaluation. Although machine learning has enabled unbiased analysis of behavior in animals, this has not yet been applied to animal models of psychiatric disease. METHODS We performed chronic social defeat stress (CSDS) in mice and evaluated behavior with PsychoGenics' SmartCube, a high-throughput unbiased automated phenotyping platform that collects >2000 behavioral features based on machine learning. We evaluated group differences at several times post-CSDS and after administration of the antidepressant medication imipramine. RESULTS SmartCube analysis after CSDS successfully separated control and defeated-susceptible mice, and defeated-resilient mice more resembled control mice. We observed a potentiation of CSDS effects over time. Treatment of susceptible mice with imipramine induced a 40.2% recovery of the defeated-susceptible phenotype as assessed by SmartCube. CONCLUSIONS High-throughput analysis can simultaneously evaluate multiple behavioral alterations in an animal model for the study of depression, which provides a more unbiased and holistic approach to evaluating group differences after CSDS and perhaps can be applied to other mouse models of psychiatric disease.

中文翻译：

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慢性社会失败压力后多维行为改变的计算分析

背景对人类抑郁症的研究依赖于试图模拟人类综合征特定特征的动物模型。大多数研究集中在一个或几个行为领域，时间和实际考虑禁止全面评估。尽管机器学习能够对动物的行为进行公正的分析，但这尚未应用于精神疾病的动物模型。方法 我们对小鼠进行慢性社交失败压力 (CSDS)，并使用 PsychoGenics 的 SmartCube 评估行为，SmartCube 是一种高通量无偏自动表型分析平台，基于机器学习收集超过 2000 个行为特征。我们在 CSDS 后和服用抗抑郁药物丙咪嗪后多次评估了组间差异。结果 CSDS 成功分离对照小鼠和易受挫败的小鼠后的 SmartCube 分析，并且挫败恢复力的小鼠更类似于对照小鼠。我们观察到 CSDS 效应随着时间的推移而增强。通过 SmartCube 评估，用丙咪嗪治疗易感小鼠诱导了 40.2% 的失败易感表型恢复。结论 高通量分析可以同时评估用于研究抑郁症的动物模型中的多种行为改变，这为评估 CSDS 后的群体差异提供了一种更加公正和整体的方法，也许可以应用于其他精神疾病小鼠模型。通过 SmartCube 评估，用丙咪嗪治疗易感小鼠诱导了 40.2% 的失败易感表型恢复。结论 高通量分析可以同时评估用于研究抑郁症的动物模型中的多种行为改变，这为评估 CSDS 后的群体差异提供了一种更加公正和整体的方法，也许可以应用于其他精神疾病小鼠模型。通过 SmartCube 评估，用丙咪嗪治疗易感小鼠诱导了 40.2% 的失败易感表型恢复。结论 高通量分析可以同时评估用于研究抑郁症的动物模型中的多种行为改变，这为评估 CSDS 后的群体差异提供了一种更加公正和整体的方法，也许可以应用于其他精神疾病小鼠模型。