Badowska Dorota M, Brzózka Magdalena M, Chowdhury Ananya, Malzahn Dörthe, Rossner Moritz J
Research Group Gene Expression, Max-Planck-Institute of Experimental Medicine, 37075, Göttingen, Germany,
Eur Arch Psychiatry Clin Neurosci. 2015 Sep;265(6):483-96. doi: 10.1007/s00406-014-0532-6. Epub 2014 Sep 19.
Psychosocial stress-particularly in combination with genetic vulnerability-is a critical environmental risk factor for psychiatric diseases in humans. Isolation rearing (IR) and social defeat (SD) paradigms model psychosocial risk factors in rodents, while enriched environment (EE) protects them from behavioural deficits. Studying the influence of various environmental conditions, e.g., on genetic mouse models can help to dissect the complex gene-environment relationships underlying human psychiatric diseases. Such studies may require analysing multiple mouse cohorts; however, the comparability of behavioural experiments is challenging and often compromised by practical limitations such as group sizes and influences of handling. Therefore, protocol standardization as well as appropriate statistical normalization is necessary to compare different experiments. In this study, we analysed two independent cohorts to compare the behavioural profiles of wild-type male mice subjected to IR and SD. In both cases, EE conditions served as a reference. Multivariate statistics was applied to merge the data from individual measures into broader categories (such as curiosity, anxiety and fear memory) by estimating their calibrated joint effect within a category. Plotting and overlaying these calibrated effect sizes in a single graph allowed intuitive comparison of IR and SD behavioural profiles. This approach allows analysing multiple behavioural tests at once, which is more relevant to psychiatric syndromes than focusing on single behavioural measures. Our method revealed that motivation and fear memory are impaired by both conditions, whereas ambulation and pain sensitivity are affected only by IR and curiosity is mainly diminished upon SD. Thus, IR could be a paradigm of choice in studies focusing on positive symptoms, while SD might be more relevant for negative and cognitive symptoms.
心理社会压力——尤其是与遗传易感性相结合时——是人类精神疾病的一个关键环境风险因素。隔离饲养(IR)和社会挫败(SD)范式模拟了啮齿动物的心理社会风险因素,而丰富环境(EE)则可保护它们免受行为缺陷的影响。研究各种环境条件(例如)对基因小鼠模型的影响有助于剖析人类精神疾病背后复杂的基因-环境关系。此类研究可能需要分析多个小鼠队列;然而,行为实验的可比性具有挑战性,并且常常受到诸如组大小和处理影响等实际限制的影响。因此,为了比较不同的实验,方案标准化以及适当的统计归一化是必要的。在本研究中,我们分析了两个独立的队列,以比较接受IR和SD的野生型雄性小鼠的行为特征。在这两种情况下,EE条件均作为对照。应用多变量统计通过估计类别内的校准联合效应,将个体测量的数据合并为更广泛的类别(如好奇心、焦虑和恐惧记忆)。在单个图表中绘制并叠加这些校准效应大小,可以直观地比较IR和SD的行为特征。这种方法允许一次性分析多个行为测试,这比关注单一行为测量与精神综合征更相关。我们的方法表明,两种条件均会损害动机和恐惧记忆,而移动和疼痛敏感性仅受IR影响,好奇心主要在SD时降低。因此,IR可能是专注于阳性症状研究的首选范式,而SD可能与阴性和认知症状更相关。