Depression is a chronic disease that affects nearly twice as many women as men, and symptoms can differ by sex. Preclinical models disproportionately use male subjects and test a single behavioral endpoint immediately at the cessation of stress. We conducted variable stress in male and female mice for 6, 28, and 56 days, and measured behavior with a battery chosen to match research domain criteria. To examine individual differences, we generated a composite z score to measure stress susceptibility across behavioral tests. We also tested behavior following a 30-day recovery period to evaluate the duration of the stress effects. Females, but not males, were susceptible to 6 days of variable stress when behavioral testing started 24 h later. If behavioral testing was conducted 30 days later both males and females expressed stress related behaviors. Males and females were stress susceptible to 28 days of variable stress and effects were long lasting. Both sexes habituated to 56 days of variable stress, but anxiety associated measures still showed persistence. Performance on specific behavioral tests was often different between individuals and between sexes, and not all stressed animals were susceptible to all tested behaviors. These studies confirm that behavioral sex differences are detected in response to variable stress, and reveal information about individual differences. Use of a test battery that measures varying endophenotypes can be combined into a single stress susceptibility score as a tool similar to the scales/inventories used for the study of depression in humans. We present these data with the goal of furthering the field's understanding sex differences and how they shape the biology of mood disorders.

中文翻译：

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使用可变压力测试性别差异的极限。

抑郁症是一种慢性疾病，影响的女性人数几乎是男性的两倍，而且症状可能因性别而异。临床前模型不成比例地使用男性受试者，并且在压力停止时立即测试单个行为终点。我们在雄性和雌性小鼠中进行了6天，28天和56天的可变压力，并选择了符合研究领域标准的电池来测量行为。为了检查个体差异，我们生成了一个综合z评分来衡量行为测试中的压力敏感性。我们还测试了30天恢复期后的行为，以评估压力影响的持续时间。当行为测试在24小时后开始时，女性而不是男性易受6天可变压力的影响。如果在30天后进行行为测试，则男性和女性都表达了与压力相关的行为。雄性和雌性易受28天可变压力的影响，效果持久。男女都习惯了56天的压力变化，但是与焦虑相关的措施仍然显示出持久性。个体之间和性别之间，在特定行为测试中的表现通常是不同的，并且并非所有压力大的动物都容易受到所有测试行为的影响。这些研究证实，在对可变压力的反应中，可以检测到行为性别差异，并揭示有关个体差异的信息。可以将用于测量各种内表型的测试电池与单个压力敏感性评分结合起来，作为一种类似于研究人类抑郁症的量表/清单的工具。我们提出这些数据的目的是进一步推动该领域的发展。