Among the central goals of stress neurobiology research is to understand the mechanisms by which stressors change neural circuit function to precipitate or exacerbate psychiatric symptoms. Yet despite decades of effort, psychiatric medications that target the biological substrates of the stress response are largely lacking. We propose that the clinical advancement of stress response-based therapeutics for psychiatric disorders may be hindered by ‘hidden variables’ in stress research, including considerations of behavioral study design (stressors and outcome measures), individual variability, sex differences, and the interaction of the body’s stress hormone system with endogenous circadian and ultradian rhythms. We highlight key issues and suggest ways forward in stress neurobiology research that may improve the ability to assess stress mechanisms and translate preclinical findings.

应激神经生物学研究的核心目标之一是了解应激源改变神经回路功能以促成或加剧精神症状的机制。然而，尽管经过数十年的努力，针对应激反应的生物基础的精神科药物仍然很缺乏。我们认为，基于压力反应的精神疾病疗法的临床进展可能会受到压力研究中“隐藏变量”的阻碍，包括对行为研究设计（压力源和结果测量）、个体差异、性别差异以及性别差异的相互作用的考虑。体内的应激激素系统具有内源性昼夜节律和超昼夜节律。我们强调关键问题并提出压力神经生物学研究的前进方向，这可能会提高评估压力机制和转化临床前研究结果的能力。