Hidden variables in stress neurobiology research

Ashley L. Holloway, Talia N. Lerner*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)9-17
Number of pages9
JournalTrends in Neurosciences
Issue number1
StatePublished - Jan 2024


  • behavior
  • circadian rhythm
  • hypothalamic–pituitary–adrenal (HPA) axis
  • individual differences
  • psychiatric disorders
  • sex differences

ASJC Scopus subject areas

  • General Neuroscience


Dive into the research topics of 'Hidden variables in stress neurobiology research'. Together they form a unique fingerprint.

Cite this