The impacts of trauma and stress on orexin expression and signalling: A systematic review

Orexins are excitatory hypothalamic neuropeptides which modulate various stress-related physiological functions. This systematic review aims to evaluate the current literature on the impacts of trauma and stress on orexin expression and signalling.

A systematic review of primary research was conducted using Embase, PsycInfo, MEDLINE, and PubMed databases from inception to December 2025, following PRISMA criteria. Our search strings included keywords related to trauma, stress, posttraumatic stress disorder (PTSD), and orexins. Both preclinical and clinical studies evaluating the impacts of trauma and stress on orexin expression and signalling were included.

In preclinical studies (n = 6), acute stress is associated with increased orexin neuronal activation and concentration (1.55-fold increase, p< 0.05), as well as increased orexin receptor expression in the posterior hypothalamus (1.3-fold increase, p<0.01). Chronic stress and PTSD is associated with increased orexin receptor responsivity (t = 3.51, p= 0.011). Childhood trauma is associated with decreased orexin receptor 1 (OX₁ receptor) expression in the hypothalamus (p< 0.05) and amygdala (2-fold decrease, p<0.05). In a clinical study, childhood trauma was associated with increased plasma orexin-B concentration and Major Depressive Disorder (p < 0.001).

Acute trauma exposure and stress are associated with increased orexin expression, and chronic trauma exposure and PTSD are associated with increased receptor responsivity and decreased receptor expression. The research strategic priority is to replicate these findings in clinical samples not taking medication, and examine differences by age, sex, and type and length of trauma exposure.