STUDY OBJECTIVES: Narcolepsy type 1 (NT1) is a chronic sleep-wake disorder, characterized by a loss of hypocretin production. Unexpectedly, in postmortem tissue of people with NT1, there is a loss of corticotrophin-releasing hormone (CRH) in the paraventricular nucleus. CRH is known as an activator of the hypothalamic-pituitary-adrenal axis in response to stress. This activation results in the release of the stress hormones adrenocorticotropic hormone (ACTH) and cortisol. We hypothesize an altered physiological and psychological stress response in NT1. METHODS: Participants were people with NT1 (n = 14) and matched healthy controls (n = 12). The Trier Social Stress Test for Groups (TSST-G), a validated socially evaluated stress test in controlled settings, induced acute stress. We measured ACTH and cortisol levels in the blood before and at three timepoints after the TSST-G. We also measured subjective stress and heart rate levels. RESULTS: In both groups, acute stress led to increases in ACTH (p = .006), cortisol (p <
.001), heart rate (p <
.001), and subjective stress (p <
.001). Subjectively, people with NT1 experienced more stress than controls (p <
.001). No differences were found in heart rate, cortisol, and ACTH between people with NT1 and controls at any timepoint. Secondary analyses showed that men with NT1 had lower cortisol levels immediately after stress induction than men in the control group (p = .002). CONCLUSIONS: People with NT1 show an increased subjective stress response, but no changes in their endocrine or cardiovascular stress reactivity. Further research is required to determine the impact of reduced CRH production and gender in NT1.