The brain-skin connection: A narrative review of neuroendocrine and immune pathways

Chang Chuen Tan; Krystal Valerie Soh; Eugene Wang; Ellie Ci-En Choi

doi:10.1016/j.jdin.2025.10.008

The brain-skin connection: A narrative review of neuroendocrine and immune pathways

JAAD Int. 2025 Oct 28:24:112-123. doi: 10.1016/j.jdin.2025.10.008. eCollection 2026 Feb.

Authors

Chang Chuen Tan¹, Krystal Valerie Soh¹, Eugene Wang¹, Ellie Ci-En Choi^{1

2}

Affiliations

¹ Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
² Division of Dermatology, Department of Medicine, National University Hospital, Singapore.

Abstract

Background: Stress is a well-established trigger for many skin diseases; yet its biological mechanisms are poorly understood.

Objective: To synthesize current evidence on brain-skin pathways, emphasizing key mediators and feedback loops that explain how stress exacerbates skin disease and vice versa.

Methods: A comprehensive search through August 25, 2025, using terms related to brain-skin communication, psychodermatology, and stress-related pathophysiology included both in-vivo and in-vitro animal and human studies.

Results: 159 articles were included and synthesized. Key findings highlight a bidirectional brain-skin axis involving the brain and pituitary, adrenal glands, peripheral nerves and skin. Stress triggers the brain and pituitary to release corticotropin-releasing hormone and adrenocorticotropic hormone; adrenal glands to secrete cortisol, catecholamines and androgens; and peripheral nerves to release neuropeptides such as Substance P and calcitonin gene-related peptide. These are implicated in skin inflammation while skin-derived mediators (cytokines, chemokines, neurotrophins) may disrupt and cross the blood-brain barrier, amplifying neuroinflammation, and psychiatric symptoms. Together, these form a self-sustaining feedback perpetuating both dermatologic and psychological disease.

Limitations: Much of the mechanistic understanding is derived from animal models; high-quality human data remain limited.

Conclusion: Understanding the brain-skin axis identifies therapeutic targets and guides future research on stress-related skin disease.

Keywords: Substance P; acne; atopic dermatitis; bidirectional communication; brain-skin axis; cytokines; hypothalamic-pituitary-adrenal axis; immune pathways; inflammation; mental health; neuroendocrine; neuroimmune; psoriasis; psychodermatology; skin barrier; stress.