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

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

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

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.

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.

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

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