Bidirectional Brain–Skin Signalling in Skin Health, Pigmentation and Ageing

This research project is a PRISMA-ScR scoping review designed to map and synthesise the current evidence on the bidirectional brain–skin axis in skin health, pigmentation and ageing. The review will examine how the brain, central nervous system, neuroendocrine signalling, neuroimmune pathways and psychological states may influence skin biology, and conversely, how cutaneous inflammation, barrier dysfunction, itch, pain, pigmentation disorders and visible skin disease may affect brain function, mood, stress biology and neuroimmune responses. The purpose of this review is to clarify the biological and clinical relationship between the brain and the skin by identifying the key mechanisms through which brain-derived or brain-regulated signals interact with skin cells, including epidermal keratinocytes, melanocytes, dermal fibroblasts and extracellular matrix components such as collagen and elastin. Particular attention will be given to neuroendocrine mediators such as cortisol, corticotropin-releasing hormone, adrenocorticotropic hormone and glucocorticoids; neurotransmitters including dopamine, serotonin, noradrenaline, acetylcholine, GABA and glutamate; and neuropeptides such as substance P, calcitonin gene-related peptide, α-melanocyte-stimulating hormone, β-endorphin and oxytocin. The review will explore whether changes in brain function and neurochemical balance associated with ageing, chronic stress, depression, anxiety and post-traumatic stress disorder are linked to measurable changes in skin health. These may include altered epidermal barrier function, impaired keratinocyte differentiation, melanocyte activation, pigmentation changes, dermal fibroblast senescence, collagen degradation, extracellular matrix remodelling, delayed wound healing, oxidative stress, inflammation and accelerated skin ageing. Where available, the review will also map evidence relating to specific brain regions or neural systems, including the hypothalamus, amygdala, hippocampus, prefrontal cortex, insula, limbic system and dopaminergic reward pathways. The project will also investigate the reverse direction of signalling: how the skin may communicate with the brain through sensory nerves, cytokines, immune mediators, neuropeptides, itch and pain pathways, inflammatory skin disease, barrier disruption and psychosocial distress related to visible skin conditions. This aspect of the review is important because skin is not only a passive target of brain-derived stress signals; it is also an active neuroimmunoendocrine organ capable of generating local hormones, cytokines, neuropeptides and sensory signals that may influence emotional regulation, stress responses and brain activity. A scoping review methodology is appropriate because the evidence base is broad, interdisciplinary and mechanistically diverse. Relevant literature will be identified through structured searches of PubMed using modular search strategies covering brain–skin axis terminology, neuroendocrine and neuroimmune signalling, neurotransmitters, psychological stress, depression, anxiety, PTSD, ageing, gene expression, keratinocytes, melanocytes, fibroblasts, collagen, pigmentation, barrier function and skin ageing. Eligible studies may include human clinical studies, observational studies, experimental studies, animal models, in vitro skin-cell studies, transcriptomic or molecular studies, and relevant reviews that provide mechanistic or conceptual insight. The review will follow the PRISMA extension for Scoping Reviews, with transparent reporting of search strategies, eligibility criteria, screening process, study selection and evidence mapping. Extracted data will include study type, population or model, brain-related exposure or mechanism, skin-related outcome, biological mediator, cell type, molecular pathway, disease or ageing context, and direction of signalling. Evidence will be organised into major mechanistic domains, including HPA-axis signalling, autonomic nervous system signalling, neuropeptide activity, neurotransmitter-related skin-cell regulation, inflammatory and cytokine pathways, oxidative stress and senescence, pigmentation biology, epidermal barrier regulation, fibroblast–collagen remodelling and skin-to-brain sensory or immune feedback. The expected outcome of this project is a comprehensive evidence map showing how the brain and skin communicate through overlapping neuroendocrine, neuroimmune, sensory and cellular pathways. The review is expected to identify well-supported mechanisms, such as stress-related HPA-axis activation and glucocorticoid effects on barrier function, inflammation, wound healing and extracellular matrix regulation. It is also expected to highlight emerging or less established areas, such as the possible influence of dopamine, serotonin and reward-pathway changes on skin ageing, melanocyte activity, fibroblast biology and inflammatory skin responses. A further expected outcome is the development of a clearer conceptual framework for the brain–skin axis in ageing and skin health. This framework may help explain how chronic psychological stress, mood disorders, neurochemical changes and brain ageing could contribute to visible and biological skin ageing through inflammation, oxidative stress, altered cell signalling, impaired repair mechanisms and extracellular matrix degradation. It may also help clarify how inflammatory or distressing skin conditions may feed back to the brain, contributing to anxiety, depression, altered stress responses or reduced quality of life. This review will not aim to prove a single causal pathway, because the current evidence is likely to vary in quality, model system and clinical relevance. Instead, the project will identify the breadth of evidence, map key mechanisms, clarify knowledge gaps and propose priorities for future research. These may include the need for more human translational studies, better integration of dermatological outcomes with neuroendocrine and neuroimaging markers, more studies on neurotransmitter effects in skin cells, and more rigorous investigation of pigmentation, collagen remodelling and skin ageing in relation to brain health and psychological states. Overall, this research project aims to advance understanding of the skin as an active neuroimmunoendocrine organ and to position skin health and ageing within a broader biological network involving the brain, stress systems, mood regulation, immune signalling and cellular ageing. Its findings may be relevant to dermatology, aesthetic medicine, psychodermatology, ageing science, wellbeing medicine and future integrative approaches to skin health.