Brain–skin axis: what the research says

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"The skin is a mirror of what you experience." It is a phrase you read everywhere, and one that is usually not accompanied by anything explaining why. In recent years, however, research has reconstructed with considerable precision the biological steps connecting the brain to the skin, and they are worth describing — including the points where the evidence is still weak.

This article is based primarily on a review published in October 2025 in JAAD International, which selected 159 studies out of 814 reviewed, and on research published in 2025 in Science Immunology. You will find all the references at the end.

A methodological premise that the review authors state explicitly: much of what we know comes from animal models and in vitro studies. Human studies are mostly small, observational, and cross-sectional, and there are few controlled trials. The mechanisms described below are therefore well characterized at the biological level, but not all have been confirmed with the same degree of certainty in humans.

Article written by Elisa Avalle, founder of LeLang Skin Care and a dermocosmetics specialist. Cover image generated with the support of artificial intelligence.

First of all: where the nerves are located in the skin

The connection between the brain and the skin is not a metaphor; it is an anatomical structure — and understanding it makes everything else much more concrete.

Cutaneous innervation is of two types. That of the autonomic nervous system reaches the arrector pili muscles and blood vessels: it is responsible for goosebumps and vasoconstriction in the cold, that is, phenomena we do not consciously control. Sensory innervation consists of afferent fibers that originate from two plexuses, one deep in the dermis and one just beneath the epidermis.

From these plexuses branch free nerve endings and encapsulated nerve endings — Pacinian corpuscles in the deep dermis, Meissner's corpuscles in the dermal papillae, followed by Krause and Ruffini corpuscles. Encapsulated endings are far fewer than free ones.

Two details that change how you read everything that follows.

The first: free nerve endings are also found in the epidermis, not only in the dermis. In other words, the nerve extends all the way to the skin's most superficial layer — and this is the anatomical foundation of neurocosmetics. You do not need to reach the dermis to encounter a nerve ending.

The second: the fibres are not distributed uniformly. They are extremely numerous on the face and extremities, and relatively sparse on the back. The face is not more reactive than the rest of the body because of suggestion: it is the most densely innervated area we have.

Finally, the basal layer contains Merkel cells, mechanoreceptors that respond to vibrational stimuli. They have extensions that infiltrate between the keratinocytes and register the slightest change in the epidermal structure, transmitting it to the nerve ending with which they form the so-called Merkel complex.

The skin has its own stress axis

The most interesting point is also the least well known. There is the classic hypothalamic-pituitary-adrenal axis: under stress, the hypothalamus releases CRH, the pituitary produces POMC, from which ACTH and MSH are derived, and the adrenal glands respond with cortisol, catecholamines and androgens.

But there is also a peripheral HPA axis within the skin itself. Keratinocytes, mast cells, sebocytes and melanocytes locally produce the same hormones, replicating the central stress response on a smaller scale and regulating inflammation in an autocrine and paracrine manner.

In other words, the skin does not simply endure the stress coming from the brain: it produces its own version locally.

What CRH does when it reaches the skin

CRH is the most direct link between psychological stress and skin inflammation, acting on several fronts simultaneously.

• It activates mast cells, which release histamine, TNF-α and IL-6, increasing vascular permeability and facilitating the infiltration of immune cells.
• It stimulates sebocytes to produce IL-6 and IL-8, a mechanism implicated in acne and seborrhoeic dermatitis.
• It increases matrix metalloproteinases, the enzymes that break down the structural proteins of the dermis: hence the slower healing, increased skin fragility and accelerated ageing observed under chronic stress.
• It triggers a vicious cycle: it promotes the local synthesis of cortisol, which in turn reinforces the release of CRH.

This last point explains why skin stress, once triggered, tends to maintain itself.

Cortisol and the barrier

The review is detailed on cortisol: it increases free radicals and reduces epidermal lipids, hyaluronic acid, type 1 collagen, and stratum corneum hydration. All these factors weaken the skin barrier and increase vulnerability to irritation, dryness, and infections.

Catecholamines - adrenaline and noradrenaline - do something different: they cause vasoconstriction, reducing cutaneous blood flow. This leads to hypoxia, oxidative stress, and delayed healing. They also stimulate sebum production, which is the other link between stress and acne.

This second point calls for an anatomical clarification, because it makes clear how the connection actually works: the sebaceous gland is not innervated. No nerve reaches it - it is surrounded by blood vessels, not nerve fibers. Stress does not "talk" to it through the nervous system: it reaches it hormonally, through the bloodstream. This is why the effect on sebum is observed over weeks rather than within a few hours, unlike redness, which can appear within a few seconds precisely because the blood vessels are innervated.

A detail relevant to many women: adrenal androgens such as DHEA are converted locally in the skin into testosterone and dihydrotestosterone, which act on sebocytes, keratinocytes, and fibroblasts. A systemic hormonal imbalance is not necessary for the skin to be exposed to more androgens: it is enough for it to produce them locally.

The 2025 discovery: when stress shuts down defenses

This brings us to the latest and most surprising study, published in Science Immunology in 2025.

The researchers showed that psychological stress impairs the response to Staphylococcus aureus through an unexpected pathway: dermal fibroblasts. Under stress, adrenergic signaling activates TGFβ, which in turn blocks fibroblasts’ ability to produce cathelicidin, an antimicrobial peptide that the skin uses as a first-line defense. The bacterium finds free rein.

The confirmation is that blocking adrenergic signaling or TGFβ restores normal defense: the mechanism is not a correlation but a causal chain.

However, this is a study using a mouse model. It is an important result, but it has not yet been shown that it works the same way in humans. I’m writing this because the difference matters, and because in beauty communications, results in mice are often presented as if they directly concerned people.

The 2025 review nevertheless confirms the general picture on a broader basis: chronic stress reduces the production of antimicrobial peptides through cortisol, catecholamines, and neuropeptides, and this deficiency is implicated in atopic dermatitis, psoriasis, and rosacea.

The reference to rosacea is not coincidental. Cathelicidin is the same molecule involved in the mechanism of rosacea together with kallikrein 5, the pathway targeted by actives such as azelaic acid. In other words, stress and rosacea reach the same molecular target from two different directions.

Not just cortisol

For years, popular explanations focused almost exclusively on cortisol. More recent literature presents a more nuanced picture, and it is worth updating it.

Neuropeptides

Substance P and CGRP are released by cutaneous nerve endings and cause mast cell degranulation, vasodilation, and recruitment of immune cells. They are the main causes of what is known as neurogenic inflammation: inflammation that begins in the nerve, not in the immune system. Both also amplify the perception of itching and pain, which explains why the same irritation feels more intense under stress.

This brings us back to the anatomical fact mentioned at the beginning: the nerve endings in the face and extremities are more numerous, and it is in these areas that neurogenic inflammation is most evident. It is no coincidence that reactive skin is especially common on the face.

NGF

Nerve growth factor is produced under stress by keratinocytes, mast cells, and fibroblasts. It helps healing, but its chronic overexpression leads to hyperproliferation, overactivity of the sebaceous glands, and barrier disruption, contributing to stress-induced skin aging.

Oxytocin and sleep

Two less predictable elements. Acute stress increases oxytocin, which has a protective effect; chronic stress reduces it, resulting in slower healing and more inflammation. And elevated nighttime cortisol suppresses melatonin, disrupting the circadian rhythm and increasing the production of pro-inflammatory mediators.

In other words: sleeping poorly is not an accessory factor; it is part of the mechanism.

The skin speaks to the brain

The newer aspect concerns the reverse direction. Cytokines produced by inflamed skin can reach the central nervous system: IL-17 and IL-22 weaken the tight junctions of the blood-brain barrier, facilitating the infiltration of immune cells and sustaining neuroinflammation.

This is the biological reason why people with a chronic skin condition are more likely to experience anxiety and depression - in addition, of course, to the psychological burden of living with it. The two mechanisms compound and reinforce each other.

What a neurocosmetic can really do

Let's get to the question that matters to people who buy cosmetics, and I'll try to answer it without sugarcoating.

A review published in 2026 in the journal Cosmetics offers a useful definition: neurocosmetics are products formulated to interact with cutaneous neurosensory, neuroimmune, or neuroendocrine pathways relevant to the brain-skin axis. It also adds a distinction rarely seen on packaging: this definition should be kept separate from generic marketing claims about psychological or emotional benefits, which may reflect expectation, sensory pleasure, or the context of use more than any actual modulation of the cutaneous nervous system.

In other words: when a cream "reduces stress," much of the effect may come from the fragrance, texture, and the act of taking five minutes for yourself. This is not deceptive - the perceived well-being is real - but it is not the same as acting on a receptor.

The same review explicitly addresses the ethical issues surrounding claims about mood and stress in cosmetic products. As a company, this is an area where I prefer to take a cautious approach: a cosmetic can improve the appearance and comfort of the skin and make a moment of the day more enjoyable. It does not treat anxiety or replace medical or psychological support.

That said, there are active ingredients with documented mechanisms. The Tephrosia purpurea extract is among the most studied in this field - and transparency matters here too: the available efficacy data come from the manufacturer's tests, not independent studies. The general concept is explained in the article on neurocosmetics.

What this means in practice

If research shows that stress affects the barrier, lipids, hyaluronic acid, collagen, and antimicrobial peptides, the practical consequences are less spectacular than marketing would have us believe, but more solid.

1. Protecting the barrier comes first, because it is the target on which cortisol's effects are best documented.
2. Simplify during difficult periods. Skin with reduced antimicrobial defenses and a weakened barrier is not the right time to introduce acids and retinoids.
3. Sleep is part of the routine, not an afterthought.
4. Don't expect a cosmetic product to solve the cause. If stress is chronic, the skin is the symptom.

The practical side — which products, in what order, and with which active ingredients — can be found in the article on reactive skin, cortisol, and barrier routine. If, instead, you want to understand why your skin has become reactive, the analysis of the causes of skin sensitivity is the starting point.

What we still don't know

I’ll end where I began, because it seems to me the most honest part.

The review authors point out three limitations: most of the evidence comes from animal or in vitro models; human studies are small and observational, so they cannot establish causal links; and almost all of them have examined one system at a time, providing little information about how neuroimmune and endocrine pathways actually interact.

The research is heading in that direction, the mechanisms are plausible and partly demonstrated. But we are far from being able to say that a cream changes your stress axis. When someone promises this, they are going beyond what the evidence allows.