Review Outlines Role of Brain-Skin Connection in Psoriasis Pathogenesis

In a recently published review, researchers examined the brain-skin connection and the pathogenesis of psoriasis, focusing on the serotonergic system.

In a recently published review, researchers examined the brain-skin connection and the pathogenesis of psoriasis, focusing on the serotonergic system.

Currently, psoriasis affects around 125 million people worldwide and its pathogenesis is attributed to a combination of genetic and environmental factors. Specifically, an interaction between innate immune cells, adaptive immune cells, and keratinocytes results in an inflammatory process, which manifests in the skin.

“To understand psoriasis, it is essential to comprehend the processes underlying the skin immunity and neuroendocrinology,” researchers said.

The brain-skin connection has been widely investigated as the skin has a “fully functional peripheral equivalent of the hypothalamic-pituitary-adrenal axis (HPA).”

In addition, it has been documented serotonin acts as a mediator between the skin and the neuroendocrine system. Serotonin also contributes to the effects of psychological stress on the disruption of skin homeostasis and stress has been deemed an aggregator of psoriasis.

“New evidence suggests that in addition to the model of immune-pathogenesis of psoriasis, other components such as neuropeptides released by the cutaneous nervous system and the skin microbiome may also be mediators in the process,” researchers said.

Serotonin aids in cell proliferation, regulation of leukocyte chemotaxis, cytokine production and activation of T cells, among other functions. The receptors for serotonin are 5-HT receptors, which have an important role in regulating immune signaling. In the skin, 5-HT is involved in inflammation and immunomodulation and “is also a main factor in depression, which is one of the main comorbidities of psoriasis.” Studies have found the 5-HT transporter is differently expressed in skin of patients with psoriasis compared with healthy skin.

Both the skin and the brain have a common origin, deriving from one of the 3 primary germ layers of the embryo. “The neuroendocrine function of the skin relies on its capacity to communicate with the central neuroendocrine system and to regulate local homeostasis, by producing and/or releasing hormones, neuropeptides, neurotransmitters and other bioregulators,” researchers said.

When it comes to the genetic basis of psoriasis, researchers note disease concordance is higher in monozygotic twins than in dizygotic twins.

“The brain—skin connection helps explain why psychological stress can have effects on skin, including the development or exacerbation of skin diseases such as psoriasis, atopic dermatitis and eczema,” researchers conclude. To better define prognoses and develop personalized medicine for patients with psoriasis, researchers suggest data from large-scale studies ought to be combined with individual genetic profiles.


Martins A M, Ascenso A, Ribeiro HM, et al. The brain—skin connection and the pathogenesis of psoriasis: A review with a focus on the serotonergic system. Cells. 2020; 9(4):796. doi: 10.3390/cells9040796.