The Brain-Skin Axis in Psoriasis-Psychological, Psychiatric, Hormonal, and Dermatological Aspects

Abstract

Psoriasis is a chronic inflammatory skin disease with systemic manifestation, in which psychological factors play an important role. The etiology of psoriasis is complex and multifactorial, including genetic background and environmental factors such as emotional or physical stress. Psychological stress may also play a role in exacerbation of psoriasis, by dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, sympathetic-adrenal-medullary axis, peripheral nervous system, and immune system. Skin cells also express various neuropeptides and hormones in response to stress, including the fully functional analog of the HPA axis. The deterioration of psoriatic lesions is accompanied by increased production of inflammatory mediators, which could contribute to the imbalance of neurotransmitters and the development of symptoms of depression and anxiety. Therefore, deregulation of the crosstalk between endocrine, paracrine, and autocrine stress signaling pathways contributes to clinical manifestations of psoriasis, which requires multidisciplinary approaches.

Keywords: hormones; psoriasis; psychiatric disorders; psychological stress; psychoneuroimmunology.

Figure 1

Brain–skin axis: association between psoriasis and depression. Stress acts via several pathways to exacerbate psoriasis, via the central and peripheral HPA axes, regulation of cytokine production, and activation of the sympathetic nervous system. The final messengers of the sympathetic nervous system and HPA, norepinephrine and cortisol, can directly engage in regulation of various immune cells to modulate immune responses. Direct action of CRH induces inflammatory responses in psoriasis. CRH and CRH-related peptides can be produced by several cells in the skin and stimulate the local production of cytokines in the skin. By binding to CRH-R on mast cells, CRH induces mast cell degranulation and releases proinflammatory factors, which induces further inflammation in psoriasis. The increase in cortisol levels causes the exacerbation of psoriasis and the activation of Th-17 cells, which leads to an increase in the levels of pro-inflammatory cytokines IL-17, TNF-α contributing to the development and intensification of depressive disorders. Vitamin D₃ (Vit D₃) is synthesized in the skin from its precursor 7-DHC under the influence of UVB and metabolized to its active form, 1,25(OH)₂D₃.