Serotonergic Mechanisms in Psoriasis

Abstract: Psoriasis is a chronic inflammatory disease with a prevalence in Sweden of 2-3%. Stress worsens psoriasis. Serotonin, a monoamine and a neurotransmitter, is a well-documented signal substance in situations like stress and in regulation of inflammatory processes. Serotonin produces its effects via about 21 receptors (R), of which the most characterized are 5-HT1AR and 5-HT2AR. The amplitude and duration of activation of the serotonergic system is determined by the serotonin transporter protein (SERT). The aim of the thesis is to elucidate the serotonergic mechanisms involved in psoriasis. In the first study there was a decreased expression of 5-HT1AR and an increased 5-HT2AR expression in the involved skin as compared to normal skin. This differential expression concord with their antagonistic effects, 5-HT1AR inhibiting inflammation and 5-HT2AR promoting inflammation. These two receptors could be potential targets for anti-inflammatory therapies in psoriasis. The expression of 5-HT3R was absent in involved skin and evident in the basal epidermis of the non-involved skin. In Study II the expression of SERT was increased in involved skin as compared to non-involved and normal skin and there was co-localization with caspase-3, a key regulator of apoptosis. This indicates that SERT might play a role in regulating apoptosis in inflammatory cells in psoriasis. SERT might thus constitute a valuable therapeutic target. In Study III an increased SERT expression in inflammatory cells in the epidermis was positively correlated to psoriasis severity and to chronic stress. This implicates that SERT expression could be of importance for psoriasis severity and chronic stress. In the last study, a broad population-based cohort study, SSRI use among patients with plaque psoriasis was associated with a decreased need for systemic psoriasis treatment. SSRI may have a protective effect in psoriasis. In conclusion, a role for the serotonergic system was implicated for the chronic inflammation in psoriasis.