Psoriasis is a chronic inflammatory disease of the skin that affects between 2-3% of Americans. It is characterized by erythematous, scaling, infiltrated plaques and histology that shows a markedly hyperproliferative epithelium (acanthosis) with infiltration of neutrophils and CD4+ (helper) and CD8+ (cytotoxic/suppressor) lymphocytes, as well as growth and dilation of blood vessels in the papillary dermis with CD4+ lymphocytes. Cytokines (small molecular weight messenger proteins) produced by T helper (Th)1 and Th17 lymphocytes, antigen presenting cells, and leukocytes have been implicated as being critical to the development of lesions. The condition is chronic, persistent and difficult to treat. Although not fatal, psoriasis can involve almost the whole body surface, typically requiring lifelong treatment and, on occasion, may be a source of significant morbidity. A growing literature suggests that the disease also is associated with higher rates of cardiovascular disease and metabolic syndrome, suggesting that inflammation is not only localized to skin. In many patients, psychological or life stress precedes onset of disease flares. Other literature suggests that stress is associated with increased production of many of the proinflammatory cytokines involved in psoriasis, including interleukin (IL)-6 and tumor necrosis factor (TNF)-1. Psoriasis patients commonly report significant reductions in quality of life, as well as social stigmatization, increased rates of anxiety and depression, and increased thoughts of suicide. The increased psychological distress associated with this skin disease may well be amplified by the process of inflammation itself, as proinflammatory cytokines are currently hypothesized to induce depression and anxiety. Thus, psoriasis appears to have a strong psychoneuroimmunological component to it, such that signals from the brain may exacerbate disease, and the disease itself may induce psychological distress. Psoriasis patients may well benefit from low-cost, adjunctive psychological interventions that are intended to decrease psychological distress, but which may also ameliorate the skin disease and inflammatory processes by interrupting the feedback loop between the stress response and psoriatic flares. In the proposed randomized clinical trial, we will examine the effects of Mindfulness Based Stress Reduction (MBSR) versus a psychoeducational treatment called Living Well on immunological markers of inflammation and keratinocyte proliferation, psoriasis severity, and psychological well-being in a population of patients reporting high stress levels who suffer from mild-moderate psoriasis. Our immunological markers include examination of relevant cells and cytokines in both lesional and normal skin biopsies, as well as monitoring blood cytokine levels. PUBLIC HEALTH RELEVANCE: Psoriasis is an inflammatory skin disease, and may also be a systemic condition associated with increased prevalence of metabolic syndrome;it affects millions of individuals in the US and is associated with significant heath care costs estimated at approximately $4.3 billion/year. Stress is frequently associated with flares in disease activity, and psoriasis patients commonly suffer from high rates of psychological distress, including depression, anxiety, and social isolation. In the proposed randomized control trial, we will examine the low cost, adjunctive intervention Mindfulness Based Stress Reduction (MBSR) for patients reporting high stress levels;outcomes include changes in inflammatory processes in the skin;cytokine levels in blood;disease severity;and psychological well-being.