Psoriasis vulgaris has established associations with psychiatric conditions such as depression, anxiety, and chronic stress. This review aims to evaluate current theories and evidence regarding the role of proinflammatory cytokines and neuropeptides in connecting systemic inflammation, psychological stress, and inflammatory skin diseases, namely psoriasis. A literature review was conducted to analyze studies that explore the connections between psoriasis, psychiatric conditions, and biological mediators, including inflammatory cytokines [interferon (IFN)-γ, interleukin (IL)-1, IL-2, IL-6, IL-12, tumor necrosis factor (TNF)-α, IL-22, IL-17], neuropeptides [calcitonin gene-related peptide (CGRP), substance P (SP), and vasoactive intestinal peptide (VIP)], as well as the hypothalamic-pituitary-adrenal (HPA) axis. Existing literature indicates that psychiatric state can influence cutaneous conditions through immune, neural, and endocrine mediators. The elevated rates of anxiety and depression observed in psoriasis patients are likely due to both the inflammatory process itself and the chronic stress associated with disease management, highlighting the importance of managing stress, and addressing mental health to improve clinical outcomes. While the literature suggests proinflammatory cytokines and neuropeptides may be key links between systemic inflammation, psoriasis, and psychiatric comorbidities, further research is necessary to continue to elucidate physiological mechanisms and explore the potential for new treatment modalities.