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A shared neuroimmune pathway involving CRH, mast cells, and Th17 cells may underlie the link between psoriatic arthritis and depression, offering new targets.

Depression is common in patients with psoriatic arthritis (PsA), with a systematic review finding a prevalence between 9% and 22%. A review article published in Biomedicine & Pharmacotherapy reports that PsA and depression may share immunoinflammatory mechanisms.

“By systematically summarizing the research results from recent years, we find that PsA and depression are interrelated and point to a common cause of inflammation,” wrote a research team from Beijing, China. “Both PsA and depression exhibit pathological changes characterized by inflammatory responses driven by key immune cells, such as mast cells (MCs) and Th17 cells.”

The release of proinflammatory cytokines, including tumor necrosis factor–α, interleukin-1, interleukin-6, and interleukin-17, exacerbate both conditions, the researchers wrote. Additionally, the pathogenesis of PsA and depression involves specific neuroendocrine hormones and neurotransmitters, including adrenocorticotropin-releasing hormone (CRH), adrenocorticotropin, cortisol, monoamine neurotransmitters, and brain-derived neurotrophic factor, according to the article.

“Notably, the signaling pathway involving CRH, MCs, and Th17 cells plays a crucial role in linking PsA with depression; thus, this pathway may help clarify their connection,” the authors wrote.

The pathway may also offer new targets for the treatment of patients with PsA and depression. Inhibiting CRH and its receptors reduced inflammation and eased joint symptoms in previous studies. Other investigations have suggested that the altered regulation of stress hormones associated with depression is caused by elevated secretion of hypothalamic CRH.

“These findings suggest that inhibiting CRH and its receptors may have therapeutic potential for treating patients with PsA and depression,” the researchers wrote.

MCs, meanwhile, are essential in mediating the neuroimmune response between PsA and depression. With biologic therapies focusing on abnormal interleukin-17 signaling now common for the treatment of PsA, a multitarget drug based on the CRH-MC-TH17 pathway represents a potential research direction.

“The neuroimmune response mediated by the CRH-MC-Th17 pathway is a significant contributor to the vicious cycle between PsA and depression, providing both a theoretical foundation and novel therapeutic targets for their treatment,” the authors wrote. “Further investigations into the shared neuroimmune response alterations associated with PsA and depression through the CRH-MC-Th17 pathway are essential for advancing the identification of new drug targets and liberating patients from this detrimental cycle.”