Neuropeptides including CGRP, substance P, and VIP may be key biological links between psoriasis, systemic inflammation, and the high rates of depression and anxiety seen in psoriasis patients.
3 neuropeptides identifiedCGRP, substance P, and VIP as potential biological bridges between psoriatic skin inflammation and psychiatric comorbidities through shared neural-immune pathways
What the researchers found
The review identifies three neuropeptides — CGRP, substance P, and VIP — as potential biological links between psoriasis and psychiatric comorbidities. These neuropeptides are active in skin (where they drive inflammation and psoriatic lesion formation) and in the brain (where they influence mood, stress responses, and anxiety circuits).
Inflammatory cytokines elevated in psoriasis (IFN-γ, IL-1, IL-2, IL-6, IL-12, TNF-α, IL-22, IL-17) also cross the blood-brain barrier and affect neurotransmitter systems involved in depression. The HPA stress axis provides a bidirectional pathway where psychological stress can worsen psoriasis and psoriatic inflammation can exacerbate depression and anxiety.
Why it matters
Understanding the biological link between skin inflammation and mental health could transform how psoriasis is treated. If neuropeptides like CGRP and substance P drive both skin disease and mood disorders, targeting these peptides might treat both conditions simultaneously. Current psoriasis treatments that reduce inflammation may already be improving mental health — a benefit that deserves recognition and study.
How the study worked
Narrative literature review analyzing studies on the connections between psoriasis, psychiatric conditions (depression, anxiety), and biological mediators including inflammatory cytokines, neuropeptides (CGRP, substance P, VIP), and the HPA axis.
What this study cannot tell us
This is a narrative review without systematic methodology. The neuropeptide-psychiatry connection in psoriasis is largely theoretical, based on the known activities of these molecules rather than direct studies proving they cause psychiatric symptoms in psoriasis patients. The relative contribution of neuropeptides versus other factors (social stigma, chronic disease burden) to psychiatric comorbidity is unclear.
How to read the evidence
This is a narrative literature review synthesizing existing evidence about neuropeptide roles in psoriasis and psychiatric conditions. While it provides a useful conceptual framework, it does not present new experimental data.
When this study was published
Published in 2025 in Acta Physiologica, this review reflects the current understanding of the neuroimmune basis of psoriasis-psychiatry comorbidity.
The bigger picture
This review sits at the intersection of dermatology, psychiatry, and neuroscience. The concept that neuropeptides serve as molecular bridges between skin disease and brain function aligns with the growing recognition of psychodermatology as a discipline. As anti-CGRP therapies are already approved for migraine, understanding CGRP's role in psoriasis-depression could open unexpected therapeutic applications.
Questions still open
- Would anti-CGRP therapies (developed for migraine) improve both psoriasis symptoms and associated depression?
- Can neuropeptide levels in psoriasis patients predict who will develop psychiatric comorbidities?
- Does successful psoriasis treatment with biologics improve depression through reduced neuropeptide signaling?
Common questions
Why do so many psoriasis patients also have depression?
Could treating psoriasis help with depression and anxiety?
Read the original research
Proinflammatory cytokines and neuropeptides in psoriasis, depression, and anxiety.
Acta physiologica (Oxford, England), 241(3), e70019
Citation
Keenan, Emily L; Granstein, Richard D. (2025). Proinflammatory cytokines and neuropeptides in psoriasis, depression, and anxiety.. Acta physiologica (Oxford, England), 241(3), e70019. https://doi.org/10.1111/apha.70019