Part 2: Psoriasis and Mental Health: The Inflammatory and Biochemical Pathways

This 4-part video series brings together leading dermatologists to explore the intersection of mental health and chronic skin disease, a connection that continues to gain recognition in both research and clinical practice. Across the series, experts examine how psychiatric comorbidities influence dermatologic outcomes, review data on the mental health impact of chronic inflammatory conditions, and discuss how dermatologists can thoughtfully address these concerns in patient care.  

The inflammation–depression connection

In Part 2, Drs Lebwohl and Fried deepen their exploration by discussing the biochemical basis linking psoriasis and depression. Dr Lebwohl begins with an intriguing observation: bupropion, a well-known antidepressant, is also a TNF inhibitor, illustrating biochemical overlap between inflammatory pathways and mood regulation.

Some inflammatory mediators elevated in psoriasis are also implicated in depression, suggesting a shared biological landscape beyond the psychosocial burden of visible skin disease.

Is depression in psoriasis biologic, psychologic, or both?

Dr Fried addresses a longstanding question: are psychiatric symptoms in psoriasis primarily due to disease burden, or are they driven by central biologic mechanisms?

He emphasizes that the answer is unequivocally both. Inflammatory cytokines released from skin lesions enter the systemic circulation, cross the blood–brain barrier, and alter neurotransmitter uptake, affecting serotonin, norepinephrine, and dopamine. These changes directly contribute to mood symptoms.

This dual mechanism reinforces that addressing inflammation can also address psychiatric symptoms.

Future directions: neurotransmitter testing and combined therapies

Dr Fried discusses emerging possibilities for objectively measuring neurotransmitters through blood, urine, or imaging strategies. If clinicians could quantify depletion in patients with inflammatory skin disease, they might feel more confident pairing SSRIs or SNRIs with biologics when needed.

He highlights growing evidence that depression is, in part, an inflammatory disorder and that antidepressants themselves have anti-inflammatory effects, making them strong potential partners to biologic therapy.

Examining suicidality concerns with bimekizumab

The conversation shifts to the suicidality warning for bimekizumab, one of the fastest and most effective psoriasis therapies available. Dr Lebwohl reviews a publication by Blauvelt et al that examined Phase 2 and 3 clinical trial data and found no increased risk of suicidality in patients treated with bimekizumab compared to the general population and compared to patients treated with other IL-17 or IL-23 inhibitors.

Despite this, the warning remains on the label, and some clinicians avoid prescribing it. Dr Lebwohl cautions that this hesitancy may prevent high-need patients from accessing a highly effective treatment.

Psychological improvement with effective therapy

Dr Lebwohl closes by sharing another notable trial finding: in pivotal trials, among patients receiving bimekizumab, 93% reported no or minimal depression, compared with 81% of placebo-treated patients. This reinforces that improving skin disease can significantly improve psychological well-being.

Key takeaways

• Psoriasis and depression may share overlapping inflammatory pathways
• Inflammatory cytokines can influence neurotransmitter activity and mood
• Treating systemic inflammation can improve both skin and psychiatric symptoms
• Clinical trial data show no increase in suicidality with bimekizumab compared with placebo, the general population, or other biologics

Click here to view the other videos in the series.