Journal Article Annotations
2025, 2nd Quarter

Psychodermatology

Annotations by J. Jewel Shim, MD, FACLP, FAPA
September, 2025

Bipolar disorder among individuals with atopic dermatitis: a case-control study in the All of Us Research Program .
Role of Inflammation and Cytokine Dysregulation in Depression in Patients with Inflammatory Skin Conditions.
MRI-based neuroimaging alterations in immune-related skin diseases: a 3rd review.

Of interest:

Reported psychiatric adverse events among isotretinoin users: Monitoring priorities from a 20-year FDA Adverse Event Reporting System database study .

PUBLICATION #1 — Psychodermatology

Bipolar disorder among individuals with atopic dermatitis: a case-control study in the All of Us Research Program .

Anthony Mitchel Wride, Gloria F Chen, Ryan Fan, Audrey C Leasure, Stephen Scott Jones, Daniel F Levey, William Damsky, Jeffrey M Cohen

Abstract: Clin Exp Dermatol. 2025 Mar 26;50(4):760-763. doi: 10.1093/ced/llae451.

Background:
Atopic dermatitis (AD) has been associated with psychiatric comorbidities.

Objectives:
To characterize the association between AD and bipolar disorder (BPD) with a case-control study of the National Institutes of Health All of Us Research Program.

Methods:
We used Systematized Nomenclature of Medicine diagnostic codes to identify cases of AD. Four age-, sex- and race/ethnicity-matched controls were found for each case using propensity score matching. After controlling for age, sex, race/ethnicity, income, smoking status and depression, the relationship between AD and BPD was evaluated using logistic regression.

Results:
We identified 13 431 AD cases and 53 724 matched controls. Participants with AD were more likely than controls to have BPD (7.8% vs. 4.6%, P < 0.001). After adjusting for demographics and comorbidities, we observed a significant association (odds ratio 1.49, 95% confidence interval 1.37-1.62; P < 0.001).

Conclusions:
Compared with individuals without AD, individuals with AD have 1.49-fold increased odds of having BPD. Further investigation is needed to gain a better understanding of this association.

Annotation

The finding:
This is a case control study using data from an NIH database, examining the association between atopic dermatitis (AD) and bipolar disorder, furthering work done in Taiwan and in the UK with that found an association between the inflammatory skin condition and bipolar mood disorder. This study did confirm this association, identifying an odds ratio of 1.49 for bipolar disorder in patients with AD.

Strength and weaknesses:
A major strength is that this study used a large, diverse cohort. Weaknesses include the retrospective nature of the study, which limited the type of information available to the investigators, such as the severity of disease. The database itself was comprised mostly of groups historically under-represented in biomedical research and thus limits the generalizability of the results to the larger population

Relevance:
These results add to the growing body of knowledge regarding immunological factors and their association with mental health disorders and may inform future therapeutics for both types of diseases.

PUBLICATION #2 — Psychodermatology

Role of Inflammation and Cytokine Dysregulation in Depression in Patients with Inflammatory Skin Conditions.

Olivia M Katamanin, Isabella J Tan, Jillian Barry, Mohammad Jafferany

Abstract: Am J Clin Dermatol. 2025 Jan;26(1):35-43. doi: 10.1007/s40257-024-00905-9. Epub 2024 Dec 2.

The growing field of psychodermatology examines the interplay between dermatological and psychiatric comorbidities. While current literature recognizes that cutaneous and psychiatric conditions often coexist within patients, the relationship between dysregulated inflammation and depression in patients with inflammatory skin conditions has not been thoroughly explored. This review seeks to describe the connection between cutaneous disease and depression via shared inflammatory cytokine pathways. A review of current literature was conducted, and studies addressing the co-occurrence of depression and inflammatory skin diseases were included. This review focuses on depression in patients with psoriasis, atopic dermatitis, and hidradenitis suppurativa. Studies that focused on the prevalence of depression in these populations, shared inflammatory pathways, and co-management of cutaneous and psychiatric disorders were chosen. The literature revealed a high prevalence of depression in individuals with inflammatory skin conditions compared with those without cutaneous disease. Recent studies described how proinflammatory cytokines in inflammatory skin diseases can elicit inflammation in the brain, leading to depressive symptoms. Certain subsets of cytokines that mediate inflammatory pathways were associated with both cutaneous inflammation and depression, highlighting shared pathology. Antiinflammatory medications targeting shared cytokines found reductions in both cutaneous and depressive symptoms. Practitioners have emphasized interdisciplinary approaches to treating both conditions, including psychotherapy and pharmacological methods. There is a clear association between inflammatory cutaneous diseases and depression. Co-management of these conditions, including interdisciplinary methods, is essential for patients' well-being. Future research addressing similar links between other cutaneous and psychiatric conditions could yield new treatment opportunities as well.

Annotation

The finding:
This is a review of the current knowledge of the role of inflammation and the immune system in the pathogenesis of depression and inflammatory skin disorders. It further underscores the growing body of evidence regarding these mechanisms and highlights several treatment approaches which apply the knowledge regarding these shared inflammatory cytokine pathways to potentially address both the skin condition and depression

Strength and weaknesses:
This is merely a review of the existing literature rather than a research study. However, it presents a clear overview of the shared pathophysiology underlying both inflammatory dermatoses and depression and as such, the recommendation to use a comprehensive, collaborative approach to treating these conditions.

Relevance:
This review broadens our view of the causes of depression and offers a novel approach for treatment.

PUBLICATION #3 — Psychodermatology

MRI-based neuroimaging alterations in immune-related skin diseases: a comprehensive review.

Siqi Tan, Ziyan Chen, Liu Yunyao, Yang Hedan, Tong Lin.

Abstract: Arch Dermatol Res. 2025 Mar 8;317(1):529. doi: 10.1007/s00403-025-04023-2.

The skin, as the largest organ in the human body, serves as the primary physical barrier and plays a crucial role in the immune defense process. Immune-related skin diseases encompass a spectrum of complex dermatological conditions characterized by aberrant immune responses, including the production of autoantibodies and dysregulation of inflammatory mediators. Growing evidence suggest a heightened prevalence of comorbid neuropsychiatric disorders among patients with immune-related skin diseases, indicative of potential shared pathogenesis. In recent years, the brain connectome, delineating the intricate network of neural connections, has gained prominence in elucidating various neurological and psychiatric conditions. Researchers have begun to investigate whether alterations in brain connectivity occur in patients with immune-related skin diseases, thereby exploring the connectome perspective in understanding the pathogenesis of these diseases. This review aims to synthesize and analyze recent neuroimaging studies about immune-related skin diseases, including systemic lupus erythematosus, psoriasis, chronic spontaneous urticaria, and atopic dermatitis. We mainly discussed the connectome studies related to these diseases and summarized the underlying mechanisms associated with their clinical manifestations, progression, and treatment. Then from our perspectives, we believe that interdisciplinary collaborations encompassing fields such as neurology, psychiatry, dermatology, and neuroimaging will be instrumental in advancing our understanding of immune-related skin diseases. Furthermore, multi-omics approaches will enable a comprehensive exploration of the molecular mechanisms underlying these neural changes, facilitating the identification of novel diagnostic biomarkers and therapeutic targets.

Annotation

The finding:
This is a review of the existing brain connectome studies relating to immune-related skin diseases, specifically systemic lupus erythematosus (SLE), psoriasis, chronic spontaneous urticaria (CSU), and atopic dermatitis (AD). Most of the existing studies are with SLE, and indicate both structural and functional abnormalities, though causality could not be established. Neuroimaging studies examining psoriasis, CSU and AD to date are limited but have also demonstrated alterations in structure and functional connectivity.

Strength and weaknesses:
This a review article rather than a research study but provides a detailed summary of the current literature and suggests areas for further investigation. It further emphasizes the importance of a multidisciplinary approach to the understanding and treatment of mental health disorder and immune-related skin diseases.

Relevance:
The review enlarges our understanding of the potential brain mechanisms that are involved in the development of mental health and dermatological conditions.

PUBLICATION #4 — Psychodermatology

Reported psychiatric adverse events among isotretinoin users: Monitoring priorities from a 20-year FDA Adverse Event Reporting System database study .

Wenjia Nie, Xiaopeng Wu, Yuting Xia, Liyun Zheng, Hengcheng Lu.

Abstract: J Am Acad Dermatol j.jaad.2025.02.072. Epub 2025 Feb 28.

Background and objective:
Psychiatric monitoring during isotretinoin treatment may be warranted. However, beyond depression and suicide, it is unclear which psychiatric adverse events (AEs) should be prioritized for monitoring.

Methods:
Psychiatric AEs reported in FAERS from January 2004 to June 2024 were analyzed using disproportionality analysis, with reporting odds ratios >1 identifying positive signals. A clinical priority scoring system ranked the importance of these signals, and time-to-onset analysis evaluated their temporal patterns. Sensitivity analyses assessed the robustness of findings.

Results:
Among the 19,412 cases of isotretinoin-related psychiatric AEs, 50 positive signals included over 20 cases each. Twenty-five important signals were identified and grouped into categories of depressive disorder, suicide and self-injury, anxiety disorder, mood change, bipolar disorder, psychosis, and affective disorder. Acne patients exhibited more important signals compared to nonacne patients. The median time-to-onset for moderate-priority signals was 80 days (IQR: 31, 265), displaying an early failure-type pattern (α = 0.55, 95% CI: 0.54-0.56).

Limitation:
Cross-sectional study.

Conclusion:
Mood disturbances, suicide and self-injury, and psychosis are key psychiatric AEs that require focused monitoring, particularly among acne patients. Intensified early monitoring, followed by continuous assessment, may help reduce the harm associated with these events.

Annotation (unstructured)

This study summarizes the isotretinoin related psychiatric adverse events (AE) as reported to the FDA between 2004-2024. It confirms the evidence that isotretinoin may increase the risk for psychiatric AE, particularly in patients with acne. Mood disorder, suicide, self-injury, and psychosis were highlighted as the most serious AE. It also identified that such symptoms can occur relatively early in the treatment course.