Psychodermatology

Article information
Title:Major depressive disorder shares systemic immune signatures and potential therapeutic targets with inflammatory skin diseases
PubMed ID: 41673463
First Author Last Name: He

Abstract:
Major depressive disorder (MDD) is a prevalent neuropsychiatric disorder associated with significant morbidity and mortality. Increasing evidence suggests that a subset of MDD patients exhibit a dysregulated immune system. However, few clinical studies have tested the efficacy of anti-inflammatory drugs in reducing symptoms of depression. In contrast, targeted immunomodulatory drugs have revolutionized the treatment of inflammatory skin disorders, such as atopic dermatitis (AD) and psoriasis. To assess the viability of a targeted treatment approach in MDD, we first compared the blood proteomic profiles of patients with MDD to those of patients with AD, psoriasis, and healthy controls (HCs). We demonstrated that the proteomic signatures of MDD patients share Th2 skewing and dysregulation of other immune/neurovascular-related proteins with AD. Next, we performed an in-silico drug repurposing analysis to test whether common biologics used in dermatology could also affect the dysregulated proteomic signature observed in MDD patients. This computational approach identified dupilumab, which targets the IL-4 receptor α subunit (IL-4Rα) and thus inhibits the Th2 axis, as significantly affecting the MDD signature by reversing the dysregulation of several inflammatory proteins related to Th2 signaling. Finally, in a mouse model of chronic social defeat stress (CSDS), we showed that pharmacological inhibition of IL-4Rα prevented stress-induced social avoidance behavior. Our findings underscore the potential role of the Th2 axis in MDD, highlighting the potential of specifically targeting Th2 as a disease-modifying treatment. Additionally, the back-translational drug repurposing strategy employed in this study may offer a novel approach to identify immunomodulatory drugs in psychiatry.

Annotation
The finding:
The study was based on the premise that up to a third of patients with MDD have features demonstrating low grade inflammation, and that there is an established association between depression and inflammatory dermatoses. The study authors questioned whether anti-inflammatory drugs could be used as a novel treatment strategy for MDD. They performed two analyses, one in-silico, examining the effect of biologics used to treat inflammatory skin conditions on the MDD inflammatory signature, and the second, using a back-translational approach in a mouse model of chronic social defeat stress, the best validated mouse model for psychosocial stress. The study authors did find significant results in both analyses demonstrating the effects of reversing the dysregulation of inflammatory proteins involved in T-helper cell signaling and observed more resilience in mice treated with an anti-inflammatory drug.

Strength and weaknesses:
This is the first study of its kind, comparing the serum proteonomic phenotype of MDD with that of AD and psoriasis, in search of shared proteonomic features which could offer novel disease modulating targeted therapeutics. The study is limited by lack of actual and in-situ effects of the monoclonal antibody on patients with depression as the analyses were done retrospectively in-silico and in a mouse model. Data regarding depression symptoms was not collected from subjects with AD or psoriasis, and disease course (number of previous episodes of depression) for MDD subjects was also not queried.

Relevance:
As existing pharmacotherapeutics for MDD are limited in effectiveness for at least a third of patients, the exploration of novel, disease modulating approaches is essential.

Article information
Title: The skin microbiome and affective symptoms: neuroimmune, neuroendocrine, and sensory pathways linking inflammatory dermatoses to mood and anxiety burden
PubMed ID: 42031220
First Author Last Name: Coccurello

Abstract:
The skin functions as a neuro-immuno-endocrine organ with an extensive microbial interface capable of bidirectional signaling with the central nervous system. While the gut-brain axis is well established, the skin-microbiota-brain (SMB) axis remains underexplored, particularly with respect to affective symptom dimensions (depression, anxiety, stress) that commonly co-occur with chronic inflammatory dermatoses. This review synthesizes evidence across clinical, translational, and experimental studies and organizes it by strength (associational findings, mechanistic plausibility, and limited interventional signals). We outline a systems-level model in which cutaneous microbial dysbiosis is associated with brain-relevant pathways via immune, neuropeptide, and metabolic routes. Candidate mediators include cytokines (IL-6, IL-17, TNF-α), neuropeptides (e.g., substance P, CGRP), and microbial-derived metabolites (e.g., SCFA-like compounds and tryptophan catabolites). These signals are hypothesized to influence neuroimmune tone and neurovascular signaling based largely on broader systemic inflammation and stress biology; direct causal evidence specifically attributing affective outcomes to skin microbiome perturbations in humans remains limited. In parallel, top-down neuroendocrine signaling via hypothalamic-pituitary-adrenal (HPA) axis activation, cortisol-related signaling, and sympathetic outflow can alter skin barrier function, antimicrobial peptide expression, and microbial ecology, potentially contributing to symptom-maintaining loops (e.g., itch-sleep disruption-stress). Importantly, we consider counterarguments (psychosocial burden, reverse causality, treatment effects, and the localized nature of lesions) and identify research priorities required to test causality (longitudinal sampling, mechanistic biomarker panels, and preregistered interventional studies with affective endpoints and mediation analyses). By integrating dermatological, microbiological, and neuroimmunological evidence within a symptom-centered framework, the SMB axis is positioned as a biologically plausible but still evolving model that may help explain affective symptom burden in subsets of patients with inflammatory skin disease and guide mechanism-informed translational research.

Annotation
The finding:
The authors sought to synthesize the current evidence regarding the co-occurrence of affective symptoms with chronic inflammatory dermatoses and whether the skin-microbiota-brain axis provides plausible routes for skin-brain communication. They further describe how the skin is a neuro-immuno-endocrine organ and how skin microbiota may play a role in modulating inflammation and immune signaling - via cutaneous dysbiosis and barrier disruption, neural signaling via skin sensory neurons, and metabolic signaling mediated by bioactive metabolites of cutaneous commensals. They highlight a circular relationship between associated symptoms/factors of inflammatory dermatoses (itch, pain, systemic inflammation, social factors associated with disfiguring elements of the skin disorder and associated emotional distress, and sleep disruption), leading to affective symptoms which in turn dysregulate immune function via activation of the HPA-axis.

Strength and weaknesses:
This work enlarges the existing mechanistic knowledge regarding the association of inflammatory skin conditions with affective disorders, and as such provides potential therapeutic targets to modulate both diseases. This model is yet to be fully established as there are a number of counter arguments and alternative explanations for the observed findings to date. Current knowledge is limited by the quality of the evidence as most studies have been cross-sectional, methodologically heterogeneous, and lack of controls of key confounding factors such as antibiotics, anti-inflammatory medications, diet, and skincare routines. Other factors like host genetic variation have also been under-examined. To date, there is limited evidence demonstrating that modulating the skin microbiota has resulted in changes in inflammatory markers or observed clinical change in affective symptoms.

Relevance:
This study offers another model to conceptualize the co-morbidity between inflammatory dermatoses and affective disorders and offers potential alternative approaches for treating both types of diseases.

Article information
Title: Compulsive Skin Picking in Anorexia Nervosa: A Qualitative Study of Emotional and Interoceptive Dysregulation
PubMed ID: 41978120
First Author Last Name: Mariusz

Abstract:
Background:
Body-focused repetitive behaviors (BFRB), including compulsive skin picking, are observed in patients with anorexia nervosa (AN). However, their functional significance remains unclear. AN is characterized by chronic energy restriction and altered interoceptive processing, which may contribute to persistent internal tension beyond overt eating symptoms. This study aimed to explore the functional meaning of compulsive skin picking as a potential behavioral marker of emotional and interoceptive dysregulation relevant to clinical assessment and treatment planning.

Methods:
A qualitative descriptive study was conducted among 33 hospitalized patients with AN who reported recurrent skin picking leading to tissue damage. Patients were undergoing structured nutritional rehabilitation. Individual semi-structured interviews were performed.

Results:
Patients with AN described a consistent emotional and physiological sequence preceding skin picking: increased internal tension followed by short-term relief and subsequent self-directed negative emotions. Episodes occurred in contexts of emotional overload, understimulation, reduced emotional awareness, and, in some cases, hunger- or meal-related stress. Participants described the behavior as partly intentional, serving to reduce tension, but at times occurring almost automatically. It was closely connected with eating-related anxiety and dissatisfaction with the body.

Conclusions:
The findings indicate that compulsive skin picking in AN may reflect underlying emotional and interoceptive instability, instead of being an unrelated co-occurring symptom. In the broader context of chronic energy restriction, such behaviors may reflect attempts to modulate internally generated physiological arousal. Incorporating routine assessment of BFRB into clinical practice could improve the identification of ongoing emotional instability and support more coordinated multidisciplinary care. Future studies combining qualitative insights with physiological measures would help clarify the mechanisms underlying this association.

Annotation:
This was a qualitative study exploring whether skin picking could be a potential behavioral indicator of emotional and interoceptive dysregulation in anorexia nervosa (AN), based on a known significant association between AN and skin picking. Individuals with AN are hypothesized to have altered interoceptive processing, potentially caused by chronic energy deficiency, which activates neuroendocrine stress pathways. They further describe difficulties reconciling the dissonance between bodily signals (indicating hunger) and the need to exert cognitive control over their food intake. Some authors have posited that maladaptive behavioral strategies may be implemented to resolve this conflict. Semi-structured interviews were conducted with 33 hospitalized patients with AN who had recurrent skin picking with tissue damage. The majority of subjects described a similar course of increased internal tension leading to skin picking, followed by short-term relief of tension and subsequent onset of self-directed negative emotions. The study investigators concluded that skin picking, rather than being an unrelated, comorbid condition, was an indicator of emotional instability and interoceptive dysfunction. Limitations included a small sample size comprised only of females from a single center, limiting the generalizability of the results. Standardized, quantitative measures of skin picking severity and interoceptive awareness were not performed. The cross-sectional study design precluded determining cause-effect between the metabolic state and skin picking behaviors.