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Abstract The Dermatology Life Quality Index (DLQI) should be used to assess treatment success in psoriasis (PSO). However, the DLQI does not assess the importance and achievement of treatment goals. The Patient Benefit Index (PBI) is a questionnaire that takes both into account. Currently, there is insufficient knowledge about the modulating variables of the PBI and whether it can complement the assessment of the DLQI. In a longitudinal cohort study, 82 patients with PSO were assessed before and up to sixteen weeks after a new treatment episode. The PBI was compared with patients with atopic dermatitis (AD) (n = 61). The effects of gender, age, type of therapy, improvement in body surface area (BSA), anxiety/depression, DLQI and individual coping were assessed. “Getting better skin quickly” was most important in PSO. Improved BSA, anxiety/depression, DLQI, male gender and initiation of biological therapy had the most positive effects. Partial mediation was found for the reduction of anxiety/depression and improved coping. The PBI may be considered an appropriate outcome measure of treatment success in PSO, complementing the DLQI. Patients with clinically relevant anxiety/depression and inadequate coping should be offered adjuvant psychosomatic treatment.

IntroductionPrenatal mental health problems are associated with morbidity for the pregnant person, and their infants are at long-term risk for poor health outcomes. We aim to explore how the SARS-CoV-2 pandemic affected the mental health of pregnant people in the United Kingdom (UK), and to further identify resilience factors which may have contributed to varying mental health outcomes. We also aim to examine the quality of antenatal care provided during the pandemic in the UK and to identify potential inadequacies to enhance preparedness for future events.MethodsDuring June-November 2020, we recruited 3666 individuals in the UK for the EPPOCH pregnancy cohort (Maternal mental health during the COVID-19 pandemic: Effect of the Pandemic on Pregnancy Outcomes and Childhood Health). Participants were assessed for depression, anxiety, anger and pregnancy-related anxiety using validated scales. Additionally, physical activity, social support, individualized support and personal coping ability of the respondents were assessed as potential resilience factors.ResultsParticipants reported high levels of depression (57.05%), anxiety (58.04%) and anger (58.05%). Higher levels of social and individualized support and personal coping ability were associated with lower mental health challenges. Additionally, pregnant individuals in the UK experienced higher depression during the pandemic than that reported in Canada. Finally, qualitative analysis revealed that restrictions for partners and support persons during medical appointments as well as poor public health communication led to increased mental health adversities and hindered ability to make medical decisions.DiscussionThis study revealed increased mental health challenges among pregnant individuals in the UK during the SARS-CoV-2 pandemic. These results highlight the need for reassessing the mental health support measures available to pregnant people in the UK, both during times of crisis and in general.

BackgroundStudies measuring hair cortisol concentration (HCC) have been increasingly conducted to document stress-related, endocrine changes aggregated over time. Previous studies have shown that HCC reflects abnormalities in the hypothalamic–pituitary-adrenocortical axis (HPA axis) in the context of somatic diseases, such as Cushing’s syndrome. HCC variations also reveal a corresponding alteration in HPA-axis-function in mental disorders, highlighting its potential role as a biomarker for interventions targeting mental health problems.AimsThe aim of this study was to investigate the role of HCC in various psychological and neuropsychiatric interventions and to explore the extent to which HCC can serve as a predictive or outcome parameter in such interventions by conducting a PRISMA-compliant review of the literature.MethodsFrom May to July 2022, the databases Web of Science, Google Scholar, PsychINFO, and ResearchGate were systematically searched using different combinations of relevant keywords. Studies of different types that examined HCC in the context of a wide range of psychological and neuropsychiatric interventions were included. Studies in languages other than English or German and animal studies were excluded. The MMAT tool was used, to assesses the Risk of bias.ResultsThe initial search identified 334 studies. After applying the inclusion and exclusion criteria, 14 publications with a total number of 1,916 participants were identified. An association between HCC and PTSD, depressive disorders, and ongoing social and family stress can be documented. The effect of relaxation techniques, mental training, CBT, or PTSD therapy on HCC has been studied with equivocal results. Some studies found decreased HCC after treatment, while others did not show a clear effect. Baseline HCC appears to be of particular importance. In some studies, higher baseline HCC was associated with increased treatment response, providing a predictive value for HCC.DiscussionHCC is increasingly being used as a biomarker for the mapping of psychological and neuropsychiatric interventions. However, due to the wide range of study populations and interventions, results are still heterogeneous. Nevertheless, HCC seems to be an encouraging biological parameter to describe the trajectory of different interventions aimed at improving mental health.

Abstract The role of stress and its neuroendocrine mediators in tinnitus is unclear. In this study, we measure cortisol as an indicator of hypothalamus–pituitary–adrenal (HPA) axis alterations and brain-derived neurotrophic factor (BDNF) as a marker of adaptive neuroplasticity in hair of chronic tinnitus patients to investigate relationships with tinnitus-related and psychological factors. Cross-sectional data from chronic tinnitus inpatients were analyzed. Data collection included hair sampling, pure tone audiometry, tinnitus pitch and loudness matching, and psychometric questionnaires. Elastic net regressions with n-fold cross-validation were performed for cortisol (N = 91) and BDNF (N = 87). For hair-cortisol (R2 = 0.10), the strongest effects were sampling in autumn and body-mass index (BMI) (positive), followed by tinnitus loudness (positive) and smoking (negative). For hair-BDNF (R2 = 0.28), the strongest effects were hearing aid use, shift work (positive), and tinnitus loudness (negative), followed by smoking, tinnitus-related distress (Tinnitus Questionnaire), number of experienced traumatic events (negative), and physical health-related quality of life (Short Form-12 Health Survey) (positive). These findings suggest that in chronic tinnitus patients, higher perceived tinnitus loudness is associated with higher hair-cortisol and lower hair-BDNF, and higher tinnitus-related distress with lower hair-BDNF. Regarding hair-BDNF, traumatic experiences appear to have additional stress-related effects, whereas hearing aid use and high physical health-related quality of life appear beneficial. Implications include the potential use of hair-cortisol and hair-BDNF as biomarkers of tinnitus loudness or distress and the need for intensive future research into chronic stress-related HPA axis and neuroplasticity alterations in chronic tinnitus.

To facilitate the recovery process of chronic and hard-to-heal wounds novel pro-resolving treatment options are urgently needed. We investigated the pro-regenerative properties of soluble CD83 (sCD83) on cutaneous wound healing, where sCD83 accelerated wound healing not only after systemic but also after topical application, which is of high therapeutic interest. Cytokine profile analyses revealed an initial upregulation of inflammatory mediators such as TNFα and IL-1β, followed by a switch towards pro-resolving factors, including YM-1 and IL-10, both expressed by tissue repair macrophages. These cells are known to mediate resolution of inflammation and stimulate wound healing processes by secretion of growth factors such as epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF), which promote vascularization as well as fibroblast and keratinocyte differentiation. In conclusion, we have found strong wound healing capacities of sCD83 beyond the previously described role in transplantation and autoimmunity. This makes sCD83 a promising candidate for the treatment of chronic- and hard-to-heal wounds.

ObjectiveTraumatic childhood experiences and psychosocial stress may predispose the evolvement of somatic diseases. Psoriasis is a multifactorial chronic inflammatory skin disease that often associates with current and past stress. Both may entail pathological alterations in major stress axes and a balance shift in the level of T helper type 1 (Th1) and 2 (Th2) cytokines, affecting the development and course of psoriasis. Until now, it is unclear whether traumatic stress experiences during the childhood or current stress are more frequent in psoriatic compared to skin-healthy individuals, and if they interact with treatment outcome.MethodIn a prospective cohort study, the impact of acute and early childhood stress on the course of dermatological treatment were studied in patients with moderate to severe psoriasis (PSO). Patients were examined before (T1) and about 3 months after (T2) the beginning of a new treatment episode. Assessments included clinical outcomes (Psoriasis Area and Severity Index—PASI, Structured Clinical Interview SCID-I) and patient-reported outcomes (PRO) (Childhood Trauma Questionnaire-CTQ, Perceived Stress Scale-PSS, itching/scratching, Dermatology Life Quality Index-DLQI, Hospital Anxiety and Depression Scale, Body Surface Area, Self-Administered PASI).ResultsN = 83 PSO patients (median age 53.7, IQR 37.8, 62.5) and n = 66 skin-healthy control subjects (HC) (median age 51.5, IQR 33.3, 59.2) participated. PSO had higher CTQ physical neglect than HC, as well as higher PRO levels. The positive impact of improved skin on the skin-related quality of life was moderated by the perceived stress. Acute stress at T1 had a positive effect both on the skin severity and the skin-related quality of life. CTQ total closely interacted with baseline psoriasis severity, and was associated with higher improvement from T1 to T2.ConclusionOne might tentatively conclude, that chronic psychosocial stressors like childhood maltreatment may predispose the manifestation of psoriasis. The latter may be amplified by acute psychological stressors. In addition, the present evidence suggests that systemic therapies work well in PSO, with childhood trauma and acute psychosocial stress. Both should therefore be routinely assessed and addressed in PSO.

BackgroundCurrently, there are no objective markers to measure treatment efficacy in chronic (distressing) tinnitus. This study explores whether stress-related biomarkers cortisol and brain-derived neurotrophic factor (BDNF) measured in hair samples of chronic tinnitus patients change after compact multimodal tinnitus-specific cognitive behavioral therapy.MethodsIn this longitudinal study, hair-cortisol and hair-BDNF levels, self-reported tinnitus-related distress (Tinnitus Questionnaire; TQ), and perceived stress (Perceived Stress Questionnaire; PSQ-20) were assessed before and 3 months after 5 days of treatment in N = 80 chronic tinnitus patients. Linear mixed-effects models with backward elimination were used to assess treatment-induced changes, and a cross-lagged panel model (structural equation model) was used for additional exploratory analysis of the temporal associations between TQ and hair-BDNF.ResultsAt follow-up, a reduction in TQ (p < 0.001) and PSQ-20 scores (p = 0.045) was observed, which was not influenced by baseline hair-cortisol or hair-BDNF levels. No changes in biomarker levels were observed after treatment. The exploratory analysis tentatively suggests that a directional effect of baseline TQ scores on hair-BDNF levels at follow-up (trend; p = 0.070) was more likely than the opposite directional effect of baseline hair-BDNF levels on TQ scores at follow-up (n.s.).DiscussionWhile the treatment effectively reduced tinnitus-related distress and perceived stress in chronic tinnitus patients, this effect was not mirrored in biological changes. However, the lack of changes in hair-cortisol and hair-BDNF levels might have been influenced by the treatment duration, follow-up interval, or confounding medical factors, and therefore must be interpreted with caution. The relationship between tinnitus-related distress and hair-BDNF levels should be explored further to obtain a better understanding of stress-related effects in chronic tinnitus.

Background: The alpha7 nicotinic acetylcholine receptor (Chrna7) plays an essential anti-inflammatory role in immune homeostasis and was recently found on mast cells (MC). Psychosocial stress can trigger MC hyperactivation and increases pro-inflammatory cytokines in target tissues such as the skin. If the cholinergic system (CS) and Chrna7 ligands play a role in these cascades is largely unknown.Objective: To elucidate the role of the CS in the response to psychosocial stress using a mouse-model for stress-triggered cutaneous inflammatory circuits.Methods: Key CS markers (ACh, Ch, SLURP-1, SLURP-2, Lynx1, Chrm3, Chrna7, Chrna9, ChAT, VAChT, Oct3, AChE, and BChE) in skin and its MC (sMC), MC activation, immune parameters (TNFα, IL1β, IL10, TGFβ, HIF1α, and STAT3) and oxidative stress were analyzed in skin from 24 h noise-stressed mice and in cultured MC (cMC) from C57BL/6 or Chrna7-Knockout mice.Results: First, Chrna7 and SLURP-1 mRNA were exclusively upregulated in stressed skin. Second, histomorphometry located Chrna7 and SLURP-1 in nerves and sMC and demonstrated upregulated contacts and increased Chrna7+ sMC in stressed skin, while 5 ng/mL SLURP-1 degranulated cMC. Third, IL1β+ sMC were high in stressed skin, and while SLURP-1 alone had no significant effect on cMC cytokines, it upregulated IL1β in cMC from Chrna7-KO and in IL1β-treated wildtype cMC. In addition, HIF1α+ sMC were high in stressed skin and Chrna7-agonist AR-R 17779 induced ROS in cMC while SLURP-1 upregulated TNFα and IL1β in cMC when HIF1α was blocked.Conclusions: These data infer that the CS plays a role in the regulation of stress-sensitive inflammatory responses but may have a surprising pro-inflammatory effect in healthy skin, driving IL1β expression if SLURP-1 is involved.

Objective: In experimental settings, systemically elevated inflammation markers interfere with major depression treatment. In German healthcare, compulsory national health insurance covers treatment of a wide variety of depressive disorders, if it follows evidence-based medicine guidelines combining recommended therapies. To date, little is known about the relevance of immune system cytokine production with regard to real-world clinical care for patients with moderate depression.Methods: Seventy three patients with moderate depression subjected to multimodal psychotherapeutic inpatient therapy (mPT) following a psychodynamic concept at a German university hospital were included. As a primary outcome, mPT success, evidenced by delta HADS “depression,” was analyzed according to tumor necrosis factor alpha (TNFα) production by peripheral blood mononuclear cells (PBMC) after phytohemagglutinin (PHA) challenge at baseline. Secondary outcomes addressed the inflammatory response and mental health comparing high and low TNFα-producers.Results: First, higher PBMC TNFα production at baseline predicted a better mPT-outcome (R2 0.162, p = 0.014). Second, patients with high TNFα (hTNF) at baseline produced significantly more acute inflammatory cytokines [interleukin (IL)1β, IL6), TH1/TH2 cytokines [interferon gamma (IFNγ), IL4] as well as eotaxin and IL2 compared to low TNFα producers (lTNF) (Cohen's ds between −0.532 and −1.013). Demographic data, diagnosis subtype-distribution, medication, systemic inflammation markers [C-reactive protein (CRP), high mobility group box 1 (HMGB1), leptin], anxiety and depression (HADS) did not differ. From baseline to mPT-discharge, HADS “depression” decreased in both hTNF (11.31 to 5.47, p = 0.001, d = 1.184) and lTNF patients (11.50–7.92, p = 0.001, d = −0.765), while PBMC cytokine production decreased significantly in hTNF (Cohen's ds between −0.304 and −0.345) with a significant group by time interaction for TH1/TH2 ratio. At the end of therapy, comparison of TNF groups revealed significantly lower depression-scores in hTNF compared to lTNF patients (5.47 compared to 7.92, p = 0.035, d = 0.504).Conclusions: Our study demonstrates successful treatment of depression in a clinical care setting using multimodal psychotherapy based on a psychodynamic concept following guideline recommendation. The greatest improvement in patient depression was linked to the highest production of TNFα by PBMCs at baseline. Our study contributes to the definition of patient subpopulations with differing cytokine responses that are related to succesful treatment of depression.

The human hair follicle is a neuroendocrine mini-organ that can be used to study aging processes in vitro. Neurotrophins maintain homeostasis in hair biology via the Trk-family of receptors. TrkA, the high affinity receptor for nerve growth factor (NGF), is expressed in hair follicle melanocytes and keratinocytes, where it regulates proliferation, differentiation and apoptosis and may thereby play a role in hair pigmentation and growth. We investigated TrkA expression during the human hair cycle and the effects of a selective high affinity TrkA agonist, Gambogic Amide, on hair pigmentation and hair growth in human hair follicles in vitro. In human scalp skin, TrkA expression was strongest in proliferating melanocytes re-establishing the pigmentary unit in the hair bulb during the early hair growth phase, anagen. During high anagen and in the de-composing pigmentary-unit of the regression phase, catagen, bulb-melanocytes lost TrkA expression and only undifferentiated outer root sheath melanocytes maintained it. In cultured human anagen hair follicles, Gambogic Amide was able to prevent gradual pigment loss, while it stimulated hair shaft elongation. This was achieved by increased melanocyte activation, migration and dendricity, highlighted by distinct c-KIT-expression in melanocyte sub-populations. Our results suggest that Gambogic Amide can maintain hair follicle pigmentation by acting on undifferentiated melanocytes residing in the outer root sheath and making them migrate to establish the pigmentary-unit. This suggests that the selective TrkA agonist Gambogic Amide acts as an anti-hair greying and hair growth promoting molecule in vitro.

Mouse models show that experimental stress mimicking prolonged life-stress exposure enhances neurogenic inflammation, induces adaptive immunity cytokine-imbalance characterized by a shift to Type 1 T-helper cell cytokines and increases apoptosis of epithelial cells. This affects hair growth in otherwise healthy animals. In this study, we investigate whether a prolonged naturalistic life-stress exposure affects cytokine balance and hair parameters in healthy humans. 33 (18 exam, 15 comparison) female medical students with comparable sociobiological status were analyzed during a stressful final examination period, at three points in time (T) 12 weeks apart. T1 was before start of the learning period, T2 between the three-day written exam and an oral examination, and T3 after a 12 week rest and recovery from the stress of the examination period. Assessments included: self-reported distress and coping strategies (Perceived Stress Questionnaire [PSQ], Trier Inventory for the Assessment of Chronic Stress [TICS]), COPE), cytokines in supernatants of stimulated peripheral blood mononucleocytes (PBMCs), and trichogram (hair cycle and pigmentation analysis). Comparison between students participating in the final medical exam at T2 and non-exam students, revealed significantly higher stress perception in exam students. Time-wise comparison revealed that stress level, TH1/TH2 cytokine balance and hair parameters changed significantly from T1 to T2 in the exam group, but not the control. However, no group differences were found for cytokine balance or hair parameters at T2. The study concludes that in humans, naturalistic stress, as perceived during participation in a major medical exam, has the potential to shift the immune response to TH1 and transiently hamper hair growth, but these changes stay within a physiological range. Findings are instructive for patients suffering from hair loss in times of high stress. Replication in larger and more diverse sample populations is required, to assess suitability of trichogram analysis as biological outcome for stress studies.