Stress Affects Mast Cell Proteases in Murine Skin in a Model of Atopic Dermatitis-like Allergic Inflammation.

Stress exposure worsens allergic inflammatory diseases substantially. Mast cells (MCs) play a key role in peripheral immune responses to neuroendocrine stress mediators such as nerve growth factor (NGF) and substance P (SP). Mast cell proteases (MCPs) and cholinergic factors (Chrna7, SLURP1) were recently described to modulate MC stress response. We studied MCPs and Chrna7/SLURP1 and their interplay in a mouse model for noise induced stress (NiS) and atopic dermatitis-like allergic inflammation (AlD) and in cultured MC lacking Chrna7. We found that the cholinergic stress axis interacts with neuroendocrine stress mediators and stress-mediator cleaving enzymes in AlD. SP-cleaving mMCP4+ MC were upregulated in AlD and further upregulated by stress in NiS+AlD. Anti-NGF neutralizing antibody treatment blocked the stress-induced upregulation in vivo, and mMCP4+ MCs correlated with measures of AlD disease activity. Finally, high mMCP4 production in response to SP depended on Chrna7/SLURP1 in cultured MCs. In conclusion, mMCP4 and its upstream regulation by Chrna7/SLURP1 are interesting novel targets for the treatment of allergic inflammation and its aggravation by stress.

Vitiligo - a disease: A position paper on stigmatization, life quality impairment and psychosocial comorbidity.

Vitiligo is a common disorder characterized by the visible loss of skin pigmentation. Non-segmental vitiligo (NSV) is the major subtype. The disease is caused by autoimmune-mediated destruction of melanocytes. Vitiligo leads to stigmatization and a significant reduction in quality of life. Disregarding the psychosocial burden, vitiligo is sometimes viewed solely as a cosmetic problem and, according to a global survey, is diagnosed on average only after 2.4 years. This delay contributes to a considerable burden of disease, including suicidal ideation. Stigmatization promotes the development of psychological comorbidities such as anxiety and depressive disorders, with prevalence rates varying by country and study (0.1%-67.9%). Data for Germany are heterogeneous and largely based on estimates. Due to psychosocial factors, the inflammatory component, and a higher incidence of somatic comorbidities, NSV may be regarded as an inflammatory systemic disease. We recommend optimizing care by incorporating the assessment of quality of life as a standard in routine care, in addition to monitoring disease activity. Moreover, early screening for psychological comorbidities is crucial to initiate appropriate treatment before the condition becomes chronic and cumulative (irreversible) impairments occur. The goal is a personalized and patient-centered integrated care approach that sustainably improves the health status of those affected.

The impact of perceived stress on the hair follicle: Towards solving a psychoneuroendocrine and neuroimmunological puzzle.

While popular belief harbors little doubt that perceived stress can cause hair loss and premature graying, the scientific evidence for this is arguably much thinner. Here, we investigate whether these phenomena are real, and show that the cyclic growth and pigmentation of the hair follicle (HF) provides a tractable model system for dissecting how perceived stress modulates aspects of human physiology. Local production of stress-associated neurohormones and neurotrophins coalesces with neurotransmitters and neuropeptides released from HF-associated sensory and autonomic nerve endings, forming a complex local stress-response system that regulates perifollicular neurogenic inflammation, interacts with the HF microbiome and controls mitochondrial function. This local system integrates into the central stress response systems, allowing the study of systemic stress responses affecting organ function by quantifying stress mediator content of hair. Focusing on selected mediators in this "brain-HF axis" under stress conditions, we distill general principles of HF dysfunction induced by perceived stress.

[Psychodermatology: Foundations for new developments in integrated care]. / Psychodermatologie: Grundlagen für den Aufbruch zu neuen Versorgungsformen.

The burden of a skin disease is easily understood by any observer due to its visibility: psychosocial issues are therefore ubiquitous in dermatology. Current evidence now shows that this relationship is two-way, as psychosocial stress can cause skin disease and its worsening. This interrelationship poses a major challenge.

[S1 Guideline Post-COVID/Long-COVID]. / S1-Leitlinie Post-COVID/Long-COVID.

The German Society of Pneumology initiated the AWMFS1 guideline Post-COVID/Long-COVID. In a broad interdisciplinary approach, this S1 guideline was designed based on the current state of knowledge.The clinical recommendation describes current post-COVID/long-COVID symptoms, diagnostic approaches, and therapies.In addition to the general and consensus introduction, a subject-specific approach was taken to summarize the current state of knowledge.The guideline has an expilcit practical claim and will be continuously developed and adapted by the author team based on the current increase in knowledge.

Effects of Early Life Stress on Bone Homeostasis in Mice and Humans.

Bone pathology is frequent in stressed individuals. A comprehensive examination of mechanisms linking life stress, depression and disturbed bone homeostasis is missing. In this translational study, mice exposed to early life stress (MSUS) were examined for bone microarchitecture (µCT), metabolism (qPCR/ELISA), and neuronal stress mediator expression (qPCR) and compared with a sample of depressive patients with or without early life stress by analyzing bone mineral density (BMD) (DXA) and metabolic changes in serum (osteocalcin, PINP, CTX-I). MSUS mice showed a significant decrease in NGF, NPYR1, VIPR1 and TACR1 expression, higher innervation density in bone, and increased serum levels of CTX-I, suggesting a milieu in favor of catabolic bone turnover. MSUS mice had a significantly lower body weight compared to control mice, and this caused minor effects on bone microarchitecture. Depressive patients with experiences of childhood neglect also showed a catabolic pattern. A significant reduction in BMD was observed in depressive patients with childhood abuse and stressful life events during childhood. Therefore, future studies on prevention and treatment strategies for both mental and bone disease should consider early life stress as a risk factor for bone pathologies.

Comparison of patient-reported need of psycho-oncologic support and the doctor's perspective: how do they relate to disease severity in melanoma patients?

OBJECTIVE: Psycho-neuro-immune research suggests an association between cancer outcomes and psychosocial distress. Objective criteria to determine patients' levels of distress are important to establish potential links to disease outcomes. METHODS: We compared three patient-reported with one doctor-reported measures of psycho-oncologic distress frequently used in routine cancer care and investigated associations with standard disease severity parameters in melanoma patients. We enrolled n = 361 patients, successively seen at two outpatient university clinics in Germany. In the naturalistic study, n = 222 patients had been diagnosed <180 days and were seen for the first time (Group I); n = 139 had been diagnosed >180 days and were in after-care (Group II). RESULTS: Across groups, only moderate associations were seen between patient- reported and doctor-reported measures. Regarding clinical variables, disease severity and perceived need of psycho-oncologic support reported by patients or doctors showed hardly any association. After subgroup stratification, in patients of Group II, patient-reported and doctor-reported instruments showed some small associations with disease parameters commonly linked to more rapid cancer progression in patients who are in cancer after-care. CONCLUSIONS: Overall, the few and low associations suggest that need of psycho-oncologic support and clinical variables were largely independent of each other and doctors' perception may not reflect the patient's view. Therefore, the assessment of the patient perspective is indispensable to ensure that melanoma patients receive appropriate support, as such need cannot be derived from other disease parameters or proxy report. More research is needed applying psychometrically robust instruments that are ideally combined with sensitive biomarkers to disentangle psycho-neuro-immune implications in melanoma patients. Copyright © 2015 John Wiley & Sons, Ltd.

Stressed skin?--a molecular psychosomatic update on stress-causes and effects in dermatologic diseases.

A pathogenetically relevant link between stress, in terms of psychosocial stress, and disease was first described in the 1970s, when it was proven that viral diseases of mucous membranes (such as rhinovirus and Coxsackie virus infections) develop faster and more severe after stress exposure. Since then, there has been an annual increase in the number of publications which investigate this relationship and break it down to the molecular level. Nevertheless, the evidences for the impact of psychosocial stress on chronic inflammatory skin diseases and skin tumors are hardly known. In the present review, we outline current insights into epidemiology, psychoneuroimmunology, and molecular psychosomatics which demonstrate the manifold disease-relevant interactions between the endocrine, nervous, and immune systems. The focus is on stress-induced shifts in immune balance in exemplary disorders such as atopic dermatitis, psoriasis, and malignant melanoma. The objective of this article is to convey basic psychosomatic knowledge with respect to etiology, symptomatology, and therapeutic options for chronic skin diseases. Particular attention is directed towards the underlying molecular relationships, both from a somatic to mental as well as a mental to somatic perspective.

Psychosocial stress affects the change of mental distress under dermatological treatment-A prospective cohort study in patients with psoriasis.

Psoriasis is a chronic-inflammatory, immune-mediated disease leading to a state of increased systemic inflammation. Mental comorbidities often occur in the patients and may additionally affect the therapy outcome. Currently, it is unknown whether the disease severity, psychosocial stress or health-related quality of life determines the manifestation of anxiety/depression, or vice versa, in psoriasis. The interplay between these variables during the dermatological treatment of psoriasis remains to be elucidated in order to initiate appropriate psychological interventions and to identify patients at risk for comorbid anxiety/depression. In a prospective cohort study, the impact of disease severity, health-related quality of life and psychosocial stress on anxiety/depression were examined during the dermatological treatment in patients with moderate to severe psoriasis (patients with psoriasis = PSO). Patients were examined before (T1) and about 3 months after (T2) the beginning of a new treatment episode, in most cases by means of systemic therapy. Data were analysed, exploratory, using Bivariate Latent Change Score Models and mediator analyses. Assessments included patient-reported outcomes (Hospital Anxiety and Depression Scale/HADS, Perceived Stress Scale/PSS, Childhood Trauma Questionnaire/CTQ, Dermatology Life Quality Index-DLQI, Body Surface Area-BSA), at both T1 and T2. 83 PSO patients (37.3% women, median age 53.7, IQR 37.8-62.5, median BSA 18.0, IQR 9.0-40.0) with complete data of HADS and DLQI were included. In the total group, a higher anxiety/depression at T1 was associated with a lower improvement in psoriasis severity in the course of the dermatological treatment (γBSA  = 0.50, p < 0.001). In subgroups of PSO with low/high CTQ scores, anxiety/depression at T1 had no impact on the change in psoriasis severity. Only by tendency, in CTQ subgroups, a higher psoriasis severity at T1 was linked with a higher improvement in anxiety/depression at T2 (low/high CTQ, γHADS  = -0.16/-0.15, p = 0.08). An improvement in the health-related quality of life was positively associated with an improvement in anxiety/depression (Pearson's r = 0.49, p = 0.02). Here, the reduction of acute psychosocial stress seems to be a decisive factor, mediating this association (ß = 0.20, t [2,60] = 1.87; p = 0.07, 95% CI -0.01, 0.41). The results allude, that the initial severity of anxiety/depression may presumably have an impact on the treatment outcome in the total group. In contrast, analysing subgroups of patients with high/low childhood trauma, the impact of the initial disease severity on the course of anxiety/depression after a switch to a new dermatological treatment could not be conclusively ruled out. The latter results from the latent change score modelling should be treated cautiously because of the small sample size. A common aetiopathological mechanism for psoriasis and anxiety/depression might be assumed with impact of dermatological treatment on both. The change in perceived stress seems to play an important role in the manifestation of anxiety/depression, substantiating the need for adequate stress management in patients with increased psychosocial stress during their dermatological treatment.

Substance P is a key mediator of stress-induced protection from allergic sensitization via modified antigen presentation.

Interaction between the nervous and immune systems greatly contributes to inflammatory disease. In organs at the interface between our body and the environment, the sensory neuropeptide substance P (SP) is one key mediator of an acute local stress response through neurogenic inflammation but may also alter cytokine balance and dendritic cell (DC) function. Using a combined murine allergic inflammation/noise stress model with C57BL/6 mice, we show in this paper that SP--released during repeated stress exposure--has the capacity to markedly attenuate inflammation. In particular, repeated stress exposure prior to allergen sensitization increases DC-nerve fiber contacts, enhances DC migration and maturation, alters cytokine balance, and increases levels of IL-2 and T regulatory cell numbers in local lymph nodes and inflamed tissue in a neurokinin 1-SP-receptor (neurokinin-1 receptor)-dependent manner. Concordantly, allergic inflammation is significantly reduced after repeated stress exposure. We conclude that SP/repeated stress prior to immune activation acts protolerogenically and thereby beneficially in inflammation.

Hair cortisol as outcome parameter for psychological and neuropsychiatric interventions-a literature review.

Background: Studies 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. Aims: The 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. Methods: From 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. Results: The 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. Discussion: HCC 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.

Hair brain-derived neurotrophic factor (BDNF) as predictor of developing psychopathological symptoms in childhood.

BACKGROUND: Dysregulation in the expression of neurotrophins is implicated in the pathophysiology of several mental disorders. Peripheral brain-derived neurotrophic factor (BDNF) can be measured in hair and might represent a marker of adequate neuroplasticity regulation. In early developmental periods, neuroplasticity regulation might be particularly important, but BDNF markers have not yet been analyzed in this regard. We used the hair-BDNF concentration (HBC) to investigate the prediction of emerging symptoms of anxiety/depressive and attention-deficit hyperactivity disorder (ADHD) in the developmentally crucial period from preschool to school age. METHODS: 117 children (58 girls, 59 boys) participated in a longitudinal study at the ages of 4-5 (T1) and 8 (T2) years. At T1, HBC was measured in a 3 cm hair segment. At T1 and T2, symptom domains were assessed using a multi-method (clinical interview, questionnaire) and multi-informant approach. RESULTS: T1 HBC was significantly negatively associated with T1 anxiety/depressive symptoms (r = -0.27) and predicted T2 anxiety disorder symptoms (r = -0.34) after controlling for the T1 symptoms. T1 HBC also predicted T2 depressive disorder symptoms (r = -0.18) but was not associated with ADHD symptom development. LIMITATIONS: BDNF hair analysis is a new method with a not yet large number of studies on methodological issues. Our study adds evidence to the validity of the method. CONCLUSIONS: Prediction of anxiety/depressive symptom development by HBC was shown. As this study was the first to use HBC in this context, cross-validation is necessary and worthwhile. HBC might prove to constitute a useful, non-invasive early marker of risk for anxiety/depressive disorders in childhood.

Oxidative stress coping capacity (OSC) value: Development and validation of an in vitro measurement method for blood plasma using electron paramagnetic resonance spectroscopy (EPR) and vitamin C.

Oxidative stress as a driver of disease is reinforcing the trend towards supplementation with antioxidants. While antioxidants positively influence the redox status when applied at physiological doses, higher concentrations may have pro-oxidative effects. Precise assessment methods for testing the supply of antioxidants are lacking. Using in-situ-irradiation as stressor and electron paramagnetic resonance (EPR) spectroscopy as readout system for formed radicals, a stress response assessment method was developed, using protein solutions and plasma samples from transfusion medicine. The method was validated in a double-blind placebo-controlled in vivo cross-over pilot study in blood plasma samples of individuals before and after vitamin C supplementation. Reference measurements were performed for the exogenous antioxidants ß-carotene and vitamin C, and glutathione as an endogenous representative. Malondialdehyde was studied for oxidative stress indication. Protein solutions without antioxidants showed a linear increase in radical concentration during irradiation. The in-vitro-addition of vitamin C or plasma samples from subjects displayed two slopes (m1, m2) for radical production, whereby m1 represented the amount of antioxidants and proteins, m2 only the protein content. These two slopes in combination with the intervening transition area (T) were used to calculate the oxidative stress coping capacity (OSC), which correlated positively with vitamin C concentration in blood plasma, while oxidative stress biomarkers showed only fluctuations within their reference ranges. Furthermore, a selective radical quenching mechanism for vitamin C was observed: the proportion of reactive oxygen species (ROS) in the plasma samples was degraded in dependence to the vitamin C concentration ingested. The proportion of lipid oxygen species (LOS) remained stable while the ascorbyl radical increased with higher vitamin C intake. OSC may represent a sensitive method to detect treatment effects on the redox status in vivo in future validation and treatment studies, and potentially in clinical routine.

Perspectives of (/memorandum for) systems thinking on COVID-19 pandemic and pathology.

Is data-driven analysis sufficient for understanding the COVID-19 pandemic and for justifying public health regulations? In this paper, we argue that such analysis is insufficient. Rather what is needed is the identification and implementation of over-arching hypothesis-related and/or theory-based rationales to conduct effective SARS-CoV2/COVID-19 (Corona) research. To that end, we analyse and compare several published recommendations for conceptual and methodological frameworks in medical research (e.g., public health, preventive medicine and health promotion) to current research approaches in medical Corona research. Although there were several efforts published in the literature to develop integrative conceptual frameworks before the COVID-19 pandemic, such as social ecology for public health issues and systems thinking in health care, only a few attempts to utilize these concepts can be found in medical Corona research. For this reason, we propose nested and integrative systemic modelling approaches to understand Corona pandemic and Corona pathology. We conclude that institutional efforts for knowledge integration and systemic thinking, but also for integrated science, are urgently needed to avoid or mitigate future pandemics and to resolve infection pathology.

Profound disturbances of sexual health in patients with acne inversa.

BACKGROUND: Acne inversa (AI) leads chronically to painful eruptions and extensive scarring in predominantly intimate areas. We hypothesized an impairment of sexual life caused by the disease. OBJECTIVES: By means of validated questionnaires, sexual health and quality of life were assessed in patients with AI and in healthy control subjects. METHODS: A self-administered questionnaire was given to 85 voluntary study participants. In all, 45 women (24 patients vs 21 control subjects) and 40 men (20 patients vs 20 control subjects) were enrolled in the study. The Female Sexual Function Index, the International Index of Erectile Function, and the Frankfurt Self-Concept Scale for Sexuality were used to assess sexual health. Quality of life was measured with the Dermatology Life Quality Index. RESULTS: This study demonstrated, for the first time to our knowledge, that patients with AI have sexual dysfunctions and sexual distress in comparison with matched control subjects. Sexual distress was particularly higher in female than in male patients with AI. Surprisingly, severity of cutaneous alterations correlated neither with sexual dysfunctions nor with sexual distress. However, the sexual dysfunction and sexual distress negatively correlated with the quality of life in female patients with AI who had a lower quality of life compared with gender-matched control subjects and male patients. LIMITATIONS: Small sample size is the main limitation of this study. CONCLUSIONS: Sexual health is diminished in patients with AI. We underscore the need for physicians to implement attention on the impact of AI on sexual health and quality of life when treating patients for this disease.

Childhood Trauma and Psychosocial Stress Affect Treatment Outcome in Patients With Psoriasis Starting a New Treatment Episode.

Objective: Traumatic 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. Method: In 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). Results: N = 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. Conclusion: One 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.

Psychological Treatment Effects Unrelated to Hair-Cortisol and Hair-BDNF Levels in Chronic Tinnitus.

BACKGROUND: Currently, 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. METHODS: In 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. RESULTS: At 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.). DISCUSSION: While 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.

Hair-cortisol and hair-BDNF as biomarkers of tinnitus loudness and distress in chronic tinnitus.

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.