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.

Highlights

  • The pathogenic mechanisms linking tinnitus and stress are still not fully u­ nderstood1–3

  • Chronic stress can lead to a dysregulation of the HPA axis, which can manifest in altered stress response profiles to acute ­challenges8

  • Because the main aim of this study was to investigate associations of hair-cortisol and hair-brain-derived neurotrophic factor (BDNF) with tinnitus-related and psychological factors while controlling for confounding influences, the two biomarkers were investigated as outcome variables using elastic net regression, whereas all other assessed variables were used as predictors

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Summary

Introduction

The pathogenic mechanisms linking tinnitus and stress are still not fully u­ nderstood. Perceived tinnitus loudness and tinnitus-related distress are two distinct ­phenomena that appear linked by psychological factors like tinnitus a­ cceptance and subjective stress ­level. Common psychological conditions in tinnitus patients, such as a­ nxiety and ­depression, are known to be chronic stress-related. Chronic stress is an important factor in tinnitus patients seeking clinical help. The hypothalamus–pituitary–adrenal (HPA) axis is a primary neuroendocrine stress response system. Chronic stress can lead to a dysregulation of the HPA axis, which can manifest in altered stress response profiles to acute ­challenges. Previous studies on HPA axis function measuring salivary cortisol in tinnitus patients reported lower overall cortisol l­evels, a blunted cortisol response to an acute experimental psychosocial s­ tressor, increased. Hair washing or the use of hair products (hair mousse, hair gel, hair wax, hair spray) within 3 days prior to sampling

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