[Chronic tinnitus: An interplay between somatic and psychological factors]. / Chronischer Tinnitus im Wechselspiel somatischer und psychischer Faktoren.

Chronic tinnitus is a common, sometimes highly distressing phenomenon that can be triggered and maintained by an interplay of physical and psychological factors. Partnering with clinical psychology and psychosomatic medicine, modern otolaryngology integrates both medical (e.g., hearing loss) and psychological influences (e.g., interactions between biographical experiences, personality traits, subjective evaluation of intrapsychic and interpersonal stimuli, emotional states, and intrapsychic or interpersonal emotion regulation strategies). Both groups of variables can influence the intensity and course of chronic tinnitus symptomatology both directly and indirectly, whereby the quality and relative degrees of psychological and physical components in a person's self-experience can fluctuate. With this in mind, the present article distinguishes between chronic tinnitus symptomatology with or without hearing loss-and strongly advocates for an integrated understanding of the symptomatology within a holistic psychological frame of reference. After a brief introduction to the principles of psychosomatic medicine and psychotherapy, the article discusses psychological case conceptualization using a vulnerability-stress-coping (VSC) model as an example, outlines clinical aspects and diagnostics of chronic tinnitus symptomatology, and concludes with a conceptualization of chronic tinnitus-related distress as a function of person-centered VSC interactions.

Tinnitus at the Junction of Traditional Medicine and Modern Technology.

The WHO estimated that 430 million people worldwide suffer from moderate-to-severe hearing loss [...].

Chronic Tinnitus.

BACKGROUND: Chronic tinnitus is a commonly occurring symptom of the auditory system. Epidemiological studies assume a lifetime prevalence in men and women of 3.5% for chronic tinnitus requiring treatment. Almost 25% of all Germans have experienced at least one episode of tinnitus. No causal therapy is yet available, but numerous treatment strategies are being pursued. Rigorous scientific assessment of these procedures is essential. METHODS: For this exhaustive revision of the German clinical practice guideline, the literature in the medical databases PubMed and Cochrane Library, including existing guidelines from various countries, was systematically searched using keywords on the topic of chronic tinnitus. On the basis of the revised guideline, a separate guideline was written in language accessible to patients. RESULTS: Chronic tinnitus is often associated with hearing loss, but the mental distress caused by the ear noise is another crucial element. Apart from expert counseling, the recommended treatment comprises psychotherapeutic interventions, particularly cognitive behavioral therapy (with effect sizes of 0.54 to 0.91 for reduction of the tinnitus-related distress), and measures to improve the hearing. There is insufficient evidence regarding the effects of drug treatment, sound and music therapy, and neuromodulation (magnetic stimulation or electrostimulation). CONCLUSION: Alongside thorough and sound diagnosis and counseling, the principal treatment options for chronic tinnitus are specific cognitive behavioral therapy and expert psychotherapeutic interventions on an individual or group basis. Future-preferably interdisciplinary-research should evaluate the long-term effects of the treatment options, with particular attention to psychosomatic comorbidity.

Towards a unification of treatments and interventions for tinnitus patients: The EU research and innovation action UNITI.

Tinnitus is the perception of a phantom sound and the patient's reaction to it. Although much progress has been made, tinnitus remains a scientific and clinical enigma of high prevalence and high economic burden, with an estimated prevalence of 10%-20% among the adult population. The EU is funding a new collaborative project entitled "Unification of Treatments and Interventions for Tinnitus Patients" (UNITI, grant no. 848261) under its Horizon 2020 framework. The main goal of the UNITI project is to set the ground for a predictive computational model based on existing and longitudinal data attempting to address the question of which treatment or combination of treatments is optimal for a specific patient group based on certain parameters. Clinical, epidemiological, genetic and audiological data, including signals reflecting ear-brain communication, as well as patients' medical history, will be analyzed making use of existing databases. Predictive factors for different patient groups will be extracted and their prognostic relevance validated through a Randomized Clinical Trial (RCT) in which different patient groups will undergo a combination of tinnitus therapies targeting both auditory and central nervous systems. From a scientific point of view, the UNITI project can be summarized into the following research goals: (1) Analysis of existing data: Results of existing clinical studies will be analyzed to identify subgroups of patients with specific treatment responses and to identify systematic differences between the patient groups at the participating clinical centers. (2) Genetic and blood biomarker analysis: High throughput Whole Exome Sequencing (WES) will be performed in well-characterized chronic tinnitus cases, together with Proximity Extension Assays (PEA) for the identification of blood biomarkers for tinnitus. (3) RCT: A total of 500 patients will be recruited at five clinical centers across Europe comparing single treatments against combinational treatments. The four main treatments are Cognitive Behavioral Therapy (CBT), hearing aids, sound stimulation, and structured counseling. The consortium will also make use of e/m-health applications for the treatment and assessment of tinnitus. (4) Decision Support System: An innovative Decision Support System will be implemented, integrating all available parameters (epidemiological, clinical, audiometry, genetics, socioeconomic and medical history) to suggest specific examinations and the optimal intervention strategy based on the collected data. (5) Financial estimation analysis: A cost-effectiveness analysis for the respective interventions will be calculated to investigate the economic effects of the interventions based on quality-adjusted life years. In this paper, we will present the UNITI project, the scientific questions that it aims to address, the research consortium, and the organizational structure.

A multidisciplinary systematic review of the treatment for chronic idiopathic tinnitus.

The majority of tinnitus patients are affected by chronic idiopathic tinnitus, and almost 60 different treatment modalities have been reported. The present study is a multidisciplinary systematic analysis of the evidence for the different forms of treatment for chronic tinnitus. The results are used to form the basis of an S3 guideline. A systematic search was carried out in PubMed and the Cochrane Library. The basis for presenting the level of evidence was the evidence classification of the Oxford Centre of Evidence-based Medicine. Whenever available, randomised controlled trials were given preference for discussing therapeutic issues. All systematic reviews and meta-analyses were assessed for their methodological quality, and effect size was taken into account. As the need for patient counselling is self-evident, specific tinnitus counselling should be performed. Due to the high level of evidence, validated tinnitus-specific, cognitive behavioural therapy is strongly recommended. In addition, auditory therapeutic measures can be recommended for the treatment of concomitant hearing loss and comorbidities; those should also be treated with drugs whenever appropriate. In particular, depression should be treated, with pharmacological support if necessary. If needed, psychiatric treatment should also be given on a case-by-case basis. With simultaneous deafness or hearing loss bordering on deafness, a CI can also be indicated. For auditory therapeutic measures, transcranial magnetic or direct current stimulation and specific forms of acoustic stimulation (noiser/masker, retraining therapy, music, and coordinated reset) for the treatment of chronic tinnitus the currently available evidence is not yet sufficient for supporting their recommendation.

Cerebral Processing of Emotionally Loaded Acoustic Signals by Tinnitus Patients.

This exploratory study determined the activation pattern in nonauditory brain areas in response to acoustic, emotionally positive, negative or neutral stimuli presented to tinnitus patients and control subjects. Ten patients with chronic tinnitus and without measurable hearing loss and 13 matched control subjects were included in the study and subjected to fMRI with a 1.5-tesla scanner. During the scanning procedure, acoustic stimuli of different emotional value were presented to the subjects. Statistical analyses were performed using statistical parametric mapping (SPM 99). The activation pattern induced by emotionally loaded acoustic stimuli differed significantly within and between both groups tested, depending on the kind of stimuli used. Within-group differences included the limbic system, prefrontal regions, temporal association cortices and striatal regions. Tinnitus patients had a pronounced involvement of limbic regions involved in the processing of chimes (positive stimulus) and neutral words (neutral stimulus), strongly suggesting improperly functioning inhibitory mechanisms that were functioning well in the control subjects. This study supports the hypothesis about the existence of a tinnitus-specific brain network. Such a network could respond to any acoustic stimuli by activating limbic areas involved in stress reactivity and emotional processing and by reducing activation of areas responsible for attention and acoustic filtering (thalamus, frontal regions), possibly reinforcing negative effects of tinnitus.

Establishment of an experimental system to study the influence of electrical field on cochlear structures.

Treatment of partial hearing loss with the combined electrical and acoustical stimulation (EAS) aims at restoring the hearing while preserving the residual hearing. The aim of present study was to establish an in vitro system to study the effects of an electrical field on the auditory hair cells and spiral ganglion cells. Cochlear tissues containing the organ of Corti, spiral limbus and spiral ganglion neurons were dissected from post-natal Wistar rats (p3-p5) and cultured in the micro-channels. Electric current was homogenously applied on the apical, medial and basal parts of explants. Biphasic rectangular pulses were applied continuously over a period of 30 h or 42 h and the explants were fixed and stained to visualize the hair cells and neurites. Application of electrical field for 30 h has not induced significant changes in the number of inner or outer hair cells when compared to the control. However, after 42 h of electric stimulation, the number of hair cells decreased significantly by about 30%. The medial and basal fragments were particularly affected. The number of neurites has not been influenced but significant neuritic beading, consistent with neurodegeneration, was observed after 42 h of electric stimulation. Although performed with immature auditory tissues, our findings hint at the possibility of particular electric current inducing damage or loss of auditory hair cells, which should be considered when designing EAS electrodes.

Expression analysis of prestin and selected transcription factors in newborn rats.

Transcription factors (TFs) have a central role to play in regulating gene expression. To analyze the co-expression patterns of selected TFs with the motor protein prestin of the outer hair cells, we applied an real-time PCR approach combining several kinds of information: (i) expression changes during postnatal development, (ii) expression changes by exposure of organotypic cultures of the organ of Corti to factors which significantly affect prestin expression [thyroid hormone (T4), retinoic acid (RA), butyric acid (BA), increased KCl concentration] and (iii) changes along the apical-basal gradient. We found that the mRNA levels of the TF Brn-3c (Pou4f3), a member of the POU family, are significantly associated with the regulation of prestin during postnatal development and in cultures supplemented with T4 (0.5 µM), BA (0.5-2.0 mM), and high KCl (50 mM) concentration. The mRNA level of the constitutively active TF C/ebpb (CCAAT/enhancer binding protein beta) correlates positively with the prestin expression during postnatal development and in cultures exposed to T4 and RA (50-100 µM). The mRNA levels of the calcium-dependent TF CaRF correlates significantly with the prestin expression in cultures exposed to T4 and high KCl concentration. The observed coexpression patterns may suggest that the TFs Brn-3c, C/ebpb, and Carf contribute to regulating the expression of prestin under the investigated conditions.

Long-term improvement in tinnitus after modified tinnitus retraining therapy enhanced by a variety of psychological approaches.

This work evaluates an enhanced tinnitus retraining therapy (TRT) for patients with chronic tinnitus based on different group therapeutic interventions in a day hospital setting. Therapy for chronic tinnitus is intended to improve the way patients cope with tinnitus by learning how to reduce tinnitus-induced impairments. Short-term and long-term changes in stress variables and tinnitus-related distress were investigated using 3 psychometric instruments. Patients received 7 consecutive days of a multidisciplinary therapy at the Charité University Hospital in Berlin. The data were assessed before and after therapy, either immediately or after 3, 6 or 12 months. As a control, we used scores of tinnitus patients from the waiting list, and compared these to the scores of the therapy group 3 months after the end of treatment. The main factors of the modified TRT were Jacobson's progressive muscle relaxation, physiotherapy, education via lectures and training of selective attention, as well as changes of appraisal, mental attitude and behavior towards tinnitus. The therapy resulted in a significant reduction in both short-term and long-term tinnitus-related distress and psychometric stress variables, with the latter being more reduced in patients with higher initial scores. Moreover, our study revealed differences in psychometric parameters concerning duration of tinnitus, age and gender, which may explain the different outcomes of therapy. The outpatient setting enables the patients to test, practice and transfer strategies into their everyday life.

Geldanamycin induces production of heat shock protein 70 and partially attenuates ototoxicity caused by gentamicin in the organ of Corti explants.

BACKGROUND: Heat shock protein 70 (HSP70) protects inner ear cells from damage and death induced by e.g. heat or toxins. Benzoquinone ansamycin antibiotic geldanamycin (GA) was demonstrated to induce the expression of HSP70 in various animal cell types. The aim of our study was to investigate whether GA induces HSP70 in the organ of Corti (OC), which contains the auditory sensory cells, and whether GA can protect these cells from toxicity caused by a common aminoglycoside antibiotic gentamicin. METHODS: To address these questions, we used the OC explants isolated from p3-p5 rats. As a read-out, we used RT-PCR, ELISA and immunofluorescence. RESULTS: We found that GA at the concentration of 2 microM efficiently induced HSP70 expression on mRNA and protein level in the OC explants. Confocal microscopy revealed that HSP70 induced by GA is expressed by hair cells and interdental cells of spiral limbus. Preincubation of explants with 2 muM GA prior to adding gentamicin (500 microM) significantly reduced the loss of outer but not inner hair cells, suggesting different mechanisms of otoprotection needed for these two cell types. CONCLUSION: GA induced HSP70 in the auditory sensory cells and partially protected them from toxicity of gentamicin. Understanding the molecular mechanisms of GA otoprotection may provide insights for preventative therapy of the hearing loss caused by aminoglycoside antibiotics.

Impact of a relaxation training on psychometric and immunologic parameters in tinnitus sufferers.

OBJECTIVE: Tinnitus often entails severe psychological distress. Reversely, tinnitus may be considered as a chronic stressor. Based on this hypothesis, we investigated whether improving stress-managing capabilities would influence psychological and stress-related immunological parameters in chronic tinnitus sufferers. METHODS: Tinnitus (TPs, n=26) and non-tinnitus participants (NTPs, n=13) took part in a standardised 10-week relaxation program. An additional group of tinnitus sufferers (n=18), randomly assigned to a waiting list, served as control (TC) subjects. Mood, perceived stress, global quality of life, and tinnitus disturbance were assessed before and after the intervention. The stress-sensitive immunological parameters TNF-alpha, IL-6, and IL-10 were measured before, during, and at the end of the intervention. RESULTS: The program resulted in a significantly decreased perception of stress, anxious depression, anger, and tinnitus disturbance, paralleled by a reduction of TNF-alpha. No alterations were noted for IL-6 or IL-10. For the NTPs and TCs, no relevant psychological or immune changes could be observed. CONCLUSION: The data suggest that (1) the training offered improved stress-managing capabilities in chronic tinnitus sufferers, and (2) TNF-alpha may be conceived as a stress marker.