Lipid parameters and depression in patients with chronic tinnitus: A cross-sectional observation.

BACKGROUND: Pathophysiological theories assume importance of metabolic abnormalities in patients with major depression - and possibly chronic tinnitus. Although chronic tinnitus frequently correlates with depression, links between high-density lipoprotein (HDL) and depression are uninvestigated. METHODS: Two-hundred patients with chronic tinnitus (Mage = 55; 51% female) were examined. Serum levels of total cholesterol (TC), triglycerides (TGs), HDL, low-density lipoprotein cholesterol (LDL), non-HDL, as well as LDL/HDL and TC/HDL ratios were analysed. Questionnaires included depression subscales of the ICD-10 Symptom Rating, the Hospital Anxiety and Depression Scale (HADS_D), and the Berlin Mood Questionnaire (BSF). Multivariate analyses of covariance and linear regression models - which controlled age, tinnitus-related distress and perceived stress - investigated between-subgroup differences (p < 0.05) and linear associations between HDL indices and depression (p < 0.01). RESULTS: HDL levels did not differ for tinnitus-symptom durations, smoking and alcohol use levels, statin or antihypertensive drug use, and body-mass indices. Relative to non-to-mildly depressed patients with chronic tinnitus, patients with moderate-to-severe depression (n = 45; 23%) had significantly lower HDL levels (d = -0.35) and higher LDL/HDL (d = 0.39) and TC/HDL ratios (d = 0.40). Across participants, HDL-levels were negatively associated with depression as measured by the HADS_D and BSF_indifference scales. CONCLUSIONS: In keeping with general depression research, low serum HDL levels correlate with depressive symptomatology in patients with chronic tinnitus. This association may be influenced by proximal (e.g. modulations of HPA-axis activity) or distal factors (e.g. maladaptive coping behaviours) - both of which should be conceptualized within psychological stimulus-processing frameworks.

Vascular-Metabolic Risk Factors and Psychological Stress in Patients with Chronic Tinnitus.

Little is known about molecular correlates of chronic tinnitus. We examined interrelationships between vascular−metabolic risk factors, perceived stress, and other routine blood values in patients with chronic tinnitus. Two-hundred patients (51% female) were screened for 49 blood parameters pertaining to vascular−metabolic risk, immune function, and redox processes. They further completed perceived stress- and tinnitus-related distress questionnaires. Following descriptive analyses, gender-specific sets of age- and tinnitus-severity-adjusted regression models investigated associations between perceived stress and blood parameters. Patients reported mildly elevated levels of perceived stress. Elevated levels of total cholesterol (65% and 61% of female and male patients, respectively), non-HDL-c (43/50%), LDL-c (56/59%), and lipoprotein_a (28/14%) were accompanied by high rates of overweight (99/100%) and smoking (28/31%). A low-level inflammatory state was accompanied by reduced reactive oxygen species (ROS)-neutralizing capacity (reduced co-enzyme Q10 and SOD1 levels). Most vascular risk factors were not correlated with perceived stress, except for fibrinogen (ß = −0.34) as well as C-reactive protein (ß = −0.31, p < 0.05) in men, and MCV (ß = −0.26, p < 0.05) in women. Interrelations between blood parameters and stress levels need to be investigated within psychobehavioural frameworks across varying distress levels. Alongside psychological interventions, a low-level inflammatory state may be a route for pharmacological therapeutics.

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.

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.

Gender-Specific Risk Factors and Comorbidities of Bothersome Tinnitus.

OBJECTIVE: This study aims to identify gender-specific risk factors associated with the presence of bothersome tinnitus (compared with non-bothersome tinnitus), including sociodemographic and lifestyle factors, tinnitus-associated phenomena (hearing loss, traumatic experiences, sleep disturbances), and physical as well as mental comorbidities. METHODS: We conducted a cross-sectional study using survey data from the Swedish LifeGene cohort containing information on self-reported tinnitus (N = 7615). We (1) analyzed risk factor and comorbidity frequencies, (2) computed multivariate logistic regression models to identify predictors of bothersome tinnitus within both genders, and (3) moderated logistic regression models to compare effects between genders. RESULTS: (1) The majority of factors that differed in frequencies between bothersome and non-bothersome tinnitus were equal for both genders. Women with bothersome tinnitus specifically reported higher rates of cardiovascular disease, thyroid disease, epilepsy, fibromyalgia, and burnout, and men with bothersome tinnitus reported higher rates of alcohol consumption, Ménière's disease, anxiety syndrome, and panic (compared with non-bothersome tinnitus, respectively). (2) Across both genders, multivariate logistic regression analyses revealed significant associations between bothersome tinnitus and age, reduced hearing ability, hearing-related difficulties in social situations, and reduced sleep quality. In women, bothersome tinnitus was specifically associated with cardiovascular disease and epilepsy; in men, with lower education levels and anxiety syndrome. (3) Moderated logistic regression analyses revealed that the effects of low education and anxiety syndrome were present in men, but not in women, whereas the effects of age, reduced hearing ability and related difficulties, cardiovascular disease, epilepsy, and burnout were not gender specific. CONCLUSION: Irrespective of gender, bothersome tinnitus is associated with higher age, reduced hearing ability, hearing-related difficulties, cardiovascular disease, epilepsy, and burnout. Gender-specific effects comprise low levels of education and the presence of anxiety syndrome for men. These findings need to be interpreted with caution, yet they suggest the presence of gender-specific biopsychosocial influences in the emergence or maintenance of bothersome tinnitus. Future studies ought to investigate the underlying mechanisms of the observed relationships.