Objective and Measurable Biomarkers in Chronic Subjective Tinnitus

Kang, Dae Woong; Kim, Sung‐Soo; Park, Dong-Choon; Kim, Sang-Hoon; Yeo, Seung Geun

doi:10.3390/ijms22126619

Cited by 17 publications

(15 citation statements)

References 112 publications

(128 reference statements)

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“…No consistent effects were found for the other blood parameters studied, partially in contrast to previous tinnitus research (see Haider et al, 2021 ; Kang et al, 2021 ). For the inflammatory markers IL-6, CRP, and NLR, no associations were found with psychological or audiological tinnitus-related variables.…”

Section: Discussioncontrasting

confidence: 99%

“…Immunological disturbances in tinnitus ( Szczepek and Mazurek, 2017 ; Haider et al, 2021 ; Kang et al, 2021 ) might represent a possible link between bothersome tinnitus and depression/anxiety. Immune alterations in chronic tinnitus have not yet been studied extensively, but some previous findings include increased inflammatory parameters such as neutrophil-to-lymphocyte ratio (NLR; Ozbay et al, 2015 ; Yildiz et al, 2020 ; Demir, 2021 ) and positive associations between tinnitus-related distress and TNF-α ( Szczepek et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

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Negative Associations of Stress and Anxiety Levels With Cytotoxic and Regulatory Natural Killer Cell Frequency in Chronic Tinnitus

et al. 2022

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BackgroundDepression and anxiety are known to be associated with stress-induced changes in the immune system. Bothersome tinnitus can be related to stress and often co-occurs with depression and anxiety. This study investigates associations of psychological and audiological tinnitus-related factors with inflammatory parameters and immune cell subsets in chronic tinnitus patients as well as treatment-related effects.MethodsThis longitudinal study of inpatients treated with compact multimodal tinnitus-specific cognitive behavioral therapy included four repeated measurement sessions: baseline (N = 41), treatment end, 7.8-week (N = 35), and 13.8-week follow-up (N = 34). Data collection included audiometric testing, blood sampling, and psychometric questionnaires: Tinnitus Handicap Inventory (THI), Perceived Stress Questionnaire (PSQ-20), and Hospital Anxiety Depression Scale (HADS). Flow cytometry was used to analyze immune cell subsets. Statistical analyses comprised correlation and network analysis (cross-sectional), and linear mixed effect models (longitudinal).ResultsBootstrapped network analysis showed negative averaged cross-sectional associations of cytotoxic natural killer (NKc) cell frequency (CD56 + CD16+) and PSQ-20 (−0.21 [−0.48, 0]) and of regulatory natural killer (NKreg) cell frequency (CD56 + CD16dim/−) and HADS anxiety (−0.14 [−0.38, 0]). No significant treatment effects were found. A negative predictive effect of baseline PSQ-20 scores (β = −6.22 [−12.18, −0.26], p = 0.041) and a positive predictive effect of baseline ferritin levels (β = 8.90 [2.76, 15.03], p = 0.004) on NKc cell frequency across the repeated measurement sessions were observed.ConclusionWe observed negative relationships between perceived stress levels and NKc cell frequency and between anxiety levels and NKreg cell frequency in chronic tinnitus patients. These exploratory results suggest stress−/anxiety-related immune alterations in bothersome tinnitus but need to be tested in further confirmatory studies with larger sample sizes. The potential of NK cells as biomarkers of emotional distress in chronic tinnitus should be further investigated.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Negative Associations of Stress and Anxiety Levels With Cytotoxic and Regulatory Natural Killer Cell Frequency in Chronic Tinnitus

et al. 2022

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“…Biomarker research for chronic tinnitus is still in its infancy [ 8 , 9 , 10 , 11 , 12 ], yet a role of vascular risk factors and inflammatory processes has been suggested [ 13 , 14 ]. Other studies investigated cytokine changes [ 15 ], mean platelet volumes (MPV), and neutrophil-to-lymphocyte ratios (NLR) with inconclusive results.…”

Section: Introductionmentioning

confidence: 99%

“…Regarding biological underpinnings of perceived stress, Juster et al [ 40 ] proposed 26 putative biomarkers that included immune, vascular-metabolic and oxidative parameters that were also denoted as possible transdiagnostic markers across various psychological conditions [ 43 , 44 , 45 ]. In this vain, biomarker candidates that were identified in patients with chronic tinnitus, and that relate to cardiovascular, inflammatory, or immune-related processes [ 12 ], may or may not overlap with biomarkers of perceived stress.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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.

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“…CRP levels are increased in patients with several diseases such as cancer, HIV, or cardiovascular diseases and elevated CRP levels are related with higher mortality (Li et al, 2017 ). Furthermore, there is first evidence that CRP levels are increased in chronic tinnitus (Kang et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Higher Peripheral Inflammation Is Associated With Lower Orbitofrontal Gamma Power in Chronic Tinnitus

Becker

Keck

Rohleder

et al. 2022

Front. Behav. Neurosci.

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Chronic tinnitus, the continuous perception of a phantom sound, is a highly prevalent audiological symptom, for which the underlying pathology has not yet been fully understood. It is associated with neurophysiological alterations in the central nervous system and chronic stress, which can be related with a disinhibition of the inflammatory system. We here investigated the association between resting-state oscillatory activity assessed with Magnetoencephalography (MEG), and peripheral inflammation assessed by C-reactive protein (CRP) in a group of patients with chronic tinnitus (N = 21, nine males, mean age: 40.6 ± 14.6 years). Additionally, CRP was assessed in an age- and sex-matched healthy control group (N = 21, nine males, mean age: 40.9 ± 15.2 years). No MEG data was available for the control group. We found a significant negative correlation between CRP and gamma power in the orbitofrontal cortex in tinnitus patients (p < 0.001), pointing to a deactivation of the orbitofrontal cortex when CRP was high. No significant clusters were found for other frequency bands. Moreover, CRP levels were significantly higher in the tinnitus group than in the healthy controls (p = 0.045). Our results can be interpreted based on findings from previous studies having disclosed the orbitofrontal cortex as part of the tinnitus distress network. We suggest that higher CRP levels and the associated deactivation of the orbitofrontal cortex in chronic tinnitus patients is maintaining the tinnitus percept through disinhibition of the auditory cortex and attentional or emotional top-down processes. Although the direction of the association (i.e., causation) between CRP levels and orbitofrontal gamma power in chronic tinnitus is not yet known, inflammation reducing interventions are promising candidates when developing treatments for tinnitus patients. Overall, our study highlights the importance of considering immune-brain communication in tinnitus research.

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Objective and Measurable Biomarkers in Chronic Subjective Tinnitus

Cited by 17 publications

References 112 publications

Negative Associations of Stress and Anxiety Levels With Cytotoxic and Regulatory Natural Killer Cell Frequency in Chronic Tinnitus

Negative Associations of Stress and Anxiety Levels With Cytotoxic and Regulatory Natural Killer Cell Frequency in Chronic Tinnitus

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

Higher Peripheral Inflammation Is Associated With Lower Orbitofrontal Gamma Power in Chronic Tinnitus

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