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GDNF and BDNF gene interplay in chronic tinnitus.

ABSTRACT: BACKGROUND:Glial cell-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) play key roles in the early development of the central auditory pathway and the inner ear. Both have been successfully employed to treat experimental forms of hearing loss and are likely to operate in a broad spectrum of auditory phenotypes, including phantom perceptions of sound. We conducted a genetic association study addressing five biallelic candidate variants in 240 Caucasian subjects who had been diagnosed with tinnitus for more than 6 months. FINDINGS:Allele frequencies were determined for three GDNF and two BDNF markers, including a functional missense substitution (V66M). When data were compared to previously examined control populations, no significant allelic associations were noted after corrections for multiple testing. However, using a multiple regression approach and scores from a validated self-report questionnaire, GDNF and BDNF genotypes jointly predicted tinnitus severity in women (N=69, uncorrected p=0.04) but not in men (N=171, n.s.). CONCLUSIONS:The present findings serve as an incentive for further explorations of neurotrophic factors' role in predicting clinical features of tinnitus. Possible implications of sexually dimorphic at-risk genotypes are discussed with regard to hearing and neural plasticity.

SUBMITTER: Pg S

PROVIDER: S-EPMC3459214 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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GDNF and BDNF gene interplay in chronic tinnitus.

Pg Sand S B Langguth L M Schecklmann S T Kleinjung K

International journal of molecular epidemiology and genetics 20120831 3

<h4>Background</h4>Glial cell-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) play key roles in the early development of the central auditory pathway and the inner ear. Both have been successfully employed to treat experimental forms of hearing loss and are likely to operate in a broad spectrum of auditory phenotypes, including phantom perceptions of sound. We conducted a genetic association study addressing five biallelic candidate variants in 240 Caucasian subje ...[more]

PMID: 23050055

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Project description:BackgroundCurrently, 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.MethodsIn 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.ResultsAt 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.).DiscussionWhile 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.

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GDNF and BDNF gene interplay in chronic tinnitus.

Publications

GDNF and BDNF gene interplay in chronic tinnitus.

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