Tinnitus and tinnitus disorder: Genetic, neurobiological, and clinical differentiation

iScience. 2026 Jun 3;29(6):116080. doi: 10.1016/j.isci.2026.116080. eCollection 2026 Jun 19.

ABSTRACT

Tinnitus is the conscious perception of sound in the absence of an external acoustic source. When accompanied by emotional distress, cognitive dysfunction, or autonomic arousal leading to behavioral and functional impairment, it is termed "tinnitus disorder." This perspective synthesizes genetic, epidemiological, and neuroimaging evidence supporting the distinction between tinnitus and tinnitus disorder. Genetic studies indicate that tinnitus is linked to multiple common variants of small effect size, whereas tinnitus disorder involves rarer variants exerting larger effects. Epidemiologically, hearing loss is the primary risk factor for tinnitus, whereas personality traits like neuroticism, mood, and sleep disturbances predict tinnitus disorder. Neuroimaging identifies three interrelated neural pathways: a lateral "loudness" pathway, a descending "inhibitory" pathway, and a medial "distress" pathway that is specifically activated in tinnitus disorder, providing a neural basis for tinnitus related suffering. Future needs include the establishment of standardized diagnostic criteria and a severity grading system of tinnitus disorder.

PMID:42291209 | PMC:PMC13255023 | DOI:10.1016/j.isci.2026.116080