Hearing problems in humans and mouse models with rare copy number variants associated with schizophrenia: a scoping review protocol.

Background: Hearing loss is a risk factor for developing auditory hallucinations and other psychosis symptoms. To date, very little research has investigated hearing loss in individuals with a high genetic risk of developing schizophrenia and other types of psychosis. 13 copy number variant (CNV) loci are robustly associated with an increased risk of schizophrenia. Of these, microdeletions at 22q11.2 often lead to some hearing loss, and mouse models of this CNV display impaired auditory functioning. We hypothesise that individuals who have a high genetic risk of schizophrenia may also experience hearing problems. This scoping review will explore whether the 13 schizophrenia-associated CNVs are related to hearing problems, including peripheral hearing loss and other auditory problems, in humans and related mouse models.

Methods: Our scoping review will follow guidelines provided by the Joanna Briggs Institute and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. A systematic search will be completed using PubMed (MEDLINE), Embase, PsychINFO, and Cochrane Library databases, as well as other sources to identify relevant grey literature. Search terms will include all commonly used synonyms for hearing loss and problems with auditory perception, and both human and mouse studies that describe relevant CNVs will be included. Search lists will be screened by two authors independently, according to eligibility criteria, and data will be extracted and summarised using a narrative approach.

Conclusions: To our knowledge, this will be the first scoping review to explore auditory functioning across all CNVs that confer high schizophrenia risk. Looking ahead, if hearing problems are a clinical feature in these groups (including humans and related mouse models), they may serve as useful genetic models for future mechanistic studies.