AUTHOR=Imes Sidney , Parker David A. , Chen Marissa , Cubells Joseph F. , Walker Elaine F. , Duncan Erica 

TITLE=The acoustic startle response in 22q11 deletion syndrome: from animal models to humans

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 19 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2025.1630109

DOI=10.3389/fnins.2025.1630109

ISSN=1662-453X

ABSTRACT=The startle response is a reflexive contraction of skeletal musculature in response to a strong acoustic stimulus that is evolutionarily preserved across species. There is a broad and comprehensive literature connecting components of the startle response such as latency, magnitude and pre-pulse inhibition, to psychosis status and risk. In this review, we examine the startle response in human subjects with 22q11.2 Deletion Syndrome (22qDel) and in analogous animal models. 22qDel is a copy number variant disorder typically involving ~1.5 to 3 Mb of DNA on the proximal 22q region, which occurs in approximately 1 in 2000–6,000 births, and serves as the most robust single genetic predictor of psychosis risk (conferring ~30x higher risk). By comparing the human literature directly to the genetic mouse models, we identify areas of convergence and divergence between human and animal results and highlight gaps related to differences in neurodevelopmental stages, experimental design, stimulus outcome measurements, and genetic deletion areas in each animal model. We then highlight the translational power of the acoustic startle response and how it can be studied in conjunction with more basic cellular investigations related to basic neural function and responsiveness. Because the acoustic startle response is seen across vertebrate species with well characterized circuitry, we argue for using the acoustic startle response as a translational biological probe of underlying neurobiology relevant to 22qDel and by extension, psychosis and psychosis risk.