RT Journal Article SR Electronic T1 Parallel valence processing alterations associated with compulsive behavior in SAPAP3 knockout mice and human OCD JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.06.04.447162 DO 10.1101/2021.06.04.447162 A1 Bridget L. Kajs A1 Peter J. van Roessel A1 Gwynne L. Davis A1 Leanne M. Williams A1 Carolyn I. Rodriguez A1 Lisa A. Gunaydin YR 2021 UL http://biorxiv.org/content/early/2021/06/05/2021.06.04.447162.abstract AB Abnormalities in valence processing – the processing of aversive or appetitive stimuli – may be an underrecognized component of obsessive-compulsive disorder (OCD). Independent experimental paradigms have suggested disturbance of emotional valence systems in OCD, yet no standardized assay has been employed to assess both negative and positive valence processing in clinical studies of OCD patients, either at baseline or in response to therapeutic interventions. Additionally, preclinical rodent models are critical for treatment discovery in OCD, yet investigations examining whether rodent models of compulsive behavior similarly show alterations in valence systems have been limited. We sought to establish paradigms for assessing valence processing across both human OCD patients and in a preclinical rodent model: in OCD patients, we used validated behavioral tests to assess explicit and implicit processing of fear-related facial expressions (negative valence) and socially-rewarding happy expressions (positive valence); in the SAPAP3 knockout (KO) mouse model of compulsive behavior, we used auditory fear conditioning and extinction (negative valence) and reward-based operant conditioning (positive valence). We find that OCD patients show enhanced negative and impaired positive valence processing, and that performance on valence processing tasks correlates with clinical measures of OCD severity. We further find that SAPAP3 KO mice show heightened negative and impaired positive valence processing alterations similar to those of OCD patients. Our results show parallel valence processing abnormalities in OCD patients and a preclinical rodent model of compulsive behavior, and suggest valence processing alterations as novel therapeutic targets across a translational research spectrum.Competing Interest StatementIn the last 3 years, Dr. Rodriguez has served as a consultant for Epiodyne and received research grant support from Biohaven Pharmaceuticals and a stipend from APA Publishing for her role as Deputy Editor at The American Journal of Psychiatry. Dr. Williams has served as a scientific advisor for One Mind Psyberguide, a member of the executive advisory board for the Laureate Institute for Brain Research and holds patent 16921388 (Systems and Methods for Detecting Complex Networks in MRI Image Data) unrelated to the present study. All other authors declare that they have no conflicts of interest.