A cross-species assessment of behavioral flexibility in compulsive disorders

Abstract

BackgroundCompulsive behaviors, one of the core symptoms of Obsessive-Compulsive Disorder (OCD), are defined as repetitive behaviors performed through rigid rituals. The lack of behavioral flexibility has been as being one of the primary causes of compulsions, but studies exploring this dimension have shown inconsistencies in different tasks performed in human and animal models of compulsive behavior. The aim of this study was so to assess the involvement of behavioral flexibility in compulsion, with a similar approach across different species sharing a common symptom of compulsivity.\n\nMethods40 OCD patients, 40 healthy individually matched control subjects, 26 C57BL/6J Sapap3 KO mice and 26 matched wildtype littermates were included in this study. A similar reversal learning task was designed to assess behavioral flexibility in parallel in these two species.\n\nResultsWhen considered as homogeneous groups, OCD patients and KO mice expressing compulsive behaviors did not significantly differ from their controls regarding behavioral flexibility. When clinical subtypes were considered, only patients exhibiting checking compulsions were impaired with more trials needed to reach the reversal criterion. In KO mice, a similarly impaired subgroup was identified. For both species, this impairment did not result in a greater perseveration after reversal, but in a greater lability in their responses in the reversal condition. Moreover, this impairment did not correlate with the severity of compulsive behaviors.\n\nConclusionsIn our cross-species study, we found no consistent link between compulsive behaviors and a lack of behavioral flexibility. However, we showed in both species that the compulsive group was heterogeneous in term of performance in our reversal learning task. Among the compulsive subjects, we identified a subgroup with impaired performance not due to perseverative and rigid behaviors as commonly hypothesized, but rather to an increase in response lability.