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Translational approach to study flexibility as an endophenotype of obsessive compulsive disorders
- N. Benzina, S.L. Mondragon, N. Ouarti, L. Mallet, E. Burguiere
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- Journal:
- European Psychiatry / Volume 29 / Issue S3 / November 2014
- Published online by Cambridge University Press:
- 17 April 2020, p. 546
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Behavioral flexibility is the ability of a subject to change its behavior according to contextual cues. In humans, Obsessive Compulsive Disorders (OCD) is characterized by repetitive behavior, performed through rigid rituals. This phenomenological observation has led to explore the idea that OCD patients may have diminished behavioral flexibility. To address this question we developed innovative translational approaches across multiple species, including human patients suffering from obsessive-compulsive disorders, and rodent genetic models of OCD to provide original data in the perspective of enlightening the neurocognitive bases of compulsive behaviors. Behavioral flexibility may be challenged in experimental tasks such as reversal learning paradigms. In these tasks, the subject has to respond to either of two different visual stimuli but only one stimulus is positively rewarded while the other is not. After this first association has been learned, reward contingency are inverted, so that the previously neutral stimulus is now rewarded, while the previously rewarded stimulus is not. Performance in reversal learning is indexed by the number of perseverative errors committed when participants maintain their response towards previously reinforced stimulus in spite of negative reward. Unsurprisingly, this behavioral task has been adapted to mice using various response modalities (T-maze, lever press, nose-poke). Using animal models of compulsive behaviors give much more possibilities to study the deficient functions and their underlying neural basis that could lead to pathological repetitive behaviors. Here we present new behavioral set-ups that we developed in parallel in human (i.e. healthy subjects and OCD patients) and mice (i.e. controls and SAPAP3-KO mice) to study the role of the behavioral flexibility as a possible endophenotype of OCD. We observed that the subjects suffering of compulsive behaviors showed perseverative maladaptive behaviors in these tasks. By comparing the results of a similar task-design in humans and mouse models we will discuss the pertinence of such translational approach to further study the neurocognitive basis of compulsive behaviors.
Compulsivity and probabilistic reversal learning in OCD and cocaine addiction
- P. Smith, N. Benzina, F. Vorspan, L. Mallet, K. N’Diaye
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- Journal:
- European Psychiatry / Volume 30 / Issue S2 / November 2015
- Published online by Cambridge University Press:
- 15 April 2020, pp. S110-S111
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Compulsive behavior is a core symptom of both obsessive compulsive disorder (OCD) and cocaine addiction (CA). Across both pathologies, one can identify a priori goal-directed actions (purportedly anxiolytic checking or washing in OCD and pleasure-seeking drug use in addiction) that turn into rigid, ritualized and repetitive behaviors over which the patient loose control. One possible psychopathological mechanism underlying compulsivity is behavioral inflexibility, namely a deficit in the aptitude to dynamically adapt to novel contexts and changing reward rules. The probabilistic reversal learning paradigm allows to objectively assess behavioral flexibility by challenging participants with a task where they have to learn through trials-and-errors which of two stimuli is the most-often rewarded one, while adjusting to sudden inconspicuous contingency reversals. We therefore hypothesized that both OCD and CA would be associated with impaired cognitive flexibility, as measured through perseverative response rate following contingency reversals in this task. Interestingly, impulsivity may also be assessed within this task via the tendency of participants to switch from one stimulus to the other following probabilistic errors. To investigate cognitive inflexibility in relation to CA and OCD respectively, we first compared the performance in a probabilistic reversal learning task of cocaine users, ex cocaine users (abstinent for 2 months or more), and controls, as well as that of participants from the general population whose obsessive-compulsive traits were assessed using the OCI-R, a well-validated self-questionnaire. Our task yielded results similar to those found in the literature: cocaine addicts changed their responses more often, and learned less effectively. Ex-cocaine addicts performed better than addicts but worse than controls, suggesting that addicts’ poor results may be in part explained by reversible cognitive consequences of addiction. Addicts with less cognitive impairments may also be less likely to relapse. Regarding the relationship of flexibility to subclinical OCD traits, we found no link between OCI-R score and perseveration, or between impulsiveness and excessive switching.