A cross-species assessment of behavioral flexibility in compulsive disorders.

Lack of behavioral flexibility has been proposed as one underlying cause of compulsions, defined as repetitive behaviors performed through rigid rituals. However, experimental evidence has proven inconsistent across human and animal models of compulsive-like behavior. In the present study, applying a similarly-designed reversal learning task in two different species, which share a common symptom of compulsivity (human OCD patients and Sapap3 KO mice), we found no consistent link between compulsive behaviors and lack of behavioral flexibility. However, we showed that a distinct subgroup of compulsive individuals of both species exhibit a behavioral flexibility deficit in reversal learning. This deficit was not due to perseverative, rigid behaviors as commonly hypothesized, but rather due to an increase in response lability. These cross-species results highlight the necessity to consider the heterogeneity of cognitive deficits in compulsive disorders and call for reconsidering the role of behavioral flexibility in the aetiology of compulsive behaviors.

[New pathophysiological approaches to obsessive-compulsive disorder]. / Nouvelles approches physiopathologiques du trouble obsessionnel-compulsif.

New pathophysiological approaches to obsessive-compulsive disorder. Since the beginning of research in the 1980s, it has been consistently shown that obsessive-compulsive disorder (OCD) is neurobiologically underpinned by the dysfunction of a so-called cortico-striato-thalamo-cortical loop (CSTC). Within this loop, various structures have been identified as being affected, foremost among which are the orbitofrontal and anterior cingulate cortices, as well as the caudate nucleus, one of the structures of the striatum. More recently, a large number of studies have contributed to broadening this classical view of the altered CSTC loop by revealing the involvement of broader cerebral networks involving notably the temporal and parietal cortices. These functional and structural alterations are underpinned by an impairment of certain neurotransmission systems. While serotonin was the first to be incriminated due to the efficacy of serotonergic antidepressants, it turns out that years of research in genetics and neuroimaging have invalidated this hypothesis in favour of a new target: glutamate. Our understanding of the pathophysiology of OCD is thus constantly being refined through the combination of increasingly precise neuroanatomical, neurochemical, and genetic data, and will ultimately contribute to the development of new therapies for this disorder.

Nouvelles approches physiopathologiques du trouble obsessionnel-compulsif. Depuis le début des recherches menées dans les années 1980, il a été montré avec consistance que le trouble obsessionnel-compulsif (TOC) est sous-tendu sur le plan neurobiologique par la dysfonction d'une boucle dite cortico-striato-thalamo-corticale (CSTC). Au sein de cette boucle, diverses structures ont été identifiées comme altérées ; au premier rang desquelles les cortex orbitofrontal et cingulaire antérieur, ainsi que le noyau caudé, une des structures du striatum. Plus récemment, un grand nombre d'études ont contribué à élargir cette vision classique d'altération de la boucle CSTC en révélant l'implication de réseaux cérébraux plus larges impliquant notamment les cortex temporal et pariétal. Ces altérations, tant fonctionnelles que structurelles, sont sous-tendues par un déséquilibre de certains systèmes de neurotransmission. Alors que la sérotonine fut la première incriminée du fait de l'efficacité des antidépresseurs sérotoninergiques, il s'avère que des années de recherche en génétique et neuro-imagerie ont invalidé cette hypothèse au profit d'une nouvelle cible : le glutamate. Notre compréhension de la physiopathologie du TOC est ainsi en constant raffinement grâce à la combinaison des données de plus en plus fines neuroanatomiques, neurochimiques, et génétiques ; et contribue à terme au développement de nouvelles thérapeutiques pour ce trouble.

Cognitive Dysfunction in Obsessive-Compulsive Disorder.

Obsessive-compulsive disorder (OCD) is a mental disorder featuring obsessions (intrusive thoughts) and compulsions (repetitive behaviors performed in the context of rigid rituals). There is strong evidence for a neurobiological basis of this disorder, involving limbic cortical regions and related basal ganglion areas. However, more research is needed to lift the veil on the precise nature of that involvement and the way it drives the clinical expression of OCD. Altered cognitive functions may underlie the symptoms and thus draw a link between the clinical expression of the disorder and its neurobiological etiology. Our extensive review demonstrates that OCD patients do present a broad range of neuropsychological dysfunctions across all cognitive domains (memory, attention, flexibility, inhibition, verbal fluency, planning, decision-making), but some methodological issues temper this observation. Thus, future research should have a more integrative approach to cognitive functioning, gathering contributions of both experimental psychology and more fundamental neurosciences.