Cross-species models of OCD spectrum disorders

Abstract

Several axis-I neuropsychiatric disorders are characterised by repetitive motor habits suggestive of underlying inhibitory dyscontrol, and may constitute members of a putative obsessive-compulsive (OC) spectrum. Notable examples include obsessive-compulsive disorder (OCD) and trichotillomania (repetitive hair-pulling). Multiple tiers of evidence link these conditions with underlying dysregulation of fronto-striatal circuitry and monoamine systems. These abnormalities represent key targets for existing and novel treatment interventions. Nonetheless, the brain bases of these conditions, and treatment mechanisms, remain poorly characterised. Animal models of repetitive habits and inhibitory control problems show great potential for augmenting our understanding of the pathophysiology and treatment of OC spectrum conditions. Here, we begin by describing clinical features of OC spectrum disorders, and criteria used to assess the validity of animal models of symptomatology. Namely, face validity (phenomenological similarity between inducing conditions and specific symptoms of the human phenomenon), predictive validity (similarity in response to treatment) and construct validity (similarity in underlying physiological or psychological mechanisms). We then survey animal models of OC spectrum conditions within this framework, focusing on (i) ethological models; (ii) genetic and pharmacological models; and (iii) behavioral models. Key future research directions are highlighted.