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Translational Approaches to Studying Repetitive Behavior and Resistance to Change in Autism

Meeting Summary
Washington, D.C.

Sponsored by:
National Institute of Mental Health

In September 2007, NIMH held a multidisciplinary workshop to identify major trends, gaps, and opportunities in clinical and basic research on repetitive behavior and resistance to change in autism. Autism is a neurobiological disorder with extreme heterogeneity in its behavioral presentation. The core symptoms of the disorder include markedly abnormal or impaired development in social interaction and communication. In addition, a third component of autism includes restricted, repetitive, and stereotyped patterns of behavior, interests, and activities.

It is this third part of the triad of impairments in autism that is significant for families, teachers, colleagues, and strangers who may interact with affected individuals. The behavioral presentation may include stereotyped motor movements (rocking, hand flapping, clapping, etc.), repetitive self-injurious behavior, a rigid adherence to nonfunctional routines or rituals, an insistence on sameness and distress upon even the smallest changes, and an inflexible problem-solving style.

At present, although there are some pharmacological treatment options for repetitive behaviors and resistance to change, there is a significant need for more therapeutic alternatives. Animal studies have been vital for identifying mechanisms of disease, generating new hypotheses that are relevant to humans, and subsequently providing a pathway for developing novel treatments.

Workshop participants focused on the broad range and complexity of behaviors in this domain and on the use of model systems as a way to break down this complexity and examine potential underlying mechanisms or core deficits that may mediate these behaviors. An animal model may also be used to determine how these processes develop before they become manifest. Participants stressed that it will be by understanding these neurobiological mechanisms that more specialized treatments will be developed for autism.

The presentations covered a range of significant new findings within this domain, including the role of the cortico-striatal-thalamic circuitry in mediating these behaviors, and the importance of rare gene variants to the pathophysiology of autism. Much attention was paid to the issue of how to develop model organisms, as well as how to develop the appropriate behavioral tasks through which to model aspects of a disorder such as autism. Participants discussed the problem of complexity versus simplicity when working with animals. Specifically, participants addressed the difference between selecting a model system that contains as many of the component behavioral traits as possible, in order to move closer to the human condition, versus choosing a system through which one very well-defined and delineated symptom can be modeled, and attempting to determine the pathophysiology within that one domain.

It was noted that development plays a critical role in repetitive behaviors and resistance to change, and determining when these behaviors emerge and what brain changes drive their progression will be critical to future research endeavors. Participants emphasized that these behaviors in autism occur in the context of deficits in the social domain, and understanding how these domains interact at the very earliest stages and progress across development is essential to conceptualize the disorder. Model systems that inform both of these domains will be the most relevant for understanding autism.