Repetitive behaviors form a core feature of autism spectrum disorders (ASD), and frequently carry substantial impairment. However, our understanding of the neural basis of stereotypy and repetitive behaviors in ASD and their treatment is limited. Follow-up studies show the remarkable persistence of repetitive behaviors as a stable component of the phenotype. No one treatment has been solidly established for this aspect of the ASD phenotype. Recently, risperidone, a second generation atypical antipsychotic, was observed to robustly reduce stereotypic behaviors in a sample of children with autism, and this improvement was maintained for up to 6 months of continued treatment. The proposed study attempts to deepen our understanding of repetitive behaviors in ASD and its treatment by examining the changes in key neural circuits associated with risperidone treatment using functional MRI. Our pilot data suggests risperidone has powerful effects on brain activation, providing clues to the underpinnings of these ASD behavioral features and one of its mechanisms of effect. Our overarching hypothesis is that prominent stereotyped and perservative behaviors in autism reflect disordered cortico-striatal function, likely influenced by autism risk genes, and that successful treatment is associated with greater normalization of ventral striatal activation.
Our Specific Aims for the project are as follows:
By combining studies of pharmacologic treatment with established neuroimaging paradigms, we believe that our proposed investigation will shed light on the neural underpinnings of this important component of the ASD phenotype and a common element of other childhood neuropsychiatric disorders. Similarly, data from our proposed investigation should help to clarify key sites of action for targeted treatments and potentially serve to identify subgroups of individuals with ASD who are more likely to benefit from certain interventions. Lastly, our study may shed light on the extent to which the core domains of ASD should be approached in a modular versus a holistic fashion with regards to its neurobiology.
Pervasive developmental disorders (F84)
Originally created: 18 Jun 2009 Current author: System Admin
Jane & Terry Semel Institute for Neuroscience & Human Behavior
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