Functional Neuroimaging of Psychopharmacologic Treatment for Autism

Gabriel S. Dichter, Ph.D.

University of North Carolina School of Medicine

Funded in December, 2006: $100000 for 3 years
LAY SUMMARY . HYPOTHESIS . SELECTED PUBLICATIONS .

LAY SUMMARY

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fMRI Imaging May Reveal How Medication Modifies Repetitive Behaviors in Autism

Researchers will use fMRI imaging in high-functioning adults with autism to explore whether the drug Citalopram reduces their repetitive behaviors by stimulating brain circuits in frontal brain regions. The results may lead to the development of improved drugs to fully prevent this behavioral aspect of autism.

A hallmark of autism is engaging in pervasive repetitive behaviors.  While prior fMRI studies have defined neural circuits that are involved in a range of autism behaviors, research to date has not defined how current medications work to try to alleviate some of these symptomatic behaviors.  The UNC investigators’ prior fMRI studies have shown that the brain’s frontostriatal areas are under-activated during certain repetitive behaviors.

They now will use fMRI to see whether Citalopram treatment helps to alleviate repetitive behaviors by activating neural circuits in the frontostraitum. Repetitive behaviors and executive function abilities will be assessed in 18 high-functioning adults with autism who have been medication-free for three months, as they undertake specific tasks in the fMRI scanner.  After three months of Citalopram treatment, the adults will be retested to see whether the medication is associated with reduced repetitive behaviors and with increased frontostriatal activation. Participants’ neural activation levels will be compared to those of healthy study participants to determine whether even greater stimulation is needed to approach normal activation levels.  

Significance:  The results may characterize how Citalopram activates specific neural circuitry to alleviate repetitive behaviors. Moreover, if circuit activation achieved is found to be less than normal, the findings might lead to the development of more potent therapies that stimulate this circuitry more fully to eradicate or prevent this manifestation of autism.

HYPOTHESIS

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Hypothesis:
It is hypothesized that psychopharmacologic intervention will improve symptoms of restricted repetitive behaviors and enhance neural activation in relevant frontostriatal brain regions in individuals with autism.

Goals
Neuroimaging techniques may provide insights into dysfunctional brain circuits in autism, as well as clues for developing new treatments for this disorder.  The purpose of this proposal is to use state-of-the-art brain imaging methods to study the frontostriatal effects of a well-tolerated and commonly prescribed medication in high-functioning adults with autism.  The ultimate goal of this program of research is to characterize relations between brain functioning and symptom expression in autism, as well as to provide a framework for future research aimed at developing novel and rational approaches to treatment.  To date, there is no research that has used brain imaging technology to study how medications reduce symptoms in autism.  This omission is notable because brain imaging techniques are well-suited to studying changes in brain functioning following treatment.

Methods:
Adults with high functioning autism or Asperger’s disorder and age-, gender-, and IQ-matched neurotypical participants will be recruited. Participants with autism will receive psychopharmacologic treatment for up to 12 weeks.  Participants will complete an fMRI task designed to recruit frontostriatal brain regions pre- and post-imaging.  Brain imaging will be conducted at the Duke-UNC Brain Imaging and Analysis Center (BIAC).

SELECTED PUBLICATIONS

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Dichter G.S. and Belger A. Social stimuli interfere with cognitive control in autism. Neuroimage. 2007 Apr 15;35(3):1219-30.

Shafritz K.M., Dichter G.S., Baranek G.T., and Belger A. The neural circuitry mediating shifts in behavioral response and cognitive set in autism. Biol Psychiatry. 2008 May 15;63(10):974-80.