Multiple functional magnetic resonance imaging (fMRI) studies have implicated frontostriatal brain regions, including the anterior cingulate and prefrontal cortex, as a neurobiological mediator of restricted and repetitive behaviors in autism spectrum disorders (ASDs). Despite the emergence of pharmacotherapeutic agents that reduce autism symptoms, no studies to date have assessed changes in regional brain activation assessed with fMRI in response to autism treatments.
Objectives:
In the present study, we used fMRI to investigate changes in regional brain functioning in individuals with an ASD due to citalopram treatment administered in a randomized placebo controlled double-blind context. Citalopram is a selective serotonin reuptake inhibitor (SSRI) that has shown promise in reducing repetitive behaviors for some, but not all individuals with autism. We sought to determine the effects of citalopram treatment, relative to placebo treatment, on frontostriatal functioning in participants with high functioning autism. We also sought to assess for potential relations between changes in restricted repetitive behaviors and changes in regional brain function due to citalopram treatment. Finally, in an exploratory manner we investigated whether pre-treatment fMRI scans predicted response to treatment.
Methods:
We assessed twelve individuals with an ASD (IQ > 70) who demonstrated high levels of repetitive behaviors as defined by baseline Children’s Yale-Brown Obsessive Compulsive Scales (CYBOCS-PDD) scores of eight or greater. Brain activation in response to a visual oddball target detection task was assessed both before and after double-blind treatment with citalopram or placebo administered for 12 weeks. The Clinical Global Impressions (CGI), CYBOCS-PDD, and The Repetitive Behavior Subscale Revised (RBS-R) were administered at both scan sessions.
Results:
Consistent with recent larger-scale clinical trial data, both treatment groups showed significant symptom reductions on measures of global functioning and of repetitive behaviors. Additionally, there were no significant differences in response to citalopram or placebo treatment. Brain imaging data revealed increased activation to target events in the inferior frontal gyrus (IFG) and the anterior cingulate cortex (ACC) and decreased activation in the superior frontal gyrus (SFG) after treatment with either citalopram or placebo. Further, less activation to target events in the IFG and the ACC at baseline predicted greater improvement in RBS-R total scores after treatment. RBS-R total scores were correlated with pretreatment activation in the IFG and the ACC and post-treatment activation in the IFG and ACC.
Conclusions:
These pilot data provide preliminary evidence that autism treatments that reduce symptoms produce measurable changes in brain activation. Future studies with larger samples and different compounds should continue to investigate the utility of fMRI to predict response to treatment and to elucidate the potential mechanisms of action of effective autism interventions.