Abstract
Autism spectrum disorder (ASD) and obsessive compulsive disorder (OCD) show overlapping symptomatology and deficits in inhibitory control, which are associated with altered functioning and glutamatergic signaling in fronto-striatal circuitry. These parameters have never been examined together. The purpose of the current study was to investigate functioning during inhibitory control and its association with fronto-striatal glutamate concentrations across these disorders using a multi-center, longitudinal approach. Adolescents with ASD (n = 24), OCD (n = 15) and controls (n = 35) underwent two magnetic resonance imaging (MRI) sessions with a one-year interval. This included proton magnetic resonance spectroscopy (1H-MRS; n = 74) and functional MRI during an inhibitory control task (n = 53). We investigated 1H-MRS data and fMRI data separately as well as integrated in a multimodal analysis using linear models focusing on diagnosis and continuous measures of overlapping compulsivity symptoms. ACC glutamate was reduced over time in the ASD group compared with controls, while striatal glutamate decreased over time independent of diagnosis. Increased compulsive behavior seemed to be associated with increased striatal activity during failed inhibitory control. The integrated analyses showed differential involvement of increased striatal glutamate during failed but decreased striatal glutamate during successful inhibitory control in the OCD group compared to controls and ASD, suggesting different underlying mechanisms for OCD compared to ASD.
Highlights
Autism spectrum disorder (ASD) and obsessive compulsive disorder (OCD) are two separate neurodevelopmental disorders with distinct diagnostic characteristics [1], they are highly comorbid and a comparison of symptoms has suggested that there are more similarities than differences between them [2,3,4]
In our multi-modal analysis we found effects of fronto-striatal glutamate, diagnosis and time associated with alterations in fronto-striatal neural activity during both failed and successful inhibitory control
Neural activation in the anterior cingulate cortex (ACC) during failed inhibitory control was modulated by striatal glutamate, diagnosis and time
Summary
Autism spectrum disorder (ASD) and obsessive compulsive disorder (OCD) are two separate neurodevelopmental disorders with distinct diagnostic characteristics [1], they are highly comorbid and a comparison of symptoms has suggested that there are more similarities than differences between them [2,3,4]. Individuals with these disorders typically show compulsive behaviors, which are defined as the repetitive, irresistible urge to perform certain behaviors or thoughts, and diminished control over this urge [5]. Autism spectrum disorder (ASD) and obsessive compulsive disorder (OCD) are neurodevelopmental disorders with overlapping symptomatology Both show deficits in inhibitory control, which are associated with altered functioning and glutamate concentrations in the frontostriatal circuitry. Conclusions: Significant differences in fronto-striatal glutamate were observed in ASD and OCD, affecting functional activity during failed- and successful inhibitory control differently, especially in OCD, with effects changing over time
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