Abstract
Autism spectrum disorder (ASD) symptoms frequently occur in individuals with attention-deficit/hyperactivity disorder (ADHD). While there is evidence that both ADHD and ASD have differential structural brain correlates, knowledge of the structural brain profile of individuals with ADHD with raised ASD symptoms is limited. The presence of ASD-like symptoms was measured by the Children's Social Behavior Questionnaire (CSBQ) in a sample of typically developing controls (n = 154), participants with ADHD (n = 239), and their unaffected siblings (n = 144) between the ages of 8 and 29. Structural magnetic resonance imaging (MRI) correlates of ASD ratings were analysed by studying the relationship between ASD ratings and grey matter volumes using mixed effects models which controlled for ADHD symptom count and total brain volume. ASD ratings were significantly elevated in participants with ADHD relative to controls and unaffected siblings. For the entire group (participants with ADHD, unaffected siblings and TD controls), mixed effect models revealed that the left caudate nucleus volume was negatively correlated with ASD ratings (t = 2.83; P = 0.005). The current findings are consistent with the role of the caudate nucleus in executive function, including the selection of goals based on the evaluation of action outcomes and the use of social reward to update reward representations. There is a specific volumetric profile associated with subclinical ASD-like symptoms in participants with ADHD, unaffected siblings and controls with the caudate nucleus and globus pallidus being of critical importance in predicting the level of ASD-like symptoms in all three groups.
Highlights
Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are both severely impairing, highly heritable neurodevelopmental disorders [1,2] [3]
Structural magnetic resonance imaging (MRI) correlates of Autism spectrum disorder (ASD) ratings were analysed by studying the relationship between ASD ratings and grey matter volumes using mixed effects models which controlled for attentiondeficit/hyperactivity disorder (ADHD) symptom count and total brain volume
ASD ratings for the entire group showed an insignificant decline with age (t = 0.036, P = 0.971), which was entirely due to the ADHD diagnosis group (Fig 2)
Summary
Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are both severely impairing, highly heritable neurodevelopmental disorders [1,2] [3]. Structural and functional MRI studies have found the caudate nucleus to be altered (with both increased volume and activation and decreased volume and activation relative to controls) in ASD and to be associated with dysfunctions in multiple domains related to ASD, such as repetitive and stereotyped behaviour [46], reward processing [47] and executive function [48], [49] Based on this literature, our hypothesis was that the caudate nucleus may have a significant role [34,46], [1,50], while structures such as the cerebellum [23], amygdala-hippocampal complex [24,25,26,27], frontotemporal regions [25,26,28], [29,30], and nucleus accumbens [31], may have a contributory but potentially subsidiary role, in predicting the extent to which subclinical ASD-like symptoms are expressed in patients with ADHD but not in their unaffected siblings or controls. Subcortical brain volumes were segmented to investigate the role of the caudate, while allowing for the investigation of other structures that have been less frequently implicated in ASD symptoms, such as the globus pallidus, the nucleus accumbens, putamen [26], thalamus [56], brain stem [57], hippocampus, and amygdala [58]
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