Brain volumetric correlates of autism spectrum disorder symptoms in attention deficit/hyperactivity disorder.

Laurence O’Dwyer,Nanda Rommelse,Janita Bralten,Marcel P Zwiers,Eelco V Van Dongen,Jan K Buitelaar,Dirk Heslenfeld,Jaap Oosterlaan,Pieter Hoekstra,Corina U Greven,Catharina A Hartman,Colby Tanner,Barbara Franke

doi:10.1371/journal.pone.0101130

Abstract

Autism spectrum disorder (ASD) symptoms frequently occur in subjects with attention deficit/hyperactivity disorder (ADHD). While there is evidence that both ADHD and ASD have differential structural correlates, no study to date has investigated these structural correlates within a framework that robustly accounts for the phenotypic overlap between the two disorders. The presence of ASD symptoms was measured by the parent-reported Children’s Social and Behavioural Questionnaire (CSBQ) in ADHD subjects (n = 180), their unaffected siblings (n = 118) and healthy controls (n = 146). ADHD symptoms were assessed by a structured interview (K-SADS-PL) and the Conners’ ADHD questionnaires. Whole brain T1-weighted MPRAGE images were acquired and the structural MRI correlates of ASD symptom scores were analysed by modelling ASD symptom scores against white matter (WM) and grey matter (GM) volumes using mixed effects models which controlled for ADHD symptom levels. ASD symptoms were significantly elevated in ADHD subjects relative to both controls and unaffected siblings. ASD scores were predicted by the interaction between WM and GM volumes. Increasing ASD score was associated with greater GM volume. Equivocal results from previous structural studies in ADHD and ASD may be due to the fact that comorbidity has not been taken into account in studies to date. The current findings stress the need to account for issues of ASD comorbidity in ADHD.

Highlights

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are both severely impairing, highly heritable neurodevelopmental disorders [1,2]
Following model simplification based on Akaike’s Information Criterion (AIC), the optimal model for ASD symptoms is shown in Table 2 and Table 3
There was a non-significant increase in the ASD scores for unaffected siblings relative to controls, which is in line with studies showing moderate increases in ASD symptoms in unaffected siblings of ADHD subjects [40], [63]

Summary

Introduction

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are both severely impairing, highly heritable neurodevelopmental disorders [1,2]. ASD is characterised by impaired social and communicative skills as well as restricted and repetitive behaviours and interests, whereas ADHD is characterised by severe inattention and/or hyperactivity and impulsivity [3]. Both disorders frequently co-occur with estimates for the presence of ADHD within ASD ranging from 30% to 80%, while the presence of ASD in ADHD is estimated at 20% to 50% [1], [2,4,5,6]. Studies have documented an overlap of genetic factors that relate to both ASD and ADHD [4]. These findings suggest that there are shared etiological pathways for ASD and ADHD which need to be studied in more detail

Objectives

Results

Conclusion