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PLoS One. 2016 Nov 2;11(11):e0165620. doi: 10.1371/journal.pone.0165620. eCollection 2016.

Decreased Left Caudate Volume Is Associated with Increased Severity of Autistic-Like Symptoms in a Cohort of ADHD Patients and Their Unaffected Siblings.

Author information

Radboud UMC, Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Nijmegen, The Netherlands.
Department of Ecology and Evolution, University of Lausanne, Lausanne, Switzerland.
King's College London, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, United Kingdom.
Karakter Child and Adolescent Psychiatry University Center Nijmegen, Nijmegen, The Netherlands.
Department of Human Genetics, Radboud UMC, Nijmegen, The Netherlands.
Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Psychiatry, Nijmegen, The Netherlands.
Department of Clinical Neuropsychology, VU University, Amsterdam, The Netherlands.
Department of Cognitive Psychology, V.U. University, Amsterdam, The Netherlands.
Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.


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.

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Conflict of interest statement

The research leading to these results was funded by the European Community’s Seventh Framework Programme and the Innovative Medicines Initiative Joint Undertaking, resources of which are composed in part by the European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in kind contribution. Jan Buitelaar has been a consultant to/member of advisory board of and/or speaker for Janssen Cilag BV, Eli Lilly and Servier. He is not an employee of any of these companies. He is not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, and royalties. There are no patents, products in development or marketed products to declare. Pieter Hoekstra has been a member of advisory board of Eli Lilly and Shire and has received research funding from Shire. All other authors report no biomedical financial interests or potential conflicts of interest. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

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