title: Distinct effects of ASD and ADHD symptoms on reward anticipation in participants with ADHD, their unaffected siblings and healthy controls: a cross-sectional study.
abstract: BACKGROUND
  Autism spectrum disorder (ASD) traits are continuously distributed throughout the population, and ASD symptoms are also frequently observed in patients with attention-deficit/hyperactivity disorder (ADHD). Both ASD and ADHD have been linked to alterations in reward-related neural processing. However, whether both symptom domains interact and/or have distinct effects on reward processing in healthy and ADHD populations is currently unknown.
  
  
  METHODS
  We examined how variance in ASD and ADHD symptoms in individuals with ADHD and healthy participants was related to the behavioural and neural response to reward during a monetary incentive delay (MID) task. Participants (mean age: 17.7 years, range: 10-28 years) from the NeuroIMAGE study with a confirmed diagnosis of ADHD (n = 136), their unaffected siblings (n = 83), as well as healthy controls (n = 105) performed an MID task in a magnetic resonance imaging (MRI) scanner. ASD and ADHD symptom scores were used as predictors of the neural response to reward anticipation and reward receipt. Behavioural responses were modeled using linear mixed models; neural responses were analysed using FMRIB's Software Library (FSL) proprietary mixed effects analysis (FLAMEO).
  
  
  RESULTS
  ASD and ADHD symptoms were associated with alterations in BOLD activity during reward anticipation, but not reward receipt. Specifically, ASD scores were related to increased insular activity during reward anticipation across the sample. No interaction was found between this effect and the presence of ADHD, suggesting that ASD symptoms had no differential effect in ADHD and healthy populations. ADHD symptom scores were associated with reduced dorsolateral prefrontal activity during reward anticipation. No interactions were found between the effects of ASD and ADHD symptoms on reward processing.
  
  
  CONCLUSIONS
  Variance in ASD and ADHD symptoms separately influence neural processing during reward anticipation in both individuals with (an increased risk of) ADHD and healthy participants. Our findings therefore suggest that both symptom domains affect reward processing through distinct mechanisms, underscoring the importance of multidimensional and multimodal assessment in psychiatry.
authors: Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands ; Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors: Eelco V
authors: EV
authors: van Dongen
authors: Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands ; Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors: Daniel
authors: D
authors: von Rhein
authors: Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands ; Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors: Laurence
authors: L
authors: O'Dwyer
authors: Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands ; Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors: Barbara
authors: B
authors: Franke
authors: Department of Psychiatry, University Medical Centre Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.
authors: Catharina A
authors: CA
authors: Hartman
authors: Department of Clinical Neuropsychology, VU University, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands.
authors: Dirk J
authors: DJ
authors: Heslenfeld
authors: Department of Psychiatry, University Medical Centre Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.
authors: Pieter J
authors: PJ
authors: Hoekstra
authors: Department of Clinical Neuropsychology, VU University, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands.
authors: Jaap
authors: J
authors: Oosterlaan
authors: Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands ; Karakter, Child and Adolescent Psychiatry University Center Nijmegen, Reinier Postlaan 12, 6525 GC Nijmegen, The Netherlands.
authors: Nanda
authors: N
authors: Rommelse
authors: Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlands ; Karakter, Child and Adolescent Psychiatry University Center Nijmegen, Reinier Postlaan 12, 6525 GC Nijmegen, The Netherlands.
authors: Jan
authors: J
authors: Buitelaar
keywords: ADHD; ASD; Comorbidity; Reward; Reward anticipation