Original Article

Citation: Translational Psychiatry (2016) 6, e845; doi:10.1038/tp.2016.107
Published online 28 June 2016

Disentangling the autism−anxiety overlap: fMRI of reward processing in a community-based longitudinal study
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N Mikita1, E Simonoff1,2, D S Pine3, R Goodman1, E Artiges4,5,6,7, T Banaschewski8, A L Bokde9, U Bromberg10, C Büchel10, A Cattrell11, P J Conrod12,13, S Desrivières11, H Flor14, V Frouin15, J Gallinat16, H Garavan17,18, A Heinz19, B Ittermann20, S Jurk21, J L Martinot4,5,6,22, M L Paillère Martinot4,5,6,22, F Nees14, D Papadopoulos Orfanos15, T Paus23,24,25,26, L Poustka8,27, M N Smolka21, H Walter19, R Whelan28, G Schumann11,29 and A Stringaris1,29

  1. 1Department of Child and Adolescent Psychiatry, King’s CollegeLondon, Institute of Psychiatry, Psychology & Neuroscience, London, UK
  2. 2NIHR Biomedical Research Centre and Dementia Unit at SouthLondon and Maudsley NHS Foundation Trust and the Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
  3. 3Section on Development and Affective Neuroscience, National Institute of Mental Health, Bethesda, MD, USA
  4. 4Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 “Neuroimaging & Psychiatry”, Service Hospitalier Frédéric Joliot, Orsay, France
  5. 5University Paris-Sud 11, Orsay, France
  6. 6University Paris Descartes - Sorbonne Paris Cité, Paris, France
  7. 7Psychiatry Department, Orsay Hospital, Orsay, France
  8. 8Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
  9. 9Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College, Dublin, Ireland
  10. 10University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
  11. 11Medical Research Council - Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
  12. 12Department of Psychiatry, Universite de Montreal, CHU Ste Justine Hospital, Montreal, QC, Canada
  13. 13Department of Psychological Medicine and Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
  14. 14Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
  15. 15Neurospin, Commissariat à l'Energie Atomique, CEA-Saclay Center, Paris, France
  16. 16Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  17. 17Department of Psychiatry, University of Vermont, Burlington, VT, USA
  18. 18Department of Psychology, University of Vermont, Burlington, VT, USA
  19. 19Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité, Universitätsmedizin Berlin, Berlin, Germany
  20. 20Physikalisch-Technische Bundesanstalt, Braunschweig, Germany
  21. 21Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany
  22. 22AP-HP, Department of Adolescent Psychopathology and Medicine, Maison de Solenn, Cochin Hospital, Paris, France
  23. 23Rotman Research Institute, Baycrest, Toronto, ON, Canada
  24. 24Child Mind Institute, New York, NY, USA
  25. 25Department of Psychology, University of Toronto, Toronto, ON, Canada
  26. 26Department of Psychiatry, University of Toronto, Toronto, ON, Canada
  27. 27Department of Child and Adolescent Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
  28. 28Department of Psychology, University College Dublin, Dublin, Ireland

Correspondence: N Mikita, Departmentof Child and Adolescent Psychiatry, PO85, King’s College London, Institute of Psychiatry, Psychology & Neuroscience, De Crespigny Park, London SE5 8AF, UK. E-mail: nina.mikita@kcl.ac.uk

29These authors contributed equally to this work.

Received 29 January 2016; Revised 1 April 2016; Accepted 20 April 2016

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Abstract

Up to 40% of youth with autism spectrum disorder (ASD) also suffer from anxiety, and this comorbidity is linked with significant functional impairment. However, the mechanisms of this overlap are poorly understood. We investigated the interplay between ASD traits and anxiety during reward processing, known to be affected in ASD, in a community sample of 1472 adolescents (mean age=14.4 years) who performed a modified monetary incentive delay task as part of the Imagen project. Blood-oxygen-level dependent (BOLD) responses to reward anticipation and feedback were compared using a 2x2 analysis of variance test (ASD traits: low/high; anxiety symptoms: low/high), controlling for plausible covariates. In addition, we used a longitudinal design to assess whether neural responses during reward processing predicted anxiety at 2-year follow-up. High ASD traits were associated with reduced BOLD responses in dorsal prefrontal regions during reward anticipation and negative feedback. Participants with high anxiety symptoms showed increased lateral prefrontal responses during anticipation, but decreased responses following feedback. Interaction effects revealed that youth with combined ASD traits and anxiety, relative to other youth, showed high right insula activation when anticipating reward, and low right-sided caudate, putamen, medial and lateral prefrontal activations during negative feedback (all clusters PFWE<0.05). BOLD activation patterns in the right dorsal cingulate and right medial frontal gyrus predicted new-onset anxiety in participants with high but not low ASD traits. Our results reveal both quantitatively enhanced and qualitatively distinct neural correlates underlying the comorbidity between ASD traits and anxiety. Specific neural responses during reward processing may represent a risk factor for developing anxiety in ASD youth.