. 2016 Jun 28;6(6):e845.

doi: 10.1038/tp.2016.107.

Disentangling the autism-anxiety overlap: fMRI of reward processing in a community-based longitudinal study

N Mikita¹, E Simonoff^{1

2}, D S Pine³, R Goodman¹, E Artiges^{4

5

6

7}, T Banaschewski⁸, A L Bokde⁹, U Bromberg¹⁰, C Büchel¹⁰, A Cattrell¹¹, P J Conrod^{12

13}, S Desrivières¹¹, H Flor¹⁴, V Frouin¹⁵, J Gallinat¹⁶, H Garavan^{17

18}, A Heinz¹⁹, B Ittermann²⁰, S Jurk²¹, J L Martinot^{4

5

6

22}, M L Paillère Martinot^{4

5

6

22}, F Nees¹⁴, D Papadopoulos Orfanos¹⁵, T Paus^{23

24

25

26}, L Poustka^{8

27}, M N Smolka²¹, H Walter¹⁹, R Whelan²⁸, G Schumann¹¹, A Stringaris¹

Affiliations

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

PMID: 27351599
PMCID: PMC4931605
DOI: 10.1038/tp.2016.107

Disentangling the autism-anxiety overlap: fMRI of reward processing in a community-based longitudinal study

N Mikita et al. Transl Psychiatry. 2016.

. 2016 Jun 28;6(6):e845.

doi: 10.1038/tp.2016.107.

Authors

Affiliations

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

PMID: 27351599
PMCID: PMC4931605
DOI: 10.1038/tp.2016.107

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.

PubMed Disclaimer

Conflict of interest statement

Dr Banaschewski has served as an advisor or consultant to Bristol-Myers Squibb, Desitin Arzneimittel, Eli Lilly, Medice, Novartis, Pfizer, Shire, UCB and Vifor Pharma; he has received conference attendance support, conference support or speaking fees from Eli Lilly, Janssen McNeil, Medice, Novartis, Shire and UCB; and he is involved in clinical trials conducted by Eli Lilly, Novartis and Shire; the present work is unrelated to these relationships. Dr Gallinat has received research funding from the German Federal Ministry of Education and Research, AstraZeneca, Eli Lilly, Janssen-Cilag and Bristol-Myers Squibb; he has received speaking fees from AstraZeneca, Janssen-Cilag and Bristol-Myers Squibb. Dr Goodman is the owner of Youthinmind, Ltd., which provides no-cost and low-cost software and websites related to the Development and Well-Being Assessment and the Strengths and Difficulties Questionnaire. Ms Mikita received a one-off honorarium from John Wiley & Sons. Dr Stringaris has received grant or research support from the Guy's & St Thomas' Charity, University College London for a joint project with Johnson & Johnson, the Wellcome Trust and the National Institute for Health Research; he also receives royalties from Cambridge University Press and Oxford University Press. The remaining authors declare no conflict of interest.

Figures

**Figure 1**
Interaction between autism spectrum disorder (ASD) traits and anxiety. Showing mean blood-oxygen-level dependent (BOLD) responses during reward anticipation and 95% confidence intervals at the cluster peak [45, -16, -11] located in the middle temporal gyrus. A similar pattern of results emerged for a peak in the right insula.

**Figure 2**
Interaction between autism spectrum disorder (ASD) traits and anxiety. Showing mean blood-oxygen-level dependent (BOLD) responses during negative reward feedback and 95% confidence intervals at cluster 1 peak [21, 59, 7] in the right superior frontal gyrus. The same pattern of results emerged for the two other clusters with peaks in the right caudate and left middle temporal gyrus, and middle frontal gyrus.

See this image and copyright information in PMC

References

1. Mandy W, Roughan L, Skuse D. Three dimensions of oppositionality in autism spectrum disorder. J Abnorm Child Psychol 2014; 42: 291–300. - PubMed
1. Simonoff E, Jones CR, Pickles A, Happé F, Baird G, Charman T. Severe mood problems in adolescents with autism spectrum disorder. J Child Psychol Psychiatry 2012; 53: 1157–1166. - PubMed
1. Mazefsky CA, Conner CM, Oswald DP. Association between depression and anxiety in high-functioning children with autism spectrum disorders and maternal mood symptoms. Autism Res 2010; 3: 120–127. - PMC - PubMed
1. Van Steensel FJA, Bogels SM, Perrin S. Anxiety disorders in children and adolescents with autistic spectrum disorders: a meta-analysis. Clin Child Fam Psychol Rev 2011; 14: 302–317. - PMC - PubMed
1. Mikita N, Hollocks MJ, Papadopoulos AS, Aslani A, Harrison S, Leibenluft E et al. Irritability in boys with autism spectrum disorders: an investigation of physiological reactivity. J Child Psychol Psychiatry 2015; 56: 1118–1126. - PMC - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- scite Smart Citations
Medical
- MedlinePlus Consumer Health Information
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Disentangling the autism-anxiety overlap: fMRI of reward processing in a community-based longitudinal study

Affiliations

Disentangling the autism-anxiety overlap: fMRI of reward processing in a community-based longitudinal study

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical