title: Disentangling the autism-anxiety overlap: fMRI of reward processing in a community-based longitudinal study.
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.
authors.affiliation: Department of Child and Adolescent Psychiatry, King's CollegeLondon, Institute of Psychiatry, Psychology & Neuroscience, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Mikita
authors.affiliation: Department of Child and Adolescent Psychiatry, King's CollegeLondon, Institute of Psychiatry, Psychology & Neuroscience, London, UK.|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.
authors.forename: E
authors.initials: E
authors.lastname: Simonoff
authors.affiliation: Section on Development and Affective Neuroscience, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Pine
authors.affiliation: Department of Child and Adolescent Psychiatry, King's CollegeLondon, Institute of Psychiatry, Psychology & Neuroscience, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Goodman
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry", Service Hospitalier Frédéric Joliot, Orsay, France.|University Paris-Sud 11, Orsay, France.|University Paris Descartes - Sorbonne Paris Cité, Paris, France.|Psychiatry Department, Orsay Hospital, Orsay, France.
authors.forename: E
authors.initials: E
authors.lastname: Artiges
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Banaschewski
authors.affiliation: Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College, Dublin, Ireland.
authors.forename: A L
authors.initials: AL
authors.lastname: Bokde
authors.affiliation: University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Bromberg
authors.affiliation: University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Büchel
authors.affiliation: Medical Research Council - Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Cattrell
authors.affiliation: Department of Psychiatry, Universite de Montreal, CHU Ste Justine Hospital, Montreal, QC, Canada.|Department of Psychological Medicine and Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
authors.forename: P J
authors.initials: PJ
authors.lastname: Conrod
authors.affiliation: Medical Research Council - Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Desrivières
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Flor
authors.affiliation: Neurospin, Commissariat à l'Energie Atomique, CEA-Saclay Center, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Frouin
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Gallinat
authors.affiliation: Department of Psychiatry, University of Vermont, Burlington, VT, USA.|Department of Psychology, University of Vermont, Burlington, VT, USA.
authors.forename: H
authors.initials: H
authors.lastname: Garavan
authors.affiliation: Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité, Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Heinz
authors.affiliation: Physikalisch-Technische Bundesanstalt, Braunschweig, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Ittermann
authors.affiliation: Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Jurk
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry", Service Hospitalier Frédéric Joliot, Orsay, France.|University Paris-Sud 11, Orsay, France.|University Paris Descartes - Sorbonne Paris Cité, Paris, France.|AP-HP, Department of Adolescent Psychopathology and Medicine, Maison de Solenn, Cochin Hospital, Paris, France.
authors.forename: J L
authors.initials: JL
authors.lastname: Martinot
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry", Service Hospitalier Frédéric Joliot, Orsay, France.|University Paris-Sud 11, Orsay, France.|University Paris Descartes - Sorbonne Paris Cité, Paris, France.|AP-HP, Department of Adolescent Psychopathology and Medicine, Maison de Solenn, Cochin Hospital, Paris, France.
authors.forename: M L
authors.initials: ML
authors.lastname: Paillère Martinot
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Nees
authors.affiliation: Neurospin, Commissariat à l'Energie Atomique, CEA-Saclay Center, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Papadopoulos Orfanos
authors.affiliation: Rotman Research Institute, Baycrest, Toronto, ON, Canada.|Child Mind Institute, New York, NY, USA.|Department of Psychology, University of Toronto, Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Paus
authors.affiliation: Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.|Department of Child and Adolescent Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
authors.forename: L
authors.initials: L
authors.lastname: Poustka
authors.affiliation: Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
authors.forename: M N
authors.initials: MN
authors.lastname: Smolka
authors.affiliation: Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité, Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Walter
authors.affiliation: Department of Psychology, University College Dublin, Dublin, Ireland.
authors.forename: R
authors.initials: R
authors.lastname: Whelan
authors.affiliation: Medical Research Council - Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Schumann
authors.affiliation: Department of Child and Adolescent Psychiatry, King's CollegeLondon, Institute of Psychiatry, Psychology & Neuroscience, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Stringaris
mesh_terms: D000293:Adolescent; D059031:Anticipation, Psychological / Q000502:physiology; D001008:Anxiety Disorders / Q000000981:diagnostic imaging* / Q000503:physiopathology; D000067877:Autism Spectrum Disorder / Q000000981:diagnostic imaging*; D001921:Brain / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology; D015897:Comorbidity; D004292:Dominance, Cerebral / Q000502:physiology; D005246:Feedback; D005260:Female; D005500:Follow-Up Studies; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000503:physiopathology; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000503:physiopathology; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology; D012201:Reward
chemical_list: D010100:Oxygen