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Atypical Arousal Regulation in Children With Autism but Not With Attention-Deficit/Hyperactivity Disorder as Indicated by Pupillometric Measures of Locus Coeruleus Activity

  • Author Footnotes
    1 NB and SB contributed equally to this work.
    Nico Bast
    Correspondence
    Address correspondence to Nico Bast, Ph.D.
    Footnotes
    1 NB and SB contributed equally to this work.
    Affiliations
    Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Autism Research and Intervention Center of Excellence, University Hospital Frankfurt, Goethe-University, Frankfurt am Main, Germany
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  • Author Footnotes
    1 NB and SB contributed equally to this work.
    Sara Boxhoorn
    Footnotes
    1 NB and SB contributed equally to this work.
    Affiliations
    Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Autism Research and Intervention Center of Excellence, University Hospital Frankfurt, Goethe-University, Frankfurt am Main, Germany
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  • Hans Supér
    Affiliations
    Catalan Institution for Research and Advanced Studies, Barcelona, Spain
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  • Bartosz Helfer
    Affiliations
    National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, United Kingdom

    Institute of Psychology, University of Wrocław, Wrocław, Poland
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  • Leonie Polzer
    Affiliations
    Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Autism Research and Intervention Center of Excellence, University Hospital Frankfurt, Goethe-University, Frankfurt am Main, Germany
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  • Christoph Klein
    Affiliations
    Clinic for Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, Medical Center–University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

    Department of Child and Adolescent Psychiatry, Medical Faculty, University of Cologne, Cologne, Germany

    Department of Psychiatry, National and Kapodistrian University of Athens, Athens, Greece
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  • Hannah Cholemkery
    Affiliations
    Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Autism Research and Intervention Center of Excellence, University Hospital Frankfurt, Goethe-University, Frankfurt am Main, Germany
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  • Christine M. Freitag
    Affiliations
    Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Autism Research and Intervention Center of Excellence, University Hospital Frankfurt, Goethe-University, Frankfurt am Main, Germany
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  • Author Footnotes
    1 NB and SB contributed equally to this work.
Published:April 26, 2021DOI:https://doi.org/10.1016/j.bpsc.2021.04.010

      Abstract

      Background

      Atypical arousal regulation may explain slower mean reaction time (MRT) in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder compared with typical development. The locus coeruleus–norepinephrine system (LC-NE) underlies arousal regulation and adapts its activity to the utility of a task. LC-NE tonic and phasic activity are indexed by baseline pupil size (BPS) and stimulus-evoked pupillary response (SEPR).

      Methods

      The study assessed pupillometry in ASD (n = 31, 3 female/28 male), attention-deficit/hyperactivity disorder (n = 28, 3 female/25 male), and typically developing control subjects (n = 31, 16 female/15 male) during a visuospatial reaction-time task that manipulates arousal by conditions with low and high task utility. We estimated linear mixed models of BPS, SEPR, and MRT in a per-trial analysis to investigate arousal regulation of task performance.

      Results

      Slower MRT occurred in the ASD group compared with the typically developing control group during low-utility conditions while controlling for dimensional ASD and attention-deficit/hyperactivity disorder symptoms. In low-utility conditions, BPS and SEPR were inversely related and both were associated with faster MRT. Increased ASD symptoms across groups were associated with higher BPS during low-utility conditions. Changes in BPS and SEPR between task-utility conditions were smaller in the ASD group.

      Conclusions

      Slower visuospatial task performance in ASD is specific to low task utility. Arousal was associated with task performance and showed altered activity in ASD. Increased BPS during low-utility conditions suggested increased LC-NE tonic activity as an ASD symptom marker in children. Smaller changes in BPS and SEPR in ASD indicated attenuated LC-NE activity adaptation in response to high-utility conditions. Slower performance and atypical arousal regulation are probably associated with attenuated LC-NE activity adaptation.

      Keywords

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