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Threat Neurocircuitry Predicts the Development of Anxiety and Depression Symptoms in a Longitudinal Study

  • Author Footnotes
    1 YP and JDK contributed equally to this work.
    Yujia Peng
    Footnotes
    1 YP and JDK contributed equally to this work.
    Affiliations
    School of Psychological and Cognitive Sciences and Beijing Key Laboratory of Behavior and Mental Health, Peking University, Beijing, China

    Institute for Artificial Intelligence, Peking University, Beijing, China

    Beijing Institute for General Artificial Intelligence, Beijing, China

    Department of Psychology, University of California, Los Angeles, Los Angeles, California
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  • Author Footnotes
    1 YP and JDK contributed equally to this work.
    Jeffrey D. Knotts
    Footnotes
    1 YP and JDK contributed equally to this work.
    Affiliations
    Department of Psychology, University of California, Los Angeles, Los Angeles, California

    Department of Psychological and Brain Sciences, Dartmouth College, Hanover, New Hampshire
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  • Katherine S. Young
    Affiliations
    Department of Psychology, University of California, Los Angeles, Los Angeles, California

    Social, Genetic and Development Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom

    NIHR Maudsley Biomedical Research Centre, King’s College London, London, United Kingdom
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  • Susan Y. Bookheimer
    Affiliations
    Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California
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  • Robin Nusslock
    Affiliations
    Department of Psychology, Northwestern University, Evanston, Illinois
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  • Richard E. Zinbarg
    Affiliations
    Department of Psychology, Northwestern University, Evanston, Illinois

    Family Institute at Northwestern University, Evanston, Illinois
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  • Nicholas J. Kelley
    Affiliations
    Department of Psychology, Northwestern University, Evanston, Illinois

    Department of Psychology, University of Southampton, Southampton, United Kingdom
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  • Aileen M. Echiverri-Cohen
    Affiliations
    Department of Psychology, University of California, Los Angeles, Los Angeles, California
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  • Michelle G. Craske
    Correspondence
    Address correspondence to Michelle G. Craske, Ph.D.
    Affiliations
    Department of Psychology, University of California, Los Angeles, Los Angeles, California

    Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California
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  • Author Footnotes
    1 YP and JDK contributed equally to this work.
Published:January 11, 2022DOI:https://doi.org/10.1016/j.bpsc.2021.12.013

      Abstract

      Background

      Owing to high heterogeneity and comorbidity, the shared and unique neural mechanisms underlying the development of anxiety and major depressive disorders remain unclear. Using a dimensional model describing shared versus unique symptoms associated with anxiety and depression, this study investigated how longitudinal changes in symptom dimensions relate to threat neurocircuitry.

      Methods

      Participants were 18- to 19-year-olds (N = 279, 186 females) who completed self-report measures of anxiety and depression at baseline and at 10, 20, and 30 months. Linear slopes of symptom dimensions of general distress, fear, and anhedonia-apprehension were estimated through a trilevel factorial model. In addition, functional magnetic resonance imaging scans were obtained while participants performed Pavlovian fear conditioning tasks at baseline and 30 months, including three phases of fear acquisition, extinction, and extinction recall. Neural responses in regions of interest related to threat neural circuitry (e.g., amygdala, ventromedial prefrontal cortex, and subgenual anterior cingulate cortex) were extracted.

      Results

      Linear mixed models used to estimate relationships between changes of symptom dimensions and neural responses revealed two major findings: 1) greater neural responses to threatening stimuli during fear acquisition at baseline were associated with a greater increase in fear symptoms during the 30-month prospective period; and 2) elevated neural responses to the extinguished stimulus during extinction recall at 30 months were negatively associated with changes in general distress, suggesting that greater increases in general distress are associated with larger deficits in extinction memory.

      Conclusions

      These findings improve our understanding of pathophysiological pathways underlying the development of anxiety and depression, while separating symptom dimensions that are shared versus unique between the two disorders.

      Keywords

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