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Establishing Evidence for Clinical Utility of a Neuroimaging Biomarker in Major Depressive Disorder: Prospective Testing and Implementation Challenges

  • Mary E. Kelley
    Correspondence
    Address correspondence to Mary E. Kelley, Ph.D.
    Affiliations
    Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia
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  • Ki Sueng Choi
    Affiliations
    Center for Advanced Circuit Therapeutics, Icahn School of Medicine at Mount Sinai, New York, New York

    Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, New York
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  • Justin K. Rajendra
    Affiliations
    Scientific and Statistical Computing Core, National Institute of Mental Health/National Institutes of Health/U.S. Department of Health and Human Services, Bethesda, Maryland
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  • W. Edward Craighead
    Affiliations
    Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia

    Department of Psychology, Emory University, Atlanta, Georgia
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  • Jeffrey J. Rakofsky
    Affiliations
    Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia
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  • Author Footnotes
    1 BWD and HSM contributed equally to this work.
    Boadie W. Dunlop
    Footnotes
    1 BWD and HSM contributed equally to this work.
    Affiliations
    Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia
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  • Author Footnotes
    1 BWD and HSM contributed equally to this work.
    Helen S. Mayberg
    Footnotes
    1 BWD and HSM contributed equally to this work.
    Affiliations
    Center for Advanced Circuit Therapeutics, Icahn School of Medicine at Mount Sinai, New York, New York

    Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York
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  • Author Footnotes
    1 BWD and HSM contributed equally to this work.
Published:February 25, 2021DOI:https://doi.org/10.1016/j.biopsych.2021.02.966

      Abstract

      Background

      Although a number of neuroimaging biomarkers for response have been proposed, none have been tested prospectively for direct effects on treatment outcomes. To the best of our knowledge, this is the first prospective test of the clinical utility of the use of an imaging biomarker to select treatment for patients with major depressive disorder.

      Methods

      Eligible participants (n = 60) had a primary diagnosis of major depressive disorder and were assigned to either escitalopram or cognitive behavioral therapy based on fluorodeoxyglucose positron emission tomography activity in the right anterior insula. The overall study remission rate after 12 weeks of treatment, based on the end point Hamilton Depression Rating Scale score, was then examined for futility and benefit of the strategy.

      Results

      Remission rates demonstrated lack of futility at the end of stage 1 (37%, 10/27), and the study proceeded to stage 2. After adjustment for the change in stage 2 sample size, the complete remission rate did not demonstrate evidence of benefit (37.7%, 95% confidence interval, 26.3%–51.4%, p = .38). However, total remission rates (complete and partial remission) did reach significance in post hoc analysis (49.1%, 95% confidence interval, 37.6%–60.7%, p = .020).

      Conclusions

      The study shows some evidence for a role of the right anterior insula in the clinical choice of major depressive disorder monotherapy. The effect size, however, is insufficient for the use of insula activity as a sole predictive biomarker of remission. The study also demonstrates the logistical difficulties in establishing clinical utility of biomarkers.

      Keywords

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          Erratum to: “Establishing Evidence for Clinical Utility of a Neuroimaging Biomarker in Major Depressive Disorder: Prospective Testing and Implementation Challenges,” by Kelley et al. (Biol Psychiatry 2021); https://doi.org/10.1016/j.biopsych.2021.02.966 .
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