Predicting cognitive-behavioral therapy outcomes in obsessive-compulsive disorder from inhibitory control neural activity: A mega-analysis and machine learning study from the ENIGMA-OCD consortium
European Neuropsychopharmacology, pp. 113879
Abstract
Objective Cognitive behavioral therapy (CBT) is an effective treatment for obsessive-compulsive disorder (OCD), yet it remains difficult to predict who will respond. This study investigates associations between neural activity during inhibitory control tasks and CBT outcomes, and its value as a predictive marker of CBT outcome. Methods Using fMRI data from individuals performing an inhibitory control task across five ENIGMA-OCD samples (n=130, age range=8-57, 54% female), mass-univariate associations were analyzed between response inhibition and error processing activity and three CBT outcomes: response, remission, and change in symptom severity. Random forest classifier and support vector machine models using leave-one-sample-out and 5-fold cross-validation were used to predict CBT response and remission from fMRI activity and clinical data. Results Remission after CBT was associated with weaker activity in default mode regions during response inhibition and in the right supramarginal gyrus during error processing. Greater symptom reduction was linked to weaker pre-treatment activity across frontoparietal, dorsal attention, visual, and subcortical regions during response inhibition, and stronger default mode activity during error processing. These group-level effects were partially confirmed with machine learning, which predicted CBT response using inhibitory and error-related activity with modest AUC values of 0.66-0.67. Prediction of CBT remission or using other data types did not exceed chance-level. Conclusion Wide-spread weaker activity during response inhibition and stronger activity in default mode regions during error processing pre-treatment appear beneficial for CBT. Despite modestly predictive AUC-values, these findings cannot yet be translated into clinically relevant individual markers of CBT outcome.
Authors 26
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Nadža Džinalija corresponding
Amsterdam Neuroscience · Amsterdam University Medical Centers · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Neuroscience, Compulsivity Impulsivity & Attention, Amsterdam, The Netherlands
Amsterdam University Medical Center, Vrije University Amsterdam, Department of Psychiatry, Department of Anatomy & Neurosciences, Amsterdam, The Netherlands
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Amsterdam Neuroscience · Amsterdam University Medical Centers · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Neuroscience, Compulsivity Impulsivity & Attention, Amsterdam, The Netherlands
Amsterdam University Medical Center, Vrije University Amsterdam, Department of Psychiatry, Department of Anatomy & Neurosciences, Amsterdam, The Netherlands
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New York State Psychiatric Institute · Columbia University
Affiliation as printed
Center for OCD and Related Disorders, New York State Psychiatric Institute, New York, NY, USA
Columbia University Irving Medical College, Columbia University, New York, NY, USA
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Icahn School of Medicine at Mount Sinai
Affiliation as printed
Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Instituto de Salud Carlos III · Bellvitge University Hospital · Institut d'Investigació Biomédica de Bellvitge · Universitat de Barcelona
Affiliation as printed
Centre for Biomedical Research in the Mental Health Network, Carlos III Health Institute, Madrid, Spain
Department of Clinical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
Department of Psychiatry, Bellvitge Biomedical Research Institute, Bellvitge University Hospital, Barcelona, Spain
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Instituto de Salud Carlos III · Institut d'Investigació Biomédica de Bellvitge · Centro de Investigación Biomédica en Red de Salud Mental · Universitat de Barcelona
Affiliation as printed
CIBERSAM, Carlos III Health Institute, Madrid, Spain
Department of Clinical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
Department of Psychiatry, Bellvitge Biomedical Research Institute-IDIBELL, Barcelona, Spain
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Willem B. Bruin Aachen Section Forensic Family & Youth Care Institute of Education and Child Studies
Leiden University · Amsterdam Neuroscience · Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Amsterdam Neuroscience, Amsterdam, The Netherlands
Amsterdam University Medical Center, University of Amsterdam, Department of Psychiatry, Amsterdam, The Netherlands
Section Forensic Family and Youth Care, Institute of Education and Child Studies, Leiden University, Leiden, The Netherlands
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Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
Affiliation as printed
August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain
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Hospital Clínic de Barcelona · Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
Affiliation as printed
August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain
Department of Adult Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic, Barcelona, Spain
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Haukeland University Hospital · Molde Hospital
Affiliation as printed
Bergen Center for Brain Plasticity, Haukeland University Hospital, Bergen, Norway
Department of Psychiatry, Hospital of Molde, Molde, Norway
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Haukeland University Hospital · Senter for Krisepsykologi · University of Bergen
Affiliation as printed
Bergen Center for Brain Plasticity, Haukeland University Hospital, Bergen, Norway
Centre for Crisis Psychology, University of Bergen, Bergen, Norway
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Amsterdam University Medical Centers · Levvel
Affiliation as printed
Amsterdam University Medical Center, Department of Child and Adolescent Psychiatry, Amsterdam, The Netherlands
Levvel, Amsterdam, The Netherlands
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Haukeland University Hospital · University of Bergen
Affiliation as printed
Bergen Center for Brain Plasticity, Haukeland University Hospital, Bergen, Norway
Department of Clinical Psychology, University of Bergen, Bergen, Norway
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Bellvitge University Hospital · Institut d'Investigació Biomédica de Bellvitge
Affiliation as printed
Department of Psychiatry, Bellvitge Biomedical Research Institute, Bellvitge University Hospital, Barcelona, Spain
Department of Radiology, Bellvitge University Hospital, Barcelona, Spain
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Instituto de Salud Carlos III · Bellvitge University Hospital · Institut d'Investigació Biomédica de Bellvitge · Universitat de Barcelona
Affiliation as printed
Centre for Biomedical Research in the Mental Health Network, Carlos III Health Institute, Madrid, Spain
Department of Clinical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain
Department of Psychiatry, Bellvitge Biomedical Research Institute, Bellvitge University Hospital, Barcelona, Spain
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Haukeland University Hospital · University of Bergen
Affiliation as printed
Bergen Center for Brain Plasticity, Haukeland University Hospital, Bergen, Norway
Department of Biomedicine, Faculty of Medicine, University of Bergen, Bergen, Norway
Department of Radiology, Haukeland University Hospital, Bergen, Norway
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Instituto de Salud Carlos III · Bellvitge University Hospital · Institut d'Investigació Biomédica de Bellvitge · Universitat de Barcelona
Affiliation as printed
Centre for Biomedical Research in the Mental Health Network, Carlos III Health Institute, Madrid, Spain
Department of Psychiatry, Bellvitge Biomedical Research Institute, Bellvitge University Hospital, Barcelona, Spain
Department of Social Psychology and Quantitative Psychology, Institute of Neurosciences, University of Barcelona, Barcelona, Spain
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Amsterdam UMC Location University of Amsterdam · Amsterdam Neuroscience · Levvel
Affiliation as printed
Amsterdam Neuroscience, Amsterdam, The Netherlands
Amsterdam UMC location University of Amsterdam, Department of Psychiatry, Amsterdam, The Netherlands
Levvel, Academic Center for Child and Adolescent Psychiatry and Specialized Youth Care, Amsterdam, The Netherlands
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University of Southern California
Affiliation as printed
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA
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Haukeland University Hospital · University of Bergen
Affiliation as printed
Bergen Center for Brain Plasticity, Haukeland University Hospital, Bergen, Norway
Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway
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Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
Affiliation as printed
August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain
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South African Medical Research Council · University of Cape Town
Affiliation as printed
Neuroscience Institute, University of Cape Town, Cape Town, South Africa
South African Medical Research Council Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry, University of Cape Town, Cape Town, South Africa
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University of Southern California
Affiliation as printed
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA
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Humboldt-Universität zu Berlin · Berlin Institute of Health at Charité - Universitätsmedizin Berlin · Charité - Universitätsmedizin Berlin · University of Amsterdam
Affiliation as printed
Department of Developmental Psychology, University of Amsterdam, Amsterdam, The Netherlands
Research Division of Mind and Brain, Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt University of Berlin, and Berlin Institute of Health, Charité Campus Mitte, Berlin, Germany
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Amsterdam Neuroscience · Amsterdam University Medical Centers · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Neuroscience, Compulsivity Impulsivity & Attention, Amsterdam, The Netherlands
Amsterdam University Medical Center, Vrije University Amsterdam, Department of Psychiatry, Department of Anatomy & Neurosciences, Amsterdam, The Netherlands
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Amsterdam Neuroscience · Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Amsterdam Neuroscience, Amsterdam, The Netherlands
Amsterdam University Medical Center, University of Amsterdam, Department of Psychiatry, Amsterdam, The Netherlands
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