Abstract
Objective: Cognitive-behavioral therapy (CBT) is considered a first-line treatment for obsessive-compulsive disorder (OCD) in pediatric and adult populations. Nevertheless, some patients show partial or null response. The identification of predictors of CBT response may improve clinical management of patients with OCD. Here, we aimed to identify structural magnetic resonance imaging (MRI) predictors of CBT response in 2 large series of children and adults with OCD from the worldwide ENIGMA-OCD consortium. Method: Data from 16 datasets from 13 international sites were included in the study. We assessed which variations in baseline cortical thickness, cortical surface area, and subcortical volume predicted response to CBT (percentage of baseline to post-treatment symptom reduction) in 2 samples totaling 168 children and adolescents (age range 5-17.5 years) and 318 adult patients (age range 18-63 years) with OCD. Mixed linear models with random intercept were used to account for potential cross-site differences in imaging values. Results: Significant results were observed exclusively in the pediatric sample. Right prefrontal cortex thickness was positively associated with the percentage of CBT response. In a post hoc analysis, we observed that the specific changes accounting for this relationship were a higher thickness of the frontal pole and the rostral middle frontal gyrus. We observed no significant effects of age, sex, or medication on our findings. Conclusion: Higher cortical thickness in specific right prefrontal cortex regions may be important for CBT response in children with OCD. Our findings suggest that the right prefrontal cortex plays a relevant role in the mechanisms of action of CBT in children.
Original language | English |
---|---|
Journal | Journal of the American Academy of Child and Adolescent Psychiatry |
DOIs | |
State | Accepted/In press - 2023 |
Externally published | Yes |
Keywords
- anxiety disorders
- cognitive-behavioral therapy
- magnetic resonance imaging
- neuroimaging
- obsessive-compulsive disorder
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Right Prefrontal Cortical Thickness Is Associated With Response to Cognitive−Behavioral Therapy in Children With Obsessive-Compulsive Disorder. / ENIGMA-OCD Working Group.
In: Journal of the American Academy of Child and Adolescent Psychiatry, 2023.Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Right Prefrontal Cortical Thickness Is Associated With Response to Cognitive−Behavioral Therapy in Children With Obsessive-Compulsive Disorder
AU - ENIGMA-OCD Working Group
AU - Bertolín, Sara
AU - Alonso, Pino
AU - Martínez-Zalacaín, Ignacio
AU - Menchón, Jose M.
AU - Jimenez-Murcia, Susana
AU - Baker, Justin T.
AU - Bargalló, Nuria
AU - Batistuzzo, Marcelo Camargo
AU - Boedhoe, Premika S.W.
AU - Brennan, Brian P.
AU - Feusner, Jamie D.
AU - Fitzgerald, Kate D.
AU - Fontaine, Martine
AU - Hansen, Bjarne
AU - Hirano, Yoshiyuki
AU - Hoexter, Marcelo Q.
AU - Huyser, Chaim
AU - Jahanshad, Neda
AU - Jaspers-Fayer, Fern
AU - Kuno, Masaru
AU - Kvale, Gerd
AU - Lazaro, Luisa
AU - Machado-Sousa, Mafalda
AU - Marsh, Rachel
AU - Morgado, Pedro
AU - Nakagawa, Akiko
AU - Norman, Luke
AU - Nurmi, Erika L.
AU - O'Neill, Joseph
AU - Ortiz, Ana E.
AU - Perriello, Chris
AU - Piacentini, John
AU - Picó-Pérez, Maria
AU - Shavitt, Roseli G.
AU - Shimizu, Eiji
AU - Simpson, Helen Blair
AU - Stewart, S. Evelyn
AU - Thomopoulos, Sophia I.
AU - Thorsen, Anders Lillevik
AU - Walitza, Susanne
AU - Wolters, Lidewij H.
AU - Thompson, Paul M.
AU - van den Heuvel, Odile A.
AU - Stein, Dan J.
AU - Soriano-Mas, Carles
N1 - Funding Information: This study was supported by Carlos III Health Institute trough FIS grant ( PI18/00856 , PI16/00950 , PI19/01171, PI19/01184 [Alonso, Soriano-Mas, Menchón]); Bertolín was supported by Río Hortega grant (CM21/00278); Martínez-Zalacaín was supported by a PFIS grant (FI17/00294); co-funded by European Social Fund (ESF) investing in your future. Jimenez-Murcia was supported by Ministerio de Ciencia, Innovación y Universidades (RTI2018-101837-B-100); and research funded by the Delegación del Gobierno para el Plan Nacional sobre Drogas ( 2017I067 , 2019I47 , and 2021I031 ). Baker was supported by JSPS KAKENHI (26461762 and 16K04344). Fitzgerald was supported by National Institute of Mental Health ( NIMH ; K23 MH082176 ) and Charles Dana Foundation ( UL1TR000433 ). Hirano was supported by AMED Brain/MINDS Beyond (JP21dm0307002) and JSPS KAKENHI (19K03309). Jahanshad was supported by NIMH (R01MH117601). Jaspers-Fayer was supported by Michael Smith Foundation for Health Research. Kuno was supported by JSPS KAKENHI (18K13315). Lazaro was supported by The Marato TV3 Foundation grants (091710). Machado-Sousa was supported by Portuguese Foundation for Science and Technology (2020.07946.BD). Marsh was supported by NIMH (R01MH104648 and R21MH101441). Morgado was supported by National funds, through the Foundation for Science and Technology (FCT) (UIDB/50026/2020 and UIDP/50026/2020). Nakagawa was supported by JSPS KAKENHI (19K03308). O’Neill was supported by NIMH (R01MH081864 and R01MH085900-01A2). Piacentini was supported by NIMH (R01MH081864). Feusner was supported by NIMH (R01MH085900-01A2). Shavitt was supported by Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (303754/2018-4 and 573974/2008-0); and FAPESP (2008/57896-8). Shimizu was supported by AMED Brain/MINDS Beyond (JP21dm0307002). Thompson was supported by the National Institutes of Health (NIH; U54 EB020403). VIDI grant awarded to van den Heuvel (91717306). Walitza was supported by the Swiss National Science Foundation (320030_130237) and by the Hartmann Müller Foundation (1460). Funding Information: The authors thank CERCA Programme/Generalitat de Catalunya for institutional support. This research was supported by CIBER -Consorcio Centro de Investigación Biomédica en Red- (CB07/09/0022), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación. The ENIGMA Working Group acknowledges the NIH Big Data to Knowledge (BD2K) award for foundational support and consortium development (U54 EB020403 to Paul M. Thompson). For a complete list of ENIGMA-related grant support please see here: http://enigma.ini.usc.edu/about-2/funding/ Funding Information: This study was supported by Carlos III Health Institute trough FIS grant (PI18/00856, PI16/00950, PI19/01171, PI19/01184 [Alonso, Soriano-Mas, Menchón]); Bertolín was supported by Río Hortega grant (CM21/00278); Martínez-Zalacaín was supported by a PFIS grant (FI17/00294); co-funded by European Social Fund (ESF) investing in your future. Jimenez-Murcia was supported by Ministerio de Ciencia, Innovación y Universidades (RTI2018-101837-B-100); and research funded by the Delegación del Gobierno para el Plan Nacional sobre Drogas (2017I067, 2019I47, and 2021I031). Baker was supported by JSPS KAKENHI (26461762 and 16K04344). Fitzgerald was supported by National Institute of Mental Health (NIMH; K23 MH082176) and Charles Dana Foundation (UL1TR000433). Hirano was supported by AMED Brain/MINDS Beyond (JP21dm0307002) and JSPS KAKENHI (19K03309). Jahanshad was supported by NIMH (R01MH117601). Jaspers-Fayer was supported by Michael Smith Foundation for Health Research. Kuno was supported by JSPS KAKENHI (18K13315). Lazaro was supported by The Marato TV3 Foundation grants (091710). Machado-Sousa was supported by Portuguese Foundation for Science and Technology (2020.07946.BD). Marsh was supported by NIMH (R01MH104648 and R21MH101441). Morgado was supported by National funds, through the Foundation for Science and Technology (FCT) (UIDB/50026/2020 and UIDP/50026/2020). Nakagawa was supported by JSPS KAKENHI (19K03308). O'Neill was supported by NIMH (R01MH081864 and R01MH085900-01A2). Piacentini was supported by NIMH (R01MH081864). Feusner was supported by NIMH (R01MH085900-01A2). Shavitt was supported by Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (303754/2018-4 and 573974/2008-0); and FAPESP (2008/57896-8). Shimizu was supported by AMED Brain/MINDS Beyond (JP21dm0307002). Thompson was supported by the National Institutes of Health (NIH; U54 EB020403). VIDI grant awarded to van den Heuvel (91717306). Walitza was supported by the Swiss National Science Foundation (320030_130237) and by the Hartmann Müller Foundation (1460). Author Contributions Conceptualization: Bertolín, van den Heuvel, Thompson, Stein, Soriano-Mas Data curation: Bertolín, Alonso, Martínez-Zalacaín, Jimenez-Murcia, Baker, Boedhoe, Brennan, Fitzgerald, Hirano, Hoexter, Huyser, Kvale, Lazaro, Marsh, Morgado, Nurmi, O'Neill, Shavitt, Simpson, Stewart, Walitza, ENIGMA-OCD Working Group, Thompson, van den Heuvel, Stein, Soriano-Mas Formal analysis: Bertolín, Boedhoe, van den Heuvel, Soriano-Mas Funding acquisition: Alonso, Fitzgerald, Hirano, Lázaro, Simpson, Marsh, Menchón, Morgado, O'Neill, Soriano-Mas, Thompson, van den Heuvel, Walitza Investigation: Bertolín, Boedhoe, van den Heuvel, Soriano-Mas Methodology: Bertolín, Boedhoe, Stein, Thompson, van den Heuvel, Soriano-Mas Project administration: Bertolín, Boedhoe, Thomopoulos, Thompson, van den Heuvel, Stein, Soriano-Mas Resources: Martínez-Zalacaín, Menchón, van den Heuvel, Stein, Thompson, Soriano-Mas Software: Bertolín, Boedhoe, Martínez-Zalacaín, Soriano-Mas Supervision: Stein, Thompson, van den Heuvel, Soriano-Mas Validation: Alonso, Martínez-Zalacaín, Menchón, Jimenez-Murcia, Baker, Bargalló, Batistuzzo, Brennan, Feusner, Fitzgerald, Fontaine, Hansen, Hirano, Hoexter, Huyser, Jahanshad, Jaspers-Fayer, Kuno, Kvale, Lazaro, Machado-Sousa, Marsh, Morgado, Nakagawa, Norman, Nurmi, O'Neill, Ortiz, Perriello, Piacentini, Picó-Pérez, Shavitt, Shimizu, Simpson, Stewart, Thomopoulos, Thorsen, Wolters, Walitza, ENIGMA-OCD Working Group, Thompson, van den Heuvel, Stein Visualization: Bertolín, Soriano-Mas Writing – original draft: Bertolín, Soriano-Mas Writing – review and editing: Bertolín, Alonso, Martínez-Zalacaín, Jimenez-Murcia, Baker, Bargalló, Batistuzzo, Boedhoe, Brennan, Feusner, Fitzgerald, Fontaine, Hansen, Hirano, Hoexter, Huyser, Jahanshad, Jaspers-Fayer, Kuno, Kvale, Lazaro, Machado-Sousa, Marsh, Morgado, Nakagawa, Norman, Nurmi, O'Neill, Ortiz, Perriello, Piacentini, Picó-Pérez, Shavitt, Shimizu, Simpson, Stewart, Thomopoulos, Thorsen, Wolters, Walitza, ENIGMA-OCD Working Group, Thompson, van den Heuvel, Stein, Soriano-Mas Disclosure: Dr. Feusner has served as a consultant to NOCD, Inc. Dr. Morgado has received CME-related honoraria or consulting fees from Angelini, AstraZeneca, Bial, Biogen, DGS-Portugal, FCT, FLAD, Janssen-Cilag, Gulbenkian Foundation, Lundbeck, Springer Healthcare, Tecnimede, Viatris and 2CA-Braga. Dr. O'Neill has been an unpaid Scientific Advisory Board member for Myriad Genetics and has received funding for clinical trial from Emalex Pharmaceuticals. Dr. Simpson has received royalties from UpToDate, Inc. and Cambridge University Press and a stipend from the American Medical Association for serving as Associate Editor of JAMA-Psychiatry. Dr. Stewart has received grant/research support from the Canadian Institutes for Health Research, the Social Sciences and Humanities Research Council (Canada), the BC Ministry of Health COVID-19 Research Priorities Fund, the BC Centre for Disease Control, the University of British Columbia Faculty of Medicine (Strategic Investment Fund), British Columbia Children's Hospital, and the BC Mental Health and Substance Use Services Research Institute. She has served on advisory boards/DSMB / speakers bureaus / travel expenses from the International OCD Foundation (IOCDF). She has served on advisory boards/DSMB of Anxiety Canada, the Youth Development Instrument Provincial Practice and Policy Group, and the British Columbia Ministry of Mental Health and Addictions. She has served as consultant / honoraria from the Misophonia Research Foundation and the Milken Institute. She has reported editorship/editorial board of Canadian Journal of Psychiatry and Annals of Clinical Psychiatry. She has reported authorship of assessment tools: Abramovitch A, Abramowitz JS, McKay D, Cham H, Anderson KS, Farrell L, Geller DA, Hanna GL, Mathieu S, McGuire JF, Rosenberg DR, Stewart SE, Storch EA, Wilhelm S. A Revision of the Obsessive-Compulsive Inventory – Child Version: The OCI-CV-R. Journal of Anxiety Disorders (accepted manuscript, January 2022). Dr. Walitza has received royalties from Thieme Hogrefe, Kohlhammer, Springer, Beltz, and Elsevier. Her work was supported by the Swiss National Science Foundation (SNF), diff. EU FP7s, Bfarm Germany, ZInEP, Olga Gertrud Thalmann, Vontobel, Unicentia, Erika Schwarz Fonds. Outside professional activities and interests are declared under the link of the University of Zurichwww.uzh.ch/prof/ssl-dir/interessenbindungen/client/web/. Dr. Wolters reports personal fees from Bohn Stafleu van Loghum, Houten, the Netherlands (publisher). Dr. Thompson has received partial research support from Biogen, Inc., for research unrelated to this manuscript. Dr. Van den Heuvel has received consultation honorarium from Lundbeck. Drs. Bertolín, Alonso, Menchón, Jimenez-Murcia, Baker, Bargalló, Batistuzzo, Boedhoe, Brennan, Fitzgerald, Hansen, Hirano, Hoexter, Huyser, Jahanshad, Jaspers-Fayer, Kuno, Kvale, Lazaro, Marsh, Nakagawa, Norman, Nurmi, Ortiz, Piacentini, Picó-Pérez, Shavitt, Shimizu, Thorsen, Stein, and Soriano-Mas, Mr. Martínez-Zalacaín, Mss. Fontaine and Machado-Sousa, Mr. Perriello, and Ms. Thomopoulos have reported no biomedical financial interests or potential conflicts of interest. Publisher Copyright: © 2022 American Academy of Child and Adolescent Psychiatry
PY - 2023
Y1 - 2023
N2 - Objective: Cognitive-behavioral therapy (CBT) is considered a first-line treatment for obsessive-compulsive disorder (OCD) in pediatric and adult populations. Nevertheless, some patients show partial or null response. The identification of predictors of CBT response may improve clinical management of patients with OCD. Here, we aimed to identify structural magnetic resonance imaging (MRI) predictors of CBT response in 2 large series of children and adults with OCD from the worldwide ENIGMA-OCD consortium. Method: Data from 16 datasets from 13 international sites were included in the study. We assessed which variations in baseline cortical thickness, cortical surface area, and subcortical volume predicted response to CBT (percentage of baseline to post-treatment symptom reduction) in 2 samples totaling 168 children and adolescents (age range 5-17.5 years) and 318 adult patients (age range 18-63 years) with OCD. Mixed linear models with random intercept were used to account for potential cross-site differences in imaging values. Results: Significant results were observed exclusively in the pediatric sample. Right prefrontal cortex thickness was positively associated with the percentage of CBT response. In a post hoc analysis, we observed that the specific changes accounting for this relationship were a higher thickness of the frontal pole and the rostral middle frontal gyrus. We observed no significant effects of age, sex, or medication on our findings. Conclusion: Higher cortical thickness in specific right prefrontal cortex regions may be important for CBT response in children with OCD. Our findings suggest that the right prefrontal cortex plays a relevant role in the mechanisms of action of CBT in children.
AB - Objective: Cognitive-behavioral therapy (CBT) is considered a first-line treatment for obsessive-compulsive disorder (OCD) in pediatric and adult populations. Nevertheless, some patients show partial or null response. The identification of predictors of CBT response may improve clinical management of patients with OCD. Here, we aimed to identify structural magnetic resonance imaging (MRI) predictors of CBT response in 2 large series of children and adults with OCD from the worldwide ENIGMA-OCD consortium. Method: Data from 16 datasets from 13 international sites were included in the study. We assessed which variations in baseline cortical thickness, cortical surface area, and subcortical volume predicted response to CBT (percentage of baseline to post-treatment symptom reduction) in 2 samples totaling 168 children and adolescents (age range 5-17.5 years) and 318 adult patients (age range 18-63 years) with OCD. Mixed linear models with random intercept were used to account for potential cross-site differences in imaging values. Results: Significant results were observed exclusively in the pediatric sample. Right prefrontal cortex thickness was positively associated with the percentage of CBT response. In a post hoc analysis, we observed that the specific changes accounting for this relationship were a higher thickness of the frontal pole and the rostral middle frontal gyrus. We observed no significant effects of age, sex, or medication on our findings. Conclusion: Higher cortical thickness in specific right prefrontal cortex regions may be important for CBT response in children with OCD. Our findings suggest that the right prefrontal cortex plays a relevant role in the mechanisms of action of CBT in children.
KW - anxiety disorders
KW - cognitive-behavioral therapy
KW - magnetic resonance imaging
KW - neuroimaging
KW - obsessive-compulsive disorder
UR - http://www.scopus.com/inward/record.url?scp=85146449204&partnerID=8YFLogxK
U2 - 10.1016/j.jaac.2022.07.865
DO - 10.1016/j.jaac.2022.07.865
M3 - Article
C2 - 36526161
AN - SCOPUS:85146449204
SN - 0890-8567
JO - Journal of the American Academy of Child and Adolescent Psychiatry
JF - Journal of the American Academy of Child and Adolescent Psychiatry
ER -