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Systematic Review: Medication Effects on Brain Intrinsic Functional Connectivity in Patients With Attention-Deficit/Hyperactivity Disorder - 26/01/21

Doi : 10.1016/j.jaac.2020.10.013 
Victor Pereira-Sanchez, MD a, b, , Alexandre R. Franco, PhD c, d, Dorice Vieira, MLS, MA, MPH e, Pilar de Castro-Manglano, MD, PhD f, Cesar Soutullo, MD, PhD g, Michael P. Milham, MD, PhD c, d, Francisco X. Castellanos, MD a, c
a NYU Grossman School of Medicine, New York, New York 
b Clinica Universidad de Navarra, Pamplona, Navarra, Spain 
c Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York 
d Child Mind Institute, New York, New York 
e NYU Health Sciences Library, New York, New York 
f Clinica Universidad de Navarra, Madrid, Spain 
g McGovern Medical School at UTHealth, Houston, Texas 

Correspondence to Victor Pereira-Sanchez, MD, Child Study Center, Department of Child and Adolescent Psychiatry, NYU Grossman School of Medicine, One Park Avenue, 7th Floor, New York, NY 10016.Child Study CenterDepartment of Child and Adolescent PsychiatryNYU Grossman School of MedicineOne Park Avenue7th FloorNew YorkNY10016

Abstract

Objective

Resting-state functional magnetic resonance imaging (R-fMRI) studies of the neural correlates of medication treatment in attention-deficit/hyperactivity disorder (ADHD) have not been systematically reviewed. Our objective was to systematically identify, assess and summarize within-subject R-fMRI studies of pharmacological-induced changes in patients with ADHD. We critically appraised strengths and limitations, and provide recommendations for future research.

Method

Systematic review of published original reports in English meeting criteria in pediatric and adult patients with ADHD up to July 1, 2020. A thorough search preceded selection of studies matching prespecified criteria. Strengths and limitations of selected studies, regarding design and reporting, were identified based on current best practices.

Results

We identified and reviewed 9 studies (5 pediatric and 4 adult studies). Sample sizes were small-medium (16–38 patients), and included few female participants. Medications were methylphenidate, amphetamines, and atomoxetine. Wide heterogeneity was observed in designs, analyses and results, which could not be combined quantitatively. Qualitatively, the multiplicity of brain regions and networks identified, some of which correlated with clinical improvements, do not support a coherent mechanistic hypothesis of medication effects. Overall, reports did not meet current standards to ensure reproducibility.

Conclusion

In this emerging field, the few studies using R-fMRI to analyze the neural correlates of medications in patients with ADHD suggest a potential modulatory effect of stimulants and atomoxetine on several intrinsic brain activity metrics. However, methodological heterogeneity and reporting issues need to be addressed in future research to validate findings which may contribute to clinical care. Such a goal is not yet at hand.

Le texte complet de cet article est disponible en PDF.

Key words : attention-deficit/hyperactivity disorder, functional magnetic resonance imaging, drug therapy, intrinsic functional connectivity, resting state


Plan


 The authors have reported no funding for this work.
 This article is part of a special series devoted to the subject of subject of child and adolescent attention-deficit/hyperactivity disorder (ADHD). The series covers a range of topics in the area including genetics, neuroimaging, treatment, and others. The series was edited by Guest Editor Jonathan Posner, MD along with Deputy Editor Samuele Cortese, MD, PhD.
 Author Contributions
 Conceptualization: Pereira-Sanchez, Franco, Castro-Manglano, Soutullo, Milham, Castellanos
 Data curation: Franco, Vieira, Castellanos
 Formal analysis: Franco
 Investigation: Pereira-Sanchez, Franco, Castellanos
 Methodology: Pereira-Sanchez, Franco, Vieira, Castro-Manglano, Soutullo, Milham, Castellanos
 Supervision: Franco, Castro-Manglano, Soutullo, Milham, Castellanos
 Validation: Franco, Castellanos
 Visualization: Franco, Vieira, Castellanos
 Writing – original draft: Pereira-Sanchez
 Writing – review and editing: Pereira-Sanchez, Franco, Vieira, Castro-Manglano, Soutullo, Milham, Castellanos
 ORCID
 Victor Pereira-Sanchez, MD: 0000-0002-2576-1549
 Alexandre R. Franco, PhD: 0000-0002-1552-1090
 Dorice Vieira, MLS, MA, MPH: 0000-0003-4232-9413
 Pilar de Castro-Manglano, MD, PhD: 0000-0003-3141-3492
 Cesar Soutullo, MD, PhD: 0000-0003-4348-0772
 Michael P. Milham, MD, PhD: 0000-0003-3532-1210
 Francisco X. Castellanos, MD: 0000-0001-9192-9437
 The authors thank Samuele Cortese, MD, PhD, of University of Southampton, for his guidance in undertaking this review. Particular credit is to be given to the authors of the reviewed studies who responded to our queries and provided additional information. Finally, we thank Fundacion Alicia Koplowitz for funding Dr. Pereira-Sanchez’s fellowship.
 Disclosure: Dr. Pereira-Sanchez has been supported by the Fundacion Alicia Koplowitz in his current position, which has no direct role in his scientific research. Dr. Soutullo has received research funds for his department (non-personal) from Texas Child Mental Health Care Consortium (Youth Depression and Suicide Network) SB11 and Adlon Therapeutics. He has served as consultant / advisory board member for Editorial Médica Panamericana, EUNETHYDIS (European Network on Hyperkinetic Disorder), and NeuroTech Solutions, Ltd. He has served in the speaker's bureau / has given talks on Continuing Medical Education (not about a specific product) for Bial – Portugal. He has received royalties from Editorial Médica Panamericana. Dr. Castellanos has served on the scientific advisory board of BOL Pharma, Israel. Drs. Franco, de Castro-Manglano, Milham and Ms. Vieira have reported no biomedical financial interests or potential conflicts of interest.


© 2020  American Academy of Child and Adolescent Psychiatry. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 60 - N° 2

P. 222-235 - février 2021 Retour au numéro
Article précédent Article précédent
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