Toward Precision Medicine in ADHD

Jan Buitelaar; Sven Bölte; Daniel Brandeis; Arthur Caye; Nina Christmann; Samuele Cortese; David Coghill; Stephen V. Faraone; Barbara Franke; Markus Gleitz; Corina U. Greven; Sandra Kooij; Douglas Teixeira Leffa; Nanda Rommelse; Jeffrey H. Newcorn; Guilherme V. Polanczyk; Luis Augusto Rohde; Emily Simonoff; Mark Stein; Benedetto Vitiello; Yanki Yazgan; Michael Roesler; Manfred Doepfner; Tobias Banaschewski

doi:https://doi.org/10.3389/fnbeh.2022.900981

Toward Precision Medicine in ADHD

Jan Buitelaar, Sven Bölte, Daniel Brandeis, Arthur Caye, Nina Christmann, Samuele Cortese, David Coghill, Stephen V. Faraone, Barbara Franke, Markus Gleitz, Corina U. Greven, Sandra Kooij, Douglas Teixeira Leffa, Nanda Rommelse, Jeffrey H. Newcorn, Guilherme V. Polanczyk, Luis Augusto Rohde, Emily Simonoff, Mark Stein, Benedetto VitielloYanki Yazgan, Michael Roesler, Manfred Doepfner, Tobias Banaschewski

Research output: Contribution to journal › Review article › Academic › peer-review

16 Citations (Scopus)

Abstract

Attention-Deficit Hyperactivity Disorder (ADHD) is a complex and heterogeneous neurodevelopmental condition for which curative treatments are lacking. Whilst pharmacological treatments are generally effective and safe, there is considerable inter-individual variability among patients regarding treatment response, required dose, and tolerability. Many of the non-pharmacological treatments, which are preferred to drug-treatment by some patients, either lack efficacy for core symptoms or are associated with small effect sizes. No evidence-based decision tools are currently available to allocate pharmacological or psychosocial treatments based on the patient's clinical, environmental, cognitive, genetic, or biological characteristics. We systematically reviewed potential biomarkers that may help in diagnosing ADHD and/or stratifying ADHD into more homogeneous subgroups and/or predict clinical course, treatment response, and long-term outcome across the lifespan. Most work involved exploratory studies with cognitive, actigraphic and EEG diagnostic markers to predict ADHD, along with relatively few studies exploring markers to subtype ADHD and predict response to treatment. There is a critical need for multisite prospective carefully designed experimentally controlled or observational studies to identify biomarkers that index inter-individual variability and/or predict treatment response.

Original language	English
Article number	900981
Journal	Frontiers in behavioral neuroscience
Volume	16
DOIs	https://doi.org/10.3389/fnbeh.2022.900981
Publication status	Published - 6 Jul 2022

Keywords

Attention-Deficit Hyperactivity Disorder (ADHD)
biomarker
heterogeneity
inter-individual variability
precision medicine

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https://doi.org/10.3389/fnbeh.2022.900981

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Buitelaar, J., Bölte, S., Brandeis, D., Caye, A., Christmann, N., Cortese, S., Coghill, D., Faraone, S. V., Franke, B., Gleitz, M., Greven, C. U., Kooij, S., Leffa, D. T., Rommelse, N., Newcorn, J. H., Polanczyk, G. V., Rohde, L. A., Simonoff, E., Stein, M., ... Banaschewski, T. (2022). Toward Precision Medicine in ADHD. Frontiers in behavioral neuroscience, 16, Article 900981. https://doi.org/10.3389/fnbeh.2022.900981

@article{ef783ac5c9d8402694067ac45058a077,

title = "Toward Precision Medicine in ADHD",

abstract = "Attention-Deficit Hyperactivity Disorder (ADHD) is a complex and heterogeneous neurodevelopmental condition for which curative treatments are lacking. Whilst pharmacological treatments are generally effective and safe, there is considerable inter-individual variability among patients regarding treatment response, required dose, and tolerability. Many of the non-pharmacological treatments, which are preferred to drug-treatment by some patients, either lack efficacy for core symptoms or are associated with small effect sizes. No evidence-based decision tools are currently available to allocate pharmacological or psychosocial treatments based on the patient's clinical, environmental, cognitive, genetic, or biological characteristics. We systematically reviewed potential biomarkers that may help in diagnosing ADHD and/or stratifying ADHD into more homogeneous subgroups and/or predict clinical course, treatment response, and long-term outcome across the lifespan. Most work involved exploratory studies with cognitive, actigraphic and EEG diagnostic markers to predict ADHD, along with relatively few studies exploring markers to subtype ADHD and predict response to treatment. There is a critical need for multisite prospective carefully designed experimentally controlled or observational studies to identify biomarkers that index inter-individual variability and/or predict treatment response.",

keywords = "Attention-Deficit Hyperactivity Disorder (ADHD), biomarker, heterogeneity, inter-individual variability, precision medicine",

author = "Jan Buitelaar and Sven B{\"o}lte and Daniel Brandeis and Arthur Caye and Nina Christmann and Samuele Cortese and David Coghill and Faraone, {Stephen V.} and Barbara Franke and Markus Gleitz and Greven, {Corina U.} and Sandra Kooij and Leffa, {Douglas Teixeira} and Nanda Rommelse and Newcorn, {Jeffrey H.} and Polanczyk, {Guilherme V.} and Rohde, {Luis Augusto} and Emily Simonoff and Mark Stein and Benedetto Vitiello and Yanki Yazgan and Michael Roesler and Manfred Doepfner and Tobias Banaschewski",

note = "Funding Information: This work was supported by an unrestricted educational grant by Medice. BF is supported by a personal grant from the Innovation Program of the Netherlands Organization for Scientific Research (NWO; grant 016-130-669). GP is supported by S{\~a}o Paulo Research Foundation (FAPESP; grant 2016/22455-8) and National Council for Scientific and Technological Development (CNPq; grant 310582/2017-2). LR is supported by the National Council for Scientific and Technological Development (CNPq; grant 308294/2018-1). Medice was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. Funding Information: JB has been in the past 3 years a consultant to/member of advisory board of / and/or speaker for Shire, Roche, Medice, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. LR has received grant or research support from, served as a consultant to, and served on the speakers' bureau of Eli Lilly and Co., Janssen, Medice, Novartis and Shire. The ADHD and Juvenile Bipolar Disorder Outpatient Programs chaired by LR have received unrestricted educational and research support from the following pharmaceutical companies: Eli Lilly and Co., Janssen, and Novartis. LR has received authorship royalties from Oxford Press and ArtMed and travel grants from Shire to take part in the 2018 APA annual meeting and from Novartis to take part of the 2016 AACAP annual meeting. Barbara Franke has received educational speaking fees from Medice and Shire. SB discloses that he has in the last 5 years acted as an author, consultant or lecturer for Shire, Medice, Roche, Eli Lilly, Prima Psychiatry, GLGroup, System Analytic, Ability Partner, Kompetento, Expo Medica, Clarion Healthcare, and Prophase. He receives royalties for text books and diagnostic tools from Huber/Hogrefe, Kohlhammer and UTB. DB serves as an unpaid scientific advisor for an EU-funded neurofeedback trial unrelated to the present work. TB served in an advisory or consultancy role for Actelion, Hexal Pharma, Lilly, Lundbeck, Medice, Neurim Pharmaceuticals, Novartis, Shire. He received conference support or speaker's fee by Lilly, Medice, Novartis and Shire. He has been involved in clinical trials conducted by Shire & Viforpharma. He received royalties from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press. The present work is unrelated to the above grants and relationships. DC served in an advisory or consultancy role for Medice, Novartis, Shire/Takeda. He received conference support or speaker's fee by Medice, Servier and Shire/Takeda. He has been involved in clinical trials conducted by Shire. He received royalties from Oxford University Press. The present work is unrelated to the above grants and relationships. In the past year, SF received income, potential income, travel expenses continuing education support and/or research support from Tris, Otsuka, Arbor, Ironshore, Shire, Akili, Enzymotec, Sunovion, Supernus and Genomind. With his institution, he has US patent US20130217707 A1 for the use of sodium-hydrogen exchange inhibitors in the treatment of ADHD. In previous years, he received support from: Shire, Ironshore, Neurovance, Alcobra, Rhodes, CogCubed, KemPharm, Enzymotec, Akili, Neurolifesciences, Lundbeck/Takeda, Otsuka, McNeil, Janssen, Novartis, Pfizer and Eli Lilly. He also receives royalties from books published by Guilford Press: Straight Talk about Your Child's Mental Health, Oxford University Press: Schizophrenia: The Facts and Elsevier: ADHD: Non-Pharmacologic Interventions. He is principal investigator of www.adhdinadults.com. Guilherme V. Polanczyk has been in the past 3 years a consultant, member of advisory board, and/or speaker for Shire/Takeda and Medice. He received travel expenses for continuing education support from Shire/Takeda and royalties from Editora Manole. In the past three years, Jeffrey Newcorn is/has been an advisor and/or consultant for Adlon Therapeutics, Akili Interactive, Alcobra, Arbor, Cingulate Therapeutics, Enzymotec, KemPharm, Lundbeck/Takeda, Medice, NLS, Rhodes, Shire, and Supernus. He was a DSMB member for Pfizer and Sunovion, and received research funds from Enzymotec, Otsuka, Shire and Supernus. He also has received speaker fees from Shire for disease-state presentations, and served as a consultant for the US National Football League. BV has served as consultant to Medice and Teva Pharm. Markus Gleitz is an employee of Medice Arzneimittel P{\"u}tter GmbH & Co. KG. MS received research support from Supernus, Shire, and Akili Interactive labs and in the past year has served in a advisory or consultancy capacity to Genomind, NLS, Shire/Takeda, Supernus, and Sunovian. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer KAJ declared a shared affiliation with the author DC to the handling editor at the time of review. Publisher Copyright: Copyright {\textcopyright} 2022 Buitelaar, B{\"o}lte, Brandeis, Caye, Christmann, Cortese, Coghill, Faraone, Franke, Gleitz, Greven, Kooij, Leffa, Rommelse, Newcorn, Polanczyk, Rohde, Simonoff, Stein, Vitiello, Yazgan, Roesler, Doepfner and Banaschewski.",

year = "2022",

month = jul,

day = "6",

doi = "https://doi.org/10.3389/fnbeh.2022.900981",

language = "English",

volume = "16",

journal = "Frontiers in behavioral neuroscience",

issn = "1662-5153",

publisher = "Frontiers Media S.A.",

}

Buitelaar, J, Bölte, S, Brandeis, D, Caye, A, Christmann, N, Cortese, S, Coghill, D, Faraone, SV, Franke, B, Gleitz, M, Greven, CU, Kooij, S, Leffa, DT, Rommelse, N, Newcorn, JH, Polanczyk, GV, Rohde, LA, Simonoff, E, Stein, M, Vitiello, B, Yazgan, Y, Roesler, M, Doepfner, M & Banaschewski, T 2022, 'Toward Precision Medicine in ADHD', Frontiers in behavioral neuroscience, vol. 16, 900981. https://doi.org/10.3389/fnbeh.2022.900981

TY - JOUR

T1 - Toward Precision Medicine in ADHD

AU - Buitelaar, Jan

AU - Bölte, Sven

AU - Brandeis, Daniel

AU - Caye, Arthur

AU - Christmann, Nina

AU - Cortese, Samuele

AU - Coghill, David

AU - Faraone, Stephen V.

AU - Franke, Barbara

AU - Gleitz, Markus

AU - Greven, Corina U.

AU - Kooij, Sandra

AU - Leffa, Douglas Teixeira

AU - Rommelse, Nanda

AU - Newcorn, Jeffrey H.

AU - Polanczyk, Guilherme V.

AU - Rohde, Luis Augusto

AU - Simonoff, Emily

AU - Stein, Mark

AU - Vitiello, Benedetto

AU - Yazgan, Yanki

AU - Roesler, Michael

AU - Doepfner, Manfred

AU - Banaschewski, Tobias

N1 - Funding Information: This work was supported by an unrestricted educational grant by Medice. BF is supported by a personal grant from the Innovation Program of the Netherlands Organization for Scientific Research (NWO; grant 016-130-669). GP is supported by São Paulo Research Foundation (FAPESP; grant 2016/22455-8) and National Council for Scientific and Technological Development (CNPq; grant 310582/2017-2). LR is supported by the National Council for Scientific and Technological Development (CNPq; grant 308294/2018-1). Medice was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. Funding Information: JB has been in the past 3 years a consultant to/member of advisory board of / and/or speaker for Shire, Roche, Medice, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. LR has received grant or research support from, served as a consultant to, and served on the speakers' bureau of Eli Lilly and Co., Janssen, Medice, Novartis and Shire. The ADHD and Juvenile Bipolar Disorder Outpatient Programs chaired by LR have received unrestricted educational and research support from the following pharmaceutical companies: Eli Lilly and Co., Janssen, and Novartis. LR has received authorship royalties from Oxford Press and ArtMed and travel grants from Shire to take part in the 2018 APA annual meeting and from Novartis to take part of the 2016 AACAP annual meeting. Barbara Franke has received educational speaking fees from Medice and Shire. SB discloses that he has in the last 5 years acted as an author, consultant or lecturer for Shire, Medice, Roche, Eli Lilly, Prima Psychiatry, GLGroup, System Analytic, Ability Partner, Kompetento, Expo Medica, Clarion Healthcare, and Prophase. He receives royalties for text books and diagnostic tools from Huber/Hogrefe, Kohlhammer and UTB. DB serves as an unpaid scientific advisor for an EU-funded neurofeedback trial unrelated to the present work. TB served in an advisory or consultancy role for Actelion, Hexal Pharma, Lilly, Lundbeck, Medice, Neurim Pharmaceuticals, Novartis, Shire. He received conference support or speaker's fee by Lilly, Medice, Novartis and Shire. He has been involved in clinical trials conducted by Shire & Viforpharma. He received royalties from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press. The present work is unrelated to the above grants and relationships. DC served in an advisory or consultancy role for Medice, Novartis, Shire/Takeda. He received conference support or speaker's fee by Medice, Servier and Shire/Takeda. He has been involved in clinical trials conducted by Shire. He received royalties from Oxford University Press. The present work is unrelated to the above grants and relationships. In the past year, SF received income, potential income, travel expenses continuing education support and/or research support from Tris, Otsuka, Arbor, Ironshore, Shire, Akili, Enzymotec, Sunovion, Supernus and Genomind. With his institution, he has US patent US20130217707 A1 for the use of sodium-hydrogen exchange inhibitors in the treatment of ADHD. In previous years, he received support from: Shire, Ironshore, Neurovance, Alcobra, Rhodes, CogCubed, KemPharm, Enzymotec, Akili, Neurolifesciences, Lundbeck/Takeda, Otsuka, McNeil, Janssen, Novartis, Pfizer and Eli Lilly. He also receives royalties from books published by Guilford Press: Straight Talk about Your Child's Mental Health, Oxford University Press: Schizophrenia: The Facts and Elsevier: ADHD: Non-Pharmacologic Interventions. He is principal investigator of www.adhdinadults.com. Guilherme V. Polanczyk has been in the past 3 years a consultant, member of advisory board, and/or speaker for Shire/Takeda and Medice. He received travel expenses for continuing education support from Shire/Takeda and royalties from Editora Manole. In the past three years, Jeffrey Newcorn is/has been an advisor and/or consultant for Adlon Therapeutics, Akili Interactive, Alcobra, Arbor, Cingulate Therapeutics, Enzymotec, KemPharm, Lundbeck/Takeda, Medice, NLS, Rhodes, Shire, and Supernus. He was a DSMB member for Pfizer and Sunovion, and received research funds from Enzymotec, Otsuka, Shire and Supernus. He also has received speaker fees from Shire for disease-state presentations, and served as a consultant for the US National Football League. BV has served as consultant to Medice and Teva Pharm. Markus Gleitz is an employee of Medice Arzneimittel Pütter GmbH & Co. KG. MS received research support from Supernus, Shire, and Akili Interactive labs and in the past year has served in a advisory or consultancy capacity to Genomind, NLS, Shire/Takeda, Supernus, and Sunovian. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer KAJ declared a shared affiliation with the author DC to the handling editor at the time of review. Publisher Copyright: Copyright © 2022 Buitelaar, Bölte, Brandeis, Caye, Christmann, Cortese, Coghill, Faraone, Franke, Gleitz, Greven, Kooij, Leffa, Rommelse, Newcorn, Polanczyk, Rohde, Simonoff, Stein, Vitiello, Yazgan, Roesler, Doepfner and Banaschewski.

PY - 2022/7/6

Y1 - 2022/7/6

N2 - Attention-Deficit Hyperactivity Disorder (ADHD) is a complex and heterogeneous neurodevelopmental condition for which curative treatments are lacking. Whilst pharmacological treatments are generally effective and safe, there is considerable inter-individual variability among patients regarding treatment response, required dose, and tolerability. Many of the non-pharmacological treatments, which are preferred to drug-treatment by some patients, either lack efficacy for core symptoms or are associated with small effect sizes. No evidence-based decision tools are currently available to allocate pharmacological or psychosocial treatments based on the patient's clinical, environmental, cognitive, genetic, or biological characteristics. We systematically reviewed potential biomarkers that may help in diagnosing ADHD and/or stratifying ADHD into more homogeneous subgroups and/or predict clinical course, treatment response, and long-term outcome across the lifespan. Most work involved exploratory studies with cognitive, actigraphic and EEG diagnostic markers to predict ADHD, along with relatively few studies exploring markers to subtype ADHD and predict response to treatment. There is a critical need for multisite prospective carefully designed experimentally controlled or observational studies to identify biomarkers that index inter-individual variability and/or predict treatment response.

AB - Attention-Deficit Hyperactivity Disorder (ADHD) is a complex and heterogeneous neurodevelopmental condition for which curative treatments are lacking. Whilst pharmacological treatments are generally effective and safe, there is considerable inter-individual variability among patients regarding treatment response, required dose, and tolerability. Many of the non-pharmacological treatments, which are preferred to drug-treatment by some patients, either lack efficacy for core symptoms or are associated with small effect sizes. No evidence-based decision tools are currently available to allocate pharmacological or psychosocial treatments based on the patient's clinical, environmental, cognitive, genetic, or biological characteristics. We systematically reviewed potential biomarkers that may help in diagnosing ADHD and/or stratifying ADHD into more homogeneous subgroups and/or predict clinical course, treatment response, and long-term outcome across the lifespan. Most work involved exploratory studies with cognitive, actigraphic and EEG diagnostic markers to predict ADHD, along with relatively few studies exploring markers to subtype ADHD and predict response to treatment. There is a critical need for multisite prospective carefully designed experimentally controlled or observational studies to identify biomarkers that index inter-individual variability and/or predict treatment response.

KW - Attention-Deficit Hyperactivity Disorder (ADHD)

KW - biomarker

KW - heterogeneity

KW - inter-individual variability

KW - precision medicine

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U2 - https://doi.org/10.3389/fnbeh.2022.900981

DO - https://doi.org/10.3389/fnbeh.2022.900981

M3 - Review article

C2 - 35874653

SN - 1662-5153

VL - 16

JO - Frontiers in behavioral neuroscience

JF - Frontiers in behavioral neuroscience

M1 - 900981

ER -

Toward Precision Medicine in ADHD

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