TY - JOUR
T1 - Candidate diagnostic biomarkers for neurodevelopmental disorders in children and adolescents
T2 - a systematic review
AU - Cortese, Samuele
AU - Solmi, Marco
AU - Michelini, Giorgia
AU - Bellato, Alessio
AU - Blanner, Christina
AU - Canozzi, Andrea
AU - Eudave, Luis
AU - Farhat, Luis C.
AU - Højlund, Mikkel
AU - Köhler-Forsberg, Ole
AU - Leffa, Douglas Teixeira
AU - Rohde, Christopher
AU - de Pablo, Gonzalo Salazar
AU - Vita, Giovanni
AU - Wesselhoeft, Rikke
AU - Martin, Joanna
AU - Baumeister, Sarah
AU - Bozhilova, Natali S.
AU - Carlisi, Christina O
AU - Leno, Virginia Carter
AU - Floris, Dorothea L.
AU - Holz, Nathalie E.
AU - Kraaijenvanger, Eline J.
AU - Sacu, Seda
AU - Vainieri, Isabella
AU - Ostuzzi, Giovanni
AU - Barbui, Corrado
AU - Correll, Christoph U.
N1 - Funding Information:
S. Cortese is supported by the UK National Institute for Health and Care Research, NIHR (grant nos. NIHR203035, RP-PG-0618-20003, NIHR203684 and NIHR130077). G. Michelini is supported by a Klingenstein Third Generation Foundation fellowship; L.C. Farhat by the São Paulo Research Foundation; D. Teixeira Leffa by a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation; G. Salazar de Pablo by the Alicia Koplowitz Foundation: C. Carlisi and V. Carter Leno by a Wellcome Trust Postdoctoral Fellowship; D. Floris by the European Union's Horizon 2020 research and innovation programme (Marie Skłodowska-Curie grant agreement no. 101025785); N. Holz by the German Research Foundation and the Radboud Excellence Fellowship. S. Cortese and M. Solmi have contributed equally to this work. Supplementary information on the study is available at https://osf.io/wp4je/?view_only=8c349f45a9ac441490981acf946c8d9a.
Funding Information:
S. Cortese is supported by the UK National Institute for Health and Care Research, NIHR (grant nos. NIHR203035, RP‐PG‐0618‐20003, NIHR203684 and NIHR130077). G. Michelini is supported by a Klingenstein Third Generation Foundation fellowship; L.C. Farhat by the São Paulo Research Foundation; D. Teixeira Leffa by a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation; G. Salazar de Pablo by the Alicia Koplowitz Foundation: C. Carlisi and V. Carter Leno by a Wellcome Trust Postdoctoral Fellowship; D. Floris by the European Union's Horizon 2020 research and innovation programme (Marie Skłodowska‐Curie grant agreement no. 101025785); N. Holz by the German Research Foundation and the Radboud Excellence Fellowship. S. Cortese and M. Solmi have contributed equally to this work. Supplementary information on the study is available at https://osf.io/wp4je/?view_only=8c349f45a9ac441490981acf946c8d9a .
Publisher Copyright:
© 2023 World Psychiatric Association.
PY - 2023/2
Y1 - 2023/2
N2 - Neurodevelopmental disorders – including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, communication disorders, intellectual disability, motor disorders, specific learning disorders, and tic disorders – manifest themselves early in development. Valid, reliable and broadly usable biomarkers supporting a timely diagnosis of these disorders would be highly relevant from a clinical and public health standpoint. We conducted the first systematic review of studies on candidate diagnostic biomarkers for these disorders in children and adolescents. We searched Medline and Embase + Embase Classic with terms relating to biomarkers until April 6, 2022, and conducted additional targeted searches for genome-wide association studies (GWAS) and neuroimaging or neurophysiological studies carried out by international consortia. We considered a candidate biomarker as promising if it was reported in at least two independent studies providing evidence of sensitivity and specificity of at least 80%. After screening 10,625 references, we retained 780 studies (374 biochemical, 203 neuroimaging, 133 neurophysiological and 65 neuropsychological studies, and five GWAS), including a total of approximately 120,000 cases and 176,000 controls. While the majority of the studies focused simply on associations, we could not find any biomarker for which there was evidence – from two or more studies from independent research groups, with results going into the same direction – of specificity and sensitivity of at least 80%. Other important metrics to assess the validity of a candidate biomarker, such as positive predictive value and negative predictive value, were infrequently reported. Limitations of the currently available studies include mostly small sample size, heterogeneous approaches and candidate biomarker targets, undue focus on single instead of joint biomarker signatures, and incomplete accounting for potential confounding factors. Future multivariable and multi-level approaches may be best suited to find valid candidate biomarkers, which will then need to be validated in external, independent samples and then, importantly, tested in terms of feasibility and cost-effectiveness, before they can be implemented in daily clinical practice.
AB - Neurodevelopmental disorders – including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, communication disorders, intellectual disability, motor disorders, specific learning disorders, and tic disorders – manifest themselves early in development. Valid, reliable and broadly usable biomarkers supporting a timely diagnosis of these disorders would be highly relevant from a clinical and public health standpoint. We conducted the first systematic review of studies on candidate diagnostic biomarkers for these disorders in children and adolescents. We searched Medline and Embase + Embase Classic with terms relating to biomarkers until April 6, 2022, and conducted additional targeted searches for genome-wide association studies (GWAS) and neuroimaging or neurophysiological studies carried out by international consortia. We considered a candidate biomarker as promising if it was reported in at least two independent studies providing evidence of sensitivity and specificity of at least 80%. After screening 10,625 references, we retained 780 studies (374 biochemical, 203 neuroimaging, 133 neurophysiological and 65 neuropsychological studies, and five GWAS), including a total of approximately 120,000 cases and 176,000 controls. While the majority of the studies focused simply on associations, we could not find any biomarker for which there was evidence – from two or more studies from independent research groups, with results going into the same direction – of specificity and sensitivity of at least 80%. Other important metrics to assess the validity of a candidate biomarker, such as positive predictive value and negative predictive value, were infrequently reported. Limitations of the currently available studies include mostly small sample size, heterogeneous approaches and candidate biomarker targets, undue focus on single instead of joint biomarker signatures, and incomplete accounting for potential confounding factors. Future multivariable and multi-level approaches may be best suited to find valid candidate biomarkers, which will then need to be validated in external, independent samples and then, importantly, tested in terms of feasibility and cost-effectiveness, before they can be implemented in daily clinical practice.
KW - ADHD
KW - autism spectrum disorder
KW - Biological markers
KW - communication disorders
KW - genome-wide association studies
KW - intellectual disability
KW - motor disorders
KW - neurodevelopmental disorders
KW - neuroimaging
KW - neurophysiology
KW - specific learning disorders
KW - tic disorders
UR - http://www.scopus.com/inward/record.url?scp=85146335106&partnerID=8YFLogxK
U2 - 10.1002/wps.21037
DO - 10.1002/wps.21037
M3 - Article
AN - SCOPUS:85146335106
SN - 1723-8617
VL - 22
SP - 129
EP - 149
JO - World Psychiatry
JF - World Psychiatry
IS - 1
ER -