Candidate diagnostic biomarkers for neurodevelopmental disorders in children and adolescents: a systematic review

Samuele Cortese, Marco Solmi, Giorgia Michelini, Alessio Bellato, Christina Blanner, Andrea Canozzi, Luis Eudave, Luis C. Farhat, Mikkel Højlund, Ole Köhler-Forsberg, Douglas Teixeira Leffa, Christopher Rohde, Gonzalo Salazar de Pablo, Giovanni Vita, Rikke Wesselhoeft, Joanna Martin, Sarah Baumeister, Natali S. Bozhilova, Christina O Carlisi, Virginia Carter LenoDorothea L. Floris, Nathalie E. Holz, Eline J. Kraaijenvanger, Seda Sacu, Isabella Vainieri, Giovanni Ostuzzi, Corrado Barbui, Christoph U. Correll

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)129-149
Number of pages21
JournalWorld Psychiatry
Issue number1
Publication statusPublished - Feb 2023


  • ADHD
  • autism spectrum disorder
  • Biological markers
  • communication disorders
  • genome-wide association studies
  • intellectual disabil­ity
  • motor disorders
  • neurodevelopmental disorders
  • neuroimaging
  • neurophysiology
  • specific learning disorders
  • tic disorders


Dive into the research topics of 'Candidate diagnostic biomarkers for neurodevelopmental disorders in children and adolescents: a systematic review'. Together they form a unique fingerprint.

Cite this