Neurobiomarkers of psychiatric disorders in children and adolescents and their significance for diagnosis and precision medicine: A narrative review

Abstract

The application of neurobiomarkers in the diagnosis and treatment of psychiatric disorders has garnered significant attention. However, due to the genetic and biological complexity of psychiatric disorders, reliable biomarkers are still lacking. In recent years, advances in genomics and neurobiology have led to new insights into the shared genetic architecture and neurobiological pathways of psychiatric disorders. Current genomic evidence indicates substantial genetic overlap among psychiatric disorders prevalent in children and adolescents, such as attention deficit/hyperactivity disorder, autism spectrum disorder, anxiety, depression, conduct disorder, and oppositional defiant disorder, suggesting that these disorders may share common neurobiological pathways and mechanisms. This review article summarizes the shared genetic architecture of various psychiatric disorders in children and adolescents, which exhibit high polygenicity and significant genetic overlap. It discusses common and rare variants affecting overlapping biological pathways involved in neurotransmitter signaling, synaptic plasticity, immune regulation, and stress response. Findings from this review suggest that pleiotropy—where genetic variants influence multiple phenotypes—plays a central role in these disorders, particularly involving genes such as CACNA1C, GRIN2B, and SETD1A, which demonstrate cross-disorder effects and copy number variations, such as deletions of NRXN1 and mutations in SHANK3. These genes are associated with autism spectrum disorder, attention deficit/hyperactivity disorder, and intellectual disabilities, showing potential as diagnostic biomarkers. The review article emphasizes the interconnected nature of psychiatric disorders by presenting evidence from genome-wide association studies, polygenic risk scores, and transcriptomic analyses. It also outlines opportunities for early identification of at-risk populations, transdiagnostic interventions targeting shared mechanisms, and biological treatments, all of which represent critical advances in clinical practice. Currently, there is a lack of highly sensitive and specific neurobiomarkers for psychiatric disorders in children and adolescents; however, research in genomics and neurobiology is opening new avenues for the diagnosis and treatment of psychiatric disorders. In-depth studies of genetic and environmental factors, along with the application of multi-omics technologies, hold promise for advancing the treatment of psychiatric disorders in children and adolescents toward more precise and personalized approaches.