Brain Anatomical Mediators of <i>GRIN2B</i> Gene Association with Attention/Hyperactivity Problems: An Integrated Genetic-Neuroimaging Study

• Main Authors: Maria Nobile, Eleonora Maggioni, Maddalena Mauri, Marco Garzitto, Sara Piccin, Carolina Bonivento, Roberto Giorda, Rossano Girometti, Barbara Tomasino, Massimo Molteni, Franco Fabbro, Paolo Brambilla
• Format: Article
• Language: English
• Published: MDPI AG 2021-07-01
• Series: Genes
• Subjects: imaging genetics; magnetic resonance imaging; neurodevelopment; mediation; gray matter volume; cortical surface area
• Online Access: https://www.mdpi.com/2073-4425/12/8/1193

This study aims to investigate the genetic and neural determinants of attention and hyperactivity problems. Using a proof-of-concept imaging genetics mediation design, we explore the relationship between the glutamatergic <i>GRIN2B</i> gene variants and inattention/hyperactivity with neuroanatomical measures as intermediates. Fifty-eight children and adolescents were evaluated for behavioral problems at three time points over approximately 7 years. The final assessment included blood drawing for genetic analyses and 3T magnetic resonance imaging. Attention/hyperactivity problems based on the Child Behavior Checklist/6-18, six <i>GRIN2B</i> polymorphisms and regional cortical thickness, and surface area and volume were estimated. Using general linear model (GLM) and mediation analyses, we tested whether <i>GRIN2B</i> exerted an influence on stable inattention/hyperactivity over development, and to what extent this effect was mediated by brain morphology. GLM results enlightened the relation between <i>GRIN2B</i> rs5796555-/A, volume in the left cingulate isthmus and inferior parietal cortices and inattention/hyperactivity. The mediation results showed that rs5796555-/A effect on inattention/hyperactivity was partially mediated by volume in the left isthmus of the cingulate cortex, suggesting a key role of this region in translating glutamatergic <i>GRIN2B</i> variations to attention/hyperactivity problems. This evidence can have important implications in the management of neurodevelopmental and psychiatric disorders.