TY - JOUR
T1 - Brain anatomical mediators of grin2b gene association with attention/hyperactivity problems
T2 - An integrated genetic‐neuroimaging study
AU - Nobile, Maria
AU - Maggioni, Eleonora
AU - Mauri, Maddalena
AU - Garzitto, Marco
AU - Piccin, Sara
AU - Bonivento, Carolina
AU - Giorda, Roberto
AU - Girometti, Rossano
AU - Tomasino, Barbara
AU - Molteni, Massimo
AU - Fabbro, Franco
AU - Brambilla, Paolo
N1 - Funding Information:
Funding: This research was funded by the Italian Ministry of Health (RF‐2016‐02364582 to M.N. and P.B., GR‐2018‐12367789 to E.M., RC 2018‐19 MIMOSA to M.N.).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/8
Y1 - 2021/8
N2 - 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 GRIN2B 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 GRIN2B polymorphisms and regional cortical thickness, and surface area and volume were estimated. Using general linear model (GLM) and mediation analyses, we tested whether GRIN2B 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 GRIN2B 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 GRIN2B variations to attention/hyperactivity problems. This evidence can have important implications in the management of neurodevelopmental and psychiatric disorders.
AB - 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 GRIN2B 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 GRIN2B polymorphisms and regional cortical thickness, and surface area and volume were estimated. Using general linear model (GLM) and mediation analyses, we tested whether GRIN2B 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 GRIN2B 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 GRIN2B variations to attention/hyperactivity problems. This evidence can have important implications in the management of neurodevelopmental and psychiatric disorders.
KW - Cortical surface area
KW - Cortical thickness
KW - Gray matter volume
KW - Imaging genetics
KW - Magnetic resonance imaging
KW - Mediation
KW - Neurodevelopment
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U2 - 10.3390/genes12081193
DO - 10.3390/genes12081193
M3 - Article
AN - SCOPUS:85112668472
SN - 2073-4425
VL - 12
JO - Genes
JF - Genes
IS - 8
M1 - 1193
ER -