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. 2021 Jul 30;12(8):1193.
doi: 10.3390/genes12081193.

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

Maria Nobile  1 , Eleonora Maggioni  2 , Maddalena Mauri  1   3 , Marco Garzitto  4 , Sara Piccin  5 , Carolina Bonivento  4 , Roberto Giorda  6 , Rossano Girometti  7 , Barbara Tomasino  4 , Massimo Molteni  1 , Franco Fabbro  4 , Paolo Brambilla  2   8   9
Affiliations

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

Maria Nobile et al. Genes (Basel). .

Abstract

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.

Keywords: cortical surface area; cortical thickness; gray matter volume; imaging genetics; magnetic resonance imaging; mediation; neurodevelopment.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
GRIN2B linkage disequilibrium. Haploview plot showing pairwise linkage disequilibrium (r2 values) for 6 SNPs of GRIN2B based on the sample’s genotypes.
Figure 2
Figure 2
Mediation model design. (A) Model of direct effect of X on Y. (B) Mediation model, where X has both direct and indirect (through M) effects on Y.
Figure 3
Figure 3
Mediation analysis 1 (MA1) results. (A) Model of direct effect of X on Y. (B) Mediation model, where X has both direct and indirect (through M) effects on Y. Significant pathways are highlighted with *. CBCL/6-18 AP: Child Behavior Checklist Attention Problems score.
See this image and copyright information in PMC

References

    1. Nobile M., Giorda R., Marino C., Carlet O., Pastore V., Vanzin L., Bellina M., Molteni M., Battaglia M. Socioeconomic status mediates the genetic contribution of the dopamine receptor D4 and serotonin transporter linked promoter region repeat polymorphisms to externalization in preadolescence. Dev. Psychopathol. 2007;19:1147–1160. doi: 10.1017/S0954579407000594. - DOI - PubMed
    1. Nobile M., Rusconi M., Bellina M., Marino C., Giorda R., Carlet O., Vanzin L., Molteni M., Battaglia M. COMT Val158Met polymorphism and socioeconomic status interact to predict attention deficit/hyperactivity problems in children aged 10–14. Eur. Child Adolesc. Psychiatry. 2009;19:549–557. doi: 10.1007/s00787-009-0080-1. - DOI - PubMed
    1. Leopold D.R., Christopher M.E., Olson R.K., Petrill S.A., Willcutt E.G. Invariance of ADHD Symptoms Across Sex and Age: A Latent Analysis of ADHD and Impairment Ratings from Early Childhood into Adolescence. J. Abnorm. Child Psychol. 2018;47:21–34. doi: 10.1007/s10802-018-0434-6. - DOI - PMC - PubMed
    1. Kuntsi J., Gayan J., Stevenson J. Parents’ and teachers’ ratings of problem behaviours in children: Genetic and contrast effects. Twin Res. 2000;3:251–258. - PubMed
    1. Rietveld M., Hudziak J., Bartels M., van Beijsterveldt T., Boomsma D. Heritability of attention problems in children: Longitudinal results from a study of twins, age 3 to 12. J. Child Psychol. Psychiatry. 2004;45:577–588. doi: 10.1111/j.1469-7610.2004.00247.x. - DOI - PubMed

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