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.
Highlights
Attention and hyperactivity problems—which are core symptoms of attention deficit/hyperactivity disorder (ADHD) but are expressed in other developmental internalizing and externalizing disorders—are complex behavior traits with a multifactorial etiology: genetic, epigenetic, and environmental factors influence their development and persistence [1,2]
We found that the CBCL/6-18 attention problems (AP) score was inversely proportional to gray matter volume (GMV) in the left isthmus of the cingulate cortex (T(54) = 2.67, p < 0.05) and in the right inferior parietal cortex (T(54) = 2.26, p < 0.05), suggesting a possible role of these regions as mediators of the effect of GRIN2B marker rs5796555-/A on inattention/hyperactivity
Our results suggest that GMV in the left isthmus of cingulate cortex may play a key role in this mechanism
Summary
Attention and hyperactivity problems—which are core symptoms of attention deficit/hyperactivity disorder (ADHD) but are expressed in other developmental internalizing and externalizing disorders (e.g., anxiety, depression, oppositional defiant, disruptive mood dysregulation disorders)—are complex behavior traits with a multifactorial etiology: genetic, epigenetic, and environmental factors influence their development and persistence [1,2].
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