Indirect association of DAT1 genotype with executive function through white matter volume in orbitofrontal cortex

Abstract

The dopamine transporter (DAT1) gene has been associated with impulsivity and executive functioning. Further, DAT1 has been associated with brain structural characteristics and resting state connectivity. This study tested an indirect effect model in which DAT1 genotype (9-repeat carriers vs. 10-repeat homozygotes) is linked to phenotypes representing impulsivity and executive function (planning behavior) through effects on white matter (WM) volumes in prefrontal cortex (PFC), particularly orbitofrontal cortex (OFC). Adolescents (ages 14–18, n=38), were recruited from substance use treatment (n=22) and the community (n=16) to increase phenotype variation. Results indicated that DAT1 10/10 genotype was associated with lower WM volume in the PFC, specifically the left OFC. Further, lower WM volume in the left OFC predicted more difficulties in self-reported planning behavior, but not impulsivity. Indirect effect analysis indicated that lower WM volume in the left OFC mediated the association between DAT1 10/10 genotype and difficulties in planning behavior. Results suggest a brain structural mechanism, involving lower WM volume in the left OFC, as a link in the association between DAT1 genotype and a specific aspect of executive function. Genetic effects on regional WM volume that are linked to behavioral outcomes could ultimately inform the development of tailored interventions that address an individual’s unique risk factors.

ANKK1 and TH gene variants in combination with paternal maltreatment increase susceptibility to both cognitive and attentive impulsivity

“…Our data did not find a nominal influence on impulsivity scores by anyone of the analyzed polymorphisms taken individually. These results, although in contrast with other studies that showed a significant interaction between BIS-11 Total scores and SLC6A3-VNTR (32), DRD4-exonIII-VNTR (56) or COMT-rs4680 (56) and between BIS-11 non-planning scores and COMT-rs4680 (57), are in line with some previous findings showing no association between BIS-11 Total scores and SLC6A3-VNTR (58,59), TH-rs6356 (60), DRD4-exonIII-VNTR (32), COMT-rs4680 (32,58,60), or ANKK1-rs1800497 (56,60).…”

Adult attention deficit hyperactivity disorder symptom profiles and concurrent problems with alcohol and cannabis: sex differences in a representative, population survey

“…These associations could be mediated by common genetic underpinnings. For example, a genetic variant of the dopamine transporter gene, a molecular target of interest in ADHD, was found in one study to be more common in women with high inattentive symptoms [ 47 ], and this same genotype has also been linked to structural and functional brain changes in cannabis use disorders [ 48 ] and processing of alcohol cues [ 49 ].…”

Sex Differences in the Association between Household Income and Children’s Executive Function

“…Executive function may mediate the effect of SEP on school performance and cognitive performance. Similarly, executive function reflects structure and functional aspects of the brain cortex and white matter [ 44 , 53 , 54 ]. To give examples, executive function is linked to cortical thickness [ 41 , 55 ], cortical function [ 53 ], white matter structure and volume [ 44 , 53 , 54 ], and functional connectivity between various brain regions, and cortex [ 42 ].…”