Influence of Catechol-O-methyltransferase on Executive Functioning Longitudinally After Early Childhood Traumatic Brain Injury

Abstract

Objective To elucidate the association of a functional catechol-O-methyltransferase (COMT) genotype (rs4680) with recovery of executive functions up to 18 months after early childhood traumatic brain injury (TBI) compared to an orthopedic injury (OI) group. Setting Outpatient Participants 134 children with a moderate to severe TBI (n=63) or OI (n=71) between the ages of 3-6 years who were followed 18 months post-injury Design Case-comparison, longitudinal cohort Main Measures The Behavior Rating Inventory of Executive Function (BRIEF), developmental neuropsychological assessment (NEPSY) of verbal fluency (VF), and a modified Stroop Test for young children (Shape School) Results The low activity COMT enzyme genotype (AA) was associated with better scores on the NEPSY VF (F=3.80, p=.02) and the Shape School (F=2.89, p =.06) in all participants when controlling for injury type (TBI vs. OI) over the first 18 months after injury. Injury type (TBI vs. OI) did not significantly moderate the effect of the COMT genotypes on executive function recovery. Conclusion This study provides preliminary evidence for a role of COMT genotypes in long-term recovery of executive function after pediatric TBI and OI. Larger studies are needed to determine the exact link between genetic variation in the COMT gene and TBI recovery in children.

Catechol-O-Methyltransferase Genotypes and Parenting Influence on Long-Term Executive Functioning After Moderate to Severe Early Childhood Traumatic Brain Injury: An Exploratory Study

“…Prior work in adult and pediatric TBI indicates the COMT rs4680 genotypes may be associated with recovery of cognitive and behavioral functioning after injury; 28,59,62 however, this prior work has not considered environmental factors also related to recovery. Similar to this prior work, results from the current study indicate that the low activity rs4680 COMT genotype (AA) is associated with improved executive functioning after traumatic injuries (i.e., TBI and OI), especially in the context of an authoritarian parenting behavior environment.…”

“…Preliminary studies suggest that variations in the COMT rs4680 genotype are related to outcomes after adult and pediatric TBI. 59–62 Recent work with the same cohort studied in this study has demonstrated an association of the COMT rs4680 genotype with executive function outcomes up to 18 months after moderate to severe TBI and orthopedic injury (OI) in children age 3–7 years at the time of injury. 62 …”

“…62 Two-hundred and thirteen participants who were enrolled in the original study were eligible for the current genetic study. The only difference between participants included in the analysis compared to those not included in demographic characteristics and study measures was that participants had slightly lower permissive parenting practices scores (Mean(SD) = 30.95(6.86) versus 32.86(6.20), p = .04) (see Table 1).…”

“…62 Genotypes identified were AA (methionine/methionine homozygote; low COMT enzyme activity; higher catecholamine levels), GA (valine/methionine heterozygote; intermediate COMT enzyme activity, intermediate catecholamine levels) and GG (valine/valine homozygote; high COMT enzyme activity; lower catecholamine levels). 62 COMT genotypes were dichotomized into low COMT enzyme genotype (AA) versus intermediate/high COMT enzyme genotypes (GA+GG) for analyses.…”

“…COMT genotypes were tested for Hardy-Weinberg equilibrium using JMP genomics software as part of the SAS program as described previously. 62 Mixed model linear regression was used to evaluate the moderating effect of genotype on associations of parenting style with post injury developmental change in parent ratings of executive dysfunction. Parenting style ratings on the PPQ were used to assess each of three parenting styles, with each style considered in a separate model.…”