Influence of COMT gene variant on working memory in survivors of childhood brain tumors

Increasingly more attention is being given to secondary neurocognitive late effects caused by treatments for childhood brain tumors. Treatments such as chemotherapy and RT often disrupt the normal myelination process in the frontal lobes, thus disrupting processes that depend on this area (e.g., working memory). Dopamine (DA) is abundant in the frontal lobes of the brain and is crucial for optimal functioning of tasks that are known to involve this area, such as working memory. Dopamine availability in the frontal lobes is especially dependent upon Catechol-O-Methyltransferase (COMT), an enzyme that degrades synaptic DA. A functional polymorphism of the COMT gene has remarkable impact on COMT activity, with the Met allele being approximately four times less active in synaptic DA degradation.;Given the importance of dopamine and COMT to working memory abilities and other frontal lobe functions, the purpose of the current study was to examine the effect of the COMT polymorphism on working memory and episodic memory abilities in a childhood brain tumor population. Participants were forty-seven patients [25 girls (53.2%)] ages 8 to 18 (M age = 13.05, SD = 2.87) who were treated for Central Nervous System (CNS) tumors with conformal radiation therapy. Thirty-nine healthy children [21 girls (53.8%)] who were siblings of patients treated for CNS tumors between the ages of 8 and 18 (M age = 12.86, SD = 2.63) also participated. As expected, survivors of pediatric brain tumors treated with conformal radiation therapy demonstrated deficits in working memory abilities compared to healthy sibling controls. Furthermore, scores on computerized self-ordered search tasks were correlated with IQ performance, and this relationship strengthened with age in both groups. However, patients did not demonstrate greater deficits on working memory tasks compared to recognition memory tasks, likely due to frontal activation by both types of tasks (i.e., computerized working memory and recognition memory tasks). Oddly, a relationship between COMT genotype and working memory was not found, but a relationship between COMT genotype and recognition memory was revealed. Possible reasons for these findings, as well as directions for future research, are discussed.