Impact of five SNPs in dopamine-related genes on executive function.
Summary of "Impact of five SNPs in dopamine-related genes on executive function."
OBJECTIVES:
Dopamine neurotransmission is a critical factor for executive function, which is controlled by the prefrontal cortex in humans. Although the contribution of genetic factors to the regulation of brain dopaminergic activity is widely acknowledged, identification of a genotype-phenotype association has not yet been clearly established. In this study, we therefore evaluated the effects of five functional single-nucleotide polymorphisms (SNPs) in specific genes related to dopamine neurotransmission on executive function in a general population. MATERIALS AND
METHODS:
Participants of the health examination at the Shimane Institute of Health Science were recruited for this study (n = 964). To evaluate executive function, the Frontal Assessment Battery (FAB) was administered. SNPs were genotyped using the TaqMan method.
RESULTS:
A significant association was found between an SNP in the catechol-O-methyltransferase (COMT) gene (rs4680) encoding the low-activity Met allele and FAB score (P = 0.003). Of note, the flexibility subset of the FAB was associated with the SNP in COMT (P = 0.003) after adjustment for confounding factors. The generalized multifactor dimensionality reduction method identified that the combination of two SNPs in the COMT gene (rs4680) and the dopamine D4 receptor gene (rs1800955) had a significant effect on FAB score.
CONCLUSIONS:
Our study indicates a contribution of rs4680 in the COMT gene to the variability in executive function, as assessed by the FAB. In addition, we have indicated that a complex gene-gene interaction between SNPs in the genes related to dopamine neurotransmission may influence executive function in a general population.
Affiliation
Department of Neurology, Shimane University School of Medicine, Izumo, Japan.
Journal Details
This article was published in the following journal.
Name: Acta neurologica Scandinavica
ISSN: 1600-0404
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22530780
- DOI: http://dx.doi.org/10.1111/j.1600-0404.2012.01673.x
Medical and Biotech [MESH] Definitions
Executive Function
A set of cognitive functions that controls complex, goal-directed thought and behavior. Executive function involves multiple domains, such as CONCEPT FORMATION, goal management, cognitive flexibility, INHIBITION control, and WORKING MEMORY. Impaired executive function is seen in a range of disorders, e.g., SCHIZOPHRENIA; and ADHD.
Genes, Lethal
Genes whose loss of function or gain of function MUTATION leads to the death of the carrier prior to maturity. They may be essential genes (GENES, ESSENTIAL) required for viability, or genes which cause a block of function of an essential gene at a time when the essential gene function is required for viability.
Receptors, Dopamine D2
A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D2-class receptor genes contain INTRONS, and the receptors inhibit ADENYLATE CYCLASE.
Receptors, Dopamine D1
A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D1-class receptor genes lack INTRONS, and the receptors stimulate ADENYLATE CYCLASE.
Dopamine Antagonists
Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME.
PubMed Articles
Predicting Sensation Seeking From Dopamine Genes: A Candidate-System Approach.
Sensation seeking is a heritable personality trait that has been reliably linked to behavioral disorders. The dopamine system has been hypothesized to contribute to variations in sensation seeking bet...
The genes for the dopamine transporter (DAT) and the D-Amino acid oxidase activator (DAOA or G72) have been independently implicated in the risk for schizophrenia and in bipolar disorder and/or their...
We examined the impact of IQ discrepancy (IQD) within (1) and above (1+) one standard deviation on executive function in HFA using the BRIEF. We hypothesized that IQD would benefit executive function....
Components of the brain reward system, i.e. the mesolimbic dopamine, laterodorsal cholinergic and ghrelin signaling systems, have been implicated in alcohol reward in preclinical studies. Genetic vari...
Assessing Executive Function in Preschoolers.
Executive function develops at an unprecedented rate during the preschool period, yet few clinicians attempt to assess executive processes in young children. The primary objective of this article is t...
Clinical Trials
The primary objective of the study is to evaluate the efficacy of SPD489 compared to placebo on executive function (self-regulation) behaviors in adults with ADHD who report clinically sig...
Donor Dopamine and Initial Graft Function
Donor pre-treatment with dopamine reduces injury to the kidney graft with consequences on the clinical performance immediately after transplantation: Donor dopamine reduces the requirement...
Brain Dopamine Function in Adults With ADHD
The purpose of the study is to investigate the functional state of dopamine cells and the dopamine transporter in ADHD subjects and controls to assess the effects of chronic methylphenidat...
Longitudinal Study of Multiple Symptoms in Advanced Lung Cancer
Primary Objectives: - To compare the severity of symptoms, their impact on affective and health-related functional status, and symptom interference among patients with advanced-st...
The ultimate goal of this study is to find specific polymorphism of candidate genes (particularly of dopaminergic and noradrenergic systems) associated with intermediate phenotypes (e.g.,...
