Altough there is increasing interest and research into the roles that genes and brain systems play in influencing psychiatric illnesses, a major obstacle in identifying these influences is the complex nature of diagnostic categories. One solution is to focus on intervening variables, or endophenotypes, that are likely more sensitive to the effects of genetic variation than are diagnostic categories. Such an endophenotype is impulsivity, the predisposition to respond to stimuli without considering the consequences. Although there is evidence supporting a neural basis of impulsivity, and evidence supporting the role of dopamine in influencing impulsivity, there have been only limited attempts to combine this information. This study tested the hypothesis that variants of two dopamine system-related gene polymorphisms (DAT and COMT) influence the neural network underlying behavioral inhibition, a more direct expression of impulsivity. Specifically, 46 healthy adults were pre-selected for genotypes of the DAT and COMT polymorphisms and performed a Stop-signal task, which measures behavioral inhibition, while undergoing functional magnetic resonance imaging (fMRI). Neural activation in a frontostriatal circuit, during trials requiring inhibition of a response, were examined across the entire group and then compared between groups with certain variants of each genotype using SPM2. Results support the role of a right-lateralized frontostriatal circuit underlying behavioral inhibition in healthy adults and support a significant role of individual differences, as neural activation varied as a function of how well individuals were able to inhibit a response. Furthermore, results of the study support (1) a significant influence of DAT on the neural response during inhibition; (2) a significant influence of COMT on the neural response during both the performance of a motor response and the inhibition of a motor response; and (3) an additive effect of DAT and COMT on neural activation during inhibition. These results further elucidate the genetic and neural basis of impulsivity, particularly with regard to individual differences in inhibitory control. Understanding the neurogenetic basis of these individual differences will be of considerable clinical significance in advancing the prediction, diagnosis, and treatment of impulsivity-related forms of mental illness.
|School:||State University of New York at Stony Brook|
|School Location:||United States -- New York|
|Source:||DAI-B 69/12, Dissertation Abstracts International|
|Subjects:||Neurosciences, Psychobiology, Genetics|
|Keywords:||Behavioral inhibition, Dopamine, Endophenotype, Impulsivity, Neurogenetic, Response inhibition, Stop-signal|
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