International Meeting for Autism Research: ERP Error Related Negativity as a Specific Phenotype for Candidate Gene Associations In ASD

ERP Error Related Negativity as a Specific Phenotype for Candidate Gene Associations In ASD

Thursday, May 12, 2011
Elizabeth Ballroom E-F and Lirenta Foyer Level 2 (Manchester Grand Hyatt)
1:00 PM
N. K. Jamison1, R. J. Robison2, M. J. Larson1,3, P. Wilson2, O. Johnston4 and M. South1,3, (1)Neuroscience, Brigham Young University, Provo, UT, (2)Psychiatry Research Clinic, University of Utah School of Medicine, Salt Lake City, UT, (3)Psychology, Brigham Young University, Provo, UT, (4)School of Accountancy, Brigham Young University, Provo, UT
Background: Although autism has been shown to be highly heritable, candidate gene approaches related to diagnostic symptoms of the autism spectrum have been inconclusive. De Guess (2010) suggests that EEG endophenotypes can help to make sense of candidate gene variants identified by large-scale association studies. We recently reported results from an EEG study showing that children diagnosed with an autism spectrum disorder (ASD) display a significantly smaller error-related negativity (ERN) pattern during the well-established Eriksen Flanker task (South et al, 2010). We hypothesized that this ERN task may provide a specific neurophysiological marker that relates to targeted gene variation in ASD.

Objectives: We investigated potential links between variations in several single nucleotide polymorphisms (SNP) and brain activity in response to the Flanker task. This kind of strategy maximizes the potential for smaller samples to highlight genotype-phenotype relationships that lead to better understanding of heterogeneity in symptom expression in ASD, and can result in improved, more individualized treatments for those with ASD and their families.

Methods: We collected behavioral and neuroimaging data from 33 children and adolescents diagnosed with ASD, ages 8-18; and 28 typically developing children (TDC), matched for age and IQ. The flanker task requires that the participant decide as quickly and accurately as possible whether the direction of a central arrow is the same as the direction of other arrows flanked on each side. Because the task moves quickly, many errors result. The ERN is a rapid negative deflection in the Event Related Potential that occurs within 100ms of making an erroneous response, such as on the Flanker task. It is associated with activity of the brain anterior cingulate cortex (ACC).

We collected saliva samples for DNA extraction using Oragene kits. Genotyping was conducted using TaqMan®, with ready SNP assays from Applied Biosystems, for SNPs in the following genes: COMT, DAT1 (SLC6A3), 5-HT1B (HTR1B), HTR2A, MAOA, , and TPH2. T-test analyses included genotype status (± expected minor allele) as the independent variable and ERP response amplitudes as dependent variables.

Results: Carriers of the minor C allele for the dopamine transporter DAT1 (rs40184) polymorphism showed significantly decreased activation associated with response to error trials but not to correct trials in the ASD group. In the TDC group, the C allele was associated with decreased activation on both error and correct trials. Those with the Val allele in the COMT Val158Met (rs4680) polymorphism exhibited a significant  decrease with the difference score between error trials and correct trials in the ASD group. There were no significant associations for either group with any of the other genes assayed.

Conclusions: Because ERP responses reflect performance and error monitoring, these findings have strong implications for the neurological basis of decision-making difficulties in autism that may arise in part from impaired awareness of internal emotional states. Findings with the DAT1 and COMT polymorphisms suggest dissimilar mechanisms in ASD and TDC groups for monitoring performance that could help account for difficulties in decision-making and impaired emotional awareness in those with ASD.

See more of: Genetics and Genomics
See more of: Genetics
See more of: Biological Mechanisms
| More