Model System:

TBI

Reference Type:

Journal

Accession No.:

J73538

Journal:


Journal of Head Trauma Rehabilitation

Year, Volume, Issue, Page(s):

, 30, 6, E54-E66

Publication Website:

Abstract:

Study investigated relationships between genetic variation that affects dopaminergic signaling and functional recovery at 6 and 12 months after traumatic brain injury (TBI). As dopamine neurotransmission impacts cognition, it was hypothesized that variants in the linked dopamine D2 receptor (DRD2) and ankyrin repeat and kinase domain (ANKK1) genes might account for some individual variability in cognitive recovery following TBI. Data were collected from 108 survivors of severe TBI who were recruited consecutively from a level 1 trauma center. Cognitive performance was evaluated using 8 neuropsychological tests targeting different cognitive domains. An overall cognitive composite was developed using normative data. Functional cognition, depression status, and global outcome were also assessed. Subjects were genotyped for 6 DRD2 tagging single-nucleotide polymorphisms and Taq1A within ANKK1. Results showed that ANKK1 Taq1A heterozygotes performed better than homozygotes across several cognitive domains at both time points post injury. When adjusting for age, Glasgow Coma Scale score, and education, the Taq1A (ANKK1) and rs6279 (DRD2) variants were associated with overall composite scores at 6 months post-TBI. At 12 months, only Taq1A remained a significant genetic predictor of cognition. Following multiple-comparisons correction, there were no significant associations between examined genetic variants and functional cognition, depression status, and global outcome. These data suggest that genetic variation within DRD2 influences cognitive recovery post-TBI. Understanding genetic influences on dopaminergic systems post-TBI may impact current treatment paradigms.

Author(s):


Failla, Michelle D., Myrga, John M., Ricker, Joseph H., Dixon, C. Edward, Conley, Yvette P., Wagner, Amy K.

Participating Centers: