Posttraumatic Brain Injury Cognitive Performance Is Moderated by Variation Within ANKK1 and DRD2 Genes.
OBJECTIVE
As dopamine neurotransmission impacts cognition, we 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 traumatic brain injury (TBI).


METHODS
Prospective cohort of 108 survivors of severe TBI, recruited consecutively from a level 1 trauma center.


METHODS
We examined relationships between DRD2 genetic variation and functional recovery at 6 and 12 months post-TBI.


METHODS
Cognitive performance was evaluated using 8 neuropsychological tests targeting different cognitive domains. An overall cognitive composite was developed using normative data. We also assessed functional cognition, depression status, and global outcome. Subjects were genotyped for 6 DRD2 tagging single-nucleotide polymorphisms and Taq1A within ANKK1.


RESULTS
ANKK1 Taq1A heterozygotes performed better than homozygotes across several cognitive domains at both time points postinjury. 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 (P = .0453 and P = .0452, respectively). At 12 months, only Taq1A remained a significant genetic predictor of cognition (P = .0128). Following multiple-comparisons correction, there were no significant associations between examined genetic variants and functional cognition, depression status, and global outcome.


CONCLUSIONS
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.
Center for Neuroscience (Drs Failla, Dixon, and Wagner), Department of Physical Medicine and Rehabilitation, School of Medicine (Drs Failla, Dixon, and Wagner and Mr Myrga), and Department of Neurological Surgery, School of Medicine (Dr Dixon), Department of Human Genetics, School of Public Health (Dr Conley), Department of Health Promotion & Development, School of Nursing (Dr Conley), and Safar Center for Resuscitation Research (Drs Wagner and Dixon), University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Rehabilitation Medicine, New York University, School of Medicine, New York (Dr Ricker); and Pittsburgh VA Healthcare System, Pittsburgh, Pennsylvania (Dr Dixon).
Michelle D
MD
Failla
John M
JM
Myrga
Joseph H
JH
Ricker
C Edward
CE
Dixon
Yvette P
YP
Conley
Amy K
AK
Wagner
D000293:Adolescent; D000328:Adult; D001930:Brain Injuries / Q000235:genetics* / Q000523:psychology*; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics* / Q000534:rehabilitation; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation; D014644:Genetic Variation; D005838:Genotype; D015600:Glasgow Coma Scale; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012680:Sensitivity and Specificity; D055815:Young Adult
C581293:DRD2 protein, human; D017448:Receptors, Dopamine D2; C489948:ANKK1 protein, human; D017346:Protein Serine-Threonine Kinases