Effect of the Dopamine D2 Receptor T Allele on Response Latency After Mild Traumatic Brain Injury

Section of Neuropsychiatry, Department of Psychiatry, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756. .
American Journal of Psychiatry (Impact Factor: 12.3). 10/2005; 162(9):1749-51. DOI: 10.1176/appi.ajp.162.9.1749
Source: PubMed


The authors tested the hypothesis that the dopamine D2 receptor T allele (formerly described as the A1 allele) would be associated with poorer performance on memory and attention tasks following mild traumatic brain injury.
Thirty-nine patients with mild traumatic brain injury and 27 comparison subjects were genotyped. All subjects completed memory and attention tests, including the California Verbal Learning Test recognition task and the Continuous Performance Test.
In both groups the T allele was associated with poorer performance on the California Verbal Learning Test recognition task. There was also a significant diagnosis-by-allele interaction on measures of response latency (Continuous Performance Test): the subjects with mild traumatic brain injury and the T allele had the worst performance.
Genetic polymorphisms modulating central dopaminergic tone can affect cognitive outcome following mild traumatic brain injury.

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Available from: C. Harker Rhodes, Sep 01, 2015
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    • "The presence of a single copy of the A1 allele (A1+) is associated with a 30–40% reduction in D2 receptor density [38]; but see [39] and reduced cognitive performance when compared to participants lacking this polymorphism (A1−). Carriers of the A1 allele perform worse on the California Verbal Learning Test of memory [40], [41] and other cognitive tasks (reviewed in [20], [42]. "
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    ABSTRACT: Complex cognitive tasks such as visual working memory (WM) involve networks of interacting brain regions. Several neurotransmitters, including an appropriate dopamine concentration, are important for WM performance. A number of gene polymorphisms are associated with individual differences in cognitive task performance. COMT, for example, encodes catechol-o-methyl transferase the enzyme primarily responsible for catabolizing dopamine in the prefrontal cortex. Striatal dopamine function, linked with cognitive tasks as well as habit learning, is influenced by the Taq-Ia polymorphism of the DRD2/ANKK1 gene complex; this gene influences the density of dopamine receptors in the striatum. Here, we investigated the effects of these polymorphisms on a WM task requiring the maintenance of 4 or 6 items over delay durations of 1 or 5 seconds. We explored main effects and interactions between the COMT and DRD2/ANKK1-Taq-Ia polymorphisms on WM performance. Participants were genotyped for COMT (Val(158)Met) and DRD2/ANKK1-Taq-Ia (A1+, A1-) polymorphisms. There was a significant main effect of both polymorphisms. Participants' WM reaction times slowed with increased Val loading such that the Val/Val homozygotes made the slowest responses and the Met/Met homozygotes were the fastest. Similarly, WM reaction times were slower and more variable for the DRD2/ANKK1-Taq-Ia A1+ group than the A1- group. The main effect of COMT was only apparent in the DRD2/ANKK1-Taq-Ia A1- group. These findings link WM performance with slower dopaminergic metabolism in the prefrontal cortex as well as a greater density of dopamine receptors in the striatum.
    PLoS ONE 01/2013; 8(1):e55862. DOI:10.1371/journal.pone.0055862 · 3.23 Impact Factor
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    • "BDNF is involved in the survival, growth and maintenance of hippocampal and cortical neurons (Binder and Scharfman 2004). While there are a number of common SNPs within the BDNF gene (McAllister et al. 2008, 2005), the most widely studied of these is the Val66Met substitution (rs6265; Sanchez et al., 2011). Within healthy populations, Met carriers tend to show impaired executive function and reduced PFC gray matter volume compared to Val homozygotes (Egan et al. 2003; Dempster et al. 2005). "
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    ABSTRACT: Recovery after Traumatic Brain Injury (TBI) is variable, even for patients with similar severity of brain injury. Recent research has highlighted the contribution that genetic predisposition plays in determining TBI outcome. This review considers the potential for genetic polymorphisms to influence recovery of cognitive and social processes following TBI. Limitations and considerations that researchers should make when assessing the potential impact of polymorphisms on TBI outcome are also discussed. Understanding the genetic factors that support neuroplasticity will contribute to an understanding of the variation in outcome following injury and help to identify potential targets for rehabilitation.
    Brain Imaging and Behavior 08/2012; 8(3). DOI:10.1007/s11682-012-9197-9 · 4.60 Impact Factor
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    • "This suggests that individuals in whom the number of D2 receptors is smaller due to genetic variation might perform less well on similar mnemonic tasks. Consistent with this suggestion, individuals with the T allele have been found to have lower levels of recognition memory performance on the California Verbal Learning Test, relative to individuals without this genetic variation (McAllister et al., 2005). "
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    ABSTRACT: The study of the biological bases of memory has a long history. Based on research with patients with specific lesions and disease, animal models, and neuroimaging studies, the neural substrate that supports declarative memory in adults has been relatively well articulated. By contrast, studies of the neural bases of memory in development is in its infancy. Yet joint consideration of the processes involved in building a memory trace, and of the time course of development of the neural structures involved, has contributed to the generation of specific predictions regarding the sources of age-related change. Specifically, there are suggestions that in infancy and very early childhood, encoding and consolidation processes account for substantial age-related variance in long-term declarative memory. With development, the locus of age-related variability in the vulnerability of memory traces shifts to the later-stage processes of memory storage and retrieval. These insights are afforded by consideration of multiple levels of analysis, from the biological to the behavioral.
    Developmental Psychobiology 01/2008; 50(1):19-31. DOI:10.1002/dev.20265 · 3.31 Impact Factor
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