C957T polymorphism of the human dopamine D2 receptor gene predicts extrastriatal dopamine receptor availability in vivo

Hirvonen, M.; Lumme, Ville; Hirvonen, Jussi; Pesonen, Ullamari; Någren, Kjell; Vahlberg, Tero; Scheinin, Harry; Hietala, Jarmo

doi:10.1016/j.pnpbp.2009.02.021

Cited by 116 publications

(107 citation statements)

References 79 publications

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“…We therefore examined the effects of the DA D2 gene (DRD2) and the NR3A gene, coding for the N-methyl-D-aspartate 3A (NR3A) subunit of the glutamate NMDA receptor, on episodic memory in young and old adults. Carriers of the DRD2 C/C genotype have higher D2 receptor densities in neocortical and limbic regions, including the hippocampus (Hirvonen et al, 2009). The DRD2 C/C genotype has also been associated with better backward serial memory, particularly in older adults .…”

Section: Study Aims and Hypothesesmentioning

confidence: 98%

Dopamine and glutamate receptor genes interactively influence episodic memory in old age

Papenberg¹,

Li²,

Nagel³

et al. 2014

Neurobiology of Aging

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a b s t r a c tBoth the dopaminergic and glutamatergic systems modulate episodic memory consolidation. Evidence from animal studies suggests that these two neurotransmitters may interact in influencing memory performance. Given that individual differences in episodic memory are heritable, we investigated whether variations of the dopamine D2 receptor gene (rs6277, C957T) and the N-methyl-D-aspartate 3A (NR3A) gene, coding for the N-methyl-D-aspartate 3A subunit of the glutamate N-methyl-D-aspartate receptor (rs10989591, Val362Met), interactively modulate episodic memory in large samples of younger (20e31 years; n ¼ 670) and older (59e71 years; n ¼ 832) adults. We found a reliable gene-gene interaction, which was observed in older adults only: older individuals carrying genotypes associated with greater D2 and N-methyl-D-aspartate receptor efficacy showed better episodic performance. These results are in line with findings showing magnification of genetic effects on memory in old age, presumably as a consequence of reduced brain resources. Our findings underscore the need for investigating interactive effects of multiple genes to understand individual difference in episodic memory.

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Section: Study Aims and Hypothesesmentioning

confidence: 98%

Dopamine and glutamate receptor genes interactively influence episodic memory in old age

Papenberg¹,

Li²,

Nagel³

et al. 2014

Neurobiology of Aging

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“…Specifically, the T allele of the C957T SNP has been linked to reduced mRNA stability, affecting the density of D2 receptors (Duan et al, 2003). This allele has also been associated with reduced extrastriatal D2 receptor availability (Hirvonen et al, 2009a) and lower striatal DA levels (Hirvonen et al, 2009b).…”

Section: Introductionmentioning

confidence: 99%

Aging magnifies the effects of dopamine transporter and D2 receptor genes on backward serial memory

Papenberg

Nagel

et al. 2013

Neurobiology of Aging

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Aging compromises dopamine transporter (DAT) and receptor mechanisms in the frontostriatal circuitry. In a sample of 1288 younger and older adults, we investigated (i) whether individual differences in genotypes of the DAT gene (i.e., SLC6A3, the DAT variable number of tandem repeat 9/9, 9/10, and 10/10) and in the D2 receptor (DRD2) gene (i.e., the C957T [rs6277] CC and any T) interactively contribute to phenotype variations in episodic memory performance; and (ii) whether these genetic effects are magnified in older adults, because of considerable declines in the dopamine functions. Our results showed that carrying genotypes associated with higher levels of striatal synaptic dopamine (DAT 9/9) and higher density of extrastriatal D2 receptors (C957T CC) were associated with better backward serial recall, an episodic memory task with high encoding and retrieval demands. Critically, the gene-gene interaction effect was reliably stronger in older than in younger adults. In line with the resource modulation hypothesis, our findings suggest that aging-related decline in brain phenotypes (e.g., dopamine functions) could alter the relations between genotypes and behavioral phenotypes (e.g., episodic memory).

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“…In addition, the C957T SNP also regulates D2 dopamine receptors availability in both the human cortex and the thalamus in vivo (Hirvonen et al. 2009b). However, the observed pattern differed from that of the striatum, which may reflect distinctive roles of D2 receptors and dopamine in striatal and extrastriatal structures.…”

Section: Discussionmentioning

confidence: 99%

“…In any case, several imaging studies have demonstrated the C957T effect upon D2 receptors in the brain (Hirvonen et al. 2004, 2009a,b). Moreover, C957T SNP is also a marker of a genomic sequence at the 5′ UTR of ANKK1 gene.…”

Section: Discussionmentioning

confidence: 99%

The ANKK1/DRD2 locus is a genomic substrate for affective priming and recognition of angry faces

et al. 2015

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IntroductionAnkyrin repeat and kinase domain containing I (ANKK1) and dopamine D2 receptor (DRD2) genes have been associated with psychopathic traits in clinical samples. On the other hand, individuals high in psychopathy show reduced affective priming and deficits in facial expression recognition. We have hypothesized that these emotion‐related cognitive phenomena are associated with Taq IA (rs18000497) SNP (single nucleotide polymorphism) of the ANKK1 gene and with C957T (rs6277) SNP of the DRD2 gene.MethodsWe performed a genetic association analysis in 94 self‐reported Caucasian healthy volunteers. The participants completed 144 trials of an affective priming task, in which primes and targets were emotional words. They also had to recognize 64 facial expressions of happiness, sadness, anger, and fear in an expression recognition task. Regarding the genetic analyses, Taq IA and C957T SNPs were genotyped.ResultsWe found that the C957T SNP TT genotype was associated with a stronger priming effect and a better recognition of angry expressions. No associations were found for the Taq IA SNP. In addition, in silico analysis demonstrated that C957T SNP is a marker of a regulatory sequence at the 5′ UTR of ANKK1 gene, thus suggesting the involvement of the whole ANKK1/DRD2 locus in cognitive–emotional processing.ConclusionsThese results suggest that affective priming and recognition of angry facial expressions are endophenotypes that lie on the pathway between the ANKK1/DRD2 locus and some deviant phenotypes.

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C957T polymorphism of the human dopamine D2 receptor gene predicts extrastriatal dopamine receptor availability in vivo

Cited by 116 publications

References 79 publications

Dopamine and glutamate receptor genes interactively influence episodic memory in old age

Dopamine and glutamate receptor genes interactively influence episodic memory in old age

Aging magnifies the effects of dopamine transporter and D2 receptor genes on backward serial memory

The ANKK1/DRD2 locus is a genomic substrate for affective priming and recognition of angry faces

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