ArticlePloS one2014
DRD2/CHRNA5 interaction on prefrontal biology and physiology during working memory.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Biological and neurocognitive correlates of comorbid post-traumatic stress disorder and alcohol use disorder: a systematic review.European journal of psychotraumatology · 2026Pooled it
- The influence of CHRNA5 and D398N missense variation on social and emotional behaviors in rodents and humans.Translational psychiatry · 2025Article
- Dopamine D2 receptor modulating mPFC-BLA circuit contributes to chronic sleep deprivation-induced memory impairment in mice.Theranostics · 2025Article
- Imaging genomics: data fusion in uncovering disease heritability.Trends in molecular medicine · 2023Review
- A polygenic score indexing a DRD2-related co-expression network is associated with striatal dopamine function.Scientific reports · 2022Article
- Expression, correlation, and prognostic significance of different nicotinic acetylcholine receptors, programed death ligand 1, and dopamine receptor D2 in lung adenocarcinoma.Frontiers in oncology · 2022Article
- The effect of rs1076560 (DRD2) and rs4680 (COMT) on tardive dyskinesia and cognition in schizophrenia subjects.Psychiatric genetics · 2020Article
- Impact of CHRNA5 polymorphisms on the risk of schizophrenia in the Chinese Han population.Molecular genetics & genomic medicine · 2019Article
- Effects of a GWAS-Supported Schizophrenia Variant in the DRD2 Locus on Disease Risk, Anhedonia, and Prefrontal Cortical Thickness.Journal of molecular neuroscience : MN · 2019Article
- A splicing-regulatory polymorphism in DRD2 disrupts ZRANB2 binding, impairs cognitive functioning and increases risk for schizophrenia in six Han Chinese samples.Molecular psychiatry · 2016Article
- Modulation of nicotine effects on selective attention by DRD2 and CHRNA4 gene polymorphisms.Psychopharmacology · 2015Article
- Genetic influences on nicotinic α5 receptor (CHRNA5) CpG methylation and mRNA expression in brain and adipose tissue.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2015Article
- Nicotinergic Modulation of Attention-Related Neural Activity Differentiates Polymorphisms of DRD2 and CHRNA4 Receptor Genes.PloS one · 2015Article
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16 authors.
Funding
Abstract
backgroundPrefrontal behavior and activity in humans are heritable. Studies in animals demonstrate an interaction between dopamine D2 receptors and nicotinic acetylcholine receptors on prefrontal behavior but evidence in humans is weak. Therefore, we hypothesize that genetic variation regulating dopamine D2 and nicotinic acetylcholine receptor signaling impact prefrontal cortex activity and related cognition. To test this hypothesis in humans, we explored the interaction between functional genetic variants in the D2 receptor gene (DRD2, rs1076560) and in the nicotinic receptor α5 gene (CHRNA5, rs16969968) on both dorsolateral prefrontal cortex mediated behavior and physiology during working memory and on prefrontal gray matter volume.
methodsA large sample of healthy subjects was compared for genotypic differences for DRD2 rs1076560 (G>T) and CHNRA5 rs16969968 (G>A) on prefrontal phenotypes, including cognitive performance at the N-Back task, prefrontal physiology with BOLD fMRI during performance of the 2-Back working memory task, and prefrontal morphometry with structural MRI.
resultsWe found that DRD2 rs1076560 and CHNRA5 rs16969968 interact to modulate cognitive function, prefrontal physiology during working memory, and prefrontal gray matter volume. More specifically, CHRNA5-AA/DRD2-GT subjects had greater behavioral performance, more efficient prefrontal cortex activity at 2Back working memory task, and greater prefrontal gray matter volume than the other genotype groups.
conclusionsThe present data extend previous studies in animals and enhance our understanding of dopamine and acetylcholine signaling in the human prefrontal cortex, demonstrating interactions elicited by working memory that are modulated by genetic variants in DRD2 and CHRNA5.
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