ArticleMolecular psychiatry2014
Epistatic interaction between COMT and DTNBP1 modulates prefrontal function in mice and in humans.
Article in Molecular psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
37 citing papers in PubMed, 73 citations in OpenAlex.
- Tolcapone-Enhanced Neurocognition in Healthy Adults: Neural Basis and Predictors.The international journal of neuropsychopharmacology · 2017Trial
- Dysbindin-1 Mutation Alters Prefrontal Cortex Extracellular Glutamate and Dopamine In Vivo.International journal of molecular sciences · 2024Article
- Sex dimorphism controls dysbindin-related cognitive dysfunctions in mice and humans with the contribution of COMT.Molecular psychiatry · 2024Article
- Synaptic plasticity in schizophrenia pathophysiology.IBRO neuroscience reports · 2023Article
- The Role of Dopamine D3 Receptors, Dysbindin, and Their Functional Interaction in the Expression of Key Genes for Neuroplasticity and Neuroinflammation in the Mouse Brain.International journal of molecular sciences · 2023Article
- Dopamine Dynamics and Neurobiology of Non-Response to Antipsychotics, Relevance for Treatment Resistant Schizophrenia: A Systematic Review and Critical Appraisal.Biomedicines · 2023Review
- Synaptic plasticity in schizophrenia pathophysiology.IBRO neuroscience reports · 2022Article
- Dysbindin-1A modulation of astrocytic dopamine and basal ganglia dependent behaviors relevant to schizophrenia.Molecular psychiatry · 2022Article
- Genetic Interaction betweenInternational journal of molecular sciences · 2022Article
- The epistatic interaction between the dopamine D3 receptor and dysbindin-1 modulates higher-order cognitive functions in mice and humans.Molecular psychiatry · 2021Article
- Abnormalities in the copper transporter CTR1 in postmortem hippocampus in schizophrenia: A subregion and laminar analysis.Schizophrenia research · 2021Article
- Markers of copper transport in the cingulum bundle in schizophrenia.Schizophrenia research · 2021Article
- Translational genomics and beyond in bipolar disorder.Molecular psychiatry · 2021Review
- The Discrete Paired-trial Variable-delay T-maze Task to Assess Working Memory in Mice.Bio-protocol · 2020Article
- Impaired copper transport in schizophrenia results in a copper-deficient brain state: A new side to the dysbindin story.The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry · 2020Article
- The Role of Zebrafish and Laboratory Rodents in Schizophrenia Research.Frontiers in psychiatry · 2020Review
- Loss of dysbindin-1 affects GABAergic transmission in the PFC.Psychopharmacology · 2019Article
- Developmental Genes and Regulatory Proteins, Domains of Cognitive Impairment in Schizophrenia Spectrum Psychosis and Implications for Antipsychotic Drug Discovery: The Example of Dysbindin-1 Isoforms and Beyond.Frontiers in pharmacology · 2019Review
- Variations in Dysbindin-1 are associated with cognitive response to antipsychotic drug treatment.Nature communications · 2018Article
- An approach to monitoring home-cage behavior in mice that facilitates data sharing.Nature protocols · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Cognitive functions are highly heritable and the impact of complex genetic interactions, though undoubtedly important, has received little investigation. Here we show in an animal model and in a human neuroimaging experiment a consistent non-linear interaction between two genes--catechol-O-methyl transferase (COMT) and dysbindin (dys; dystrobrevin-binding protein 1 (DTNBP1))--implicated through different mechanisms in cortical dopamine signaling and prefrontal cognitive function. In mice, we found that a single genetic mutation reducing expression of either COMT or DTNBP1 alone produced working memory advantages, while, in dramatic contrast, genetic reduction of both in the same mouse produced working memory deficits. We found evidence of the same non-linear genetic interaction in prefrontal cortical function in humans. In healthy volunteers (N=176) studied with functional magnetic resonance imaging during a working memory paradigm, individuals homozygous for the COMT rs4680 Met allele that reduces COMT enzyme activity showed a relatively more efficient prefrontal engagement. In contrast, we found that the same genotype was less efficient on the background of a dys haplotype associated with decreased DTNBP1 expression. These results illustrate that epistasis can be functionally multi-directional and non-linear and that a putatively beneficial allele in one epistastic context is a relatively deleterious one in another. These data also have important implications for single-locus association analyses of complex traits.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.