ArticleMolecular psychiatry2022
Dysfunction of AMPA receptor GluA3 is associated with aggressive behavior in human.
Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
- Tissue and Sex-Specific Transcriptomic Signatures Underlying Aggression behavior of Chinese Mitten Crab (Eriocheir sinensis).Marine biotechnology (New York, N.Y.) · 2026Article
- Genetic Variants from Large Cohorts and Familial Studies Implicate Common Mechanisms in Schizophrenia.Biology · 2026Review
- Review
- Mapping aggressive behaviors and testosterone among schizophrenia patients in acute stage.Schizophrenia (Heidelberg, Germany) · 2025Article
- Article
- AMPA and NMDA Receptors in Hippocampus of Rats with Fluoride-Induced Cognitive Decline.International journal of molecular sciences · 2024Article
- Genetic Diversity in Schizophrenia: Developmental Implications of Ultra-Rare, Protein-Truncating Mutations.Genes · 2024Review
- Gain-of-function and loss-of-function variants in GRIA3 lead to distinct neurodevelopmental phenotypes.Brain : a journal of neurology · 2024Article
- Roles of AMPA receptors in social behaviors.Frontiers in synaptic neuroscience · 2024Review
- Article
- The molecular pathology of schizophrenia: an overview of existing knowledge and new directions for future research.Molecular psychiatry · 2023Review
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Authors and funding
22 authors at 12 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inappropriate aggression in humans hurts the society, families and individuals. The genetic basis for aggressive behavior, however, remains largely elusive. In this study, we identified two rare missense variants in X-linked GRIA3 from male patients who showed syndromes featuring aggressive outbursts. Both G630R and E787G mutations in AMPA receptor GluA3 completely lost their ion channel functions. Furthermore, a guanine-repeat single nucleotide polymorphism (SNP, rs3216834) located in the first intron of human GRIA3 gene was found to regulate GluA3 expression with longer guanine repeats (rs3216834-10G/-11G) suppressing transcription compared to the shorter ones (-7G/-8G/-9G). Importantly, the distribution of rs3216834-10G/-11G was elevated in a male violent criminal sample from Chinese Han population. Using GluA3 knockout mice, we showed that the excitatory neurotransmission and neuronal activity in the medial prefrontal cortex (mPFC) was impaired. Expressing GluA3 back into the mPFC alleviated the aggressive behavior of GluA3 knockout mice, suggesting that the defects in mPFC explained, at least partially, the neural mechanisms underlying the aggressive behavior. Therefore, our study provides compelling evidence that dysfunction of AMPA receptor GluA3 promotes aggressive behavior.
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