ArticleTranslational psychiatry2023
Excitatory/inhibitory imbalance in autism: the role of glutamate and GABA gene-sets in symptoms and cortical brain structure.
Article in Translational psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 4 of them syntheses that pooled it.
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Who cites it
66 citing papers in PubMed, 4 syntheses or guidelines pooled it, 89 citations in OpenAlex.
- Efficacy of pharmacological and microbiota-based therapies in preclinical models of autism spectrum disorder: a systematic review.Molecular psychiatry · 2026Pooled it
- Neural excitation/inhibition imbalance and neurodevelopmental pathology in human copy number variant syndromes: a systematic review.Journal of neurodevelopmental disorders · 2025Pooled it
- Uncovering convergence and divergence between autism and schizophrenia using genomic tools and patients' neurons.Molecular psychiatry · 2025Pooled it
- Autism, youth suicide, and psychedelics: A review of the 21st century evidence.Journal of the Chinese Medical Association : JCMA · 2024Pooled it
- Safety and efficacy of AST-001 in children with autism spectrum disorder: a 52-week multicenter long-term follow-up study.Frontiers in psychiatry · 2026Trial
- Retinal GABAergic Alterations in Adults with Autism Spectrum Disorder.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Trial
- Article
- Genetic and pharmacological evidence linking CB1R signaling to hippocampal GABAergic dysfunction in ASD mouse model.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Excitation/inhibition balance subtypes in autism and their genetic, neural, and clinical profiles.Journal of neural transmission (Vienna, Austria : 1996) · 2026Article
- ARX mutation-associated interneuron defects provide insights into mechanisms underlying developmental epilepsies.Brain : a journal of neurology · 2026Article
- Hidden causal inference delineates dynamic lncRNA regulation in autism spectrum disorder.Briefings in bioinformatics · 2026Article
- Task-Related Aperiodic EEG (1/f) Activity in Autism.Autism research : official journal of the International Society for Autism Research · 2026Article
- Social regression stems from a latent phase of GABAergic dysfunction and sensory breakdown in a model of synaptopathy.Molecular psychiatry · 2026Article
- Sensory Reactivity in Autism: Integrating Behavioural, Affective, Physiological, and Neural Dimensions.Current psychiatry reports · 2026Review
- Diverse excess GABA modes drive autism and epilepsy-autism comorbidity.Journal of neural transmission (Vienna, Austria : 1996) · 2026Article
- The prenatal sex steroid theory of autism after 25 years.Nature human behaviour · 2026Review
- Altered spectral patterns of aperiodic electroencephalography in autism.Psychiatry and clinical neurosciences · 2026Article
- VGLUT1 and PSD-95 Expression Remains Stable in the Prefrontal and Cerebellar Cortices of the VPA Autism Rat Model.Developmental neurobiology · 2026Article
- Pregistered movie-fMRI analyses reveal altered visual feature encoding in autism in pSTS.bioRxiv : the preprint server for biology · 2026Article
- Aperiodic and periodic neural activity during sleep in autism spectrum disorders.BMC medicine · 2026Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 10 institutions in 8 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The excitatory/inhibitory (E/I) imbalance hypothesis posits that imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) mechanisms underlies the behavioral characteristics of autism. However, how E/I imbalance arises and how it may differ across autism symptomatology and brain regions is not well understood. We used innovative analysis methods-combining competitive gene-set analysis and gene-expression profiles in relation to cortical thickness (CT) to investigate relationships between genetic variance, brain structure and autism symptomatology of participants from the AIMS-2-TRIALS LEAP cohort (autism = 359, male/female = 258/101; neurotypical control participants = 279, male/female = 178/101) aged 6-30 years. Using competitive gene-set analyses, we investigated whether aggregated genetic variation in glutamate and GABA gene-sets could be associated with behavioral measures of autism symptoms and brain structural variation. Further, using the same gene-sets, we corelated expression profiles throughout the cortex with differences in CT between autistic and neurotypical control participants, as well as in separate sensory subgroups. The glutamate gene-set was associated with all autism symptom severity scores on the Autism Diagnostic Observation Schedule-2 (ADOS-2) and the Autism Diagnostic Interview-Revised (ADI-R) within the autistic group. In adolescents and adults, brain regions with greater gene-expression of glutamate and GABA genes showed greater differences in CT between autistic and neurotypical control participants although in opposing directions. Additionally, the gene expression profiles were associated with CT profiles in separate sensory subgroups. Our results suggest complex relationships between E/I related genetics and autism symptom profiles as well as brain structure alterations, where there may be differential roles for glutamate and GABA.
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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.