ArticleNature communications2021
mTOR-related synaptic pathology causes autism spectrum disorder-associated functional hyperconnectivity.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 1 of them a synthesis that pooled it.
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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.
The trial behind it
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Who cites it
100 citing papers in PubMed, 1 synthesis or guideline pooled it, 144 citations in OpenAlex.
- Identification of novel driver risk genes in CNV loci associated with neurodevelopmental disorders.HGG advances · 2024Pooled it
- An Open-Label Case Series of Glutathione Use for Symptomatic Management in Children with Autism Spectrum Disorder.Medical sciences (Basel, Switzerland) · 2023Trial
- Increased inflammatory cytokines in the temporal cortex in autism spectrum disorder.Brain, behavior, & immunity - health · 2026Article
- Stable depression subtypes identified using functional connectome normative deviation models and their response to rTMS.Molecular psychiatry · 2026Article
- Altered striatal long-term potentiation in the eIF4E-TG mouse model of autism spectrum disorder.iScience · 2026Article
- Review
- Review
- Dynamic Functional Synchronization Profiles in Autism Differ by Spatial Scale and Along Hierarchical Cortical Gradients.Biological psychiatry global open science · 2026Article
- Cerebellar Contributions to Cerebral Connectivity in Severe Mental Illness: A Developmental Cascade and Predictive-Modeling Framework with Autistic Disorder as the Focal Case.Brain sciences · 2026Review
- Acute rapamycin treatment reveals distinct mechanisms of dysfunction in a maternal inflammation mouse model.Nature communications · 2026Article
- Exploratory Analysis of Autophagy-related Genes and Immune Infiltration in Human Hippocampal Tissue of Temporal Lobe Epilepsy.Molecular neurobiology · 2026Article
- Nitric Oxide-Mediated S-Nitrosylation of TSC2 Drives mTOR dysregulation across Shank3 and Cntnap2 Models of Autism Spectrum Disorder.Molecular psychiatry · 2026Article
- Divergence between neural and retinal lineage specification during human brain development by signal transduction.Journal of advanced research · 2026Article
- Autism subtypes identified using cross-species functional connectivity analyses.Nature neuroscience · 2026Article
- Differential brain neuroimmune profiles and altered immune balance in autism spectrum disorder compared with psychotic disorder and neurotypical controls.Research square · 2026Article
- Converging neurotrophic-immune signaling in autism spectrum disorder: integrative roles of klotho, GDNF/GFRA-1, IGF-1 and GLP-1 pathways.Metabolic brain disease · 2026Review
- Depression in Autism Spectrum Disorder: Neurobiological Convergence and Emerging Therapeutic Strategies.Biology · 2026Review
- Targeting synaptic plasticity and acetylcholine dysregulation in the medial prefrontal cortex: Rosmarinic acid attenuates Autism-like phenotypes in Shank3BPsychopharmacology · 2026Article
- Connectomic and behavioural alterations in creatine transporter deficiency are partially normalized by gene therapy.Brain : a journal of neurology · 2026Article
- <p>Harnessing MSC‑derived exosomes to modulate the pathophysiology of ASD: Recent advances and therapeutic implications (Review)</p>.International journal of molecular medicine · 2026Review
40 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 5 institutions in 5 countries.
Funding
Abstract
Postmortem studies have revealed increased density of excitatory synapses in the brains of individuals with autism spectrum disorder (ASD), with a putative link to aberrant mTOR-dependent synaptic pruning. ASD is also characterized by atypical macroscale functional connectivity as measured with resting-state fMRI (rsfMRI). These observations raise the question of whether excess of synapses causes aberrant functional connectivity in ASD. Using rsfMRI, electrophysiology and in silico modelling in Tsc2 haploinsufficient mice, we show that mTOR-dependent increased spine density is associated with ASD -like stereotypies and cortico-striatal hyperconnectivity. These deficits are completely rescued by pharmacological inhibition of mTOR. Notably, we further demonstrate that children with idiopathic ASD exhibit analogous cortical-striatal hyperconnectivity, and document that this connectivity fingerprint is enriched for ASD-dysregulated genes interacting with mTOR or Tsc2. Finally, we show that the identified transcriptomic signature is predominantly expressed in a subset of children with autism, thereby defining a segregable autism subtype. Our findings causally link mTOR-related synaptic pathology to large-scale network aberrations, revealing a unifying multi-scale framework that mechanistically reconciles developmental synaptopathy and functional hyperconnectivity in autism.
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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.