ArticleProceedings of the National Academy of Sciences of the United States of America2012
Autism gene variant causes hyperserotonemia, serotonin receptor hypersensitivity, social impairment and repetitive behavior.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 193 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
193 citing papers in PubMed, 4 syntheses or guidelines pooled it, 335 citations in OpenAlex.
- Pooled it
- Autism, youth suicide, and psychedelics: A review of the 21st century evidence.Journal of the Chinese Medical Association : JCMA · 2024Pooled it
- Subjective and objective sleep alterations in medication-naïve children and adolescents with autism spectrum disorder: a systematic review and meta-analysis.Epidemiology and psychiatric sciences · 2023Pooled it
- Tackling Missing Heritability by Use of an Optimum Curve: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2019Pooled it
- The effect of cannabidiol (CBD) on low-frequency activity and functional connectivity in the brain of adults with and without autism spectrum disorder (ASD).Journal of psychopharmacology (Oxford, England) · 2019Trial
- Effects of cannabidiol on brain excitation and inhibition systems; a randomised placebo-controlled single dose trial during magnetic resonance spectroscopy in adults with and without autism spectrum disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Trial
- Exploring sleep quality of young children with autism spectrum disorder and disruptive behaviors.Sleep medicine · 2018Trial
- Miscompartmentalization of microbiota-derived TMAO is a reversible driver in autism spectrum disorder.iScience · 2026Article
- Spatiotemporal dynamics of β-arrestin-mediated Src activation in 5-HT7 receptor signaling pathway.The FEBS journal · 2026Article
- Shielding the First 24 Postnatal Months of Life: A Proposal for a Prospective Cohort Study of Early-Life Electromagnetic Exposure and Autism Risk.Alpha psychiatry · 2026Article
- Review
- Network analysis of serotonin CNVs shows biological convergence from genetic heterogeneity and discriminates between autism and developmental delay.Scientific reports · 2026Article
- Optogenetic Regulation of Localization and Function of Serotonin Transporter by Modulating Its Interaction with Soluble Guanylate Cyclase.International journal of molecular sciences · 2026Article
- Integrated Metabolomic and Transcriptomic Analyses Reveal Alterations in the Serotonergic Synapse Pathway and a Robust Diagnostic Model in Ulcerative Colitis.Metabolites · 2026Article
- Melatonin ameliorates autistic-like behaviors by restoring gut microbiota-derived tryptophan metabolites.Cellular and molecular life sciences : CMLS · 2026Article
- The Gut Microbiota-Tryptophan-Brain Axis in Autism Spectrum Disorder: A New Frontier for Probiotic Intervention.Microorganisms · 2026Review
- Sex-dependent serotonergic signaling across development: molecular mechanisms shaping vulnerability to neurodevelopmental and mental disorders.Frontiers in pharmacology · 2026Review
- Prenatal fentanyl exposure affects social dominance and myelination patterns in the adult mouse brain.Neuropharmacology · 2025Article
- Analysis of neuronal activity impairment in iPSC-derived neurons from idiopathic autism patients.iScience · 2025Article
- Role of Phosphorylation of Serotonin and Norepinephrine Transporters in Animal Behavior: Relevance to Neuropsychiatric Disorders.International journal of molecular sciences · 2025Review
133 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
20 authors at 6 institutions in 2 countries.
Funding
Abstract
Fifty years ago, increased whole-blood serotonin levels, or hyperserotonemia, first linked disrupted 5-HT homeostasis to Autism Spectrum Disorders (ASDs). The 5-HT transporter (SERT) gene (SLC6A4) has been associated with whole blood 5-HT levels and ASD susceptibility. Previously, we identified multiple gain-of-function SERT coding variants in children with ASD. Here we establish that transgenic mice expressing the most common of these variants, SERT Ala56, exhibit elevated, p38 MAPK-dependent transporter phosphorylation, enhanced 5-HT clearance rates and hyperserotonemia. These effects are accompanied by altered basal firing of raphe 5-HT neurons, as well as 5HT(1A) and 5HT(2A) receptor hypersensitivity. Strikingly, SERT Ala56 mice display alterations in social function, communication, and repetitive behavior. Our efforts provide strong support for the hypothesis that altered 5-HT homeostasis can impact risk for ASD traits and provide a model with construct and face validity that can support further analysis of ASD mechanisms and potentially novel treatments.
Indexed as
Identifiers
What OpenQuestion holds
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.