ArticleThe Journal of clinical investigation2016
Serotonin transporter variant drives preventable gastrointestinal abnormalities in development and function.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
What it found
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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
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.
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Who cites it
91 citing papers in PubMed, 136 citations in OpenAlex.
- Interaction of the Gut Microbiota and the Enteric Nervous System: Implications in Gastrointestinal Disorders Associated With Autism Spectrum Disorder.Autism research : official journal of the International Society for Autism Research · 2026Review
- Enteric and Sympathetic Nervous System Pathways Mediate Early Life Stress Effects on Gut Motility and Pain: Mechanistic Findings With Human Correlation.Gastroenterology · 2026Article
- Maternal separation-induced changes in breast milk fatty acid composition are associated with altered gut microbiota and serotonergic gene expression in neonatal mice.Molecular biomedicine · 2026Article
- Dup15q model mice exhibit impaired gastrointestinal motility and a constipation-like phenotype, alleviated by prucalopride.Translational psychiatry · 2026Article
- Fundamentals of Neurogastroenterology: Basic Science.Gastroenterology · 2026Review
- The brain-gut axis in autism spectrum disorder: from gastrointestinal dysfunction to neuroimmune mechanisms.Frontiers in psychiatry · 2026Review
- Associations between maternal exposure to per- and polyfluoroalkyl substances and functional constipation in children at 3 and 4 years: the Japan Environment and Children's Study.Environmental health and preventive medicine · 2026Article
- Mapping Resting-State Brain Functional Specialization to Neurotransmitter Profiles in Autism Spectrum Disorder.CNS neuroscience & therapeutics · 2025Article
- A Frank Assessment of SHANK: Impacts of Pathogenic Variations in SHANK3 on Preclinical Models of Phelan McDermid Syndrome.Autism research : official journal of the International Society for Autism Research · 2025Review
- Autism Spectrum Disorder: From Experimental Models to Probiotic Application with a Special Focus onNutrients · 2025Review
- Hyperinsulinemia-induced upregulation of adipocyte TPH2 contributes to peripheral serotonin production, metabolic dysfunction, and obesity.The Journal of clinical investigation · 2025Article
- Prenatal exposure to selective serotonin reuptake inhibitors and risk of disorders of gut-brain interaction in children.Molecular psychiatry · 2025Article
- Modulating autism spectrum disorder pathophysiology using a trace amine-focused approach: targeting the gut.Molecular medicine (Cambridge, Mass.) · 2025Review
- Intestinal Epithelial Serotonin as a Novel Target for Treating Disorders of Gut-Brain Interaction and Mood.Gastroenterology · 2025Article
- Article
- Can depression lead to chronic constipation, or does chronic constipation worsen depression? NHANES 2005-2010 and bidirectional mendelian randomization analyses.BMC gastroenterology · 2024Article
- Clinical, developmental and serotonemia phenotyping of a sample of 70 Italian patients with Phelan-McDermid Syndrome.Journal of neurodevelopmental disorders · 2024Article
- The regulation of enteric neuron connectivity by semaphorin 5A is affected by the autism-associated S956G missense mutation.iScience · 2024Article
- Autism spectrum disorders and the gastrointestinal tract: insights into mechanisms and clinical relevance.Nature reviews. Gastroenterology & hepatology · 2024Review
- Faster Gastrointestinal Transit, Reduced Small Intestinal Smooth Muscle Tone and Dysmotility in theInternational journal of molecular sciences · 2024Article
31 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
10 authors at 3 institutions in 1 country.
Funding
Abstract
Autism spectrum disorder (ASD) is an increasingly common behavioral condition that frequently presents with gastrointestinal (GI) disturbances. It is not clear, however, how gut dysfunction relates to core ASD features. Multiple, rare hyperfunctional coding variants of the serotonin (5-HT) transporter (SERT, encoded by SLC6A4) have been identified in ASD. Expression of the most common SERT variant (Ala56) in mice increases 5-HT clearance and causes ASD-like behaviors. Here, we demonstrated that Ala56-expressing mice display GI defects that resemble those seen in mice lacking neuronal 5-HT. These defects included enteric nervous system hypoplasia, slow GI transit, diminished peristaltic reflex activity, and proliferation of crypt epithelial cells. An opposite phenotype was seen in SERT-deficient mice and in progeny of WT dams given the SERT antagonist fluoxetine. The reciprocal phenotypes that resulted from increased or decreased SERT activity support the idea that 5-HT signaling regulates enteric neuronal development and can, when disturbed, cause long-lasting abnormalities of GI function. Administration of a 5-HT4 agonist to Ala56 mice during development prevented Ala56-associated GI perturbations, suggesting that excessive SERT activity leads to inadequate 5-HT4-mediated neurogenesis. We propose that deficient 5-HT signaling during development may contribute to GI and behavioral features of ASD. The consequences of therapies targeting SERT during pregnancy warrant further evaluation.
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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.