Increased serotonin axons (immunoreactive to 5-HT transporter) in postmortem brains from young autism donors
Abstract
Imaging studies of serotonin transporter binding or tryptophan retention in autistic patients suggest that the brain serotonin system is decreased. However, treatment with drugs which increase serotonin (5-HT) levels, specific serotonin reuptake inhibitors (SSRIs), commonly produce a worsening of the symptoms. In this study we examined 5-HT axons that were immunoreactive to a serotonin transporter (5-HTT) antibody in a number of postmortem brains from autistic patients and controls with no known diagnosis who ranged in age from 2 to 29 years. Fine, highly branched, and thick straight fibers were found in forebrain pathways (e.g. medial forebrain bundle, stria terminalis and ansa lenticularis). Many immunoreactive varicose fine fibers were seen in target areas (e.g. globus pallidus, amygdala and temporal cortex). Morphometric analysis of the stained axons at all ages studied indicated that the number of serotonin axons was increased in both pathways and terminal regions in cortex from autism donors. Our findings provide morphological evidence to warrant caution when using serotonin enhancing drugs (e.g. SSRIs and receptor agonist) to treat autistic children. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.
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Increased numbers of 5-HT axons and terminals were reported in various brain regions via immunocytochemical labeling of 5-HT transporter in post-mortem autism subjects aged 2-29, questioning wide use of SSRIs as therapeutic agents.
“An increased number of 5-HT axons and terminals were reported in a variety of brain regions via immunocytochemical labeling of 5-HT transporter in post-mortem autism subjects aged 2–29 years old bringing into question the wide use of SSRIs as therapeutic agents [187].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [187]
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- Authors
- Azmitia, E. C., Singh, J. S., & Whitaker-Azmitia, P. M.
- Affiliations
- New York University (US)
- Corresponding author
- Azmitia, Efrain C.
- ORCID
- Azmitia, Efrain C.
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2011-06
- Volume
- 60
- Issue
- 7-8
- Pages
- 1347-1354
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W1999133104
- Cited by
- 107
- References
- 53
- Citations by year
- 2025: 6 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 10 · 2019: 6 · 2018: 8 · 2017: 6 · 2016: 8 · 2015: 8 · 2014: 11 · 2013: 13 · 2012: 9
- FWCI
- 6.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- autism spectrum disorder, serotonin, serotonin transporter, serotonergic system, serotonin reuptake inhibitors, SSRI adverse effects, autism pharmacotherapy, postmortem brain, axon morphology, medial forebrain bundle, stria terminalis, ansa lenticularis, globus pallidus, amygdala, temporal cortex
- MeSH terms
- Adolescent, Adult, Autistic Disorder, Autopsy, Axons, Brain, Child, Child, Preschool, Female, Globus Pallidus, Humans, Male, Medial Forebrain Bundle, Nerve Fibers, Serotonin, Temporal Lobe, Prosencephalon, Subthalamus, Serotonin Plasma Membrane Transport Proteins, Young Adult
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