Genetic and pharmacological manipulations of the serotonergic system in early life: neurodevelopmental underpinnings of autism-related behavior
Open accessAbstract
Serotonin, in its function as neurotransmitter, is well-known for its role in depression, autism and other neuropsychiatric disorders, however, less known as a neurodevelopmental factor. The serotonergic system is one of the earliest to develop during embryogenesis and early changes in serotonin levels can have large consequences for the correct development of specific brain areas. The regulation and functioning of serotonin is influenced by genetic risk factors, such as the serotonin transporter polymorphism in humans. This polymorphism is associated with anxiety-related symptoms, changes in social behavior, and cortical gray and white matter changes also seen in patients suffering from autism spectrum disorders (ASD). The human polymorphism can be mimicked by the knockout of the serotonin transporter in rodents, which are as a model system therefore vital to explore the precise neurobiological mechanisms. Moreover, there are pharmacological challenges influencing serotonin in early life, like prenatal/neonatal exposure to selective serotonin reuptake inhibitors (SSRI) in depressed pregnant women. There is accumulating evidence that this dysregulation of serotonin during critical phases of brain development can lead to ASD-related symptoms in children, and reduced social behavior and increased anxiety in rodents. Furthermore, prenatal valproic acid (VPA) exposure, a mood stabilizing drug which is also thought to interfere with serotonin levels, has the potency to induce ASD-like symptoms and to affect the development of the serotonergic system. Here, we review and compare the neurodevelopmental and behavioral consequences of serotonin transporter gene variation, and prenatal SSRI and VPA exposure in the context of ASD.
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Serotonin exerts a significant trophic and modulatory function in neurodevelopmental processes such as proliferation, migration, and differentiation in cortical areas, including the PFC.
“It has become widely accepted that serotonin exerts a significant trophic and modulatory function in neurodevelopmental processes such as proliferation, migration and differentiation in cortical areas, including the PFC [119, 123, 125–129].”
From Development of prefrontal cortex (2022) · cites this paper as [127]
The Introduction (page unavailable) describes serotonin as modulating developmental processes, and the section on 5-HTT knockout mice and rats (page unavailable) reports altered neuronal morphology and innervation in the PFC. The passages support a developmental role in cortical areas, including the PFC, but do not specifically establish effects on proliferation, migration, and differentiation there. (LLM, conf=0.84)
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- Authors
- Kinast, K., Peeters, D., Kolk, S. M., Schubert, D., & Homberg, J. R.
- Affiliations
- Radboud University Nijmegen (NL)
- Radboud University Medical Center (NL)
- Corresponding author
- Homberg, Judith R.
- Venue
- Frontiers in Cellular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2013
- Volume
- 7
- Pages
- 72-72
- ISSN
- 1662-5102 (ISSN-L)
- PMC
- PMC3679613
- OpenAlex
- W1977605690
- Cited by
- 57
- References
- 185
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 3 · 2020: 5 · 2019: 1 · 2018: 5 · 2017: 3 · 2016: 4 · 2015: 14 · 2014: 9 · 2013: 3
- FWCI
- 5.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- serotonin, serotonergic system, autism spectrum disorder, brain development, serotonin transporter, serotonin transporter knockout, selective serotonin reuptake inhibitors, prenatal SSRI exposure, valproic acid, prenatal drug exposure, anxiety, social behavior
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