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1College of Letters and Science (Alumnus), University of California, Durant Hall, MC 2920, Berkeley, CA 94720, USA. bksanders@cal.berkeley.edu
Pharmacological Reports : PR
|February 15, 2013
Summary
Selective serotonin reuptake inhibitors may affect autism animal models by altering steroidogenesis. Epitestosterone (epiT) may play a role in epigenetic regulation and sex differences in brain disorders like autism.
Area of Science:
- Neuroscience
- Endocrinology
- Genetics
Background:
- Selective serotonin reuptake inhibitors (SSRIs) like citalopram are used to treat depression and may impact animal models of autism spectrum disorder (ASD).
- SSRIs can affect 3α-hydroxysteroid dehydrogenase activity, influencing steroidogenesis and potentially testosterone (T) levels.
- Sex steroids can modulate serotonin (5-HT) homeostasis, and genetic variants in the serotonin transporter (SERT) are linked to ASD-like behaviors.
Purpose of the Study:
- To explore the intricate relationship between SSRI exposure, steroidogenesis, and neurodevelopmental disorders, specifically focusing on potential mechanisms in autism animal models.
- To investigate the role of epitestosterone (epiT) in epigenetic regulation and its potential connection to sex differences observed in autism incidence.
Main Methods:
- Literature review and analysis of existing studies on SSRI effects, steroidogenesis, and ASD.
- Examination of the interaction between sex steroids, serotonin transporter (SERT) function, and the enzyme AKR1C21 responsible for epitestosterone (epiT) production.
- Analysis of sex-based differences in brain epitestosterone (epiT) production in rodents and potential implications for human neurodevelopmental disorders.
Main Results:
- Citalopram exposure has been shown to alter cortical network function and induce autistic-like behaviors in male rats.
- Citalopram can increase serum testosterone (T) levels, and sex steroids may influence 5-HT homeostasis.
- Epitestosterone (epiT), a product of AKR1C21, is inhibited by sex steroids and may be involved in epigenetic regulation; rodent studies show higher brain epiT in females.
Conclusions:
- The interplay between SSRIs, steroidogenesis, and 5-HT signaling warrants further investigation in the context of autism animal models.
- Epitestosterone (epiT) emerges as a potential mediator in the epigenetic regulation of gene expression and may contribute to understanding sex differences in autism and other brain disorders.
- The role of epitestosterone (epiT) in brain development is under-researched and represents a significant gap in our understanding of neurodevelopmental disorders.
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