Psychoactive pharmaceuticals induce fish gene expression profiles associated with human idiopathic autism.

Idiopathic autism, caused by genetic susceptibility interacting with unknown environmental triggers, has increased dramatically in the past 25 years. Identifying environmental triggers has been difficult due to poorly understood pathophysiology and subjective definitions of autism. The use of antide...

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Main Authors: Michael A Thomas, Rebecca D Klaper
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3368908?pdf=render
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spelling doaj-e8a06ae0d7ba4ad3b1c7b6c122f3081a2020-11-25T01:48:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0176e3291710.1371/journal.pone.0032917Psychoactive pharmaceuticals induce fish gene expression profiles associated with human idiopathic autism.Michael A ThomasRebecca D KlaperIdiopathic autism, caused by genetic susceptibility interacting with unknown environmental triggers, has increased dramatically in the past 25 years. Identifying environmental triggers has been difficult due to poorly understood pathophysiology and subjective definitions of autism. The use of antidepressants by pregnant women has been associated with autism. These and other unmetabolized psychoactive pharmaceuticals (UPPs) have also been found in drinking water from surface sources, providing another possible exposure route and raising questions about human health consequences. Here, we examined gene expression patterns of fathead minnows treated with a mixture of three psychoactive pharmaceuticals (fluoxetine, venlafaxine & carbamazepine) in dosages intended to be similar to the highest observed conservative estimates of environmental concentrations. We conducted microarray experiments examining brain tissue of fish exposed to individual pharmaceuticals and a mixture of all three. We used gene-class analysis to test for enrichment of gene sets involved with ten human neurological disorders. Only sets associated with idiopathic autism were unambiguously enriched. We found that UPPs induce autism-like gene expression patterns in fish. Our findings suggest a new potential trigger for idiopathic autism in genetically susceptible individuals involving an overlooked source of environmental contamination.http://europepmc.org/articles/PMC3368908?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Michael A Thomas
Rebecca D Klaper
spellingShingle Michael A Thomas
Rebecca D Klaper
Psychoactive pharmaceuticals induce fish gene expression profiles associated with human idiopathic autism.
PLoS ONE
author_facet Michael A Thomas
Rebecca D Klaper
author_sort Michael A Thomas
title Psychoactive pharmaceuticals induce fish gene expression profiles associated with human idiopathic autism.
title_short Psychoactive pharmaceuticals induce fish gene expression profiles associated with human idiopathic autism.
title_full Psychoactive pharmaceuticals induce fish gene expression profiles associated with human idiopathic autism.
title_fullStr Psychoactive pharmaceuticals induce fish gene expression profiles associated with human idiopathic autism.
title_full_unstemmed Psychoactive pharmaceuticals induce fish gene expression profiles associated with human idiopathic autism.
title_sort psychoactive pharmaceuticals induce fish gene expression profiles associated with human idiopathic autism.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2012-01-01
description Idiopathic autism, caused by genetic susceptibility interacting with unknown environmental triggers, has increased dramatically in the past 25 years. Identifying environmental triggers has been difficult due to poorly understood pathophysiology and subjective definitions of autism. The use of antidepressants by pregnant women has been associated with autism. These and other unmetabolized psychoactive pharmaceuticals (UPPs) have also been found in drinking water from surface sources, providing another possible exposure route and raising questions about human health consequences. Here, we examined gene expression patterns of fathead minnows treated with a mixture of three psychoactive pharmaceuticals (fluoxetine, venlafaxine & carbamazepine) in dosages intended to be similar to the highest observed conservative estimates of environmental concentrations. We conducted microarray experiments examining brain tissue of fish exposed to individual pharmaceuticals and a mixture of all three. We used gene-class analysis to test for enrichment of gene sets involved with ten human neurological disorders. Only sets associated with idiopathic autism were unambiguously enriched. We found that UPPs induce autism-like gene expression patterns in fish. Our findings suggest a new potential trigger for idiopathic autism in genetically susceptible individuals involving an overlooked source of environmental contamination.
url http://europepmc.org/articles/PMC3368908?pdf=render
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