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 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.
Department of Biological Sciences, Idaho State University School, Pocatello, Idaho, United States of America. mthomas@isu.edu
Michael A
MA
Thomas
Rebecca D
RD
Klaper
D000818:Animals; D001321:Autistic Disorder / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D002220:Carbamazepine / Q000633:toxicity; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003511:Cyclohexanols / Q000633:toxicity; D003530:Cyprinidae / Q000235:genetics / Q000378:metabolism*; D005473:Fluoxetine / Q000633:toxicity; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D046228:Microarray Analysis; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011619:Psychotropic Drugs / Q000633:toxicity*; D011971:Receptors, Immunologic / Q000378:metabolism; D000069470:Venlafaxine Hydrochloride; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D015815:Cell Adhesion Molecules; D003511:Cyclohexanols; D009419:Nerve Tissue Proteins; D011619:Psychotropic Drugs; D011971:Receptors, Immunologic; D014874:Water Pollutants, Chemical; C091529:plexin; D005473:Fluoxetine; D002220:Carbamazepine; D000069470:Venlafaxine Hydrochloride