Idiopathic autism has been on the rise in recent years and is thought to be caused by a mixture of genetic risk factors as well as some as yet unknown environmental factors. Research suggests a link between antidepressant use by pregnant women and the development of autism. Further, some unmetabolized psychoactive pharmaceuticals (UPPs) have made their way into drinking water from sources at the surface posing a potential environmental risk of exposure. To study the potential link between UPPs and autism, Drs. Michael Thomas and Rebecca Klaper exposed fathead minnows to a mixture of three psychoactive pharmaceuticals at doses similar to the highest levels found in the environment:
1. fluoxetine (i.e. Prozac) - antidepressant
2. venlafaxine (i.e. Effexor) - antidepressant
3. carbamazepine (i.e. Carbatrol, Epitol, Equetro, Tegretol) - anticonvulsant used to treat seizures
They then analyzed gene expression levels between animals exposed to either individual or combined pharmaceuticals and compared the results with genes involved in ten different human neurological disorders. What they found was that genes associated with idiopathic autism were enriched. These results suggest that environmental sources of UPPs induce gene expression patterns in minnows that are similar to autism in humans. Further work is needed to determine if idiopathic autism in humans may be attributed to similar enviromental contaminants.
Thomas MA, Klaper RD (2012) Psychoactive Pharmaceuticals Induce Fish Gene Expression Profiles Associated with Human Idiopathic Autism. PLoS ONE 7(6): e32917. doi:10.1371/journal.pone.0032917
Yeah, I'm not buying it yet. We're not fish constantly bathed in water. Has anyone looked at the epidemiological ramifications of this theory? You would predict that there should be a large difference among humans drinking well-water and tap water from municipal sources (presumably containing more of these non-metabolized compounds).
Leaving a lot of the theoretical criticisms that come to mind aside and turning to the paper itself, there are a lot of issues. Firstly, the doses they use are extremely high, 100-1000x what's seen in tap water and 15-100x that found in raw sewage. Their justification for this is extremely weak. One of the autism gene sets upregulated by exposure would be predicted to be protective against autism. They don't discuss this much. Finally, Parkinson's disease associated gene sets were also significantly upregulated, but they seriously down-play this finding. They try to spin their results to suggest that maybe these non-metabolized compounds are leading to an increase in ASD, but then in that same vein we should also expect an increase in PD (gene sets associated with which are, in many cases presented, more significantly altered). Has that occurred (I don't actually know the answer to that)?
Wouldn't a more straight-forward experiment have been to just treat female mice with various degrees of pure or contaminated water, gut them pregnant, and then do microarrays and behavior on the offspring? Call me unimpressed.
While it is true that we are not constantly bathed in water, I think that the presence of these UPPs in our drinking water and the rise of autism may not simply be coincidence. Austism is a serious issue and the fact that these UPPs are environmental factors known to induce gene expression of autism are found in the common drinking water supply is very troubling. I would like to see this experimented on a larger scale and possibly with animals more similar to humans to see the effects.