Thursday, 7 June 2012

Autism's environmental exposome: fish and pharmaceuticals

It's late and it's been a long day but I'm somewhat intrigued by the publication of a paper by Thomas & Klaper* (full-text) recently published in PLoS ONE on unmetabolised psychoactive pharmaceuticals, gene expression in fish and autism.

Intrigued not only because the combination of fish, drugs and autism feature heavily in this paper but also because the findings presented in this study offer some interesting proposals about "autism's environmental exposome" which translated means how environment, and various exposure events in the environment, might be linked to autism.

The paper is full-text but here is a brief summary:

  • Based on some very logical assumptions about any potential candidate environmental 'trigger' for autism (plausible mechanism, existing in sufficient quantities in the environment, ability to pass from mother to foetus, historical increase in concentration coincident to the rise in autism cases), the authors set about looking at the possibility that pharmaceutical drug residues persistent in the environment may be linked to idiopathic autism - that is autism not secondary to other conditions such as Rett Syndrome (RTT) or Fragile-X syndrome (FXS).
  • Allowing for the fact that the use of human participants is not all that ethical in looking at such a relationship, the authors tested mixtures of so-called unmetabolised psychoactive pharmaceuticals (UPPs) on a fish model and the ability of UPPs to induce autism-like gene changes modelled from other data. I might add that gene models of other conditions including ADHD, schizophrenia, depression and bipolar disorder were also included in the analytical mix.
  • I can't claim to be an expert on the techniques employed but fish (fathead minnows) were housed in tanks which either contained the UPPs mix made up of a mixture of fluoxetine, venlafaxine and carbamazepine in concentrations described as ".. the highest observed environmental concentrations" compared with control tanks (no pharmaceuticals included). Duration of exposure was over the course of 18 days.
  • The authors conducted a "... gene-class analysis of expression patterns induced by the pharmaceutical treatments"; in other words, examining fish brain tissue from exposed animals to see what happened to gene expression as a result of exposure.
  • Lo and behold, gene enrichment linked to idiopathic autism came out on top following exposure to UPPs. Gene models of a few other conditions also showed some changes following UPPs exposure but not to the extent or consistency as that noted in autism. The importance of idiopathic autism showing gene enrichment over so-called secondary autism (following cases of RTT or FXS) is not be underestimated given the link to genes already noted in cases of RTT and FXS.
  • The authors make the connection between their reported findings and elevated levels of serotonin (5-HT) being implicated in autism spectrum conditions. Further, the proposed connection between maternal SSRI use and elevated offspring autism risk (discussed in this post) also comes into play. The potential added value from this study is that exposure to these classes of medication need not necessarily be voluntary.

I won't lie to you when I say that I am really quite excited by these findings. Accepting important factors such as the focus being on fish not humans, the quite high amount of exposure over a relatively small time period and the assumption that the 'autism genes' are in fact autism genes, I would certainly like to see some independent replication of this study.

I've talked about environment in relation to autism previously (here) and how things just 'aint what they used to be in terms of our interaction with the chemical environment. Without trying to push too hard an environmental agenda for autism, some cases of autism, or misrepresent what the word 'chemical' actually means (see here), there are some really important considerations to take from this study; not least on how we dispose of our pharmaceuticals and the potential risks attached to (unwitting) exposure to them.

If there are any positive points to come from this study, a primary one is the experimental model and methodology used. So whether replacing UPPs with other chemical components such as those speculatively listed in the 'top 10 hit list' recently discussed might produce similar effects, would be a study worth doing. Indeed thinking back to the chlorination by-products and autistic behaviour paper published last year (here), another important experiment waiting to be done using the fish in a pot gene expression model.

* Thomas MA. & Klaper RD. Psychoactive pharmaceuticals induce fish gene expression profiles associated with human idiopathic autism. PLoS ONE. June 2012