Possible link between the environmental cycle of medicine and neurological disorders

Recently, a US research group has found that exposure of the embryo to low levels of psychopharmaceuticals (carbamazepine, fluoxetine and venlafaxine) relevant to the environment may cause neurological disorders like autism. This group has been investigating the genetic effects of these medicines on embryos for some time. Gaurav Kaushik and colleagues observed already that these agents pass through the gut and placenta and can reach the brain of the developing embryo. g1)
 
Because humans and animals share a large number of genes, comparative research into external influences on our genes in animals is useful. Michael Thomas his research group observed that a cocktail of these three psychopharmaceuticals in the brain of young fish activates genes related to autism, parkinson and multiple sclerosis in humans. The relationship with autism was particularly convincing. m1), m2)  It was expected that such an effect would also occur in human embryos.

Indeed, it now appears that low concentrations of these chemicals in human cells, both individually and in a mixture, damage genes responsible for brain development. m2)  The lowest studied effect concentration of carbamazepine (10 microgram/L) and the highest concentration of this drug found in eg. Dutch drinking water (almost 0,1 microgram/L) are not far apart. Moreover humans are exposed to these and other pharmaceuticals via imported food grown on soil treated with contaminated water and sewage sludge (called biosolids). And from other resarch it is known that compounds like carbamazepine accumulate in various organs, including the brain.

For some time now it has been known that medicines excreted by humans and animals are poorly biodegradable and end up in surface water, drinking water, soil and agricultural crops. This means that humans and animals are constantly exposed to a cocktail of low concentrations of medication at all stages of development. Given the importance for public health and socio-economic implications, a package of measures to prevent the environmental cycle of human and veterinary medicines should be developed throughout the medicine chain. On October 27 2017, The Green Pharmacy Conference 2017. has been held at the University Hospital in Utrecht to discuss this issue and its approach. The principal author of the research mentioned here also gave a presentation.


g1) Gaurav Kaushik, David P. Huber, Ken Aho, Bruce Finney, Shawn Bearden, Konstantinos S. Zarbalis, Michael A. Thomas, 2016, Maternal exposure to carbamazepine at environmental concentrations can cross intestinal and placental barriers, Biochemical and Biophysical Research Communications 474 (2016) 291e295.
m1) M.A. Thomas, P.P. Joshi, R.D. Klaper, 2012, Gene-class analysis of expression patterns induced by psychoactive pharmaceutical exposure in fathead minnow (Pimephales promelas) indicates induction of neuronal systems, Comp. Bio-chem. Physiolo. C-Toxicol. Pharmacol. 155 (1). 

m2) M.A. Thomas, R.D. Klaper, 2012, Psychoactive pharmaceuticals induce fish gene expression profiles associated with human idiopathic autism, Plos One 7 (6).
g2) Gaurav Kaushik, Yu Xia, Jean C. Pfau, Michael A. Thomas, Dysregulation of autism-associated synaptic proteins by psychoactive pharmaceuticals at environmental concentrations, Neuroscience Letters, September 28 2017, https://doi.org/10.1016/j.neulet.2017.09.058.