Stress Management: Biological Consequences

"They [research fish] acted very strangely and their stress response was weird."
"These kinds of exploratory behaviours [fish examining parameters of new tank] are super important in all vertebrates. It's kind of a coping behaviour [where an animal establishes how it must react in its new surroundings]."
"What we found is that it [the change] persists for two generations. We call that transgenerational effects."
"We are in generation 1.5 of fluoxetine [Prozac] use now. It came on the market in 1987."
"There are also major benefits to these types of drugs; in fact, they can be life-saving in some situations. However, it is important to follow a physician's advice and take the prescribed dose."
"The future discussion should take into account that such medications have longer-term effects than we ever imagined, as our work clearly shows that what we do today can influence future generations."
Professor Vance Trudeau, researcher, University of Ottawa

Effects of Antidepressants Span Three Generations in Fish

ffects of Antidepressants Span Three Generations in Fish The Scientist

"It was a really challenging study. The variables had to be consistent, generation after generation."
"A short dose can actually affect generations to come -- six days early on in life."
Dr. Marilyn Vera-Chang, University of Ottawa biology research associate

University of Ottawa’s Dr. Marilyn Vera-Chang checks on her fish in the lab. Julie Oliver / Postmedia

In a new research experiment conducted at a University of Ottawa laboratory, fish eggs and newly-hatched fish were exposed to Prozac at levels typical of what, in a human pregnancy, would cross the placenta to reach an embryo. The side-effects of such drugs had been studied for years by these researchers but their new point of entry was the potential effects of the drugs on reproduction. Humans suffering from depression are routinely prescribed drugs such as Prozac but the chemicals comprising the drugs don't remain in situ; they are passed with the patient's urine and end up in streams, rivers and lakes.

Needless to say aquatic creatures and most certainly fish are then exposed to these chemicals. And since sewage treatment is ineffective in disposing of the chemicals they remain, however diluted, in water that will be circulated and reused, exposing other animals including people when the water is returned to their household taps, to such chemicals, albeit in obviously lesser potency. This is the wider effect of pharmaceuticals used for a wide multitude of treatments within societies that are now medicated beyond anything imagined a generation or two earlier.

The research laboratory where Professor Trudeau and Dr. Vera-Chang work was the locus of efforts to examine possible changes in the reproductive systems of the following fish generations representing offspring of fish exposed to Prozac. The results of their new study surprised them in that they witnessed an unexpected change in fish behaviour. Introduced to a new tank, fish typically mimic what they would do in their natural environment to explore new surroundings. In a tank they swim up down and about. In their natural habitat this aids fish to understand when it is safe to search for food and when to hide.

The Prozac-exposed fish failed to exhibit the expected exploration when placed in a new tank; they swam to the tank's bottom and there they remained. Although Prozac was the only drug of its kind used, it was anticipated that similar results would occur when other drugs of the same class of antidepressants were used, since they all target a brain chemical, serotonin. When the two researchers understood that tranquilizer-exposed fish begot two following generations with the same altered behaviours they assumed an "epigenetic" effect was occurring.

This is an effect where children and grandchildren of the fish that had been exposed as eggs or newly-hatched to Prozac are endowed with normal genes yet there is as-yet-not-fully-understood effect that turns the genes' normal actions and reactions on and off in a peculiar manner. They also discovered present unusual amounts of the stress hormone cortisol; unusual in that they were lower than they normally would be. There is the usual scientific caution that zebra fish are not humans.

FILE – Prozac. Darron Cummings / AP

And as such Professor Trudeau, despite the findings cautions he would "absolutely not" advise people who use Prozac or any other antidepressants to cease doing so. There is evidence that women who use the drug during pregnancy have children with low cortisol who are "a little bit more timid" than other children. "That was known, and our bigger question was: Does it go away? What about their kids? ... What are the implications for humans?"

The paper, published in PNAS, one of the world's three top-ranked science journals, will certainly draw wide attention since such antidepressants are widely prescribed and used. Sewage treatment plants cannot remove pharmaceuticals that are flushed through people's toilets. The active chemicals remain stable even when they're flushed out of the human body in urine. Yet though these drugs are in such wide use, Professor Trudeau who studies hormones and the brain, emphasizes how little we know of effects drugs used may cause effects to future generations decades from the present.

A zebrafish treated with the antidepressant fluoxetine doesn’t explore its tank as much as control fish.

Movie courtesy of the University of Ottawa

"These are major, major, important questions. In the last ten years, there are now a few key examples where scientists are showing the effects of certain chemicals that get transferred across generations."
"They [researchers] found effects on behaviour [with the use of non-drug chemicals: Bisphenol-A found in plastics and vanclozalin, a fungus-killing chemical used on fruits and vegetables], on stress hormones, on brain function that transfer across generations."
"Not all pharmaceuticals will give a generational effect. But there is now a pattern developing [where] we have to start asking the question: Is there something beneficial passed on or is there something negative passed on? But most definitely we have to start thinking about this."
"It is absolutely a big issue. It is up and coming, though I would say that most physicians would not be thinking about it -- not yet, anyway."
Professor Vance Trudeau, researcher, University of Ottawa