Mood-modifying drugs for humans also alter fish behavior

Contact: Natasha Pinol npinol@aaas.org 202-326-6440 American Association for the Advancement of Science

Trace amounts of pharmaceuticals in rivers and streams inspire changes in wildlife

This release is available in Arabic, French, Japanese, Spanish, Swedish, and Chinese.

             IMAGE:   This is a perch (Perca fluviatilis).

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Pharmaceutical drugs that end up in the world’s waterways after being excreted, flushed and treated at wastewater treatment plants may lead to unexpected ecological impacts, according to a new study of wild European perch. Tomas Brodin and colleagues from Umeå University in Sweden discovered that the fish ate faster, became bolder and acted less social after being subjected to an anxiety-moderating drug, known as Oxazepam.

The psychiatric drug is used to treat anxiety in humans. But, Oxazepam residues often wind up in natural aquatic systems, downstream from sewage treatment plants, where their effects on ecosystems have been unknown. Now, Brodin and the other researchers have dosed wild perch with amounts of Oxazepam equivalent to those found in Sweden’s rivers and streams, and their results suggest that even small amounts of the drug can alter the behavior and the foraging rates of these fish.

The related report appears in the 15 February issue of the journal Science, which is published by AAAS, the nonprofit science society.

“While alone, fish that were exposed to Oxazepam dared to leave safe refuge and enter novel, potentially dangerous areas,” explained Brodin. “In contrast, unexposed fish stayed hidden in their refuge. The exposed fish seemed much less stressed and scared, behaving calmer and bolder.”

             IMAGE:   These are shoaling perch.

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Perch that were exposed to the drug also devoured their food quicker than unexposed fish—a behavioral quirk that the researchers say could alter the composition of species in the water and lead to ecological events, such as increased algal blooming, over time. Since fish are generally integral pieces of their food webs, changes in their eating patterns could disturb ecological balances, according to the researchers.

The fish that were given Oxazepam during the study also became anti-social, distancing themselves from other perch and putting themselves at greater risk of predation. “Perch that were exposed to Oxazepam lost interest in hanging out with the group, and some even stayed as far away from the group as possible,” explained Brodin.

The fish in the study accumulated concentrations of the drug in their muscle tissues that were comparable to those found in wild fish, according to the researchers. So it’s likely that the fish in Sweden’s surface waters, many of which are being exposed to similarly diluted doses of Oxazepam, may be experiencing changes in their behavior and feeding rates as well, they say.

             IMAGE:   This is the Umeå University research team in front of the mass spectrometer, where the water and fish samples were analyzed. From left to right: Micael Jonsson, Jonatan Klaminder, Tomas…

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This study by Brodin and his colleagues singled out a particular psychiatric drug that has been found in natural systems. But, a veritable cocktail of drugs can be found in waterways worldwide, making the discovery of Oxazepam’s effects on fish that much more important.

More comprehensive studies are needed before general conclusions can be drawn about how such pharmaceutically induced changes to behavior might affect ecosystems, but these current findings suggest that the concentrations of Oxazepam in Sweden’s surface waters could have unexpected ecological and evolutionary consequences over time.

“The solution to this problem isn’t to stop medicating people who are ill but to try to develop sewage treatment plants that can capture environmentally hazardous drugs,” concluded Jerker Fick, a co-author of the Science report, in a press release from Umeå University.

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The report by Brodin et al. was supported by a Young Researcher Award from Umeå University, the Swedish Research Council Vetenskapsrådet and FORMAS, and a small starting grant from the strong research environment “The environment’s chemistry—from molecules to the ecosystem.”

The American Association for the Advancement of Science (AAAS) is the world’s largest general scientific society, and publisher of the journal, Science as well as Science Translational Medicine and Science Signaling. AAAS was founded in 1848, and includes some 261 affiliated societies and academies of science, serving 10 million individuals. Science has the largest paid circulation of any peer-reviewed general science journal in the world, with an estimated total readership of 1 million. The non-profit AAAS is open to all and fulfills its mission to “advance science and serve society” through initiatives in science policy; international programs; science education; and more. For the latest research news, log onto EurekAlert!, www.eurekalert.org, the premier science-news Web site, a service of AAAS.

Medicine residues may threaten fish reproduction

2010 study posted for filing

Contact: Joakim Larsson joakim.larsson@fysiologi.gu.se 46-317-863-589 University of Gothenburg

Researchers at Umeå University and the Sahlgrenska Academy at the University of Gothenburg, Sweden, have discovered that traces of many medicines can be found in fish that have been swimming in treated waste water. One such medicine, the hormone levonorgestrel, was found in higher concentrations in the blood of fish than in women who take the contraceptive pill. Elevated levels of this hormone can lead to infertility in fish.

The study is published in the journal Environmental Science and Technology. The fish in the study were exposed to treated waste water from three sewage treatment works in Stockholm, Umeå and Gothenburg. The study shows that levonorgestrel – which is found in many contraceptive pills, including the morning-after pill – can impact on the environment and constitutes a risk factor for the ability of fish to reproduce. Levonogestrel is designed to mimic the female sex hormone progesterone and is produced synthetically.

A study from Germany showed very recently that less than a billionth of a gram of levonorgestrel per litre inhibited the reproduction of fish in aquarium-based trials.
”We are finding these levels in treated waste water in Sweden,” explains Jerker Fick at the Department of Chemistry at Umeå University.

For around ten years it has been known that synthetic oestrogen from contraceptive pills can affect fish that live downstream from sewage treatment works. The new study shows that synthetic progesterone-like hormones in contraceptive pills also carry risks.

The fish in the study were exposed to undiluted waste water, whilst in the natural environment there tends to be a degree of dilution in watercourses. But the study pointed out that there are also watercourses with very little dilution, and probably treatment plants that filter out the hormone less effectively than those included in the study. These findings will help to improve our understanding of which substances need to be removed from waste water.

“If we know how our medicines affect the environment, we will be in a better position to choose environmentally friendly alternatives, though we must always put the health of patients first,” says Joakim Larsson at the Sahlgrenska Academy, one of the researchers behind the study.

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CONTRACEPTIVE PILLS

Combined contraceptive pills contain synthetic forms of female sex hormones, such as synthetic oestrogen and progesterone-like hormones. The hormones that go into the pills vary between products, but levonorgestrel is a progesterone-like hormone that is used in many contraceptive pills, hormone implants and morning-after pills. It is thought that around 80-90 million women use the contraceptive pill worldwide, and that around 400,000 of them are Swedish.

The study was carried out as part of the MistraPharma research programme (www.mistrapharma.se).

Language learning makes the brain grow

Contact: Johan Mårtensson johan.martensson@psychology.lu.se 46-707-554-401 Lund University

At the Swedish Armed Forces Interpreter Academy in the city of Uppsala, young people with a flair for languages go from having no knowledge of a language such as Arabic, Russian or Dari to speaking it fluently in the space of 13 months. From morning to evening, weekdays and weekends, the recruits study at a pace unlike on any other language course.

As a control group, the researchers used medicine and cognitive science students at Umeå University – students who also study hard, but not languages. Both groups were given MRI scans before and after a three-month period of intensive study. While the brain structure of the control group remained unchanged, specific parts of the brain of the language students grew. The parts that developed in size were the hippocampus, a deep-lying brain structure that is involved in learning new material and spatial navigation, and three areas in the cerebral cortex.

“We were surprised that different parts of the brain developed to different degrees depending on how well the students performed and how much effort they had had to put in to keep up with the course”, says Johan Mårtensson, a researcher in psychology at Lund University, Sweden.

Students with greater growth in the hippocampus and areas of the cerebral cortex related to language learning (superior temporal gyrus) had better language skills than the other students. In students who had to put more effort into their learning, greater growth was seen in an area of the motor region of the cerebral cortex (middle frontal gyrus). The areas of the brain in which the changes take place are thus linked to how easy one finds it to learn a language and development varies according to performance.

Previous research from other groups has indicated that Alzheimer’s disease has a later onset in bilingual or multilingual groups.

“Even if we cannot compare three months of intensive language study with a lifetime of being bilingual, there is a lot to suggest that learning languages is a good way to keep the brain in shape”, says Johan Mårtensson.

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The study was performed by a group of researchers at Lund University and the Umeå Centre for Functional Brain Imaging in collaboration with the Swedish Armed Forces Interpreter Academy. The findings have been published in the scientific journal NeuroImage. http://www.sciencedirect.com/science/article/pii/S1053811912006581

For more information, please contact Johan Mårtensson, johan.martensson@psychology.lu.se, +46 707 554401.

Tamiflu survives sewage treatment ( oseltamivir )

Contact: Jerker Fick jerker.fick@chem.umu.se 46-480-446-225 Public Library of Science

Swedish researchers have discovered that oseltamivir (Tamiflu); an antiviral drug used to prevent and mitigate influenza infections is not removed or degraded during normal sewage treatment. Consequently, in countries where Tamiflu is used at a high frequency, there is a risk that its concentration in natural waters can reach levels where influenza viruses in nature will develop resistance to it. Widespread resistance of viruses in nature to Tamiflu increases the risk that influenza viruses infecting humans will become resistant to one of the few medicines currently available for treating influenza.

”Antiviral medicines such as Tamiflu must be used with care and only when the medical situation justifies it,” advises Björn Olsen, Professor of Infectious Diseases with the Uppsala University and the University of Kalmar. “Otherwise there is a risk that they will be ineffective when most needed, such as during the next influenza pandemic.”

The Swedish research group demonstrated that oseltamivir, the active substance in Tamiflu, passes virtually unchanged through sewage treatment.

“That this substance is so difficult to break down means that it goes right through sewage treatment and out into surrounding waters,” says Jerker Fick, Doctor in Chemistry at Umeå University and the leader of this study.

The Swedish research group also revealed that the level of oseltamivir discharged through sewage outlets in certain countries may be so high that influenza viruses in nature can potentially develop resistance to the drug.

“Use of Tamiflu is low in most countries, but there are some exceptions such as Japan, where a third of all influenza patients are treated with Tamiflu,” explains Jerker Fick.

Influenza viruses are common among waterfowl, especially dabbling ducks such as mallards. These ducks often forage for food in water near sewage outlets. Here they can potentially encounter oseltamivir in concentrations high enough to develop resistance in the viruses they carry.

“The biggest threat is that resistance will become common among low pathogenic influenza viruses carried by wild ducks.” adds Björn Olsen.  These viruses could then recombinate with viruses that make humans sick to create new viruses that are resistant to the antiviral drugs currently available.

The Swedish researchers advise that this problem must be taken seriously so that humanity’s future health will not be endangered by too frequent and unnecessary prescription of the drug today.

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This press release refers to an upcoming article in PLoS ONE. The release has been provided by the article authors and/or their institutions.  Any opinions expressed in this are the personal views of the contributors, and do not necessarily represent the views or policies of PLoS. PLoS expressly disclaims any and all warranties and liability in connection with the information found in the release and article and your use of such information.

Their study was published in the high-ranked journal PLoS ONE. The entire article is available free online, and can be read at the following address: http://www.plosone.org/doi/pone.0000986

Citation: Fick J, Lindberg RH, Tysklind M, Haemig PD, Waldenstro¨m J, et al (2007) Antiviral Oseltamivir Is not Removed or Degraded in Normal Sewage Water Treatment: Implications for Development of Resistance by Influenza A Virus. PLoS ONE 2(10): e986. doi:10.1371/journal.pone.0000986

PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT (URL live from October 2): http://www.plosone.org/doi/pone.0000986

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