Why don't antidepressants work in some patients?

Mouse study shows it may be down to your environment.

SSRI antidepressants (Selective Serotonin Reuptake Inhibitors, the best known being Prozactm) are amongst the most commonly taken medicines. However, there seems to be no way of knowing in advance whether or not SSRIs will work effectively. Now a group of European researchers has developed a new theory of SSRI action, and tested it in stressed mice. The results, which are presented at the ECNP conference in Vienna, show why the circumstances we find ourselves in may influence whether an antidepressant works or not.

According to researcher, Silvia Poggini (Istituto Superiore di Sanità, Rome), "There is no doubt that antidepressants work for many people, but for between 30 and 50% of depressed people, antidepressants don't work. No-one knows why. This work may explain part of the reason."

The researchers have proposed that simply increasing the levels of serotonin, by taking an SSRI, does not cause a recovery from depression, but puts the brain into a condition where change can take place -- it increases the plasticity of the brain, making it more open to being changed. "In a certain way it seems that the SSRIs open the brain to being moved from a fixed state of unhappiness, to a condition where other circumstances can determine whether or not you recover" said Ms Poggini. According to the researchers, it is the environmental conditions you find yourselves in at the time of the treatment which determines whether you are likely to get better or worse.

To test this, they took a sample of mice which they subjected to stress for two weeks. They started treating the mice with the SSRI fluoxetine, and split the group. They continued to stress half (n=12) of the group of mice but the other half of the mice were subjected to a more comfortable environment. They then tested all the mice to measure the levels of the stress-related cytokines in the brain. Cytokines are protein-related molecules which aid cell to cell communication in the immune system.

They found that mice kept in a more comfortable environment showed an increase in the expression of pro-inflammatory cytokines and decreased anti-inflammatory-related genes, as well as showing fewer signs of depression, whereas those under continuous stress showed the opposite effect (i.e. a decrease in pro-inflammatory cytokines, and an increase in anti-inflammatory gene expression, with more signs of depression). The fluoxetine-treated mice exposed to the comfortable environment showed a 98% increase in the pro-inflammatory cytokines IL-1β while mice kept in a stressed environment and treated with fluoxetine showed a 30% decrease in the pro-inflammatory cytokines TNF-α.

This indicates that the environment determines the response to antidepressants. According to Silvia Poggini, "This work indicates that simply taking an SSRI is probably not enough. To use an analogy, the SSRIs put you in the boat, but a rough sea can determine whether you will enjoy the trip. For an SSRI to work well, you may need to be in a favourable environment. This may mean that we have to consider how we can adapt our circumstances, and that antidepressant treatment would only be one tool to use against depression."

She cautioned "Our studies have a number of limitations. First of all, we are not explaining the complete range of actions of SSRIs. It's also an animal model, so clinical and epidemiological studies are needed to further test the validity of the hypothesis. Our results are preliminary and we strongly recommend that patients stick to the treatment prescribed by their doctors."

Commenting, Dr Laurence Lanfumey (Centre de Psychiatrie et Neuroscience Inserm, Paris), Member of the ECNP Executive Committee, said, "This original study is a nice model for combined behavioral and pharmacological treatments in depression- like disorders. The idea that environment could impact the output of a pharmacological treatment has been suggested for years, but this work brings direct biological evidences of such an interaction. Although the present work also raised several questions, this kind of experiment is important to do to bridge the gap between behavior and SSRIs efficacy."

Modern environment blamed for 40% rise in children’s cancer cases

The number of cancer cases in children has leapt by 40 per cent in less than two decades because of pollution, pesticides and gadgets, new analysis has shown.

There are 1,300 more diagnoses of the disease a year in people under the age of 25 compared to 1998 – costing the NHS £130 million extra a year.

Cases of colon cancer in children are up 200 per cent, while thyroid cancer cases have more than doubled.

Ovarian and cervical cancer cases have also seen stark rises – up by 70 per cent and 50 per cent respectively, analysis of ONS data by the charity Children with Cancer UK found.

Around 4,000 children and young people develop cancer each year and it is the leading cause of death in children aged one to 14 in the UK.

The 40 per cent jump in cases over 16 years is partially attributed to population growth, as the incidence rate per 100,000 people has risen by 30 per cent.

However, Professor Denis Henshaw, scientific director at Children with Cancer UK, said that lifestyle and environmental factors could play a part in the rise.

“These significant rises in cancer cases cannot be explained by improvements in cancer diagnosis or registration alone – lifestyle and environmental causal factors must be considered.”

He said that burnt barbecues, the electric fields of power lines, and hairdriers were contributors to the rise, as well as a pregnant women’s diet and working shifts.

“We were shocked to see the figures, and it’s the modern lifestyle I’m afraid. Many items on the list of environmental causes are now known to be carcinogenic, such as air pollution and pesticides and solvents.”

He added: “What’s worrying is it is very hard to avoid a lot of these things. How can you avoid air pollution? It sometimes feels like we are fighting a losing battle.”

Children with Cancer UK are calling on the Government and medical and science community to ensure children with cancer have access to precision medicine by 2020.

The charity is hosting a three-day international conference on childhood cancer which begins today. It will look at precision medicine, immunotherapy and influenceable causes of childhood cancer.

Precision medicine – which considers an individual’s genes, environment and lifestyle to provide more targeted treatment – needs to be offered to all young people within the framework of clinical trials by 2020, the charity’s medical director has claimed.

Philae: Lost comet lander is found

Europe's comet lander Philae has been found.

The little robot is visible in new images downloaded from the Rosetta probe in orbit around the icy dirt-ball 67P/Churyumov-Gerasimenko.

European Space Agency (Esa) officials say there is no doubt about the identification - "it's as clear as day", one told the BBC.

Philae was dropped on to the comet by Rosetta in 2014 but fell silent 60 hours later when its battery ran flat.

Although it relayed pictures and data about its location to Earth, the lander's actual resting place was a mystery.

It was assumed Philae had bounced into a dark ditch on touchdown - an analysis now borne out by the latest pictures, which were acquired from a distance of 2.7km from the icy body.

Wait after comet landing 'bounce'

The images from Rosetta's high-resolution Osiris camera were downlinked to Earth late on Sunday night, and have only just been processed.

Philae is seen wedged against a large over-hang. Its 1m-wide box shape and legs are unmistakable, however.

Rosetta had previously surveyed this location - dubbed Abydos - without success.

"Candidate detections" were made but none were very convincing.

The difference today is a closer-in perspective and a change in the seasons on the comet, which means the hiding place is now better illuminated.

The discovery comes just a few weeks before controllers plan to crash-land Rosetta itself on to the comet to formally end its mission.

"With only a month left of the Rosetta mission, we are so happy to have finally imaged Philae, and to see it in such amazing detail," says Cecilia Tubiana from the Osiris team.

Although there is no hope of reviving the lander - some of its equipment will have been broken in the cold of space - simply knowing its precise resting place will help scientists make better sense of the data it returned during its three days of operation back in 2014.

"This wonderful news means that we now have the missing 'ground-truth' information needed to put Philae's three days of science into proper context, now that we know where that ground actually is!" said Matt Taylor, Esa's Rosetta project scientist.

 

 

Scientists Find 3.7 Billion-Year-Old Fossil, Oldest Yet

Scientists have found what they think is the oldest fossil on Earth, a remnant of life from 3.7 billion years ago when Earth's skies were orange and its oceans green.

In a newly melted part of Greenland, Australian scientists found the leftover structure from a community of microbes that lived on an ancient seafloor, according to a study in Wednesday's journal Nature .

The discovery shows life may have formed quicker and easier than once thought, about half a billion years after Earth formed . And that may also give hope for life forming elsewhere, such as Mars, said study co-author Martin VanKranendonk of the University of New South Wales and director of the Australian Center for Astrobiology.

"It gives us an idea how our planet evolved and how life gained a foothold," VanKranendonk said.

Scientists had thought it would take at least half a billion years for life to form after the molten Earth started to cool a bit, but this shows it could have happened quicker, he said. That's because the newly found fossil is far too complex to have developed soon after the planet's first life forms, he said.

In an outcrop of rocks that used to be covered with ice and snow which melted after an exceptionally warm spring, the Australian team found stromatolites, which are intricately layered microscopic layered structures that are often produced by a community of microbes. The stromatolites were about .4 to 1.6 inches high (1 to 4 centimeters).

It "is like the house left behind made by the microbes," VanKranendonk said.

Scientists used the layers of ash from volcanoes and tiny zircon with uranium and lead to date this back 3.7 billion years ago, using a standard dating method, VanKranendonk said.

"It would have been a very different world. It would have had black continents, a green ocean with orange skies," he said. The land was likely black because the cooling lava had no plants, while large amounts of iron made the oceans green. Because the atmosphere had very little oxygen and oxygen is what makes the sky blue, its predominant color would have been orange, he said.

The dating seems about right, said Abigail Allwood , a NASA astrobiologist who found the previous oldest fossil, from 3.48 billion years ago, in Australia. But Allwood said she is not completely convinced that what VanKranendonk's team found once was alive. She said the evidence wasn't conclusive enough that it was life and not a geologic quirk.

"It would be nice to have more evidence, but in these rocks that's a lot to ask," Allwood said in an email.

Zika vaccine trials begin – but fears remain over virus’s impact

There’s finally some progress in the fight against Zika. A vaccine is being given to 160 people in Zika-hit Puerto Rico, and a preliminary study has identified two existing drugs that seem to protect human brain cells from the virus.

The vaccine, developed by Inovio Pharmaceuticals, contains a synthetic DNA fragment similar to one in the virus itself. The company hopes that people who receive it will develop immune protection against Zika.

The two drugs that might be useful as a treatment came from an analysis of thousands of compounds, including some drugs that are used to treat other conditions. Zika seems to target cells that make new neurons in the brain and stop them from working properly. This is thought to cause the horrendous brain defects seen in some babies born with the virus, and could also put infected adults at risk of memory and mood disorders.

A team of researchers from the US and China identified one drug – currently in clinical trials for liver diseases – that protects brain cells from damage, and 10 others that stop Zika from replicating, one of which is an already-approved drug used to treat worm infections. A combination of two compounds could be an effective Zika treatment, say the authors, who hope to start testing in animals soon.

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But we are still some way off having treatments ready for use on the ground, says Edwin Trevathan, a paediatric neurologist at Vanderbilt University in Nashville, Tennessee, who advises the US Centers for Disease Control and Prevention (CDC) on Zika. “Even if the vaccine development moves as quickly as we’d like, realistically it will be a year before we have something we can use to protect people,” he says.

Transmission cases

The development is welcome after a couple of weeks of bad news. Last Friday, the CDC described the first known case of Zika transmission from a man who had shown no symptoms of illness to his sexual partner, a couple of weeks after he returned from the Dominican Republic. The news came days after a finding that Zika had remained in an Italian man’s semen for six months after a trip to Haiti – around three times longer than previously seen in people.

At the same time, doctors and scientists are warning that the effects of Zika could be worse than thought, and may not affect some babies for several years, when it could impact their brain development. “It could affect parts of the brain that don’t manifest their function until the age of 2, 4 or 6,” says Travathan. “Sadly, I suspect that many of us who take care of children will see the effects of Zika for a long time. This is a problem that may have been dramatically underestimated.”

Until we have vaccines and treatments, efforts are under way to stem infections and the spread of Zika-infected mosquitoes. Last Friday, the US Food and Drug Administration recommended testing for Zika virus in all donated blood before it is used. The organisation has also fast-tracked the approval of a commercially available Zika diagnosis kit.

The CDC has set aside $6.8 million to fund public awareness, diagnosis and mosquito surveillance – although this is only a fraction of the $1.9 billion that the Obama administration has requested from Congress. And new polls suggest that most people living in Florida support the release of genetically modified mosquitoes that could help stem the spread of the virus.

Semen reshapes immune system to boost chances of pregnancy

Semen does more than fertilise eggs. In mice, it seems to prime the female’s  immune system for pregnancy, making it more likely that an embryo will successfully implant in the womb. It appears to prompt similar changes in women, a finding that could explain why IVF is more successful if couples have regular sex during treatment.

Sarah Robertson at the University of Adelaide, Australia, and her colleagues found that each time a female mouse copulates, it caused the release of immune cells called regulatory T-cells, which are known to dampen down inflammation in the body.

This process may be important for allowing embryos to implant in the womb, rather than being rejected as a foreign body. In people, low regulatory T-cell counts are linked to several reproductive problems, including unexplained infertility, miscarriage, pre-eclampsia and pre-term labour.

Does semen deserve more credit?

Examining the cervix in women, the team found signs that semen does seem to prompt immune system changes in people too. Shortly after sex, they detected the cervix begins to release immune signalling molecules, which may be a sign of increased levels of regulatory T-cells.

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“It’s as if the seminal fluid is a Trojan horse that activates the immune cells to get things ready for conception,” says Robertson.

As well as making the embryo more likely to successfully implant in the womb lining, it’s possible that such effects also minimise the chances of a woman’s body rejecting the fetus later on in pregnancy, she says. Women who conceive after limited sexual activity are more likely to develop disorders during pregnancy, she adds.

IVF help

The findings, presented at the International Congress of Immunology in Australia this week, fit with observations that semen contains several signaling molecules – including cytokines, prostaglandins, and hormones – that can have an effect on female tissue.

 

The discovery has implications for IVF. After a woman’s eggs have been fertilised in the lab, an embryo is chosen for implantation and is surgically inserted into the womb. This is one of the points where IVF can fail, if an embryo is unable to implant in a woman’s uterine lining.

Many fertility clinics advise couples to abstain from sex during IVF treatment to minimise risk of infection from seminal fluid during the implantation surgery. This is a small risk outweighed by the benefits semen can have for the female immune system, Robertson says.

This is supported by a recent review of studies that concluded that sex during IVF improves embryo implantation rates by 23 per cent. “I think it’s really good for couples to know that there’s something they can do to help their chances – it allows them to take a bit of control back,” says Robertson.

Peter Illingworth of IVF Australia says the evidence is compelling. “I personally always say to IVF patients: ‘if you want to have sex, just have sex’.” But many couples choose not to during the treatment because IVF causes a lot of discomfort, he says.  “If you’ve got ovaries the size of baseballs, sex is a much less appealing prospect.”

Conception delay

The effect of semen on a woman’s immune system could also help explain why most couples do not fall pregnant straight away, says Robertson. “In humans, it seems that at least three months of sexual cohabitation is required to give you the priming that you need,” she says.

If low levels of regulatory T-cells are for a cause of infertility,  therapies that increase them may help women who have been trying unsuccessfully to get pregnant for a long time. Treatments like these are currently being developed for immune conditions like graft-versus-host disease, but they haven’t been tested for fertility yet.

“Our results suggest that the first-line approach to treating infertility should be to tell people to go home and practise,” Robertson says. “But if that doesn’t work, tackling regulatory T cells may be the way to go.”

How a huge school of sharks 'flips the food pyramid'

Ecologists have discovered a food web beneath the waves of French Polynesia that is both unusual and spectacular.

A small channel hosts up to 700 sharks - far more than it can support based on the number of fish living there.

The predators survive by feasting every winter on huge numbers of grouper fish, which swim into the channel to spawn.

Those mobs of spawning fish concentrate prey from multiple reefs and the sharks lurk in the channel to take advantage of them, instead of hunting elsewhere.

The findings, published in the journal Current Biology, are an example of an "inverted trophic pyramid": the average biomass in the channel is skewed towards predators rather than prey.

It is only the convenient, seasonal meal delivery of spawning groupers into the Fakarava atoll's southern pass that sustains its rare concentration of gray reef sharks - the highest density of this species ever recorded.

a dense school of grouper fishGroupers gather in huge numbers to spawn during June and July / Laurent Ballesta

"We went there, in the beginning, to study the groupers, because we heard about these spawning aggregations that happen every year," said Dr Johann Mourier, who led the study for CRIOBE in French Polynesia but is now based at Macquarie University in Sydney.

"And we found this huge population of sharks. Up to 700 gray reef sharks - about two to three times higher density than found in any other reef, worldwide."

With colleagues from France and the US, Dr Mourier tagged and tracked 13 sharks using remote transmitters, to understand their behaviour; they also did regular surveys of the channel with underwater cameras and completed a census of different shark and fish species.

The team discovered that gray reef sharks in the channel, which is just 100m wide and 30m deep, fluctuated in number from about 250 in the summer to 700 in the winter.

That winter peak coincided with the spawning of the groupers, which brought together some 7,000 of the smaller fish at a time, from habitats up to 50km away.

"That's about 30 tonnes of fish; that's a big amount of food," Dr Mourier told BBC News.

shark eating a grouper Easy meal: spawning swarms of groupers deliver tonnes of food at a time / Andromede Oceanologie

The researchers witnessed the sharks taking aggressive advantage of this meal delivery, and also observed that the density of the sharks and the length of time they spent in the channel were significantly higher when the groupers were spawning.

It might sound incredibly convenient, but previous findings had suggested that when sharks live together in large groups like this - and risk tipping the balance of the trophic pyramid - they would simply travel further afield to find food.

"The idea was that sharks must make foraging excursions outside their area. They have to move to find food to survive," Dr Mourier explained.

"But in this case, we find that the spawning aggregations bring the food to them. They just can stay at the reef and save their energy."

palm trees and sandy beach The atoll of Fakarava, part of French Polynesia in the South Pacific, is a UNESCO biosphere reserve / Getty Images

The discovery has implications for conserving these species, he added. Laws to stop people fishing for sharks might not be enough to protect them - because huge spawning aggregations of fish are attractive to humans as well as to sharks.

"It's quite easy to catch your fish if they're in these huge aggregations - they're just concentrating on spawning," Dr Mourier said.

But overfishing those tempting crowds of fish could threaten the sharks themselves.

"Maybe that's why we don't find such shark densities in other reefs - because those spawning aggregations have been overfished."

2016 on Pace to Be Hottest Year Ever, CO2 at Record High: UN

The world is on track for its hottest year on record, the World Meteorological Organization says.

The world is on track for its hottest year on record and levels of carbon dioxide in the atmosphere have reached new highs, further fuelling global warming, the United Nations weather agency said Thursday.

RELATED: Climate Change Health Impacts Loom Large

June marked the 14th consecutive month of record heat for land and oceans, the World Meteorological Organization, WMO, said.

The average temperature in the first six months of 2016 was 1.3°Celsius (2.4°Fahrenheit) warmer than the pre-industrial era in the late 19th Century, according to NASA.

"This underlines more starkly than ever the need to approve and implement the Paris Agreement on climate change, and to speed up the shift to low carbon economies and renewable energy," said WMO Secretary-General Petteri Taalas.

Under December's Paris Agreement, nearly 200 governments agreed to limit global warming to "well below" 2°C (3.6°F) above pre-industrial times, while "pursuing efforts" for a ceiling of just 1.5°C. Temperatures are already nudging toward that lower limit.

"The heat has been especially pronounced in the Arctic, resulting in a very early onset of the annual melting of the Greenland ice sheet and Arctic sea ice," WMO said.

"What we’ve seen for the first six months of 2016 is really quite alarming," David Carlson, director of the WMO’s Climate Research Program, told a news briefing. "We would have thought it would take several years to warm up like this ... We don't have as much time as we thought."

RELATED: 'Climate Emergency' Declared As Jet Stream Crosses Equator

The northern hemisphere, including the state of Alaska in the United States, Canada and Russia, have posted unusually warm temperatures, he said.

The last month with global temperatures below the 20th Century average was December 1984.

A strong El Nino weather event in the Pacific Ocean, a phenomenon associated with extreme droughts, storms and floods, "has now disappeared," the WMO said in a statement.

The El Nino event developed in 2015 and contributed to the record temperatures in the first half of 2016 before disappearing in May, WMO said.

"Climate change, caused by heat-trapping greenhouse gases, will not (disappear). This means we face more heat waves, more extreme rainfall and potential for higher impact tropical cyclones," said Taalas.

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