Children with autism have elevated levels of steroid hormones in the womb .


Scientists have discovered that children who later develop autism are exposed to elevated levels of steroid hormones (for example testosterone, progesterone and cortisol) in the womb. The finding may help explain why autism is more common in males than females, but should not be used to screen for the condition.

Scientists have discovered that children who later develop autism are exposed to elevated levels of steroid hormones (for example testosterone, progesterone and cortisol) in the womb.
Credit: © Valentina R. / Fotolia

Scientists from the University of Cambridge and the Statens Serum Institute in Copenhagen, Denmark have discovered that children who later develop autism are exposed to elevated levels of steroid hormones (for example testosterone, progesterone and cortisol) in the womb. The finding may help explain why autism is more common in males than females, but should not be used to screen for the condition.

Funded by the Medical Research Council (MRC), the results are published today in the journal Molecular Psychiatry.

The team, led by Professor Simon Baron-Cohen and Dr Michael Lombardo in Cambridge and Professor Bent Nørgaard-Pedersen in Denmark, utilized approximately 19,500 amniotic fluid samples stored in a Danish biobank from individuals born between 1993-1999. Amniotic fluid surrounds the baby in the womb during pregnancy and is collected when some women choose to have an amniocentesis around 15-16 weeks of pregnancy. This coincides with a critical period for early brain development and sexual differentiation, and thus allows scientists access into this important window in fetal development. The researchers identified amniotic fluid samples from 128 males later diagnosed with an autism spectrum condition and matched these up with information from a central register of all psychiatric diagnoses in Denmark.

Within the amniotic fluid the researchers looked at 4 key ‘sex steroid’ hormones that are each synthesized, step-by-step from the preceding one, in the ‘Δ4 sex steroid’ pathway: progesterone, 17α-hydroxy-progesterone, androstenedione and testosterone. They also tested the steroid hormone cortisol that lies outside this pathway. The researchers found that levels of all steroid hormones were highly associated with each other and most importantly, that the autism group on average had higher levels of all steroid hormones, compared to a typically developing male comparison group.

Professor Baron-Cohen said: “This is one of the earliest non-genetic biomarkers that has been identified in children who go on to develop autism. We previously knew that elevated prenatal testosterone is associated with slower social and language development, better attention to detail, and more autistic traits. Now, for the first time, we have also shown that these steroid hormones are elevated in children clinically diagnosed with autism. Because some of these hormones are produced in much higher quantities in males than in females, this may help us explain why autism is more common in males.”

He added: “These new results are particularly striking because they are found across all the subgroups on the autism spectrum, for the first time uniting those with Asperger Syndrome, classic autism, or Pervasive Developmental Disorder Not-Otherwise-Specified. We now want to test if the same finding is found in females with autism.”

Dr Michael Lombardo said: “This result potentially has very important implications about the early biological mechanisms that alter brain development in autism and also pinpoints an important window in fetal development when such mechanisms exert their effects.”

Steroid hormones are particularly important because they exert influence on the process of how instructions in the genetic code are translated into building proteins. The researchers believe that altering this process during periods when the building blocks for the brain are being laid down may be particularly important in explaining how genetic risk factors for autism get expressed.

Dr Lombardo adds: “Our discovery here meshes nicely with other recent findings that highlight the prenatal period around 15 weeks gestation as a key period when important genetic risk mechanisms for autism are working together to be expressed in the developing brain.”

Professor Baron-Cohen said: “These results should not be taken as a reason to jump to steroid hormone blockers as a treatment as this could have unwanted side effects and may have little to no effect in changing the potentially permanent effects that fetal steroid hormones exert during the early foundational stages of brain development.”

He cautioned further: “Nor should these results be taken as a promising prenatal screening test. There is considerable overlap between the groups and our findings showed differences found at an average group level, rather than at the level of accurately predicting diagnosis for individuals. The value of the new results lies in identifying key biological mechanisms during fetal development that could play important roles in atypical brain development in autism.”

Story Source:

The above story is based on materials provided by University of Cambridge. The original story is licensed under a Creative Commons Licence. Note: Materials may be edited for content and length.

Journal Reference:

  1. S Baron-Cohen, B Auyeung, B Nørgaard-Pedersen, D M Hougaard, M W Abdallah, L Melgaard, A S Cohen, B Chakrabarti, L Ruta, M V Lombardo. Elevated fetal steroidogenic activity in autism. Molecular Psychiatry, 2014; DOI: 10.1038/mp.2014.48

How I discovered I have the brain of a psychopath.

I found I had the brain imaging pattern and genetic make up of a full-blown psychopath while conducting research – and yet, I turned out to be a successful scientist and family man


A human brain.
‘I had the brain imaging pattern and genetic make up of a full-blown psychopath’.

I first discovered my “hidden” psychopathy in 2006 during a series of scientific and clinical studies of murderers and patients with psychopathy and schizophrenia, as well as a separate imaging genetics study of Alzheimer’s disease in which I happened to be a control subject.

In that study, we were more than a little surprised to find that I had the brain imaging pattern and genetic make up of a full-blown psychopath. But it wasn’t until 2010, following a public talk in a University of Oslo symposium on bipolar disorder, that I first took my psychopathic traits seriously.

Upon returning to my home in Southern California, I started to ask people close to me what they really thought of me, and if they believed me to be psychopathic. And tell me they did.

The people who knew me well, including family, friends and psychiatrists who examined meall, with the exception of my mother (who later relented and told me secrets of my early life problems that she had kept to herself for over 50 years), finally told me what they felt about my psychopathic behaviors. When tested for psychopathy, I consistently scored as a “pro-social” psychopathic, and borderline to being a categorical psychopath.

There were early signs, but these disturbances were largely offset by my otherwise cheerful, positive and agreeable outgoing traits, ones that would mark me as both class clown in my high school class and Catholic boy of the year in my post-pubertal years. I was athletic, funny, good looking, and popular, often being asked to take on leadership positions from high school to this day as a professor.

But throughout those years, there was always the odd clinician, cleric, or teacher here and there who told me point blank that there was something decidedly evil about me. I always blew them off. While I laughed at their comments, they never even cracked a smile. After all, I knew my constant manipulation of people and of situations was all in good fun.

Although I made pipe bombs as a kid, and did some joy riding in stolen cars and broke into some liquor cabinets as an early teen, we always returned every piece of stolen property. And any time we were stopped by the police, my lack of anxiety meant the police always let me go, even while my buddies were hauled off for questioning. I was devilish for sure, but a sort of tolerable lovable devil. The pranks and manipulations and party mayhem got riskier and would involve tens and hundreds of others as I got older.

One thing pointed out to me was that simply taking on highly risky behaviors by myself was hardly psychopathic. It was when I endangered the lives of others, unwittingly sucked into my games, that they started to resemble psychopathy.

One example occurred in the 1990s when I was living in Africa. One of my brothers from New York visited me and I took him to the Kitum Caves in Mt Elgon, on the border of Uganda and Kenya. After the trip, about two years later, my brother called me in a fury, and really has not trusted me since. He had found out that I had taken him to the abandoned mountain and caves because that is where the deadly Marburg virus was thought to originate. Knowing he would have refused to go if I told him about the virus there (let alone sleeping around a campfire surrounded by close-in lions, hyenas and a leopard all night), I never said a word. Until he found out.

This pattern of dangerous behaviour throughout my life was a telltale sign. I had justified it, and still do, by pointing out that I always engage in the same activities as those I put in danger.

Of the 20 traits of psychopathy on the Hare psychopathy checklist, I score very high on the traits associated with “positive” behaviours within factor 1, or Aggressive Narcissism, and what is called fearless dominance in the psychopathic personality inventory. Some of these traits are prevalent in the most successful CEOs and world leaders. A recent study done on US presidents shows that those such as JFK, FDR, and Bill Clinton, with high scores on this “psychopathic” trait, are also perceived as the best leaders (even though they lied to us).

Can psychopathy be cured? I know of no case of a teenager or adult who has ever reversed categorical, full blown psychopathy. At present pre-pubescent children with signs of emerging psychopathy are undergoing behavioural re-training and although early results are promising, the real test of permanence is not yet known.

For myself, I decided to try to treat my wife and other loved ones with more care. Each time I’m about to interact with them, I pause for a moment and asked “what would a good person do here?” and notice that my instinct is to always do the most selfish thing at that moment. My wife started noticing this and after two months said “what has come over you?”. When I told her that I was trying to use my own narcissism to show that I could, against all odds, overcome my psychopathy, she said she appreciated the effort even though I was not sincere. I still don’t understand how she can accept that insincerity. Perhaps people just want to be treated with respect and kindness. I find that astonishing.

But why, in the light of the fact I have all of the biological markers for psychopathy, including a turned off limbic system, the high risk genetic alleles, and the attendant behaviours, including well over half of those listed in the psychopathy tests and low emotional empathy, did I turn out to be a successful professor and family man? One most likely reason is that although I have the genetic makeup of a “born” psychopath, some of those very same “risk” genes in someone showered with love (versus abuse or abandonment), from childbirth through the critical first few years of life, appear to offset the psychopathy-inducing effects of the other “risk” genes.

This is why I tell my 97 year old mother that the book I wrote about a young boy who could have turned out to be quite a danger to society is just about someone who will do anything to beat you in a game of Scrabble, or follow you into a deadly cave. She still doesn’t realise that the book is not about me, it is about her.

Skin cancer trial results ‘exciting’

The results of two international trials against advanced skin cancer have been hailed as “exciting and striking”.

scan of lungs

The image on the left shows melanoma which has spread into the lungs – the large grey area are tumours. On the right, the tumours have shrunk after treatment.

Both treatments, for advanced melanoma, are designed to enable the immune system to recognise and target tumours.

The findings were released at the American Society of Clinical Oncology conference in Chicago.

The experimental drugs, pembrolizumab and nivolumab, block the biological pathway cancers use to disguise themselves from the immune system.

Advanced melanoma – skin cancer which has spread to other organs – has proved very hard to treat.

Until a few years ago average survival was around six months.

Improved survival

In a trial of 411 patients evaluating pembrolizumab – 69% of patients survived at least a year.

The drug, which used to be known as MK-3475, is also being tested against other tumour types which use the same mechanism to block attack from the immune system.

Dr David Chao, consultant oncologist at the Royal Free London NHS Foundation Trust, is conducting trials in both melanoma and lung cancer patients. He said:

“Pembrolizumab looks like it has potential to be a paradigm shift for cancer therapy.”

One of his patients, Warwick Steele, aged 64, has been receiving infusions of pembrolizumab every three weeks since October.

Before the treatment started he could barely walk because the melanoma had spread to one of his lungs and he found it hard to breathe.

“I got tired simply standing up and was literally too exhausted to shave. But now I feel back to normal and can do gardening and go shopping”.

Scans of his lungs – shown above – reveal that after just three infusions, the drug appears to have completely cleared the cancer from his lung.

Warwick Steele says the treatment that cleared his lung of cancer has been a lifeline

Combination therapy

The other drug, nivolumab, was tested in combination with an existing licensed immunotherapy, ipilimumab.

In a trial of 53 patients, survival was 85% after one year, and 79% after two years.

John Wagstaff, Prof of medical oncology at Swansea College of Medicine is part of a larger trial of these two drugs.

He said: “I am convinced that this is a breakthrough in treating melanoma.

“The trial is still “blinded” so we don’t know what treatments the patients are getting, but we have seen some spectacular responses.”

Professor Peter Johnson, Cancer Research UK’s chief clinician, said: “It’s exciting to see the range of new treatments that are emerging for people with advanced melanoma.”

But doctors are urging caution. The results which have been published are of Phase I, early stage trials.

Much larger Phase III trials are underway involving many UK hospitals.

Only when they report, in about a year’s time, can clinicians be sure what the likely benefits will be.

Like all drugs, the experimental treatments have side effects. Warwick Steele said he experienced night sweats and even had two brief blackouts when on the new drug.

But he said it was well worth it, and doctors were now treating these symptoms.

Autism linked to ‘male hormones’

Exposure to high levels of “male” hormones in the womb increases the chance of a baby boy developing autism, according to researchers.

The University of Cambridge researchers say their findings from more than 300 boys help unravel the causes of autism – a condition that affects both sexes but is far more common in males.

But they say it does not mean a prenatal test for autism is near.

Nor will it necessarily be possible to stop autism by blocking the hormones.

Ultrasound scan of baby in the womb

“Start Quote

Because some of these hormones are produced in much higher quantities in males than in females, this may help us explain why autism is more common in males”

Prof Baron-Cohen Study author

The hormones in question – testosterone and three other steroid hormones – were important for foetal development, which meant it could be too risky to block them, they told the journal Molecular Psychiatry.

Autism link

But the findings did pinpoint an important window in foetal development when autism might be triggered, they said.

The study authors, Dr Michael Lombardo and Prof Simon Baron-Cohen, looked at stored samples of amniotic fluid – the liquid that surrounds a baby while in the womb – to see if there was anything about this early environment that might explain autism risk.

They found that for 128 boys who later went on to develop autism, levels of steroid hormone in the amniotic fluid that had bathed them as a baby in the womb were, on average, particularly high.

In comparison, far lower levels of steroid hormone were detected in the corresponding amniotic fluid of a control group of 217 boys without autism.

Prof Baron-Cohen said: “This is one of the earliest non-genetic biomarkers that has been identified in children who go on to develop autism.

“We previously knew that elevated prenatal testosterone is associated with slower social and language development, better attention to detail, and more autistic traits. Now, for the first time, we have also shown that these steroid hormones are elevated in children clinically diagnosed with autism.

“Because some of these hormones are produced in much higher quantities in males than in females, this may help us explain why autism is more common in males.”

The study did include some girls, but the researchers say they need to do more investigating to see if a similar association between sex hormones and autism might exist in females.

Steroid hormones influence how instructions in our genetic code – DNA – are translated into making important proteins.

The researchers believe that altering this process in early life when the building blocks for the brain are being laid down may explain how genetic risk factors for autism get expressed or “switched on”.

The exact causes of autism are unknown, although it is thought that genes and environmental factors are involved.

The developmental disorder usually starts to develop in childhood and can cause problems with social interaction, language skills and behaviour.

Prof Richard Sharpe, an expert at the University of Edinburgh, said the work was “an important first step” on the path to discovering what causes autism.

Richard Mills, of Research Autism said: “Despite a growing awareness of the biological and genetic nature of autism, there is currently no agreed biological or genetic marker for autism, with diagnosis made on the basis of early developmental history and behavioural criteria.

“So research that sheds light on this specific area is critical to our understanding of this mysterious and highly complex group of conditions.”

‘Godzilla of Earths’ identified.

There is a new class of planet out there that astronomers are calling the “mega-Earth”.

It is an object with a hard surface like our own world but much, much bigger.

The necessity for the new designation follows the discovery of a planet which has a mass some 17 times that of Earth.

Known as Kepler-10c, it orbits a star about 560 light-years away. Scientists described its properties at an American Astronomical Society meeting in Boston.


They confess it is something of a head-scratcher.

Theorists had always thought that any planet that large would pull so much hydrogen on to itself that it would look more like a Neptune or a Jupiter.

“The proper way to call it is something bigger than a ‘super-Earth, so how about ‘mega-Earth,” Prof Dimitar Sasselov, of the Harvard-Smithsonian Center for Astrophysics (CfA), told reporters. He also used the phrase, “the Godzilla of Earths!”.

Double probe

Kepler-10c, as the name suggests, was detected by the US space agency’s Kepler telescope.

This finds new worlds by looking for the tiny dip in light as they pass in front of their parent stars.

The technique gives a diameter – in this case, 29,000km, or just over two times the width of Earth – but not a mass.

For that, astronomers looked at 10c with the Harps-North instrument on the Telescopio Nazionale Galileo in the Canary Islands.

It extracts a mass measurement by examining the gravitational interaction between the planet and its host star.

Combined with the diameter, the mass number showed that Kepler-10c cannot be a gaseous world but must comprise very dense material.

Life hunt

“It’s 17 – in fact, it’s more than 17 – Earth masses, and that brings the density to 7.5 grams per cubic centimetre, which is a lot more than what we know of rock here on Earth (5.5g/cm3),” said Prof Sasselov.

“But remember, this is a very massive planet, which means those same minerals are highly compressed.

“So, what you see in the density is mostly due to compression rather than different composition. The composition comes out as being a combination of rocks and some volatiles, probably 5-15% at most of water.”

The discovery adds to our understanding of the mix of planet types we now know are out there, and tells us something new about when rocky worlds might transition to gaseous planets in their formative years.

Interestingly, the age of the host star is about 11 billion years old, which is early in the evolution of the Universe when generations of exploding stars have not had long to make the heavy elements needed to construct rocky planets.

So, Kepler-10c’s properties suggest rocky planets may have formed earlier in cosmic history than many thought possible, and that very old star systems should not be ignored in the search for life beyond Earth.

“It is [on] solid planets that is the place, as far as we know – and we very little about the origins of life – where we think the chemistry is capable of building those molecules that lead to the emergence of life from geochemistry,” says Prof Sasselov.

Carbon-capture breakthrough: Porous material polymerizes carbon dioxide at natural gas wellheads

Rice University scientists have created an Earth-friendly way to separate carbon dioxide from natural gas at wellheads.

A porous material invented by the Rice lab of chemist James Tour sequesters , a greenhouse gas, at ambient temperature with pressure provided by the wellhead and lets it go once the pressure is released. The material shows promise to replace more costly and energy-intensive processes.

Results from the research appear today in the journal Nature Communications.

Natural gas is the cleanest fossil fuel. Development of cost-effective means to separate carbon dioxide during the production process will improve this advantage over other fossil fuels and enable the economic production of gas resources with higher carbon dioxide content that would be too costly to recover using current carbon capture technologies, Tour said. Traditionally, carbon dioxide has been removed from natural gas to meet pipelines’ specifications.

The Tour lab, with assistance from the National Institute of Standards and Technology (NIST), produced the patented material that pulls only carbon dioxide molecules from flowing natural gas and polymerizes them while under pressure naturally provided by the well.

When the pressure is released, the carbon dioxide spontaneously depolymerizes and frees the sorbent material to collect more.

All of this works in ambient temperatures, unlike current high-temperature capture technologies that use up a significant portion of the energy being produced.

“If the oil and gas industry does not respond to concerns about carbon dioxide and other emissions, it could well face new regulations,” Tour said, noting the White House issued its latest National Climate Assessment last month and, this week, set new rules to cut carbon pollution from the nation’s power plants.

“Our technique allows one to specifically remove carbon dioxide at the source. It doesn’t have to be transported to a collection station to do the separation,” he said. “This will be especially effective offshore, where the footprint of traditional methods that involve scrubbing towers or membranes are too cumbersome.

“This will enable companies to pump carbon dioxide directly back downhole, where it’s been for millions of years, or use it for enhanced oil recovery to further the release of oil and natural gas. Or they can package and sell it for other industrial applications,” he said.

 Particles of nitrogen-containing porous carbon are able to capture carbon dioxide from natural gas under pressure at a wellhead by polymerizing it, according to researchers at Rice University. When the pressure is released, the carbon dioxide returns to gaseous form. Credit: Tour Group/Rice University

The Rice material, a nanoporous solid of carbon with nitrogen or sulfur, is inexpensive and simple to produce compared with the liquid amine-based scrubbers used now, Tour said. “Amines are corrosive and hard on equipment,” he said. “They do capture carbon dioxide, but they need to be heated to about 140 degrees Celsius to release it for permanent storage. That’s a terrible waste of energy.”

Rice graduate student Chih-Chau Hwang, lead author of the paper, first tried to combine amines with porous carbon. “But I still needed to heat it to break the covalent bonds between the amine and carbon dioxide molecules,” he said. Hwang also considered metal oxide frameworks that trap carbon dioxide molecules, but they had the unfortunate side effect of capturing the desired methane as well and they are far too expensive to make for this application.

The porous carbon powder he settled on has massive surface area and turns the neat trick of converting gaseous carbon dioxide into solid polymer chains that nestle in the pores.

“Nobody’s ever seen a mechanism like this,” Tour said. “You’ve got to have that nucleophile (the sulfur or nitrogen atoms) to start the polymerization reaction. This would never work on simple activated carbon; the key is that the polymer forms and provides continuous selectivity for carbon dioxide.”

Methane, ethane and propane molecules that make up may try to stick to the carbon, but the growing polymer chains simply push them off, he said.

The researchers treated their carbon source with potassium hydroxide at 600 degrees Celsius to produce the powders with either sulfur or nitrogen atoms evenly distributed through the resulting . The sulfur-infused powder performed best, absorbing 82 percent of its weight in carbon dioxide. The nitrogen-infused powder was nearly as good and improved with further processing.

Tour said the material did not degrade over many cycles, “and my guess is we won’t see any. After heating it to 600 degrees C for the one-step synthesis from inexpensive industrial polymers, the final carbon material has a surface area of 2,500 square meters per gram, and it is enormously robust and extremely stable.”

How It Works: Putting Humans In Suspended Animation.

A new human trial will chill gunshot victims to keep them alive

Brain Evolution Study Shows Humans Sacrificed Brawn For High Intelligence.

Humans may be smart because energy once devoted to brawn was given up for brains, researchers say.

The most powerful computer known is the brain. The human brain possesses about 100 billion neurons with about 1 quadrillion — 1 million billion — connections known as synapses wiring these cells together.

Humans possess more complex, powerful brains than humanity’s closest living relatives, such as monkeys and apes. One reason behind this jump in brainpower may lie in how much of the human metabolism is devoted to the human brain — it consumes a whopping 20 percent of the body’s total energy. [10 Surprising Facts About the Human Brain]

How the brain evolved

To gain insights into how the human brain evolved, scientists compared the metabolisms of humans and animals such as chimpanzees, mice and rhesus monkeys. They focused on how much energy each species devoted to the brain and body.


The researchers analyzed more than 10,000 compounds known as metabolites, which are small molecules formed by, or necessary to, metabolism, such as sugars and fats; the building blocks of proteins, DNA and cell membranes; and chemical signals given off by cells. They investigated metabolite levels in the kidney, thigh muscle and three brain regions — the primary visual cortex, which is involved in vision; the cerebellar cortex, which helps coordinate muscular activity; and the prefrontal cortex, which plays a major role in complex mental behavior, decision making and social behavior.

The investigators next compared how much the metabolisms of these animals differed with how far apart these species are evolutionarily. By analyzing human and other genomes, prior studies revealed when the ancestors of humans and other animals diverged. For instance, the ancestors of humans and rodents diverged about 75 million years ago, while divergence happened about 25 million years ago with the ancestors of rhesus monkeys and about 6 million years ago with the ancestors of chimpanzees.

For the most part, the scientists found the levels of differences between the metabolisms of these species matched how far apart they were evolutionarily. (The further apart evolutionarily, the greater the metabolism differences were.) However, they discovered the rate of change in the metabolism of the human prefrontal cortex was about four times faster than that of chimpanzees. Even more surprisingly, the rate of change in the metabolism of human muscle was more than eight times faster that that of the chimpanzee.

“Even after so many years of research of humans and human evolution, we still can uncover large unknown differences between humans and other species,” said study author Philipp Khaitovich, an evolutionary biologist at the Chinese Academy of Sciences’ Key Laboratory of Computational Biology in Shanghai.

Humans vs. chimps

To rule out the possibility that these changes simply reflected the modern human couch potato lifestyle, the scientists performed additional experiments on rhesus monkeys, moving them from a spacious countryside facility to small indoor homes and serving them fatty and sugary food for several weeks, all to imitate the environment and behavior of contemporary humans. These lifestyle changes had only a small effect on the metabolisms of the monkeys’ muscles.

“For a long time we were confused by metabolic changes in human muscle, until we realized that what other primates have in common, in contrast to humans, is their enormous muscle strength,” said lead author Katarzyna Bozek, of the Chinese Academy of Sciences’ Key Laboratory of Computational Biology in Shanghai. [The 7 Biggest Mysteries of the Human Body]

Chimps are far stronger than humans. Kevin Hunt, director of the Human Origins and Primate Evolution Lab at Indiana University, once told of watching an 85-pound (38.5 kilograms) female chimp in Africa snap branches off an ironwood tree with her fingertips, one that took Hunt two hands and all his strength to break.

To see just how much stronger chimps and rhesus monkeys are than humans, the researchers conducted muscle strength tests that involved pulling weights upward. All of the human volunteers in the experiment — who included professional athletes — were outcompeted by their primate opponents by more than twofold.

“According to our results, an average adult chimpanzee is approximately two to three times stronger than an average adult human,” Khaitovich told Live Science.

The fact that metabolic changes in human muscle are paralleled by a drastic reduction in muscle strength leads the researchers to hint that human ancestors may have swapped brains for brawn.

“It is a very simple explanation, and it could be completely wrong,” Khaitovich said. “In evolution, however, simple explanations often work well.”

“Our work opens a door to further studies of human metabolic uniqueness,” Khaitovich said. “It is a huge field that is virtually untouched by scientists.”

Commonly used anesthetic causes Alzheimer’s-related changes in brain.

Evidence continues to emerge that general anesthetics commonly used in surgery may actually produce some of the brain changes that lead to Alzheimer’s disease.

Researchers have known for many years that certain patients experience dementia-like symptoms following surgery. In 2007, a team of researchers from Massachusetts General Hospital provided some of the first evidence directly linking anesthetics to these symptoms. When the researchers applied the common anesthetic gas isoflurane to nerve cells in the laboratory, levels of the enzymes beta-secretase (BACE) and gamma-secretase both increased, as did levels of the protein caspase.


BACE and gamma-secretase, in turn, are known to damage healthy amyloid precursor proteins (APPs) in the brain, breaking them into the abnormal alpha-beta proteins that accumulate during Alzheimer’s disease. In the absence of BACE and gamma-secretase, an enzyme called alpha-secretase instead transforms APPs into a different, non-toxic protein.

These findings imply that the anesthetic isoflurane starts a chemical cascade that may lead to the accumulation of alpha-beta proteins and the development of Alzheimer’s. The elevated levels of caspase further indicate increased cell death.
Effects confirmed in living model

In order to determine whether the same effect occurs in living mammals, the same research team exposed mice to isoflurane gas, in a study published in the Annals of Neurology in 2008. The mice were given a dose similar to what humans would receive prior to surgery, and their brains were examined at 2, 6, 12 and 24 hours after exposure.

At 6 hours, levels of caspase were elevated and BACE levels had slightly increased. By 12 hours, caspase levels remained elevated and BACE levels had increased further. At 24 hours, caspase levels had returned to normal, but levels of BACE were four times higher than normal, and amyloid-beta levels had also risen. None of these changes were observed in a control group.

“These are the first in vivo results indicating that isoflurane can set off a time-dependent cascade inducing apoptosis [cell death] and enhanced levels of the Alzheimer’s-associated proteins BACE and A-beta,” lead author Zhongcong Xie, MD, PhD, said.

“[I]t’s looking like isoflurane may not be the best anesthesia to use for patients who already have higher A-beta levels, such as the elderly and Alzheimer’s patients.”

Evidence in human tests

Studies in humans also suggest a link between anesthesia and Alzheimer’s development. One study found that, among people aged 80 years and older, Alzheimer’s risk was directly correlated with exposure to general anesthesia. Another found a direct relationship between a greater exposure to general and spinal anesthesia before the age of 50 and a younger age of Alzheimer’s onset.

A study conducted by researchers from the University of Pennsylvania and published in the journal Anesthesiology in 2011 further strengthened the case. Researchers collected samples of cerebral spinal fluid from 11 people about to undergo a routine endoscopic nasal surgery, then collected a further four samples at regular intervals after the surgery. They found that, six hours after surgery, levels of the Alzheimer’s biomarker “tau protein” were significantly elevated in cerebral spinal fluid. Other biomarkers of inflammation and injury also increased.

High tau protein levels are considered a warning sign of Alzheimer’s disease.

Participants exposed to the common inhaled anesthetic sevoflurane experienced the greatest increase in inflammatory biomarkers, compared with patients given other anesthetics.

“We have long sought a clearer picture of the true impact of anesthesia and surgery on the central nervous system,” study author Dr. Roderic Eckenhoff said.

“Although not definitive, this human biomarker study gives some credibility to the notion that anesthesia and surgery produce an inflammatory insult on the brain and accelerate chronic neurodegenerative diseases like Alzheimer’s.”

Sources for this article include:


Hidden Greenland Canyons Mean More Sea Level Rise.

New maps of the bedrock beneath Greenland’s ice sheet (right) have found long, deep canyons that are likely to cause ocean-feeding glaciers  to retreat faster and farther inland than previously thought.
Scientists at NASA and the University of California, Irvine (UCI), have found that canyons under Greenland’s ocean-feeding glaciers are deeper and longer than previously thought, increasing the amount of Greenland’s estimated contribution to future sea level rise.
“The glaciers of Greenland are likely to retreat faster and farther inland than anticipated, and for much longer, according to this very different topography we have discovered,” said Mathieu Morlighem, a UCI associate project scientist who is lead author of the new research paper. The results were published Sunday in the journal Nature Geoscience.
Ice loss from Greenland has accelerated during the last few decades. However, older ice sheet models predicted the speedup would be temporary because the glaciers would soon melt back onto higher ground and stabilize. The models projected that Greenland’s contribution to global sea level rise would therefore be limited.
Morlighem’s new topography shows southern Greenland’s ragged, crumbling coastline is scored by more than 100 canyons beneath glaciers that empty into the ocean. Many canyons are well below sea level as far as 60 miles (100 kilometers) inland. Higher ground, where glaciers could stabilize, is much farther from the coastline than previously thought. The finding calls into question the idea that the recent accelerated ice loss will be short lived.
Buried under the Greenland Ice Sheet, the subcontinent’s bedrock topography has been estimated using soundings from ice-penetrating radar. However, the wet and fractured ice along the southern coastline cluttered the radar soundings so that large swaths of the bed remained invisible. To overcome that problem, Morlighem and his colleagues devised an advanced technique to create a more accurate map. The technique makes the best use of several kinds of data: ice thickness measurements derived from airborne radar; satellite radar interferometry data on the speed and direction of ice movement: and estimates of snowfall and surface melt to the sea. By combining the different types of data, they were able to map the bed topography along Greenland’s margins with unprecedented precision and detail.
“We have been able to make a quantum leap in our knowledge of bed topography beneath ice sheets in the last decade, thanks to the advent of missions like NASA’s Operation IceBridge in combination with satellite data on the speed these ice sheets are flowing,” said coauthor Eric Rignot of UCI and NASA’s Jet Propulsion Laboratory (JPL), Pasadena, California.
The same research team reported new findings on glacial melt in West Antarctica last week.
“Together the papers illustrate clearly the globe’s ice sheets will contribute far more to sea level rise than current projections show,” said Rignot.
The study used synthetic aperture radar data collected in 2008-2009 by the Japanese Advanced Land Observing System Phased Array type L-band Synthetic Aperture Radar (ALOS PALSAR), the Canadian RADARSAT-1, the German TerraSAR-X, and the European Envisat Advanced Synthetic Aperture Radar (ASAR). Ice thinning rates were derived from NASA’s Airborne Topographic Mapper and ICESat data, and ice thickness data came from NASA’s Operation IceBridge airborne campaigns.
An animation of the newly mapped bed topography is available at:

The California Institute of Technology, Pasadena, manages JPL for NASA.
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