Archive for the ‘Emory University School of Medicine’ Category

Because Kent Brantly is a physician who has watched people die of Ebola, there was an especially chilling prescience to his assessment last week, between labored breaths: “I am going to die.”

His condition was grave. But then on Saturday, we saw images of Brantly’s heroic return to U.S. soil, walking with minimal assistance from an ambulance into an isolation unit at Emory University Hospital.

“One of the doctors called it ‘miraculous,'” Dr. Sanjay Gupta reported from Emory this morning, of Brantly’s turnaround within hours of receiving a treatment delivered from the U.S. National Institutes of Health. “Not a term we scientists like to throw around.”

“The outbreak is moving faster than our efforts to control it,” Dr. Margaret Chan, director of the World Health Organization, said on Friday in a plea for international help containing the virus. “If the situation continues to deteriorate, the consequences can be catastrophic in terms of lost lives, but also severe socioeconomic disruption and a high risk of spread to other countries.”

In that light, and because Ebola is notoriously incurable (and the strain at large its most lethal), it is overwhelming to hear that “Secret Serum Likely Saved Ebola Patients,” as we do this morning from Gupta’s every-20-minute CNN reports. He writes:

Three top secret, experimental vials stored at subzero temperatures were flown into Liberia last week in a last-ditch effort to save two American missionary workers [Dr. Kent Brantly and Nancy Writebol] who had contracted Ebola, according to a source familiar with details of the treatment.

Brantly had been working for the Christian aid organization Samaritan’s Purse as medical director of the Ebola Consolidation Case Management Center in Monrovia, Liberia. The group yesterday confirmed that he received a dose of an experimental serum before leaving the country.

In Gupta’s optimistic assessment, Brantly’s “near complete recovery” began within hours of receiving the treatment that “likely saved his life.” Writebol is also reportedly improved since receiving the treatment, known as zMapp. But to say that it was a secret implies a frigid American exceptionalism; that the people of West Africa are dying in droves while a classified cure lies in wait.

The “top-secret serum” is a monoclonal antibody. Administration of monoclonal antibodies is an increasingly common but time-tested approach to eradicating interlopers in the human body. In a basic monoclonal antibody paradigm, scientists infect animals (in this case mice) with a disease, the mice mount an immune response (antibodies to fight the disease), and then the scientists harvest those antibodies and give them to infected humans. It’s an especially promising area in cancer treatment.

In this case, the proprietary blend of three monoclonal antibodies known as zMapp had never been tested in humans. It had previously been tested in eight monkeys with Ebola who survived—though all received treatment within 48 hours of being infected. A monkey treated outside of that exposure window did not survive. That means very little is known about the safety and effectiveness of this treatment—so little that outside of extreme circumstances like this, it would not be legal to use. Gupta speculates that the FDA may have allowed it under the compassionate use exemption.

A small 2012 study of monoclonal antibody therapy against Ebola found that it was only effective when administered before or just after exposure to the virus. A 2013 study found that rhesus macaques given an antibody mix called MB-003 within the 48-hour window had a 43 percent chance of surviving—as opposed to their untreated counterparts, whose survival rate was zero.

This Ebola outbreak is the largest in the history of the disease, in terms of both cases and deaths, 729 887 known so far. As Chan warned in her call for urgent international action, the outbreak is geographically the largest, already in four countries with fluid population movement across porous borders and a demonstrated ability to spread by air travel. The outbreak will be stopped by strategic quarantines and preventive education, primarily proper handling of corpses. More than 60 aid workers have become infected, but many more will be needed to stem the tide.

Dr. Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Disease (NIAID), is encouraged by the antibody treatment.

“Obviously there are plans and enthusiasm to expand this,” Fauci told me. “The limiting factor is the extraordinary paucity of treatment regimens.” Right now the total amount available, to Fauci’s knowledge, is three treatment courses (in addition to what was given to Brantly and Writebol).

NIAID did some of the original research that led to the development, but this is owned by Mapp Biopharmaceuticals. “They are certainly trying to scale up,” Fauci said, “but I’ve heard that their capability is such that it’s going to be months before they have a substantial number of doses, and even then they’re going to be limited.”

“We’re hearing that the administration of this cocktail of antibodies improved both Dr. Brantly and Ms. Writebol, but you know, we don’t know that,” Fauci said, noting the sample size (two) of this small, ad hoc study. Proving effectiveness would require a much larger group of patients being compared to an untreated group. “And we don’t know that they weren’t getting better anyway.”

Thanks to Kebmodee for bringing this to the attention of the It’s Interesting community.



by Jon Hamilton

Veterans who smoke marijuana to cope with post-traumatic stress disorder may be onto something. There’s growing evidence that pot can affect brain circuits involved in PTSD.

Experiments in animals show that tetrahydrocannabinol, the chemical that gives marijuana its feel-good qualities, acts on a system in the brain that is “critical for fear and anxiety modulation,” says Andrew Holmes, a researcher at the National Institute on Alcohol Abuse and Alcoholism. But he and other brain scientists caution that marijuana has serious drawbacks as a potential treatment for PTSD.

The use of marijuana for PTSD has gained national attention in the past few years as thousands of traumatized veterans who fought in Iraq and Afghanistan have asked the federal government to give them access to the drug. Also, Maine and a handful of other states have passed laws giving people with PTSD access to medical marijuana.

But there’s never been a rigorous scientific study to find out whether marijuana actually helps people with PTSD. So lawmakers and veterans groups have relied on anecdotes from people with the disorder and new research on how both pot and PTSD works in the brain.

An Overactive Fear System

When a typical person encounters something scary, the brain’s fear system goes into overdrive, says Dr. Kerry Ressler of Emory University. The heart pounds, muscles tighten. Then, once the danger is past, everything goes back to normal, he says.

But Ressler says that’s not what happens in the brain of someone with PTSD. “One way of thinking about PTSD is an overactivation of the fear system that can’t be inhibited, can’t be normally modulated,” he says.

For decades, researchers have suspected that marijuana might help people with PTSD by quieting an overactive fear system. But they didn’t understand how this might work until 2002, when scientists in Germany published a mouse study showing that the brain uses chemicals called cannabinoids to modulate the fear system, Ressler says.

There are two common sources of cannabinoids. One is the brain itself, which uses the chemicals to regulate a variety of brain cells. The other common source is Cannabis sativa, the marijuana plant.

So in recent years, researchers have done lots of experiments that involved treating traumatized mice with the active ingredient in pot, tetrahydrocannabinol (THC), Ressler says. And in general, he says, the mice who get THC look “less anxious, more calm, you know, many of the things that you might imagine.”

Problems with Pot

Unfortunately, THC’s effect on fear doesn’t seem to last, Ressler says, because prolonged exposure seems to make brain cells less sensitive to the chemical.

Another downside to using marijuana for PTSD is side effects, says Andrew Holmes at the National Institute on Alcohol Abuse and Alcoholism. “You may indeed get a reduction in anxiety,” Holmes says. “But you’re also going to get all of these unwanted effects,” including short-term memory loss, increased appetite and impaired motor skills.

So for several years now, Holmes and other scientists have been testing drugs that appear to work like marijuana, but with fewer drawbacks. Some of the most promising drugs amplify the effect of the brain’s own cannabinoids, which are called endocannabinoids, he says. “What’s encouraging about the effects of these endocannabinoid-acting drugs is that they may allow for long-term reductions in anxiety, in other words weeks if not months.”

The drugs work well in mice, Holmes says. But tests in people are just beginning and will take years to complete. In the meantime, researchers are learning more about how marijuana and THC affect the fear system in people.

At least one team has had success giving a single dose of THC to people during something called extinction therapy. The therapy is designed to teach the brain to stop reacting to something that previously triggered a fearful response.

The team’s study found that people who got THC during the therapy had “long-lasting reductions in anxiety, very similar to what we were seeing in our animal models,” Holmes says. So THC may be most useful when used for a short time in combination with other therapy, he says.

As studies continue to suggest that marijuana can help people with PTSD, it may be unrealistic to expect people with the disorder to wait for something better than marijuana and THC, Ressler says. “I’m a pragmatist,” he says. “I think if there are medications including drugs like marijuana that can be used in the right way, there’s an opportunity there, potentially.”


A link between the size of a father’s testicles and how active he is in bringing up his children has been suggested by scientists.

Researchers at Emory University, US, said those with smaller testicles were more likely to be involved with nappy changing, feeding and bath time.

They also found differences in brain scans of fathers looking at images of their child, linked to testicle size.

But other factors, such as cultural expectations, also played a role.

Levels of promiscuity and testicle size are strongly linked in animals, those with the largest pair tending to mate with more partners.

The researchers were investigating an evolutionary theory about trade-offs between investing time and effort in mating or putting that energy into raising children. The idea being that larger testicles would suggest greater commitment to creating more children over raising them.

The study, in Proceedings of the National Academy of Science, looked at the relationship between testicle size and fatherhood in 70 men who had children between the ages of one and two.

The team at Emory University in Atlanta performed brain scans while the men were shown pictures of their children.

It showed those with smaller testicles tended to have a greater response in the reward area of the brain than those with a larger size.

MRI scans showed a three-fold difference between the volumes of the smallest and largest testicles in the group.

Those at the smaller end of the spectrum were also more likely, according to interviews with the man and the mother, to be more active in parenting duties.

One of the researchers, Dr James Rilling, told the BBC: “It tells us some men are more naturally inclined to care-giving than others, but I don’t think that excuses other men. It just might require more effort for some than others.”

The exact nature of any link is not clear.

The researchers believe the size of the testicles, probably through the hormone testosterone, is affecting behaviour. But it is not clear if the process of having a baby may have some effect on the father.

“We know, for instance, that testosterone levels go down when men become involved fathers,” said Dr Rilling.

Further studies, involving analysing the size before and after becoming a father, are still needed.

Cultural and societal expectations on the role of the father are also not accounted for in the study.

All of the men were from the Atlanta area so the relative impact of society and biology has not been measured.

Thanks to Dr. D and Kebmodee for bringing this to the attention of the It’s Interesting community.

The fruit fly study adds to the evidence “that using toxins in the environment to medicate offspring may be common across the animal kingdom,” says biologist Todd Schlenke.

When fruit flies sense parasitic wasps in their environment, they lay their eggs in an alcohol-soaked environment, essentially forcing their larvae to consume booze as a drug to combat the deadly wasps.

The discovery by biologists at Emory University was published in the journal Science on February 22.

“The adult flies actually anticipate an infection risk to their children, and then they medicate them by depositing them in alcohol,” says Todd Schlenke, the evolutionary geneticist whose lab did the research. “We found that this medicating behavior was shared by diverse fly species, adding to the evidence that using toxins in the environment to medicate offspring may be common across the animal kingdom.”

Adult fruit flies detect the wasps by sight, and appear to have much better vision than previously realized, he adds. “Our data indicate that the flies can visually distinguish the relatively small morphological differences between male and female wasps, and between different species of wasps.”

The experiments were led by Balint Zacsoh, who recently graduated from Emory with a degree in biology and still works in the Schlenke lab. The team also included Emory graduate student Zachary Lynch and postdoc Nathan Mortimer.

The larvae of the common fruit fly, Drosophila melanogaster, eat the rot, or fungi and bacteria, that grows on overripe, fermenting fruit. They have evolved a certain amount of resistance to the toxic effects of the alcohol levels in their natural habitat, which can range up to 15 percent.

Tiny, endoparasitoid wasps are major killers of fruit flies. The wasps inject their eggs inside the fruit fly larvae, along with venom that aims to suppress their hosts’ cellular immune response. If the flies fail to kill the wasp egg, a wasp larva hatches inside the fruit fly larva and begins to eat its host from the inside out.

Last year, the Schlenke lab published a study showing how fruit fly larvae infected with wasps prefer to eat food high in alcohol. This behavior greatly improves the survival rate of the fruit flies because they have evolved high tolerance of the toxic effects of the alcohol, but the wasps have not.

“The fruit fly larvae raise their blood alcohol levels, so that the wasps living in their blood will suffer,” Schlenke says. “When you think of an immune system, you usually think of blood cells and immune proteins, but behavior can also be a big part of an organism’s immune defense.”

For the latest study, the researchers asked whether the fruit fly parents could sense when their children were at risk for infection, and whether they then sought out alcohol to prophylactically medicate them.

Adult female fruit flies were released in one mesh cage with parasitic wasps and another mesh cage with no wasps. Both cages had two petri dishes containing yeast, the nourishment for lab-raised fruit flies and their larvae. The yeast in one of the petri dishes was mixed with 6 percent alcohol, while the yeast in the other dish was alcohol free. After 24 hours, the petri dishes were removed and the researchers counted the eggs that the fruit flies had laid.

The results were dramatic. In the mesh cage with parasitic wasps, 90 percent of the eggs laid were in the dish containing alcohol. In the cage with no wasps, only 40 percent of the eggs were in the alcohol dish.

“The fruit flies clearly change their reproductive behavior when the wasps are present,” Schlenke says. “The alcohol is slightly toxic to the fruit flies as well, but the wasps are a bigger danger than the alcohol.”

The fly strains used in the experiments have been bred in the lab for decades. “The flies that we work with have not seen wasps in their lives before, and neither have their ancestors going back hundreds of generations,” Schlenke says. “And yet, the flies still recognize these wasps as a danger when they are put in a cage with them.”

Further experiments showed that the flies are extremely discerning about differences in the wasps. They preferred to lay their eggs in alcohol when female wasps were present, but not if only male wasps were in the cage.

Theorizing that the flies were reacting to pheromones, the researchers conducted experiments using two groups of mutated fruit flies. One group lacked the ability to smell, and another group lacked sight. The flies unable to smell, however, still preferred to lay their eggs in alcohol when female wasps were present. The blind flies did not make the distinction, choosing the non-alcohol food for their offspring, even in the presence of female wasps.

“This result was a surprise to me,” Schlenke says. “I thought the flies were probably using olfaction to sense the female wasps. The small, compound eyes of flies are believed to be more geared to detecting motion than high-resolution images.”

The only obvious visual differences between the female and male wasps, he adds, is that the males have longer antennae, slightly smaller bodies, and lack an ovipositor.

Further experimentation showed that the fruit flies can distinguish different species of wasps, and will only choose the alcohol food in response to wasp species that infect larvae, not fly pupae. “Fly larvae usually leave the food before they pupate,” Schlenke explains, “so there is likely little benefit to laying eggs at alcoholic sites when pupal parasites are present.”

The researchers also connected the exposure to female parasitic wasps to changes in a fruit fly neuropeptide.

Stress, and the resulting reduced level of neuropeptide F, or NPF, has previously been associated with alcohol-seeking behavior in fruit flies. Similarly, levels of a homologous neuropeptide in humans, NPY, is associated with alcoholism.

We found that when a fruit fly is exposed to female parasitic wasps, this exposure reduces the level of NPF in the fly brain, causing the fly to seek out alcoholic sites for oviposition,” Schlenke says. “Furthermore, the alcohol-seeking behavior appears to remain for the duration of the fly’s life, even when the parasitic wasps are no longer present, an example of long-term memory.”

Finally, Drosophila melanogaster is not unique in using this offspring medication behavior. “We tested a number of fly species,” Schlenke says, “and found that each fly species that uses rotting fruit for food mounts this immune behavior against parasitic wasps. Medication may be far more common in nature than we previously thought.”


Hitting the wall in the middle of a busy work day is nothing unusual, and a caffeine jolt is all it takes to snap most of us back into action. But people with certain sleep disorders battle a powerful urge to doze throughout the day, even after sleeping 10 hours or more at night. For them, caffeine doesn’t touch the problem, and more potent prescription stimulants aren’t much better. Now, a study with a small group of patients suggests that their condition may have a surprising source: a naturally occurring compound that works on the brain much like the key ingredients in chill pills such as Valium and Xanax.

The condition is known as primary hypersomnia, and it differs from the better known sleep disorder narcolepsy in that patients tend to have more persistent daytime sleepiness instead of sudden “sleep attacks.” The unknown cause and lack of treatment for primary hypersomnia has long frustrated David Rye, a neurologist at Emory University in Atlanta. “A third of our patients are on disability,” he says, “and these are 20- and 30-year-old people.”

Rye and colleagues began the new study with a hunch about what was going on. Several drugs used to treat insomnia promote sleep by targeting receptors for GABA, a neurotransmitter that dampens neural activity. Rye hypothesized that his hypersomnia patients might have some unknown compound in their brains that does something similar, enhancing the activity of so-called GABAA receptors. To try to find this mystery compound, he and his colleagues performed spinal taps on 32 hypersomnia patients and collected cerebrospinal fluid (CSF), the liquid that bathes and insulates the brain and spinal cord. Then they added the patients’ CSF to cells genetically engineered to produce GABAA receptors, and looked for tiny electric currents that would indicate that the receptors had been activated.

In that first pass, nothing happened. However, when the researchers added the CSF and a bit of GABA to the cells, they saw an electrical response that was nearly twice as big as that caused by GABA alone. All of this suggests that the patients’ CSF doesn’t activate GABAA receptors directly, but it does make the receptors almost twice as sensitive to GABA, the researchers report today in Science Translational Medicine. This effect is similar to that of drugs called benzodiazepines, the active ingredients in antianxiety drugs such as Valium. It did not occur when the researchers treated the cells with CSF from people with normal sleep patterns.

Follow-up experiments suggested that the soporific compound in the patients’ CSF is a peptide or small protein, presumably made by the brain, but otherwise its identity remains a mystery.

The idea that endogenous benzodiazepinelike compounds could cause hypersomnia was proposed in the early 1990s by Elio Lugaresi, a pioneering Italian sleep clinician, says Clifford Saper, a neuroscientist at Harvard Medical School in Boston. But several of Lugaresi’s patients later turned out to be taking benzodiazepines, which undermined his argument, and the idea fell out of favor. Saper says the new work makes a “pretty strong case.”

Based on these results, Rye and his colleagues designed a pilot study with seven patients using a drug called flumazenil, which counteracts benzodiazepines and is often used to treat people who overdose on those drugs. After an injection of flumazenil, the patients improved to near-normal levels on several measures of alertness and vigilance, the researchers report. Rye says these effects lasted up to a couple hours.

In hopes of longer-lasting benefits, the researchers persuaded the pharmaceutical company Hoffmann-La Roche, which makes the drug, to donate a powdered form that can be incorporated into dissolvable tablets taken under the tongue and a cream applied to the skin. One 30-something patient has been taking these formulations for 4 years and has improved dramatically, the researchers report in the paper. She has resumed her career as an attorney, from which her hypersomnia had forced her to take a leave of absence.

The findings are “certainly provocative,” Saper says, although they’ll have to be replicated in a larger, double-blind trial to be truly convincing.

Even so, says Phyllis Zee, a neurologist at Northwestern University in Evanston, Illinois: “This gives us a new window into thinking about treatments” for primary hypersomnia. “These patients don’t respond well to stimulants,” Zee says, so a better strategy may be to inhibit the sleep-promoting effects of GABA—or as Rye puts it, releasing the parking brake instead of pressing the accelerator.

The next steps are clear, Rye says: Identify the mystery compound, figure out a faster way to detect it, and conduct a larger clinical trial to test the benefits of flumazenil. However, the researchers first need someone to fund such a study. So far, Rye says, they’ve gotten no takers.



A SARS-like virus discovered this summer in the Middle East may infect more than just humans. The pathogen, a close cousin to the one that caused the 2002 to 2003 SARS outbreak, may also be able to infect cells from pigs and a wide range of bat species, researchers report today. The findings may help public health officials track the source of the outbreak and identify the role of wild animals and livestock in spreading the virus, researchers say.

Scientists first detected the virus in a 60-year-old man from Jeddah, Saudi Arabia, who developed severe pneumonia this past spring. Unable to identify the microbe causing the illness, doctors sent samples to Erasmus MC in Rotterdam, the Netherlands. There, scientists identified the infectious agent as a coronavirus, a group known to cause many ailments, such as the common cold and a variety of gastrointestinal infections. Cases have popped up in Qatar and Jordan as well; in total, researchers have so far confirmed nine infections, including five deaths. Several other cases are suspected but haven’t been confirmed.

Researchers have fully sequenced the virus, which they dubbed hCoV-EMC (short for human coronavirus-Erasmus Medical Center). The genome revealed that it is closely related to the SARS coronavirus.

The new study, published online in mBio, is an attempt to answer other basic questions, such as where the virus originated, how it enters cells, and what other animals it might infect, says Christian Drosten, a virologist at the University of Bonn Medical Center in Germany and one of the lead authors.

Scientists knew that the SARS virus uses a receptor called ACE2 to pry open cells. Because these receptors are mainly found deep inside the human lung, patients developed very severe illness that frequently left them too sick to spread SARS to many others; the people most at risk were health care workers who take care of patients. If hCoV-EMC used the same receptor, researchers would have a head start in understanding how it spreads and how to stop it—primarily by protecting health care workers. It might also help them in the development of drugs and vaccines.

To find out, the team engineered baby hamster kidney cells to express the human ACE2 receptor. These cells could be infected with the SARS coronavirus, as expected, but not hCoV-EMC. That finding, supported by additional experiments, led them to conclude that the new coronavirus does not use ACE2 to get in. Which receptor it uses instead is still unclear, which is a “downside” of the new study, says Larry Anderson, an infectious disease specialist at Emory University in Atlanta.

Epidemiologists also want to know which species of animals it is capable of infecting to keep the new coronavirus from spreading further. To determine what types of animals hCoV-EMC can infect, Drosten and colleagues infected cells from humans, pigs, and a wide variety of bats, the key natural reservoirs of coronaviruses. The new virus could infect all of these types of cells. “It’s unusual for a coronavirus to easily go back to bats,” Drosten says. “Most coronaviruses come from bats, but once they jump to other species, you could never get them to reinfect bat cells.” The SARS virus, for instance, originated in Chinese horseshoe bats, but once it ended up in humans, it had changed so much that scientists were unable to infect bat cells with it.

“The fact that [hCoV-EMC] can infect bat cells is consistent with the hypothesis that bats might be the origin of this virus, but this finding doesn’t prove it,” Anderson says. “This virus had to come from an animal source—there’s no other explanation for what’s going on. But we still don’t know what that source is.”

Based on the findings, however, it seems likely that the new coronavirus can infect a wide range of species, Drosten says. That means public health officials may have to start looking for infections and deaths in local wild animal and livestock populations to keep the virus in check, he says.


SHANGHAI, CHINA—Mrs. Y’s death would have stumped many experts. A young mother and loyal wife, the rural Chinese woman showed none of the standard risk factors for suicide. She was not apparently depressed or mentally ill. Villagers said she exuded happiness and voiced few complaints. But when a neighbor publicly accused Mrs. Y of stealing eggs from her henhouse, the shame was unbearable. Mrs. Y rushed home and downed a bottle of pesticide. “A person cannot live without face,” she cried before she died. “I will die to prove that I did not steal her eggs.”

Decades of research in Western countries have positioned mental illness as an overwhelming predictor of suicide, figuring in more than 90% of such deaths. Another big risk factor is gender: Men commit suicide at much higher rates than women, by a ratio of nearly 4 to 1 in the United States, according to the U.S. Centers for Disease Control and Prevention. Other common correlates include city life and divorce. But in China, says Jie Zhang, a sociologist at the State University of New York, Buffalo State, the case of Mrs. Y is “a very typical scenario.”

Zhang oversaw interviews with Mrs. Y’s family and acquaintances while researching the prevalence of mental illness among suicide victims aged 15 to 34 in rural China. Through psychological autopsies—detailed assessments after death—Zhang and coauthors found that only 48% of 392 victims had a mental illness, they reported in the July 2010 issue of the American Journal of Psychiatry. An earlier study of Chinese suicide victims put the prevalence of mental disorders at 63%—still nowhere near as high as accepted models of suicide prevention would predict. Meanwhile, other standard risk factors simply don’t hold true, or are even reversed, in China. Chinese women commit suicide at unusually high rates; rural residents kill themselves more frequently than city dwellers do; and marriage may make a person more, rather than less, volatile.

Such differences matter because China accounts for an estimated 22% of global suicides, or roughly 200,000 deaths every year. In India, meanwhile, some 187,000 people took their own lives in 2010—twice as many as died from HIV/AIDS. By comparison, the World Health Organization (WHO) estimates that suicides in high-income countries total only 140,000 a year. Suicide rates in Japan and South Korea, however, are similar to China’s (see p. 1026), suggesting that this is a regional public health issue. And yet suicide in Asia is poorly understood. “Suicide has not gotten the attention it deserves vis-à-vis its disease burden,” says Prabhat Jha, director of the Centre for Global Health Research in Toronto, Canada.

Emerging research from developing countries like China and India is now filling that gap—and overturning prevailing notions. “The focus of the study of suicide in the West is psychiatry,” Zhang says. While mental illness remains an important correlate in Asia, he says, researchers may learn more from a victim’s family, religion, education, and personality. New findings, Zhang says, suggest that some researchers may have misread correlation as causation: In both the East and the West, “mental illness might not be the real cause of suicide.”

Distressing data

Reliable data on suicide across Asia were once maddeningly scarce. In Thailand until 2003, there was no requirement that the reported cause of death be medically validated—a flaw that rendered the country’s suicide data inaccurate. In India, suicide is a crime, which means it often goes unreported. But the Thai government now has a more accurate reporting system for mortality figures, while Indian researchers are benefiting from the Million Death Study, an effort to catalog causes of death for 1 million Indians in a 16-year survey relying on interviews with family members (Science, 15 June, p. 1372). The study has already produced a disturbing revelation about reported suicide rates. “When we compare our data with police reports, you find undercounts of at least 25% in men and 36% in women,” says Jha, the study’s lead investigator.

New insights from China are particularly instructive. Because suicide carries a stigma, the Chinese government withheld data on the topic until the late 1980s. When information finally came out, it quickly became clear that the country had a serious problem. In 1990, for example, the World Bank’s Global Burden of Disease Study estimated there were 343,000 suicides in China—or 30 per 100,000 people. The U.S. rate for the same year was 12 per 100,000.

But other reports gave different figures, prompting a debate on sources. WHO’s extrapolated total was based on data that China had reported from stations covering only 10% of the population, skewed toward urban residents. As researchers focused on the problem, they arrived at more reliable figures—but also unearthed more mysteries. In an analysis in The Lancet in 2002, a group led by Michael Phillips of Shanghai Mental Health Center and Emory University School of Medicine in Atlanta estimated that from 1995 to 1999, Chinese women killed themselves more frequently than men—by a ratio of 5 to 4. “There was originally disbelief about the very different gender ratio in China,” Phillips says, although later it was accepted.

Today, the suicide sex ratio in China is roughly 1 to 1, still a significant departure from the overall U.S. male-to-female ratio of 4 to 1. In India, the male-to-female suicide ratio is 1.5 to 1, although in the 15 to 29 age group it is close to equal. And yet, WHO estimates the global sex ratio at three men to one woman. (With colleague Cheng Hui, Phillips recently used Chinese and Indian figures to lower that estimate to 1.67 to 1.) Among young adults in India, suicide is second only to maternal mortality as a cause of death for women, according to the Million Death Survey.

In both China and India, cases like Mrs. Y’s involving no apparent mental illness are common. In India, suicide is most prevalent among teenagers and young adults—the cohort that is entering the workforce, marrying, and facing new life stresses. This contrasts with the Western pattern of high suicide rates among the middle-aged, suggesting that although “there might well be some underlying psychiatric conditions, the main drivers of [suicide in India] are probably chiefly social conditions,” Jha says. While cautioning that detailed psychological autopsies are still needed in India, he says, “it’s a reasonable assumption that many of these young folks are not mentally ill.”

Convincing researchers outside Asia may prove an uphill battle. Matthew Miller, a suicide researcher at the Harvard Injury Control Research Center in Boston, says that mental illness may be underdiagnosed in Asia for reasons that aren’t fully understood. That could throw off correlation studies. Phillips, who has worked in China for over 20 years, agrees that underdiagnosis is a problem, and that “many Western researchers still believe that we are just missing cases.” But he rejects that explanation. Even accounting for underdiagnosis, he says, the finding of a lower rate of mental illness among suicide victims has held up in multiple studies. Many Chinese suicide victims, he adds, are “most certainly severely distressed, but they don’t meet the criteria of a formal mental illness.”

Lethal weapons

Assuming that suicide risk is shaped by different factors in Asia, researchers are striving to uncover the roots. One clue may lie in the high proportion of unplanned Chinese suicides. In a 2002 survey of 306 Chinese patients who had been hospitalized for at least 6 hours following a suicide attempt, Phillips and colleagues found that 35% had contemplated suicide for less than 10 minutes—and 54% for less than 2 hours. Impulsiveness among suicide victims in Asia “tends to be higher than in the West,” says Paul Yip, director of the Hong Kong Jockey Club Centre for Suicide Research and Prevention at the University of Hong Kong and one of the authors of a recent WHO report on suicide in Asia. Although impulsive personality traits are sometimes linked to illnesses like bipolar disorder, studies in China have not uncovered full-fledged personality disorders in impulsive suicide victims.

In a tragic twist, impulsive victims in Asia tend to favor highly fatal methods. After interviewing family members and friends of 505 Chinese suicide victims, Kenneth Conner, a psychiatric researcher at the University of Rochester Medical Center in New York, and colleagues reported in 2005 that those who had ingested pesticides were more likely to have acted rashly than were those who used other methods such as hanging or drowning. Pesticides are a leading cause of suicide death in China and India, and the cause of roughly half of suicides worldwide. Pesticides may also explain Asia’s unusual suicide sex ratio, Jha says. In the West, women attempt suicide just as frequently as men do, but they tend to down sleeping pills—and often survive.

The trends in Asia point to a need for innovative prevention strategies. Zhang believes efforts should focus less on mental illness and more on “educating people to have realistic goals in life and teaching them to cope with crisis.” Front and center should be universities and rural women’s organizations, both of which already have active suicide prevention programs in China, he says. Such community-based approaches appear to have been effective in Hong Kong, Yip says. Over the past decade, the territory has rolled out programs for schoolchildren on dealing with stress and outreach groups for older adults. Its suicide rate has fallen 27% since 2003.

But resources in many Asian countries are limited. The vast majority of cities in China and India still do not have 24-hour suicide prevention hotlines. That may make what scholars call means restriction—reducing access to tools commonly used in suicide—a better goal. In Sri Lanka, pesticides once accounted for two-thirds of suicide deaths. Then in 1995, the government took steps to ban the most toxic pesticides. The suicide rate plummeted by 50% in the following decade.

The varying degrees to which mental illness and suicide correlate in East and West may ultimately be beside the point, argues Zhang, who believes a third factor may be the trigger in both regions. Strain theory, which posits that societal pressures, rather than inborn traits, contribute to crime, can help explain suicide, he believes. “Psychological strains usually precede a suicidal behavior, and they also happen before an individual becomes mentally ill.”

When a person is pulled by two or more conflicting pressures, Zhang says, as with “a girl who receives Confucian values at home and then goes to school and learns about modern values and gender equality,” she may be more prone to suicide. Other situational stresses may include a sudden crisis faced by a rural woman lacking coping mechanisms—such as the case of Mrs. Y—or an incident that forces a young man to confront a gap between his aspirations and reality. Zhang found that strain theory held up for his study subjects in rural China. He plans to probe whether it also applies to older Chinese.

Ultimately, Zhang hopes to test strain theory on Americans. The U.S. National Institutes of Health “spends millions and millions of dollars every year on treating mental illness to prevent suicide,” he says. “But no matter how much money we spend, how many psychiatrists we train, or how much work we do in psychiatric clinics, the U.S. suicide rate doesn’t decrease.” It has hovered around 10 to 12 suicides per 100,000 people since 1960.

Such research may be the tip of the iceberg when it comes to debunking long-held ideas about behavior disorders. Alcoholism is another area ripe for exploration, Cheng says: The profile of alcoholics in China contrasts sharply with that in the West. Because of social pressure to drink, Chinese alcoholics are far more likely to be working and married than American counterparts, who are often unemployed and divorced, she says. Suicide, Cheng muses, “is just another example of how environment can change behavior.”