Last November, a barrier was broken in the prolific Bollywood film industry of India. A film called Dunno Y featured the first on-screen male-male kiss - a provocative scene in a country that only the year before repealed a law making homosexuality illegal. Many tagged the film as India’s version of Brokeback Mountain, a controversial and progressive step in depicting male-male romance in popular culture that reflected a growing social acceptance of homosexuality. But the full significance of those cultural changes in the South Asian country have yet to be studied, and will require perspectives from law, anthropology, medicine, and more.

Just such a discussion will take place this Saturday morning at the University of Chicago and on the internet in the roundtable event, “Sexual Identity, Health and Stigma in India: Traditional Statuses and Western Influences.” Organized by John Schneider, assistant professor of medicine and epidemiology at the University of Chicago Medical Center and director of Global Health Programs, the discussion will be available worldwide on a webcast broadcast by the UChicago Facebook page, the Global Health Initiative website, and here on ScienceLife (watch this space).

“What I tried to do is bring together scholars from a number of different disciplines to make this a truly interdisciplinary discussion,” Schneider said. “I want it to be like a Sunday morning news program - but smarter - where a topic area is chosen and everybody fires away with their background about it, leaving room for remote viewer input.”

The central topic of whether sexual identity in India is truly shifting can be addressed from any number of angles. There’s the legal status of homosexuality after the 2009 repeal of Section 377 of the Indian Penal Code by the High Court of Mumbai. Or the sexual and mental health consequences after centuries of stigmatization of men having sex with men, including the spread of HIV and other sexually transmitted diseases. Or the pop culture ripples, such as Dunno Y, that may reflect changing attitudes and sexual roles in Indian culture. All of which are set against the backdrop of a country rapidly modernizing and playing an increasingly powerful role in global economy and society.

“I think that India is going through tremendous social and cultural changes as it emerges from what would be, in old terms, a less-developed economy to now becoming something of an economic powerhouse,” said Niranjan Karnik, assistant professor of psychiatry and behavioral neuroscience and another participant in the event. “This has the potential to really change the dynamics of the society and change the way people see themselves and behaviors.”

The participants in the roundtable are all accomplished researchers and experts on India. The keynote speaker, Lawrence Cohen of the University of California, Berkeley, studies medical anthropology in the country, and has written on homosexuality, aging, and organ transplant markets. Philip Kumar and Sanjay Srivastava are researchers based in India studying sexuality and advising the government on health issues related to men who have sex with men. Schneider himself has an extensive project underway in Indian truck drivers, where he is using cell phones in building a network of men who have sex with men to study their behavior and identify potential peer outreach points.

“One of the issues we are looking at is what changes in sex position roles might be occurring over time in India,” Schneider said. “Is a Western identity rubbing off on India, or is it developing a new identity? My work will help address those questions because of the cell phone network data that triangulates often sensitive self-reported data,” Schneider said.

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The odds of acquiring a disease are often portrayed as a tug of war between two foes: genes and environment. The battle is not always evenly matched. A disease such as cystic fibrosis is entirely genetic - if a child inherits the mutated CFTR gene from both parents, no environment will prevent the condition. On the other hand, environment can trump genetics for many other diseases, such as the relationship between exposure to the toxic substance arsenic and the cancer mesothelioma. But in most places, the tug of war is a more balanced contest, with the genetic factors controlling risk competing with a range of environmental factors from diet and exercise to education and climate.

Scientists have traditionally kept score on these competitions using a measure called heritability, the percentage of a phenotype (a disease or characteristic) that is determined by genetic factors. One way to measure heritability is with twin studies, which assemble data from thousands of pairs of identical or fraternal twins as a natural experiment of whether genes or environment win out. But a new study from University of Chicago psychiatry researchers shows that the blanket term of “environment” does not have to mean things outside the body - it can also refer to the biological state inside the body.

For the paper, published last month in Behavioral Genetics, a team led by post-doc Terrie Vasilopoulos set out to test the relationship between two health conditions: hypertension and cognitive decline. Previous research examining this link established hypertension as a risk factor for the loss of cognitive ability late in life, producing decreases in performance similar to those seen in Alzheimer’s disease and other forms of dementia. Meanwhile, heritability research revealed that genetics play a large part in a person’s risk of cognitive decline in their golden years. So does the “internal environment” of hypertension - and whether it is treated - move the tug-of-war of heritability for cognitive issues toward genes or environment?

To test this hypothesis, the team used data from the Vietnam Era Twin Study of Aging - over 1,200 male-male twin pairs who served in the military between 1965 and 1975. With an age range between 51 and 60, the researchers looked at an important time in a man’s cognitive lifetime before the first signs of dementia typically set in, Vasilopoulos said.

“We really think we are capturing a very important developmental period with the guys that we’re studying, especially for cognitive phenotypes,” said Vasilopoulos, a researcher in the laboratory of Kristen Jacobson, assistant professor of psychiatry. “The groundwork for these bad things that are happening to you later in life are being laid when you’re much younger. By finding these mechanisms early in life, we can start to figure out better game plans of trying to protect people and help people make smarter choices when younger so we don’t see these bad effects when they’re older.”

The men were divided into three groups: those with hypertension receiving treatment, those with untreated hypertension, and those without hypertension. On overall measures of cognitive ability, the three groups showed no differences in performance, suggesting that the researchers were indeed looking at an age before any noticeable decline begins. But when the heritability of different cognitive measures was examined, a relationship with hypertension and anti-hypertension medication emerged.

For two measures - episodic memory and visual-spatial ability - the heritability of how a person performed on the tests actually decreased in those with untreated hypertension, relative to the other two groups. That is, in men with high blood pressure not taking medication, the “internal environment” of the disease outweighed the influence of genetics on two early warning signs of cognitive problems.

“These are the two types of cognitive domains that are first affected by age-related cognitive decline,” Vasilopoulos said. “In Alzheimer’s disease or other types of neurodegeneration or just regular aging, those are the most affected or first affected. So we really think we are honing in on the mechanisms of why hypertension is bad for cognitive performance late in life.”

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Over the year-long discussion of health disparities in the MacLean Center for Clinical Medical Ethics seminar series, the health gaps presented between American whites and blacks have been predominantly a one-way street. On nearly every health measure - from infant mortality to diabetes to cardiovascular disease - higher rates are observed for African-Americans. But there’s one health gap where the racial positions are surprisingly flipped, said James Jackson of the University of Michigan in his visit to the series in early May. Over the course of a provocative talk, Jackson demonstrated how this strange reverse disparity in mental health could be hiding a model explaining the physical health gaps that continue to resist reduction efforts.

In a 2007 study, a survey project led by Jackson measured the lifetime prevalence of major depressive disorder in African-Americans, Caribbean blacks, and white Americans. An almost complete reversal from the normal health disparity was observed, with roughly 18% of whites diagnosed with major depression at some point in their lives, compared to only 10.4% of African-Americans. The data, though replicated several times, was initially greeted with skepticism by observers who were mostly familiar with biased data based on hospital admissions, Jackson said.

“When people noticed this, they really began to contort  the data,” said Jackson, a psychologist and director of the Institute for Social Research at the U. of M. “The argument was that there must be something wrong with the way it was assessed, because everybody knows that African-Americans have to have higher rates of psychiatric disorders than whites.”

But now that the reverse disparity has been verified in many different populations, Jackson has started to ask why these differences exist. His working theory hinges on two other observations: the delayed appearance of physical health disparities over the course of life, and cultural differences in the way people cope with stress. When well-known health disparities on measures such as diabetes or hypertension are broken down by age, there is not a consistent gap between blacks and whites, but a gap that emerges and rapidly grows in middle age (45-64 years old). Putting aside differences in infant mortality rates, some evidence actually suggests that black children are healthier than white children on many measures, Jackson said.

The growing gap in health measures over the life course is paralleled by another growing gap - in the frequency of poor health behaviors. In white populations, smoking rates peak in young adulthood and then decline, while the rate in black populations accelerates with age. The same pattern holds true for heavy alcohol use and drug use, Jackson said, while frequency of vigorous physical activity declines with age faster for black females than white females. Obesity is more complex - it is the only black-white difference observed early in life, at least for females - but this gap also widens over life course, regardless of socioeconomic status.

The core of Jackson’s theory was to cast those physically unhealthy behaviors not as mere vices, but as methods people use to self-medicate themselves against the stress of daily living.

“If you’re having a bad day…you know it. At the end of the day, your stomach is upset, you have a headache. There are palpable things that are present with regard to the stress reaction to the circumstances,” Jackson said. “But if you are growing a tumor for cancer, you don’t know it, until it reaches a certain stage.”

“If you know you’re having these stress-related kinds of problems, this awareness motivates you to action - you are motivated to do something about the physiological and psychological consequences of stressors in your life. And what do you want to do? People eat comfort food to reduce stress, the activity in the chronic stress response network,” Jackson said. “If I’m stressed, a Twinkie makes me feel better.”

Self-regulating stress can also go beyond junk food, Jackson said, to severe drug and alcohol use. All of these coping strategies may help dampen the stress response and protect mental health, but only at the cost of exacerbating physical health problems.

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In the 11 years since the blueprint of human life was decoded by the Human Genome Project, much of the focus has been on when those instructions fail. Scientists have used our newfound genetic knowledge to look for the roots of common and rare diseases, the gene or genes that can increase the risk of everything from heart disease to cancer to asthma. But setting the stage for future illness is not the purpose of genes, of course. By coding for the proteins that make up the body and brain, genes lay the foundation for everything we do, feel, and probably even think.

Like the study of disease, genetic studies of human behavior have mostly focused on the abnormal - the targets of psychiatry. Mental illnesses such as schizophrenia, depression, and drug addiction have been the subjects of genetic hunts, known as genome wide association studies, where the ill are compared to controls to reveal genes that might be involved in the a particular disorder. As with diseases in the rest of the body, psychiatric disorders have mostly resisted easy genetic explanations - only a small percentage of schizophrenia, for instance, has been traced to genetic causes.

A more useful, but also vastly more complicated, approach might be to study not the binary comparison of healthy vs. sick, but the whole spectrum of human behavior. For example, rather than just looking at those with extreme enough depression symptoms for a clinical diagnosis and those who don’t, scientists could look at genes in subjects who are rarely, mildly, or frequently affected by depression, as well as those on the extremes. Such analyses may get closer to the genes and brain structures that control human behavior, both in everyday life and when it breaks down.

These types of experiments have caught the imagination of Abraham Palmer, assistant professor of human genetics at the Medical Center. In collaboration with the laboratory of Harriet de Wit, professor of psychiatry, Palmer has started to look at the behavioral trait of impulsivity, which has been associated with attention deficit disorder and predisposition to drug abuse.

“We’re coming at it from a tradition that’s very psychology, drug abuse-based, but we’re really interested in asking questions that get at the broadest range possible of behaviors,” Palmer said. “These are continuous traits that everybody in the population will have some value for. We’re not talking about it exclusively from a disease perspective. These are healthy people coming in.”

Palmer used Donald Rumsfeld’s infamous quote about known knowns, known unknowns, and unknown unknowns, to illustrate how studies of genes and behavior have classically been limited by the tunnel vision of previous knowledge. If a particular gene is already known to play a role in a behavior, scientists can study how individual variants in that gene correspond to behavior. In one such project, Palmer was part of a team that looked at the D2 dopamine receptor - a neurotransmitter receptor linked with the response to drugs of abuse - and impulsive decision-making.

Volunteers came to the laboratory and performed a “stop task,” a common psychology test. The subject is trained to look for a “go signal” and start hitting a certain keyboard key as quickly as possible until the “stop signal” sounds. The delay between the go and stop signals is steadily decreased with each round, and the ability of the subject to stop on time is measured. Researchers then compared their D2 genotype to their behavioral score, and found a link between different D2 variants and more “impulsive” results on the stop task.

These results help researchers study possible genetic predisposition for drug abuse or addition. But Palmer said he wants to expand the search beyond genes that are already implicated in behaviors and beyond psychiatric conditions.

“We’ve mostly looked at candidate genes, genes where we had reason to think it might modulate a behavior,” Palmer said. “But the more interesting question, if you had a sufficiently large sample and enough power, is to say let’s go at this with a blank state, let’s look at all the polymorphisms in a genome and pull out novel things maybe in genes we had never thought to be related to these processes.”

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Despite what beer commercials tell you, not everyone responds to alcohol in the same way. For some people, an alcoholic drink is a party-starter, increasing energy and sociability. For others, a drink can be a party-ender, producing feelings of fatigue and sluggishness. In pharmacological terms, alcohol is a mixed stimulant/depressant, able to produce a wide range of behavioral effects. But does an individual’s place on this spectrum of alcohol response predict more than their night on the town? Can it say something about their future potential to binge drink, or abuse alcohol in other ways?

Classically, psychiatrists have linked an individual’s alcohol response to their potential for abuse through one simple word: tolerance. According to the low-level response theory,  reduced “intoxicating” effects of alcohol were associated with heavier drinking, as individuals have fewer internal cues warning them to stop. But the experiments that informed the low-level response theory focused on the depressant effects of alcohol, measuring predominantly sedation in test subjects. What about the positive and rewarding effects that inspire some people to drink in the first place?

“What is intoxication? It’s really bi-modal,” said Andrea King, professor of psychiatry and behavioral neuroscience at the Medical Center. “Some people can think intoxication is great - you’re drunk, it’s fun - while others think of it as something bad, that it’s a toxic reaction.”

King studied both of those alcohol responses in a 2002 study, giving heavy and light drinkers a disguised drink in a laboratory and asking the how it made them feel on a variety of measures. The study found that heavy drinkers were indeed more likely to report positive and rewarding effects of alcohol, even when they didn’t know it was alcohol they were drinking. From that small study, King and her team sought to both expand their subject pool and follow participants for years to see how their acute responses in the lab tests might predict their future drinking behavior.

The first data from that epic undertaking - a two-year followup of nearly 200 subjects aged 21 to 35 - was published yesterday in Archives of General Psychiatry. True to King’s hypothesis, an individual’s response to a mystery drink was predictive of how their drinking behavior evolved over the following two years, with both stimulant and sedative effects playing a role. While some subjects who were heavy drinkers at the time of the original experiments curtailed their binge drinking episodes, others demonstrated an “exacerbating” trajectory, binge drinking more frequently - up to half of the days in a month.

The path a subject followed could be foretold by their acute response to alcohol in the lab. Subjects with both higher sensitivity to the rewarding effects of alcohol and lower sensitivity to its depressant effects were found to have the most alcohol problems in the follow-up period. Those subjects drank more and more often, increased the frequency of binge drinking, suffered more alcohol-related consequences, and were more likely to qualify for a diagnosis of an alcohol-use disorder.

“The results change our thinking about how alcohol responses affect the development of an alcohol-use disorder,” King said. “It’s not just overall tolerance, but also sensitivity to alcohol’s euphoric effects that increases risk for excessive drinking.”

This new theory, dubbed a “modified differentiator theory” in King’s paper, could be a game-changer for how substance abuse experts identify people at-risk for alcohol problems.  Those who respond very positively to an alcoholic drink might be warned early on that they are at elevated risk for drinking problems.

“If we know more about who’s going to become a problem drinker, we may be able to prevent future escalations and intervene earlier, before development of severe alcoholism,” King said. “The stimulant-type responder could learn that while such a response pattern may not be their fault, it could put them at risk for longer-term problems and consequences.”

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For some diseases, taking a census is easy. Most people who have cancer are diagnosed with the disease before they die and seek treatment, allowing for the collection of detailed national cancer statistics. But other diseases tend to hide in the shadows, undetected and under-counted due to infrequent diagnosis or an unwillingness of patients to seek treatment. Into this latter group falls the eating disorders: anorexia nervosa, bulimia nervosa, and other conditions. Because many of these patients try to avoid treatment, psychiatrists have long suspected the numbers are skewed because only a subset of people suffering from eating disorders find their way to their clinical practice.

“We only see the tip of the iceberg,” said Daniel Le Grange, professor of psychiatry and director of the University of Chicago Eating Disorders Program. “As clinicians and researchers, we’ve known that in the community there are thousands of people out there with eating disorder behaviors that we never see in our clinics.”

Hard data on the frequency of eating disorders in the broader community has been hard to come by. But a new survey study of over 10,000 adolescents, released last week in the Archives of General Psychiatry, confirmed that the iceberg of eating disorder prevalence among American teens is as broad below the surface as psychiatrists suspected. Almost 6 percent of those surveyed in the study met the criteria for one of the five eating disorders tested at some point in their lifetime, a number extrapolated by some media outlets to 500,000 teens in the United States.

But the total numbers were just one of the eyebrow-raising results of the research. Le Grange, a co-author on the study, sat down with ScienceLife and detailed the most significant findings of this long-awaited census, and discussed its implications for the nature of these diseases and the patients who are slipping through the field’s fingers.

1. The Myth of Rarity

Health care dollars are not infinite, and cynical as it may sound, diseases must compete for research funding and insurance reimbursements. So when conditions such as eating disorders are perceived as rare occurrences, the people who treat and study those conditions face an uphill struggle for attention and support. Thus, the under-reporting of eating disorder prevalence has held the field back from being considered as a priority concern in adolescents. The new numbers - lifetime prevalences of 0.3% for anorexia nervosa, 0.9% for bulimia nervosa, 1.6% for binge-eating disorder, and 3.3% for sub-threshold disorders - lift eating disorders into a higher tier of concern for teenage and adult health.

“The myth has been that eating disorders and especially anorexia nervosa are relatively rare disorders, and we constantly have to argue that they’re not, because that’s what it feels like when we sit in clinical practice and we are inundated by patients,” Le Grange said. “This is robust data to demonstrate that eating disorders are not rare.”

2. A Gender-Blind Illness

In the clinic, psychiatrists see far more girls with eating disorders than boys - a ratio of 9-to-1. But surprisingly, the community survey revealed roughly equal prevalence for anorexia nervosa in males and females, suggesting that boys are not less likely to suffer from the condition, but are much less likely to be diagnosed and treated. Le Grange said he suspects that physician bias may lead them to more quickly consider an eating disorder  when the patient is a she rather than a he.

“We are so convinced that anorexia nervosa is predominantly a female disorder that pediatricians and mental health professionals, when presented with a boy who’s lost weight, do not consider anorexia to be a legitimate  diagnosis,” he said. “When we do see boys in our clinic, they usually have had an extensive preliminary workup, as the clinicians don’t consider an eating disorder…until everything comes back negative.”

3. Effects Beyond Mealtime

Psychiatrists observe that eating disorders don’t typically occur in isolation, as patients often carry “co-morbid” psychiatric issues such as depression or anxiety. The community survey puts a number on this observation, finding that the majority of those that met the criteria of an eating disorder also met the criteria of at least one other psychiatric disorder. Perhaps most alarming was the very high occurrence of suicidal thoughts and attempts in adolescents with eating disorders - more than half of those with bulimia nervosa reported thinking about suicide, and more than a third reported attempts.

Also striking was that these associations were just as common for kids who exhibited “sub-threshold” eating disorders, those did not meet the full criteria for anorexia nervosa or bulimia nervosa. In the DSM-IV, the diagnostic bible of psychiatry, such patients would be lumped into the category of Eating Disorders Not Otherwise Specified (EDNOS). The health risks associated with these patients suggest that EDNOS should not be seen as any less severe an illness, Le Grange said.

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Here’s how genetic medicine was supposed to work. Once the basic menu of human genes was mapped by the Human Genome Project, scientists could turn their attention to gene variants associated with common diseases. These disease-associated variants had to be relatively common; according to the “common disease, common variant” theory, rare variants with negative effects would quickly be removed by natural selection. So hundreds of studies - called genome-wide association studies, or GWAS - were organized to compare common gene variants in people with and without a specific disease or trait. Once the gene variants associated with heart disease, diabetes, or psychiatric disorders were found, treatments to cure those diseases would follow.

But ten years later, that simple process hasn’t quite worked as well as hoped. GWAS has revealed some 400 gene variants responsible for traits and diseases. But for many of the largest medical targets, the GWAS results have fallen far short, finding variants that only explain a small fraction of the disease. For a highly heritable disease such as schizophrenia, which afflicts both members of an identical twin pair 60 percent of the time, this is a mystery. The gap between GWAS and twin studies inspired an influential 2008 Nature news story with a headline worthy of the Hardy Boys: The Case of the Missing Heritability.

One place where scientists are looking for their lost heritability has to do less with the content of a gene variant than how often it appears in a person’s genome. Copy number variants, or CNVs, are errors of replication in the genetic code where stretches of DNA are deleted or duplicated, leaving behind zero copies of a genetic region, or two copies, or even more. These copy errors are more common than traditional gene mutation (100 to 10,000 times more frequent), and some CNVs can have dramatic consequences.

“These are very frequent events,” said Elliot Gershon, professor of psychiatry and human genetics. “They are important causes of disease and they turn out to be important causes of neuropsychiatric diseases.”

Schizophrenia is one disease where several CNV associations have been found in recent years, including the latest, published last week in Nature. Gershon, whose laboratory has studied the genetics of schizophrenia and bipolar disorder, contributed “interpretation of data” to the new study and said that it adds more weight to the argument that rare copy errors, not only common variants, can be important drivers of common diseases.

“The importance of a finding like this is that rare mutations were not thought to be generally a cause of common disease,” Gershon said. “But this is another rare variant that can cause schizophrenia.”

The new CNV, a duplication found on chromosome 7, was found in 29 of 8,290 schizophrenic patients tested in the study, compared to only 2 of 7,431 controls. It’s notable, Gershon said, for being a duplication rather than a deletion - instead of eliminating genes, it appears to increase the transcription of one specific gene, called VIPR2. This gene also implicates a previously unrecognized target for potential schizophrenia therapy, the vasoactive intestinal peptide system, previously associated with brain functions such as circadian rhythms and secretion of the hormone prolactin (involved in lactation and some sexual behaviors).

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Tablets of olanzopine, an atypical antipsychotic drug (from Wikimedia Commons)

If you watch enough football games, you might come away with the impression that today’s most profitable drugs are for erectile dysfunction, cholesterol, and allergies. But far less public attention is paid to one of the most expensive classes of drugs : the antipsychotics, drugs designed to treat certain mental disorders. From 1995 to 2006, the number of doctor visits where antipsychotics were prescribed or continued tripled from 6.2 million to 16.7 million, reflecting a nearly $10 billion chunk of the industry. What’s more, the majority of those prescriptions and dollars result from off-label uses of the drugs to treat illnesses where the clinical evidence of their effectiveness and safety is not crystal clear.

Those astonishing figures come from a new study by University of Chicago and Stanford University researchers, published earlier this month in Pharmacoepidemiology and Drug Safety. In the paper, a team led by G. Caleb Alexander, assistant professor of medicine at the University of Chicago Medical Center, used physician survey data to determine the trends and costs of antipsychotic use from 1995 to 2008. The results portray a corner of the pharmaceutical industry that has evolved at a much faster pace than regulatory agencies and the best scientific evidence can keep up with.

The history of antipsychotic medications stretches back more than 50 years to the first wave of agents, now called the “typical” antipsychotics. These drugs, with names such as haloperidol and chlorpromazine (more commonly known as Thorazine), were originally developed to treat the psychotic symptoms of schizophrenia. The typical antipsychotics led the field until the mid-1990’s, when a new class of “atypical” antipsychotics with a slightly different mechanism began to appear on the market for the treatment of schizophrenia, boasting of fewer motor side effects than the older drugs.

Despite the higher cost of atypical agents - typically 5 to 10 times that of the generic, typical agents - they quickly overtook their predecessors despite unconvincing evidence that they were safer or more effective. Though the atypical agents largely avoided the short-term dyskinesia seen with older antipsychotics, longer-term studies found effects upon weight gain and other metabolic conditions, leading to diabetes in some cases. Furthermore, when directly compared against the typical agents for treatment of symptoms such as mania in bipolar syndrome, atypical drugs were no more effective than the cheaper, older medications.

Alexander’s study shows the magnitude of that turnover: in 1995, 84 percent of antipsychotics used were from the typical group; in 2008, just 7 percent were typical therapies. Furthermore, the shift wasn’t simply a one-for-one replacement. From 2002 to 2006, the overall use of antipsychotics soared, with atypical agents leading the expansion into new uses of the drugs. Ironically, there was a return to using typical agents to treat schizophrenia over the 1995-2008 period studied, while atypical antipsychotics became popular for the treatment of bipolar disorder, depression, and other disorders that were beyond the scope of the original FDA approval.

“We saw remarkable changes over time,” Alexander said. “We know from other prescription drugs that uses change or evolve over time, and one reason is clinical innovation, but there’s also substantial over-use and over-adoption of therapies beyond the evidence base.”

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ScienceLife ran 219 posts in 2010, and choosing the best of them is as hard as picking a favorite gene.  So here’s a month-by-month scan of a busy year at the University of Chicago Medical Center, full of exciting discoveries in the laboratory and the clinic. The impact of some of this research is already being felt by patients receiving improved, evidence-based medical care. For other studies, the clinical benefit may be years in the future, and may take unpredictable forms. As a closing message for 2010, we’ll re-quote the recently departed Eugene Goldwasser, whose laboratory research isolating and purifying the hormone erythropoietin has helped millions of people worldwide.

“It is a particularly impressive example of how basic research can pay a dividend that could not be anticipated at the start,” Goldwasser wrote about his life’s work, “and it is a pity that the lesson still has not been learned by those who control public funding of science.”

January: Tong Chuan-He looked at how cancer may result from cells who don’t want to grow up. Scientists studied how sleep affects the language learning skills of starlings (with painstakingly acquired video of the experiment!). Richard Jones combined two laboratory staples - Western blots and DNA micro-arrays - to develop a new method for studying protein networks. While physicians such as Tammy Utset treat patients with lupus, UChicago scientists are looking for the genetic origins of the autoimmune disorder.

February: Many Medical Center employees returned from volunteering with relief efforts in Haiti, and we filmed video interviews with Rex Haydon, Tiffany Cupp, Richard Cook, and Dima Awad on their experiences. Most of the human genome is “junk” between protein-encoding regions, but Marcelo Nobrega developed a way to find important regulatory elements in that genetic sea. Like birds, human learning can be affected by sleep, and Leila Kheirandish-Gozal reported on the impact of obstructive sleep apnea upon learning in children. Can a single protein in the brain create behaviors associated with drug addiction in rats?

March: Everyone knows air travel is stressful, but did you know that eastbound flights cause stronger cortisol changes than westbound trips? The laboratory of Milan Mrksich found a way to direct stem cells to form fat or bone by shaping them into stars or flowers, a brilliant example of bioengineering. Computational neuroscientists discovered how touch is like vision in the brain, knowledge that could be used to someday re-engineer Luke Skywalker’s robot hand. Dartmouth president and Partners in Health co-founder Jim Yong Kim visited to talk about a new, needed area of research: health care delivery.

April: Researchers at the Field Museum and the University of Chicago teamed up for the Emerging Pathogens Project, an effort to find new viruses in animals before they jump to humans. Cardiologist Martin Burke tested out a new type of internal defibrillator device that can go under the skin, instead of into the heart (the clinical trial, reported in May, was a success). In a lecture to the MacLean Center of Clinical Medical Ethics, transplant surgeon J. Michael Millis described his efforts to bring American organ transplant practices to China.

May: A trial testing the erectile dysfunction drug Viagra for a rare, untreatable lung disease failed, but pulmonologist Imre Noth found a silver lining. Lauren Sallan and Michael Coates uncovered evidence of a previously unappreciated mass extinction event 360 million years ago that changed the path of life on Earth. Researchers from the University of Chicago and around the world presented science at the frontier of biotechnology at the annual BIO conference.

June: In a study that is literally the size of an entire country, epidemiologist Habibul Ahsan measured the toll of a tragic, accidental exposure of millions to arsenic in Bangladesh. Putting a gene from fireflies into the pancreas of mice isn’t mad science, it’s an imaging tool that will help study cures for diabetes. Epigenetics, the modifications that turn genes on and off, took off in 2010, and cardiologists Stephen Archer and Jalees Rehman linked one epigenetic factor to pulmonary artery hypertension.

July: Scientists don’t often get to see the fruits of their research in the flesh, but the Celebrating the Miracles gathering of diabetic children weaned off injected insulin thanks to genetic research was a moving exception (video of the event can also be viewed). Another hot topic in science and medicine this year was the use of computational analysis to sift through rapidly accumulating data, topics explored by Gary An and Andrey Rzhetsky. Or you can build a computer model of a brain network to study the dynamics of epilepsy, like neurologist Wim van Drongelen.

August: Air pollution is a problem indoors as well as outdoors in developing countries where dung and firewood are used to cook food - a problem being tackled in a project led by Sola Olopade. A study of the hormonal changes induced by a stressful test revealed a surprising protective effect of marriage and long relationships. Microbiologist Olaf Schneewind’s laboratory developed two new strategies against MRSA, the most-wanted cause of hospital-acquired infections.

September: To study multiple sclerosis, neurologist Brian Popko’ s laboratory developed a new mouse model that can replicate the disease, then spontaneously recover. Meanwhile, a new drug to treat MS, originally isolated from fungus found in wasps, was approved by the FDA and is being studied for broader uses at the Medical Center. The micro-organisms that live in humans were analyzed as part of a “microbiome” study looking at the protective effects of breast-feeding against a intestinal disease.

October: Common wisdom on quitting smoking says to stay away from cigarette-associated cues, but research from psychiatrist Harriet de Wit’s laboratory revealed that abstinence could make craving even worse. A study of how getting a good night’s rest affects dieting results suggested that “sleeping off the pounds” isn’t merely a fantasy. Graduate student Daniel Matute solved a 100-year-old riddle about how quickly new species become reproductively incompatible with each other.

November: In perhaps our favorite study of the year, geneticist George Perry found a way to acquire the genomic information of endangered species from…poop. The evolutionary biologist Leigh Van Valen passed away, but his Lewis Caroll-inspired Red Queen Hypothesis lives on. Sometimes statistics don’t tell the whole truth, as in the curious case of the aspirin paradox - why the cardio-protective drug may actually predict worse outcomes after heart attack.

December: Evolution textbooks may need a rewrite after geneticist Manyuan Long’s laboratory discovered that new genes can be just as essential as old genes. A study by neurobiologist Nicholas Hatsopoulos proved that the only thing better than a thought-controlled device is a thought-controlled device equipped with a robot arm. Ripped from the headlines: microbiologist Jack Miller weighed in on the hype over arsenic-based bacteria, and ethicist/physician/friar Daniel Sulmasy discussed the Presidential Bioethics Commission’s report on synthetic biology.

All told, it was a great year of science and medicine. Let’s do it again in 2011! Regular posting will resume Jan. 3rd. Happy Holidays.

Even before the very rules of life were changed by the discovery of an arsenic-based microbe in a California lake (or were they? More next week.), this week seemed to be full of strange and interesting science involving animals. While ScienceLife works on a bunch of research that is under embargo until later this month (disclaimer: none of them involve extraterrestrial life), here are a few bullet-pointed studies that inspired awe and wonder this week.

• Optogenetics is the technique of creating mutant mice with cells that can be modulated with flashes of light, which is awesome. For example, a scientist can introduce a gene into a mouse strain that makes motor neurons sensitive to light, and when light is shined at those neurons, the mouse starts running. Now, researchers from Stanford and UT Southwestern have used optogenetics in the frontal cortex of a mouse strain, and found a way to produce anti-depressant-like effects (pdf). As covered by David Dobbs at Wired, the technique may offer a new non-invasive way of treating depression way down the line; for now, optogenetics requires a brain implant, which is less than ideal clinically.

• Telomeres, the long repeated sequences at the end of chromosomes, were a fashionable scientific buzzword before optogenetics was even a glimmer in science’s eye. With their companion enzyme telomerase, telomeres were hyped to be the genetic key to the  “fountain of youth,” the biological source of the cell damage that accompanies aging. But despite being the subject of last year’s Nobel Prize in Physiology or Medicine, the excitement about telomeres seemed to have faded out. But an exciting new study published in Nature this week may reignite that flame, as scientists at Harvard reversed the premature aging of a special mutant mouse with telomerase treatment. Wired, Ars Technica, and the Wall Street Journal discussed this “Ponce de Leon” effect, but Discover blog 80beats urges patience for those waiting on anti-aging pills.

• Scientists have long used animal models to study the neurobiology of fear in laboratory settings. But how do you realistically recreate situations that would cause a rat to be scared in the wild in the predator-free world of the animal facility? For one group of scientists, the answer was Robogator, a simulated predator designed to leap out at rats as they moved foraged for food in their lab environment (you can download video clips here). Researchers looked at how close the rat would approach Robogator before and after a lesion of the amgydala, a brain region thought to be involved in fear response. Before the lesion, the rats would only get food 10 inches or less from the entrance to their chamber, but after the lesion, they would go as far as 50 inches, sometimes even approaching and investigating the robot (video) without fear.

• Here’s a novel effect of environmental pollution upon wildlife: when ibis birds of South Florida are exposed to the most potent form of mercury, they opt for homosexual pairings over heterosexual matches.

Thanks to its association with the Thanksgiving turkey, tryptophan has become probably the most popular amino acid. Whether it’s being blamed for the strong post-meal desire for a nap or being rhymed with “gravy in the pan” in a dancey clothing store commercial, tryptophan is the envy of its 19 peers in the standard amino acid family. But like most scientific crossover stories, public misperception has given turkey’s tryptophan something of a bad rap as a kind of natural sleeping pill - or a convenient excuse to not do dishes.

In fact, research has shown that turkey has no more tryptophan than any other poultry or ground beef; perhaps people should pull out the old “tryptophan” excuse the next time they eat a burger, as well. Simply eating a bunch of carbohydrates, such as the rolls, potatoes, and stuffing on the table next to the turkey, can spike a person’s tryptophan and insulin. The latter, a hormone best known for causing cells to absorb blood sugar, also causes the absorption of amino acids - except tryptophan, which crosses over into the brain. There, it is turned into the neurotransmitters serotonin and melatonin, which, yes, cause sleepiness, but also have a number of other interesting behavioral effects.

The powers of tryptophan are perhaps best depicted by what happens to a person when it’s not there. Tryptophan depletion is a frequently-used tool in psychiatry research, mostly as a shortcut to reducing the levels of serotonin in the brain. Because serotonin has been implicated in depression (many anti-depressant drugs are designed to increase brain serotonin) and impulsivity, some interesting things happen when you remove its key amino acid ingredient from a person’s diet.

In 2009, the laboratory of Emil Coccaro, chair of psychiatry at the University of Chicago Medical Center, used tyrptophan depletion to study an element of intermittent explosive disorder (IED). People with IED tend to have violent temper tantrums that do harm to themselves and others, and show signs of abnormal serotonin signaling, so Coccaro’s group, led by Michael McCloskey, studied the effects of tryptophan depletion in this group. Subjects with IED and controls without the disorder were given a tryptophan-depleting drink: a chocolate-flavored liquid that contained all the other dietary amino acids. Test subjects were then given a test where the punishment for failure was an electric shock; participants were allowed to choose the intensity of their shock.

Independent of the pre-test drink, IED subjects chose a stronger shock punishment than control subjects. But after quaffing the trytophan depletion drink, both IED and control subjects were more likely to choose a higher shock than when they consumed a placebo drink. That result suggests that lower one’s tryptophan, and by extension their serontonin, increases self-aggression and self-injury.

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The common wisdom about kicking an addiction is to “isolate and conquer.” People trying to give up smoking, or coffee, or something more serious, are usually advised to stay away from reminders of their drug, such as other people smoking, the smell of coffee, or other cues that might remind them of their habit. Taken to its extreme, this isolation policy is the backbone of inpatient drug treatment programs, which remove an addict from their environment and away from addiction “triggers” for 30 days or more. At the hospital, addicts can safely pass through withdrawal symptoms, receive psychiatric care, and return to society equipped to resist the siren call of their vice.

However, research in animals throws a wrench into that theory of addiction treatment. In animals taught to hit a lever to receive addictive substances such as cocaine, heroin, or sucrose, an extended period of abstinence away from drug-related cues produces an unintended effect. Rather than decreasing the animals’ response to the cues (which in the world of a rat’s cage is usually a light or a sound rather than an ashtray or a syringe), longer periods of abstinence inspire a more robust and energetic “relapse” of lever-pressing.

This “incubation effect” suggests that the longer addicts stay away from their drug, the more likely they are to succumb to a relapse when they see or smell a drug-related trigger. But that idea had not been translated from rats to humans until an experiment performed by Gillinder Bedi and colleagues in the laboratory of Harriet de Wit, professor of psychiatry at the University of Chicago Medical Center. Published last month in the journal Biological Psychiatry, the experiment shows the first evidence that incubation of drug cues also occurs in humans. Further, their results suggest that current treatments for addiction may miss, or even run counter to, an important cause of relapse.

“Many factors contribute to relapse,” de Wit said. “One is the presence of withdrawal symptoms, the other is just the immediate difficulty of removing a habit that you had. But there might be this other factor, incubation, that grows over time without dissipating, at least for weeks or perhaps months.”

In Bedi’s experiment, cigarette smokers were paid $30 a day to abstain from smoking for as long as 35 days. As testament to the allure of nicotine, only half of the subjects recruited for the study reached their smoke-free target despite the financial rewards, de Wit said. The participants who did successfully abstain until their goal (7, 14, or 35 days) returned to the lab where they were exposed to either smoking-related cues (pictures of people smoking, lit cigarettes, ashtrays, etc.) or neutral cues or a matched show of neutral, non-smoking cues. To enhance the sensory experience, subjects held a lit cigarette while viewing the smoking cues or a pencil during the neutral session. Before and after the cues, subjects completed surveys to report how strongly they craved cigarettes.

Before the slide show sessions, participants reported expected, positive results of quitting: withdrawal symptoms and craving decreased with the more days since their last cigarette. But after viewing the parade of cigarette-related images, the opposite effect was observed. Subjects assigned to the group that abstained from smoking for a longer period of time (35 days) reported more cue-driven craving compared to those who only abstained for 7 or 14 days.

That looks a lot like the incubation effect seen in rats, and according to de Wit, may actually be an even more impressive effect than what was seen in animal studies. Whereas rats can be kept totally isolated from drug cues for as long as necessary, the subjects in Bedi’s study were presumably exposed to some smoking-related cues - friends smoking, cigarettes in movies, etc. - during a typical day of their paid abstinence. Yet in the laboratory, the cues still held the power to spark craving, and this craving increased with the number of days of abstinence. In a further surprise, most subjects returned to their smoking habits after their part in the research was finished, regardless of how long they had abstained from smoking for the study.

“I think one of the really interesting things is that almost everybody goes back to smoking, even after a month of not smoking,” de Wit said. “You would think if they could go drug-free for a month it would be pretty easy to stay quit after that, and yet they went back.”

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Yesterday we talked about how Kathleen Cagney’s research appeared to reveal an effect of the 9/11 terrorist attacks on the body mass index of people more than a thousand miles away in Dallas. By coincidence, Discover magazine published a book excerpt (from “Origins: How the Nine Months Before Birth Shape the Rest of Our Lives” by Annie Murphy Paul) yesterday that touches on how the fall of the World Trade Center might have caused post-traumatic stress disorder not just in people near the towers that morning, but also the fetuses being carried by pregnant women near the towers. Can PTSD be transmitted from mother to unborn child? And did 9/11 leave a wide swath of medical impact across the country? Fascinating research.

Oh cruel search for alien habitable worlds: new data released at an astronomy symposium this week appears to refute the existence of Gliese 581g, the “Goldilocks” planet that had everyone daydreaming of intergalactic travel two weeks ago. Though the debate over the planet’s existence is far from settled, it’s a quick, nasty reminder that leaping from a handful of data points to bold claims of Earth-like planets and alien life is a dangerous gamble. (Also, Google News hits for original Gliese 581g story = 1407 articles. For the “Gliese 581g may not exist” story = 91.)

As part of the “It Gets Better” campaign reacting to the recent run of tragic suicides by homosexual teenagers, Scientific American’s psychology blogger Jesse Bering begins a long, detailed look at the evolutionary history of suicide. Why would an organism evolve the capacity to kill itself? Bering dials down to insects that are cannibalized after copulation and explains a mathematical equation for suicidal motivation in the first part of his series.

If University of Chicago evolutionary biologist Jerry Coyne is too prolific for you on his blog, Why Evolution is True, you can get a primer on his views regarding the incompatibility of science and religion from his USA Today editorial this week. There were, of course, letters,  and a blog response from Albert Mohler of the Southern Baptist Theological Seminary.

An in-depth Reuters article about the increasing use of cardiac assist devices and the end-of-life ethics questions they raise talks to our chief of cardiac and thoracic surgery Valluvan Jeevanandam, among other experts. For more on the topic, see our post on ethicist Daniel Sulmasy, who has written about when it is ethical for physicians to turn off a person’s cardiac device, knowing that it may hasten death.

This past week has been Nobel Prize week, and while none of the winners so far have had a University of Chicago connection (unlike last year’s trio), it’s still good fun for science spectators. Trying to divine a common theme from all of a year’s winners is probably futile - the selection process at the Royal Swedish Academy of Sciences is still pretty mysterious, and doesn’t seem to follow any consistent logic in the laureates it spits out. This year, the Thomson Reuters predictions - considered by many to be the best - have produced an ohfer so far, despite throwing out anywhere from 4-7 names for each of the prizes. The 2010 list is typically scattershot, with a mix of established science and science with yet unrealized potential; the only theme I can pick up is “non-American.”

Medicine: Occasionally, the Nobel committee is accused of waiting too long to award a prize. This year’s award in physiology or medicine, awarded to British scientist Robert G. Edwards for his work on in vitro fertilization, may fit that charge. The first baby produced by IVF procedures developed by Edwards and colleague Patrick Steptoe was born more than 30 years ago, on July 25, 1978. Since then, over 4 million “test tube babies” have been born to parents who would not otherwise have been able to have children. It’s kind of amazing, then, that the leaders of IVF had not previously been awarded the Nobel Prize - and sadly, Steptoe did not live to receive the honors, having died in 1988 (Nobel rules forbid posthumous awards). According to media reports, Edwards himself is in poor health and was unable to grant interviews about winning the award. Of course, the Vatican had its own criticisms of the winners.

Physics: Rather than rewarding a scientific discovery several decades after the fact, this award was given to science that, according to many experts, hasn’t yet ripened. Russian scientists Andre Geim and Konstantin Novoselov were recognized for the development of graphene, an extremely thin and extremely strong material thought to be useful in everything from solar panels to satellites. The emphasis is on “thought to be,” because the material was only discovered in 2004, and has yet to be incorporated into a commercially available product. Interestingly, the main gripe here was that it may have been more appropriate for the chemistry Nobel rather than the physics prize. Geim also notably becomes the first scientist to win both the Nobel Prize and its illegitimate brother, the Ig Nobel Prize, which he won for his research on levitating frogs.

Chemistry: If this were a fairytale, this prize would seem to be not too stale, not too fresh, but just right. Richard Heck, Ei-ichi Negishi, and Akira Suzuki each have an organic chemistry reaction that bears their name, and are considered to have laid important early groundwork for the burgeoning field of molecular engineering. The trio invented and refined the art of “palladium-catalyzed cross-coupling,” which finds a way to stick formerly contact-shy carbon atoms together. While the process is not exactly a household name, its impact is felt in medicine cabinets around the world. “Cross-coupling methods are now used in all facets of organic synthesis, but nowhere more so than in the pharmaceutical industry, where they are used on a daily basis by nearly every practicing medicinal chemist,” organic chemist Eric Jacobsen told ScienceNOW.

Elsewhere…

In the same issue of Archives of General Psychiatry where Daniel Le Grange’s study of family-based anorexia treatment was published, another Medical Center study probed the link between ADHD and teenage suicide. A study of 125 children diagnosed with attention deficit hyperactivity disorder between 4 and 6 years of age were three times as likely to attempt suicide between ages 9 and 18, compared to a control group of non-ADHD children. “The importance of this study is simply that it confirms that ADHD in children is not something to take lightly,” lead author Benjamin Lahey, professor of epidemiology, told WebMD.

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It’s great to have a treatment that’s proven to work in a difficult psychiatric condition such as anorexia nervosa. It’s even better to have two treatments for such a disorder. But having multiple options also creates a quandary for psychiatrists: with a new patient, which treatment do you try first? Creatures of habit like the rest of us, many doctors will simply stick with the method they know best until given convincing evidence that it’s worth switching gears. To be the new treatment of choice, a method must beat out the current champion in a head-to-head battle.

One such comparison, conducted by researchers at the University of Chicago Medical Center and Stanford University, was published yesterday afternoon in the Archives of General Psychiatry. The trial compared the most common form of treatment for adolescents with anorexia, known as adolescent-focused therapy (AFT), with the newer, family-based treatment (FBT), also sometimes known as the Maudsley Approach. The latter name comes from the Maudsley Hospital in London, where Daniel Le Grange, now director of the Eating Disorders Clinic at the University of Chicago, helped develop a new approach to bringing anorexic teens back to healthy weight and eating habits.

Under adolescent-focused therapy, the therapist works directly with the patient on a one-to-one basis, emphasizing the importance of weight gain and helping them accept personal responsibility for healthy eating. Family-based treatment, as you might expect from the name, does more to incorporate the parents into that process, equipping the patient’s mother and father with the tools to encourage healthy eating at home. By doing so, the therapist hopes to avoid hospitalizing the patient while permanently adjusting the home environment, removing factors that could lead to relapse after therapy is completed.

“No one is more available to care for the kids than the parents are; no one would put the time aside in the way that parents would, and no one loves their kids more than parents do,” Le Grange told NPR’s Morning Edition (where you can also hear the perspective of one patient’s mother on family-based treatment).

The two therapies had been compared previously, but in smaller studies with only two or three dozen patients. True convincing evidence requires a randomized trial, with enough patients for the statistics to make a strong case for one of the treatments. So, combining forces between Chicago and Stanford, Le Grange and his collaborator, James Lock at Stanford, were able to gather 120 patients with anorexia nervosa (with an average age of 14-1/2) for the study.

Split evenly between FBT and AFT, the patients were followed for a year of therapy and another year of follow-up. At the end of treatment, 42 percent of those enrolled in FBT showed full remission back to at least 95 percent of expected body weight, compared to only 23 percent of those enrolled in AFT. While that comparison fell just short of statistical significance, with a p-value of .055, Le Grange said that the higher standards used in the study spoke to the effectiveness of FBT.

“We used the higher yardstick for remission of 95 percent of body weight, which we felt was clinically more appropriate,” said Le Grange, a professor of psychiatry and behavioral neuroscience.

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