New role for zebrafish in human studies: Animal model uses mysterious enzyme also found in human brains

Michael E. Baker, PhD, a researcher at the University of California, San Diego School of Medicine has discovered that zebrafish — an important animal model in disease and environmental studies — could provide the means to help scientists eventually reveal the function of a mysterious enzyme linked to the steroid cortisol, and found in the human brain.

In people and other vertebrates, steroids like cortisol perform a variety of diverse duties, including regulating immune response, bone formation and brain activity. Too much cortisol, however, is unhealthy. High levels of the steroid have been linked to type 2 diabetes and may impair the brain's ability to store memories.

The human body regulates cortisol by employing an enzyme called 11 beta-hydroxysteroid dehydrogenase-type 1 or 11beta-HSD1, which catalyzes the synthesis of cortisol in liver and fat cells. A related enzyme known as 11 beta-HSD-type3 or 11 beta-HSD3 is expressed in the brain, though its utility remains unknown.

In new findings to be published in the June 3 issue of FEBS Letters, Baker, a research professor of medicine who works in the division of nephrology-hypertension at UC San Diego's School of Medicine, reports that 11 beta-HSD3 (but not 11 beta-HSD1) is present in zebrafish, where it appears to serve an important role in fish endocrine physiology.

That makes the fish a potentially useful analog for cortisol studies, including discovering the purpose and function of 11 beta-HSD3 in human brains, which may be an evolutionary precursor to 11 beta-HSD1.

Interestingly, Baker found that the genomes of mice and rats do not contain 11 beta-HSD3, which means that inserting the appropriate gene for the enzyme in these animal models could provide additional avenues of investigation.

Journal Reference:

  1. Michael E. Baker. Evolution of 11β-hydroxysteroid dehydrogenase-type 1 and 11β-hydroxysteroid dehydrogenase-type 3. FEBS Letters, 2010; 584 (11): 2279 DOI: 10.1016/j.febslet.2010.03.036

Member Of NFL Hall Of Fame Diagnosed With Degenerative Brain Disease

The Center for the Study of Traumatic Encephalopathy (CSTE) at Boston University School of Medicine (BUSM) has announced that a recently deceased member of the NFL Hall of Fame suffered from the degenerative brain disease Chronic Traumatic Encephalopathy (CTE) when he died, becoming the 10th former NFL player diagnosed with the disease.

The week before, CSTE researchers announced CTE had been diagnosed post-mortem in a former college football player who died at 42, the first advanced case in a non-NFL football player. Most concerning, all 11 of the former NFL and college football players studied post-mortem at the CSTE have shown signs of CTE.

Lou Creekmur, former offensive lineman for the Detroit Lions and eight-time Pro Bowl player, was diagnosed with CTE by neuropathologist and CSTE co-director Ann McKee, MD. Creekmur played 10 seasons for the Detroit Lions, and was famous for breaking his nose 13 times while playing without a facemask. He died July 5, 2009 from complications of dementia following a 30-year decline that included cognitive and behavioral issues such as memory loss, lack of attention and organization skills, increasingly intensive angry and aggressive outbursts.

CTE can only be diagnosed by examining brain tissue post-mortem. Creekmur's brain was studied by McKee who determined that he was suffering from CTE and not another cause of dementia such as Alzheimer's disease. McKee said, "This is an important case because we are confident many CTE cases are misdiagnosed as Alzheimer's disease. By examining his brain, I was able to confirm that there was absolutely no sign of Alzheimer's disease or any other type of neurodegenerative disease except for severe CTE. This is the most advanced case of CTE I've seen in a football player; his brain changes were similar to those of profoundly affected professional boxers."

President and CEO of the Alzheimer's Association Mass./N.H. Chapter James Wessler stated, "This is a very important finding that could explain the underlying cause of dementia in countless individuals who have had histories of repetitive head trauma."

The Creekmur case is also important in advancing discussion of what risk factors may play a role in causing CTE other than trauma. One hypothesis that has been put forward is that anabolic steroids could play a role in CTE. However, Creekmur played in the 1950s, a time that predates documented steroid use in the NFL, so the case proves CTE does occur in the absence of steroids.

Robert Stern, PhD, CSTE co-director, added, "The U.S. House Judiciary Committee is holding a hearing on the football head injury crisis on Oct. 28, and we feel that this evidence should be part of the discussion. The long-term consequences of brain trauma in sports are a tremendous public health problem. CTE is the only fully preventable cause of dementia. We need to make changes to the game of football, at all levels of play, which will decrease the risk of CTE to both pro and amateur athletes."

Creekmur was a member the NFL's Plan 88. The Plan was named for former NFL star John Mackey's jersey number. Mackey, a Hall-of-Fame tight end for the Colts in the 1960s and 70s, suffers from severe dementia. The Plan was created by the NFL to provide financial support to families of former players who suffer from some form of dementia. Members of the Plan have been diagnosed with "dementia," which refers to progressive memory and cognitive deficits significant enough to impair daily living. During life, it is not possible to determine the underlying disease that causes dementia. However, now that a Plan 88 member has been examined pathologically, CSTE scientists have proven it is possible to determine the cause of dementia, which in this case was repetitive trauma from football.

Creekmur's wife of 33 years, Caroline Creekmur, had extensive discussions with her husband prior to death about his brain trauma history, and is confident he remembered "16 or 17" concussions, none that caused loss of consciousness or necessitated a hospital visit. He did not have any significant head trauma since retiring from the NFL.

There are approximately 100 former NFL players whose families are receiving support through Plan 88, including Ralph Wenzel, age 66, former lineman for the Pittsburgh Steelers and San Diego Chargers, who now resides in an assisted living facility with advanced dementia. Upon learning of Creekmur's CTE diagnosis, Wenzel's wife, Dr. Eleanor Perfetto, stated, "Sadly, these findings do not come as a surprise. For those of us who have watched our husbands deteriorate and lose their independence from progressive dementia, our hope is that this research will one day lead to changes in the game of football such that other players and their families will not have to experience the pain that we have experienced."

CTE is characterized by the build-up of a toxic protein called tau in the form of neurofibrillary tangles (NFTs) and neuropil threads (NTs) throughout the brain. The abnormal protein initially impairs the normal functioning of the brain and eventually kills brain cells. Early on, CTE sufferers may display clinical symptoms such as memory impairment, emotional instability, erratic behavior, depression and problems with impulse control. However, CTE eventually progresses to full-blown dementia. Although similar to Alzheimer's disease, CTE is an entirely distinct disease.

Adding Steroid Drug To MS Treatment May Reduce Disease Activity

Using a steroid drug for multiple sclerosis (MS) in addition to an MS drug may reduce the amount of disease activity more than using the MS drug alone, according to a study that will be presented as part of the Late-breaking Science Program at the American Academy of Neurology's 61st Annual Meeting in Seattle, April 25 – May 2, 2009.

For the study, people with MS received the steroid drug methylprednisolone in monthly "pulses," or three doses over three days, in addition to regular weekly treatment with the drug interferon beta-1a. The steroid drug has typically been used only to treat acute MS attacks, not as an ongoing treatment.

The study involved 341 people with relapsing-remitting MS. Half of the participants received both drugs; half received only the interferon drug plus a placebo. The participants were seen every three months during the three-year study for evaluation.

The participants had the disease for an average of three years and had not yet received a disease-modifying drug such as interferon.

Those who received both drugs had 38 percent fewer relapses, or times when the disease is active, than those receiving only the interferon drug. They also improved slightly on a test of MS disability, while the scores for the placebo group decreased slightly.

At the beginning of the study and again after three years, the researchers measured the size of lesions in the brain that are a sign of disease activity. For those receiving both drugs, the lesions stayed the same size or shrunk, while the size of the lesions grew for those taking only interferon.

"These results indicate that these two drugs may have a synergy when taken together and provide a more beneficial effect on the disease activity," said study author Mads Ravnborg, MD, of the Danish Multiple Sclerosis Research Center at Copenhagen University Hospital in Denmark. "This is a promising finding, as the benefit from interferon is only moderate and not everyone responds fully to the treatment, so anything we can do to boost those results is positive."

Controversial Performance Enhancer "Andro" Affects Brains As Well As Brawn

AMHERST, Mass. — Athletes taking the controversial performance enhancer known as "andro" may be affecting their moods as well as their muscles, suggests a study published by University of Massachusetts researchers in the July issue of the journal Endocrinology. The study was conducted by doctoral students Constanza Villalba and Catherine Auger under the direction of professor Geert de Vries. Auger is now a postdoctoral researcher at Johns Hopkins University. Although the study was conducted on rats, the implications for humans are important, according to the scientists.

"Andro," or androstenedione, is a steroid; a hormone that is produced in the body by males and females. It is sometimes sold as an over-the-counter nutritional supplement. Andro garnered attention last year when St. Louis Cardinals star hitter Mark McGwire acknowledged using it to help him train. Since then, scientists, doctors, and ethicists have been working to understand the effects of andro on the body. But while many researchers have been concentrating on how andro affects muscles and athletic performance, the UMass group of scientists has focused on what andro does to the brain. The study was conducted through the University's Center for Neuroendocrine Studies, the Neuroscience and Behavior Program, and the department of psychology.

"Steroids like andro and its more potent counterpart, testosterone, affect more than just muscle mass and home-run ability," said Villalba. "They can also affect the brain by changing the levels of neurotransmitters and consequently stimulating libido and aggression." Steroids, she explains, are critically important hormones produced in the body, in both males and females. While steroids are responsible for puberty, they also have a role in growth, behaviors, and brain development.

"Humans taking andro could potentially be susceptible to steroid-induced rage, or increased aggression as a result of the extra source of hormone," said Villalba.

Specifically, researchers studied andro's effect on a neurotransmitter called vasopressin. Vasopressin plays several roles in the brain: it governs thirst, wake-sleep cycles, and "the focus of the research" aggression. The scientists determined that, like testosterone, andro enables males to maintain high levels of vasopressin. This held true even in rats that lacked the ability to make their own male hormones.

Asthma Drugs Need To Be Maintained For Continued Benefit, Study Shows

Children whose asthma improved while taking steroid drugs for several years did not see those improvements continue after stopping the drugs, new results from a comprehensive childhood asthma study show.

The results come from the Childhood Asthma Management Program (CAMP) clinical trial, in which more than 1,000 children age 5-12 were treated for mild to moderate asthma over more than four years at eight centers, including Washington University School of Medicine in St. Louis. The children in the randomized trial were divided into three groups: one received twice-daily budesonide, an inhaled corticosteroid medication; one received nedocromil, an inhaled non-steroid medication; and one group received a placebo. All children received albuterol, a bronchodilator, and oral corticosteroids as needed for asthma symptoms.

This study, published in the Journal of Pediatrics, followed up with the children nearly five years after the end of the trial. Researchers found that the children, now in their late teens, who took the medications during the trial showed no difference in their asthma control compared with the children who received the placebo.

"The interesting thing is that as kids with asthma get older, they actually do better," said Robert C. Strunk, M.D., a Washington University pediatrician at St. Louis Children's Hospital and lead author of the study. "We used to say they were outgrowing their asthma. What we know now is that as they go from being young children to age 20, their airways get bigger. They still have asthma but don't have as much trouble from it."

Inhaled corticosteroids such as budesonide have been shown to be the most effective form of anti-inflammatory treatment for asthma by controlling symptoms and improving pulmonary function. Results from the original CAMP trial showed that using budesonide twice daily led to fewer hospitalizations and urgent care visits, fewer days in which additional asthma medications were needed and a reduced need for albuterol, a fast-acting drug for relief of acute asthma symptoms. Using nedocromil twice daily reduced urgent care visits and courses of oral steroids for severe symptoms, but did not affect the number of hospitalizations, symptoms or airway responsiveness.

Although the patients had fewer symptoms five years after stopping the daily medication, Strunk cautions that doesn't mean that they can stop using asthma medications altogether or that their asthma is cured.

"While the kids did get better with age and didn't seem to need the medicine as much, laboratory measurements indicated that they were still having symptoms, and therefore were primed to an attack if they got a bad cold or were exposed to a significant weather change," Strunk said.

The researchers determined that continued benefit of these medications likely requires continued use.

"The conclusion is that some kids get better, but the doctor, family and the patient have to pay attention to the symptoms," Strunk said. "Some of the kids are going to need medicine, and they have to be honest about that possibility."

In another part of the follow-up study, researchers looked at long-term side effects of the steroid medications on growth, bone density and fracture rate. The only side effect of budesonide was a 0.4-inch decrease in height among female patients compared to the patients who took a placebo during the trial. However, one-fourth of the girls and more than half of the boys in the trial had not reached final adult height at the end of the post-trial period, researchers said. There were no effects of the nedocromil treatment on growth.

Funding from the National Heart, Lung, and Blood Institute and the National Center for Research Resources supported this research.

Journal Reference:

  1. Strunk et al. Long-Term Budesonide or Nedocromil Treatment, Once Discontinued, Does Not Alter the Course of Mild to Moderate Asthma in Children and Adolescents. The Journal of Pediatrics, 2009; DOI: 10.1016/j.jpeds.2008.11.036

NO Help: Nitric Oxide Monitoring Does Not Help Most Children With Asthma

The level of nitric oxide (NO) in an asthmatic's exhaled breath can portend worsening asthma symptoms, and may even signify an imminent attack linked to underlying airway inflammation. This has made the monitoring of NO levels, particularly in children, of significant interest as a potential way to help clinicians fine-tune medications and improve treatment outcomes.

However, a recent multi-center prospective study found that calibrating medications based on daily monitoring of the fractional exhaled nitric oxide (FENO) and symptoms in asthmatic children showed no significant improvement over medicating based on daily symptom monitoring alone.

The results were reported in the second issue for January of the American Journal of Respiratory and Critical Care Medicine, a publication of the American Thoracic Society.

Johan C. de Jongste, M.D., Ph.D., at the Erasmus University Medical Center-Sophia Children's Hospital in the Netherlands, and colleagues randomized 151 children from 15 academic centers and hospitals with mild to moderate asthma to a 30-week monitoring course. Families were called every three weeks and reported on the daily symptoms in the prior three weeks. The child's medication was adjusted accordingly.

The researchers compared the rates of exacerbation, symptoms, use of medications and other endpoints between the last 12 weeks in the two groups. There were no significant differences whether or not FENO had been part of the daily monitoring. However, both groups enjoyed an impressive overall improvement in symptoms, despite a reduction of about 50 percent in inhaled steroid dose, suggesting considerable benefit of frequent monitoring.

"We speculate that daily supervision and frequent phone contacts have produced an improvement that could not be beaten by additional monitoring of FENO, most likely because of a ceiling effect on compliance," wrote Dr. de Jongste.

The FENO group did, however, have nearly twice as many dosage changes as the symptom-only group, which supports the idea that the lack of difference may be a reflection on the limits of compliance, rather than an inherent limitation in the technique. Still, the added cost and apparent lack of benefit of daily FENO monitoring found in this study suggests that applying the technique in this way is not of benefit to the asthmatic population at large, when compared to daily symptom monitoring.

Another possible explanation for the lack of improvement is that FENO monitoring is most likely to prompt a medication change that symptom-only monitoring would not suggest in patients whose symptoms and underlying inflammation are in discord, but the current study was not designed to assess these patients independently.

Still, in light of these findings, it is clear that FENO monitoring should only be applied to those who stand to gain the most. "There can be no doubt that adding frequent assessments of FENO to management plans of most children and adults with asthma will add unjustifiable costs without providing clinical benefit. Whether there is a role for monitoring FENO to aid management of severe asthma is untested," wrote Stephen Stick, Ph.D., of the Princess Margaret Hospital for Children in Perth, Australia and Peter Franklin, Ph.D., of the Centre for Asthma, Allergy and Respiratory Research at the University of Western Australia in Perth in an editorial that accompanied the article.

"We did not address other possible applications of frequent FENO monitoring, such as prediction of steroid effect. Loss of control, prediction and prevention of exacerbations, and tapering of steroids in symptom-free children who wheezed in the past," noted Dr. de Jongste. "We think there is good reason to study these potential applications."

Furthermore, as D. Robin Taylor, M.D., of the Dunedin School of Medicine at the University of Otago, in New Zealand, pointed out in separate editorial, "FENO measurements shed complementary light on the underlying inflammatory phenotype and, more importantly, on the potential response to anti-inflammatory treatment. Historically, this has been assessed either by empiric "trials of steroid" or, even more imperfectly. With reference to before/after changes in spirometry, serial or repeated FENO measurements in individual patients may provide additional diagnostic as well as prognostic insights."

Steroids Aid Recovery From Pneumonia, Researchers Say

Adding corticosteroids to traditional antimicrobial therapy might help people with pneumonia recover more quickly than with antibiotics alone, UT Southwestern Medical Center scientists have found.

Unlike the anabolic steroids used to bulk up muscle, corticosteroids are often used to treat inflammation related to infectious diseases, such as bacterial meningitis. Used against other infectious diseases, however, steroid therapy has been shown to be ineffective or even harmful.

In a study available online and in a future issue of the Journal of Infectious Diseases, researchers at UT Southwestern show that mice infected with a type of severe bacterial pneumonia and subsequently treated with steroids and antibiotics recovered faster and had far less inflammation in their lungs than mice treated with antibiotics alone.

"Some people might think that if you give steroids, it would counteract the effect of the antibiotic," said Dr. Robert Hardy, associate professor of internal medicine and pediatrics and the study's senior author. "But it turns out you need the antibiotic to kill the bug and the steroid to make the inflammation in the lung from the infection get better. The steroids don't kill the bugs, but they do help restore health."

Pneumonia is a lung infection typically characterized by breathing difficulties and spread by coughing and sneezing. Symptoms include headache, fever, chills, coughs, chest pain, sore throat and nausea. Pneumonia caused by the Mycoplasma pneumoniae bacterium is generally a less severe form of the disease that can occur in any age group. It accounts for 20 percent to 30 percent of all community-acquired pneumonia cases.

In the current study, mice infected with the M pneumoniae bacterium were treated daily with a placebo, an antibiotic, a steroid, or a combination of the antibiotic and steroid in order to investigate the effect on M pneumoniae-induced airway inflammation. The animals were then evaluated after one, three and six days of therapy.

"It turns out that the group that got both the antibiotic and the steroids did the best," Dr. Hardy said. "The inflammation in their lungs got significantly better."

Although antimicrobials remain the primary therapy for M pneumoniae infection, there have been several reports in recent years about physicians adding steroids to the treatment regimen of patients with severe cases, Dr. Hardy said. The problem, he said, is that those were individual case reports.

"They never had a control group, so it was impossible to tell what impact the addition of steroids had on recovery," he said.

The new findings not only suggest that giving antibiotics with steroids can help individuals with pneumonia get better faster, but also suggest a potentially more effective therapy for someone in the midst of an asthma attack due to M pneumoniae infection. Up to 20 percent of asthma attacks in children and adults have been shown to be triggered by this bacterium.

Dr. Hardy said it's too early to recommend steroids as standard treatment for people with this type of bacterial pneumonia, but the work does support the need for a clinical trial.

"Or if there are very sick patients, this combination treatment doesn't seem to worsen the disease," he said. "The good thing about our results is the data alone support moving on to a clinical study."

Focus Attention Upon Distributors Of Human Growth Hormone, Scientists Urge

A great deal of attention has been paid to the use of growth hormone (hGH) by elite athletes and a few vocal entertainers. But underlying this tip of the iceberg is a $2 billion dollar a year business, likely involving hundreds of thousands of regular people, and promoted by anti-aging and age-management clinics and compounding pharmacies who aggressively market and sell growth hormone with the claim that it has anti-aging or athletic enhancing properties.

Since their previous article in the Journal of the American Medical Association (JAMA) in 2005 on the clinical and legal aspects of growth hormone for anti-aging, in which researchers from Boston University School of Medicine, Boston Medical Center and the University of Illinois at Chicago alerted the medical community and lay public to the deceptive mass marketing and illegal distribution of growth hormone for anti-aging and athletic enhancement, the authors provide new evidence demonstrating that these deceptive and dangerous activities have grown worse.

Remarks Dr. Thomas Perls, Director of the New England Centenarian Study and an associate professor of Medicine at Boston University School of Medicine, who has monitored the anti-aging industry for over the past ten years, "despite the overwhelming evidence that the risks and dangers of growth hormone far outweigh the clinically demonstrated insignificant benefit in normally aging individuals, the prescribing, distribution and sale of hGH for alleged anti-aging aesthetic and athletic enhancement has dramatically grown over the past few years. Clearly, the coordinated and aggressive marketing campaigns of the anti-aging and age-management industries are highly and most unfortunately effective."

Clinical evidence does support the therapeutic use of hGH for children and adults with appropriate clinical indications. However, these cases are disease specific and rare. Furthermore, any effectiveness that is demonstrated in the rare medical conditions approved for hGH distribution cannot be translated into effectiveness among healthy aging adults, a deceptive assertion often made by proponents of hGH use for a wide range of panacea-like benefits.

In January, 2007, the FDA issued an alert emphasizing that prescribing and distributing hGH for anti-aging and body building is illegal. A number of high-profile government investigations such as Operations Raw Deal, Phony Pharm and Which Doctor have attempted to make a dent in the illegal distribution of hGH and anabolic steroids for unapproved uses such as anti-aging or aesthetic reasons. As stated on the Albany County District Attorney's website, in the case of Operation Which Doctor, numerous governmental agencies are "working together to take down a nationwide distribution ring of anabolic steroids, Human Growth Hormones and other controlled substances, by targeting the ring's dirty doctors, its distributors that pose as clinics, and ultimately the ring's supplier Signature Pharmacy."

Contrary to published claims, neither long-term safety nor health benefits have been demonstrated in normally aging individuals taking hGH. A review of clinical studies among healthy, normally aging individuals found that hGH supplementation does not significantly increase muscle strength or aerobic exercise capacity. However, documented adverse effects include soft tissue edema, arthralgias (joint pains), carpal tunnel-like syndrome, gynecomastia (enlarged breasts) and insulin resistance with an elevated risk of developing diabetes. Increasingly more and more animal and laboratory studies suggest an increased cancer risk.

The authors suggest that several measures need to be taken to address the inappropriate distribution and use of hGH.

Among their recommendations:

  • The public must be accurately informed by physicians and scientists who do not have a vested interest in hGH, about health risks, fraudulent marketing and illegal distribution of this drug.
  • Organizations that promote or indirectly profit from the medically inappropriate and illegal distribution of hGH that have been accredited by the Accreditation Council for Continuing Medical Education (ACCME) to offer American Medical Association Physician Recognition Award (PRA) category 1 CME credits or other categories of CME credit should, at a minimum, have their accreditation revoked.
  • U.S. manufacturers of hGH must be more effective in, and held accountable for, controlling the distribution of the drug to companies providing the drug for illegal uses.
  • Congressional hearings and media attention surrounding hGH should focus less on athletes and prominent entertainers who are also victims of deceptive marketing and pushing of hGH, and much more on the distributors who are violating federal and state laws by making the drug available for non-approved uses.

Senators Schumer and Grassley and Representative Steven Lynch deserve the public's support of their intention to strengthen and enhance the law regarding the illegal distribution of hGH. 'Strengthening the law' should entail stiffer financial and imprisonment penalties for illegally prescribing and/or distributing growth hormone for purported anti-aging, age management, aesthetic enhancement, and body building uses. Enhancing the law should include the addition of sermorlin (growth hormone releasing hormone [GHRH]) and mecasermin (insulin-like growth factor I [IGF-1]) and their analogues. GHRH (which stimulates the release of endogenous hGH) and IGF-I (which mediates many of the effects of hGH) result in hGH-like effects, and, therefore, the potential for their inappropriate use as purported anti-aging and performance enhancement therapies clearly exists.

Perl adds: "In my capacity as a reviewer of medical records seized from anti-aging clinics by the DEA, I almost never see hGH provided in isolation. It is usually a part of a complex cocktail of one or more anabolic steroids, human chorionic gonadotropin (specifically for men to decrease the obvious signs of steroid abuse such as small testicles and enlarged breasts), thyroid hormone, DHEA and other drugs. Additional drugs such as blood pressure medicines, diuretics and insulin may be given to treat the side effects of the basic cocktail."

Perls is a consultant for the US Department of Justice.

Journal Reference:

  1. S. Jay Olshansky, Thomas T. Perls. New Developments in the Illegal Provision of Growth Hormone for "Anti-Aging" and Bodybuilding. JAMA, 2008;299(23):2792-2794

Testosterone Levels Predict City Traders' Profitability

When City traders have high morning testosterone levels they make more than average profits for the rest of that day, researchers at the University of Cambridge have discovered.

The scientists hypothesize that this may be because testosterone has been found to increase confidence and appetite for risk — qualities that would augment the performance of any trader who had a positive expected return.

The influence of steroids naturally produced in the body (specifically testosterone and cortisol) may also provide insight into why people caught up in bubbles and crashes often find it difficult to make rational choices, unintentionally exacerbating financial crises.

Testosterone is a steroid hormone which controls competitive encounters as well as sexual behaviour. Testosterone in male athletes, for example, will rise prior to a competition and rise even further in a winning athlete (but decrease in a losing one). This increase of testosterone in the winner can increase confidence and risk taking and improve chances of winning yet again, leading to a positive-feedback loop termed the 'winner effect'. However, too much testosterone can have a detrimental affect on the ability to assess risk rationally.

In order to determine how hormone levels affect those working in the financial sector, the researchers followed 17 City of London male traders for eight consecutive business days. To measure the traders' hormones, they took saliva samples twice per day at 11:00 a.m. and 4:00 p.m., times that fell before and after the bulk of the day's trading. At each sampling time, traders recorded their profit and loss (P&L).

Using the trader's previous trading history, the scientists determined a daily-average to which they could compare the test results. They found that daily testosterone levels were significantly higher on days when traders made more than their one-month daily average than on other days.

The researchers also speculated that if testosterone continued to rise or became chronically elevated, it could begin to have the opposite effect on a trader's profitability by increasing risk-taking to unprofitable levels. Previous studies have shown that administered testosterone can lead to irrational decision-making. They believe that this is because testosterone has also been found to lead to impulsivity and sensation seeking, to harmful risk taking, and in extreme cases (among users of anabolic steroids) to euphoria and mania.

Testosterone may therefore underlie a secondary consequence of the 'winner effect' in which a previous win in the markets leads to increased, and eventually irrational, risk taking in the next round of trading.

Professor Joe Herbert, Cambridge Centre for Brain Repair, said: "Market traders, like some other occupations (such as air traffic controllers), work under extreme pressure and the consequences of the rapid decisions they have to make can have profound consequences for them, and for the market as a whole. Our work suggests that these decisions may be biased by emotional and hormonal factors that have not so far been considered in any detail.

"Any theory of financial decision-making in the highly demanding environment of market trading now needs to take these hormonal changes into account. Inappropriate risk-taking may be disastrous. Hormones may also be important for determining how well an individual trader performs in the highly stressful and competitive world of the market. We are now exploring this in much more detail."

The researchers also examined the effects of increased levels of cortisol, a hormone which plays a role in our response to stress, on traders. They found that it rose when the variance of the market and traders P&L rose. The results suggested that cortisol responds to economic uncertainty.

During the study, traders experienced acutely raised cortisol in association with higher volatility in the markets and the increased chances of making money that higher volatility brings. The researchers suggest, however, that rising cortisol levels can reduce appetite for risk: that is, affect a trader's risk taking in the opposite direction to testosterone. Cortisol is known to have powerful cognitive and emotional effects. Amongst these effects are heightened memory for adverse events, and alteration in mood.

Together, these effects would tend to decrease a trader's risk taking. A situation of persistently elevated cortisol might occur if financial market volatility were to rise for an extended period, something that normally happens when the economy receives an unwelcome shock or enters a depression.

Cortisol is likely, therefore, to rise in a market crash and, by increasing risk aversion, to exaggerate the market's downward movement. Testosterone, however, is likely to rise in a bubble and, by increasing risk taking, to exaggerate the market's upward movement. These steroid feedback loops may help explain why people caught up in bubbles and crashes often find it difficult to make rational choices.

Dr. John Coates, lead author, said, "Rising levels of testosterone and cortisol prepare traders for taking risk. However, if testosterone reaches physiological limits, as it might during a market bubble, it can turn risk-taking into a form of addiction, while extreme cortisol during a crash can make traders shun risk altogether."

Coates, himself a former trader, continued, "In the present credit crisis traders may feel the noxious effects of chronic cortisol exposure and end up in a psychological state known as 'learned helplessness'. If this happens central banks may lower interest rates only to find that traders still refuse to buy risky assets. At times like these economics has to consider the physiology of investors, not just their rationality."

The article 'Endogenous steroids and financial risk taking on a London trading floor' is in the 14 April 2008 edition of Proceedings of the National Academy of Sciences (PNAS).

Blood Pressure Drug May Curb Brain Damage From Alzheimer's, Depression And Schizophrenia

A drug used to treat high blood pressure and enlargement of the prostate may protect the brain from damage caused by post-traumatic stress disorder, Alzheimer's disease, depression and schizophrenia.

Prazosin, also prescribed as an antipsychotic medication, appears to block the increase of steroid hormones known as glucocorticoids, Oregon Health & Science University and Portland Veterans Affairs Medical Center researchers have found. Elevated levels of glucocorticoids are associated with atrophy in nerve branches where impulses are transmitted, and even nerve cell death, in the hippocampus.

The hippocampus is the elongated ridge located in the cerebral cortex of the brain where emotions and memory are processed.

"It's known, from human studies, that corticosteroids are not good for you cognitively," said study co-author S. Paul Berger, M.D., assistant professor of psychiatry and behavioral neuroscience, OHSU School of Medicine and the PVAMC. "We think prazosin protects the brain from being damaged by excessive levels of corticosteroid stress hormones."

The study, titled "Prazosin attenuates dexamethasone-induced HSP70 expression in the cortex," is being presented during a poster session today at Neuroscience 2007, the annual Society for Neuroscience conference in San Diego.

Scientists believe stress activates a neurochemical response in the brain that triggers the release of glucocorticoids in the brain, and that high levels of glucocorticoids in blood serum are associated with such psychiatric conditions as schizophrenia, depression, PTSD and Alzheimer's disease. This mechanism has been linked to decreases in cognitive performance in older people who are not suffering from clinical dementia.

"Our hypothesis is that just being afraid of being blown up all the time means you have high levels of steroids all the time," Berger said, referring to PTSD among military personnel.

Low levels of glucocorticoids have anti-inflammatory effects in the brain, but high levels can trigger inflammatory mechanisms that damage nerve cells by activating an enzyme that causes oxidative stress. Even a single exposure to a high dose of glucocorticoids can be sufficient to damage nerve cells: A previous study showed synthetic glucocorticoid therapy to treat autoimmune disorders such as rheumatoid arthritis can induce mood disorders, including psychosis, and cognitive impairment known as "steroid dementia" in severe forms.

To determine the effects of prazosin, OHSU and PVAMC researchers, led by Altaf Darvesh, Ph.D., formerly of the OHSU Department of Psychiatry, administered a glucocorticoid called dexamethasone to rats, then measured the expression of a protein known as heat shock protein 70, or HSP70, that serves as a marker for neurotoxicity. Pretreatment with prazosin, an alpha-1 receptor antagonist, resulted in "significant" slowing of dexamethasone-induced expression in the cerebral cortex.

"The one thing we don't know for sure is, would you have to get it before you're traumatized," Berger said. "Lots of people have high levels of corticosteroids when they're under stress, so could we give them prazosin ahead of time to protect them from brain damage?"

Berger said future research will continue to look at where and how steroids cause brain damage, and just when prazosin would have to be administered to most effectively protect the brain against damage.

"We just looked at brain damage," he said. "Steroids are known to cause cognitive impairment in both rats and people, so the next step is to see if we can correlate brain damage with cognitive effects and determine if we can protect against brain damage to protect cognition."

The study was funded by the U.S. Department of Veterans Affairs.