Blood tests may reveal psychosis

Scientists are moving closer to developing blood tests that can diagnose serious mental disorders, according to a study published this week in the journal Molecular Psychiatry.

A consortium of researchers showed they could identify blood biomarkers for two key psychotic symptoms: hallucinations and delusions. They relied on a technique termed convergent functional genomics that integrates several independent lines of evidence from human and animal models to identify and prioritize findings. The same approach has been used to look for genes and gene pathways linked to bipolar disorder, alcoholism and schizophrenia. Last year, the researchers published blood biomarkers for mood disorders.

Much more work will be required in order for such blood tests to be used for diagnosing and treating mental illnesses. However, the technology would be a milestone because psychiatric disorders now are diagnosed -- often with a great deal of uncertainty -- by evaluating symptoms. And there are few good ways to measure, biologically, how a medication is working. The study was conducted at the Indiana University School of Medicine and Roudebush VA Medical Center; Scripps Research Institute at UC San Diego; and State University of New York, Syracuse.

"Objective blood biomarkers for illness state and treatment responses would make a significant difference in our ability to assess and treat patients with psychiatric disorders, eliminating subjectivity and reliance on patient's self-report of symptoms," the authors wrote in the paper.

Perhaps such tests would even prevent health insurance companies from refusing to pay for treatments for mental illness.

-- Shari Roan

Photo credit: Mark Boster  /  Los Angeles Times

For pregnant women with MS or epilepsy, some good news

Researchers at Stanford University have found that women with multiple sclerosis or epilepsy have only a slightly higher risk of abnormal fetal growth and C-section delivery compared with women without the conditions. Let's repeat, only a slightly higher risk. Nor do they appear to suffer a higher rate of other complications compared with pregnant women in general.

Here's ...

The news release from Stanford University.

The abstract from the study, based on an analysis of a large national database and published Wednesday in the journal Neurology.

And more on pregnancy and MS (from the National Multiple Sclerosis Society) and on pregnancy and epilepsy (from the Epilepsy Foundation).

Both MS and epilepsy are relatively common in women of child-bearing years. And the findings should provide some reassurance to those with the conditions who are pregnant -- or contemplating becoming so.

-- Tami Dennis

Is a wonder pill necessarily wonderful for people with Down syndrome?

Scientists are hard at work developing a cure for the genetic disorder Down syndrome. But even if they succeed, nearly 60% of parents whose children have Down syndrome might take a pass.

In a survey conducted by researchers from the psychiatry department at the University of British Columbia in Vancouver, 27% of parents said they would not cure their children, and another 32% said they were unsure. Many parents expressed concern that a cure would change their child’s personality, said Angela Inglis, a genetic counselor who worked on the survey.

“Yes, it is a challenge, but your life will change in so many ways for the good, [but] you can’t imagine not having him,” said one parent who would decline a cure.

That feeling was not universal. Forty-one percent of parents said they would definitely treat their children for Down syndrome. Those parents said they were motivated by a desire to make their kids more independent and to give them more opportunities in life, Inglis said. She added that parents who had the hardest time caring for their children were the most inclined to seek a cure.

“It is very difficult, especially for the family dynamics,” one parent told researchers. “It changes our life because there is so much more stress and issues with a child with special needs. We often feel like giving up on life.”

Patients with Down syndrome have three copies of chromosome 21 instead of the usual two. In addition to the mental and physical symptoms, it can cause congenital heart disease, hearing problems, celiac disease, dementia and problems with the intestines, eyes, thyroid and skeleton. People with Down syndrome often live into their 50s, according to the National Institute of Child Health and Human Development.

About one in every 800 babies is born with the disorder. Pregnant women over the age of 35 are routinely offered prenatal screening for Down syndrome. Nearly two-thirds of parents surveyed said they thought prenatal testing for the disorder – through amniocentesis or chorionic villus sampling – was a “good thing,” and 60% said such testing should be available to pregnant women of any age.

The survey was conducted in Canada and included responses from 101 parents. No similar surveys have been taken in the U.S. The results were reported this week at the National Society of Genetic Counselors’ annual education conference in Atlanta.

The question about a cure might become less theoretical in the not-too-distant future.

In patients with Down syndrome, the brain loses its ability to make an important neurotransmitter called norepinephrine. But researchers from Stanford University and UC San Diego found that in genetically engineered mice that have a rodent version of the disease, injections of a drug called xamoterol returned the animals to normal function.

Once inside the mouse brains, xamoterol converted into norepinephrine and allowed the mice to build nests and complete cognitive tests just like regular animals, according to a study being published in Thursday’s edition of Science Translational Medicine. The drug kicked in within just a few hours, but its effects wore off quickly.

The researchers suggested that people with Down syndrome could be treated with Droxidopa, another drug that converts into norepinephrine in the brain. Droxidopa is currently taken by people for orthostatic hypotension in Asia, and it's in Phase 3 clinical trials in the U.S. now. It should be taken with a second drug called carbidopa that would keep it from converting to norepinephrine until it entered the brain, the researchers said.

-- Karen Kaplan

Photo: A recent survey presented parents whose children have Down syndrome with a dilemma: To cure or not to cure? Credit: Beth A. Keiser / Associated Press

To fight inflammation with food

Inflammation -- a ramped-up immune system -- seems to be linked to chronic diseases such as cancer and heart disease, and even the very fact of aging. Some foods, it turns out, promote inflammation. Others damp it down.

Shara Yurkiewicz, our 2009 summer intern, wrote a fairly extensive Health section article on the issue of anti-inflammatory foods -- you can read it right here. She noted that there's an awful lot of over-the-top prose about anti-inflammation diets --"amazing results in just 30 days!" etc. etc. -- but also that there is some science to it all -- animal studies, cell culture studies, even some in people -- and that the science in this area is developing.

In broad brush strokes, fish oil, curcumin, antioxidant-rich fruits and vegetables -- they're anti-inflammatory. Saturated fats, trans fats, corn and soybean oil, refined carbohydrates, sugars -- they're pro-inflammatory.

Now some scientists are trying to paint with a narrower brush. They've come up with -- and tested -- an inflammation index for foods.

First, the scientists did a literature search and put together a list of foods with anti-inflammatory or pro-inflammatory properties. They came up with 42.

Top of the list on the bad, pro-inflammation end: carbs. Top at the anti-inflammatory end (should you be interested, but we caution you not to run out and immediately start consuming massive amounts in a quest to live forever): magnesium.

That was step one. In step two, the researchers decided to test whether the people's diets gelled with the levels of inflammation you could measure in their blood. So they tested it 494 people. The participants were asked periodically over the course of a year what they ate, and it was all cataloged very precisely. Samples of their blood were assessed for levels of a protein called CRP, which is a marker of inflammation as well as a risk factor for heart disease.

The scientists found that the measure worked, and that diet and inflammation indexes matched up in a broad sense -- i.e. those eating a lot of anti-inflammatory foods had lower CRP levels, and vice versa. (It wasn't a smooth, continuous relationship, however.) This supports the idea that diet really does influence your inflammation, even after controlling for other lifestyle factors. 

The researchers say that their index could be a great tool for research but that it could also help people who are trying to reduce levels of inflammation in their bodies to lower their risk for chronic diseases. Though you'd think most of us could get a long way by just remembering: Carbs and fat and stuff, EAT LESS. Produce, nuts and fish and stuff: EAT MORE.

The study was done by researchers at the University of South Carolina and the University of Massachusetts, and published in the Journal of Nutrition. You can read it here.

-- Rosie Mestel

Photo credit: Kirk McKoy

Criminal behavior may be hard-wired in the brain, researchers find

Are some people born criminals?

Increasing evidence from neuroscience suggests that many aspects of antisocial behavior can be traced to dysfunctional brains. For instance, brain scans of prisoners suggest the circuitry involved in fear conditioning has gone awry in criminal minds. Deformities of certain parts of the brain that may contribute to antisocial and psychopathic behavior have also been linked to a greater risk of arrests and convictions.

For a definitive answer, scientists would have to scan the brains of thousands of young children, then check back decades later to see which ones went on to lead a life of crime. If the immature brains of the future criminals were different from the immature brains of law-abiding citizens, it would be a powerful piece of evidence that some people are biologically predisposed to criminal activity, according to a group of researchers from the University of Pennsylvania, USC and the University of York in England.

That experiment is too ambitious, but the researchers did something similar.

In the early 1970s, they traveled to the island nation of Mauritius, off the eastern coast of Africa. They recruited 1,795 3-year-olds and gave them a test designed to measure whether their amygdalas – the part of the brain involved in processing fear – were developing normally.

The test involved a series of 12 tones. Some of them were pleasant. Others were higher-pitched and were followed by a jarring sound produced by “jangling metal objects,” according to a new report in The American Journal of Psychiatry.

The toddlers were hooked up to a polygraph to measure their reactions to the noises. The high-pitched tones were supposed to make them sweat in anticipation of the unpleasant sound, while the pleasant tones weren’t supposed to elicit much response at all.

Twenty years later, the researchers scoured court records to see whether any of their subjects had committed crimes involving violence, drugs, property or serious driving offenses. (Parking fines, expired car registrations, and other petty crimes weren’t counted.)

It turned out that 137 of the subjects – nearly 8% of the total – had criminal records. Looking back at their childhood tests, the scientists found that their reactions to the pleasant and high-pitched tones were the same. That was in stark contrast to the other subjects, who learned to fear the high-pitched tones and sweated accordingly. For the comparisons, criminals were matched with two non-offenders of the same age, gender, ethnicity and socioeconomic status.

The results suggest that criminal behavior may be hard-wired – to some degree – in children as young as 3 and could be the result of a malfunctioning amygdala, the researchers wrote. If they’re not afraid that their criminal behavior will land them in jail, what else will deter them?  The result, they wrote, is “a lack of conscience.”

-- Karen Kaplan

Photo: Was this arrest predetermined? Credit: Mark Wilson AFP/Getty Images

A proposal for improving cord blood transplants

Roughly one in five hematopoietic stem cell transplants performed to treat blood disorders such as leukemia uses cord blood instead of the traditional bone marrow. Cord blood – harvested from umbilical cords shortly after birth – could be used more often if more of it were available. Nearly 14 million people worldwide have volunteered to donate their bone marrow, while the number of cord blood units available for transplant is just over 380,000.

Dutch researchers may have found a partial solution. In an article published in this week's edition of Proceedings of the National Academy of Sciences, they propose that a relatively simple change in the way donors are matched with recipients could expand the number of optimal matches by up to eighteenfold.

When patients need a bone marrow or cord blood transplant, they are matched with donors who share as many human leukocyte antigens (HLAs) as possible. The immune system checks these proteins to tell whether a cell belongs in the body or is foreign, so the closer the match, the greater the chance the transplant will take.

The researchers examined 1,121 patients who received a unit of cord blood from the New York Blood Center National Cord Blood Program. Only 62, or 6%, got blood that was HLA-matched. The remaining 1,059 patients got mismatched blood.

But by coincidence, 79, or 7%, got blood that was matched in another way – according to noninherited maternal antigens, or NIMAs. These are proteins that patients were exposed to from their mothers before they were born. As a result, the researchers speculated that patients with NIMA matches would tolerate their transplants better and have higher survival rates.

They were right.

Three years after their transplants, patients who didn’t have an HLA match but got NIMA-matched cord blood were 40% less likely to have died than patients who didn’t have either kind of match, according to the study. For the sake of comparison, patients who had an HLA match were 60% less likely to have died than patients without either kind of match.

The difference was especially pronounced in patients who were at least 10 years old. Compared with patients with no match, those with an HLA match were 70% less likely to have died and those with a NIMA match were 60% less likely to have passed away, the study found.

NIMA-matched blood had other benefits too. The transplants engrafted faster than in unmatched patients, and the incidence of graft-versus-host disease was lower. The benefits were greatest for patients who were expected to have the worst outcomes, the researchers reported.

The Dutch scientists said they intend to start using NIMA status to matching patients with cord blood and will track the results to see if these trends hold up. They urged others to do so as well.

Allowing patients to substitute one HLA-matched antigen for a NIMA-matched antigen would boost the number of possible matches by a factor of six, and allowing two substitutions would theoretically boost it as much as 18 times. The team calculated that even a sixfold increase in potential matches was the equivalent of increasing the number of cord blood units available for transplant to more than 2 million.

“Although much work lies ahead, our findings justify changing the match algorithm for CB [cord blood] transplants,” they wrote.

-- Karen Kaplan

Photo: A new matching technique could make the most of limited cord blood supplies. Credit: Los Angeles Times

Medical marijuana: A refresher on the 'medical' component

When it comes to medical marijuana, the nation's doctors seem to be softening their stance even as local officials harden theirs. All things considered, perhaps a refresher on the treatment and research realities is in order.

Today's story on medical marijuana by staff writer John Hoeffel begins: "The American Medical Assn. on Tuesday urged the federal government to reconsider its classification of marijuana as a dangerous drug with no accepted medical use, a significant shift that puts the prestigious group behind calls for more research."

And Tuesday's story begins: "As hundreds of medical marijuana dispensaries have opened this year in a startling rollout across California, unnerved local officials have started to push back aggressively. Many cities and a few counties have banned them. Others have imposed emergency moratoriums. And some have started to sue dispensaries to force them to close. So far, the state's courts have sided with local officials."

Now back to marijuana's uses and potential. This article from health journalist Judy Foreman offers an overview of marijuana's safety and effectiveness in treating pain, cancer and other conditions. It notes, "There is a growing body of studies, much of it supportive of the drug’s medical usage, though some of it cautionary.’’ For more, check out a 2008 L.A. Times Health section story by freelancer Jill U. Adams.

And here's a nice explainer, via the National Pain Foundation, on how the drug affects pain. Plus a look at the issue from ProCon.org. It poses the question: "Should marijuana be a medical option?"

"Medical" is the operative word for this element of the debate.

— Tami Dennis

Embryonic stem cells may restore brains damaged by radiation

Scientists at UC Irvine and UC San Francisco have found a potential new use for human embryonic stem cells – helping cancer patients recover the cognitive function lost when their brains are treated with radiation.

People with tumors in their head or neck often undergo radiation therapy after the cancer is surgically removed. That radiation helps kill off any malignant cells left behind. But it can also debilitate the region of the brain called the hippocampus, which is responsible for learning, memory and processing of spatial information. It is also one of only two areas in the brain known to produce new neurons.

The UC researchers wondered whether embryonic stem cells could pick up the slack. In their pluripotent state, they have the potential to grow into any type of cell in the body. When injected into the hippocampus, would they naturally replace neurons damaged or killed by radiation therapy?

To find out, they radiated the heads of 18 rats. Two days later, six of those rats got two injections of human embryonic stem cells directly into the hippocampus.

After four months, the researchers used a standard test to measure the rats’ cognitive abilities. They placed the animals in an arena with two Lego blocks – borrowed from the son of senior researcher Charles Limoli – and were allowed to explore for as long as they liked.  When they were done, the researchers took the rats out of the arena and moved one of the blocks. Five minutes later, the rats went back in.

All of the animals studied both of the blocks, but the rats that were treated with stem cells spent significantly more time nosing around the one that had been moved. They did so, the researchers say, because they remembered where it used to be and thus were curious about its new position. In fact, they spent almost as much time investigating the block as did a group of control rats that were never subjected to any radiation. But the radiated rats that didn’t get stem cells lost roughly half of their cognitive function, according to the study, published in this week's edition of Proceedings of the National Academy of Sciences.

The scientists tested the rats again 24 hours later and got similar – though less pronounced – results.

When the tests were over, the researchers euthanized the rats and studied their brains. Sure enough, the stem cells had grafted into the hippocampus, where they grew into neurons and another kind of brain cell called astrocytes. In the four months that they were in the rat brains, the stem cells didn’t appear to grow into tumors, though that might have happened if the rats lived longer.

The results suggest that embryonic stem cells could spare cancer patients much of the short-term memory loss that results from cranial radiation and perhaps boost long-term memory as well, the researchers wrote. But several hurdles would have to be cleared before it could be tried in people.

Instead of using embryonic stem cells – which many people object to because they are derived from embryos – patients could be treated with induced pluripotent stem cells. Better known as iPS cells, these reprogrammed cells have been found to behave almost exactly like embryonic stem cells in a variety of laboratory tests. They could be custom-made for cancer patients, reducing the risk that the stem cell transplants would be rejected. But more research is needed to ensure that they would not form new tumors.

“Any treatments showing promise at reversing this are worthy of pursuit,” Limoli, an associate professor of radiation oncology at UCI, said in a statement.

The experiments were funded by the National Institutes of Health and the California Institute for Regenerative Medicine.

-- Karen Kaplan

Photo: These human embryonic stem cells restored cognitive function to rats whose brains were damaged by radiation. Credit: Munjal Acharya / UCI

Rodent of the Week: New use for an old drug

Research can be serendipitous. Sometimes doctors will stumble on an effective medication or they will find a drug they expected to work on one condition actually helps another.

Such is the case with a gonorrhea medication developed in the 1930s. Preliminary evidence published this week shows that the substance, called acriflavine, may work as a cancer therapy. Researchers from Johns Hopkins University discovered that the drug has the ability to stop the growth of new blood vessels, which may then curb tumor growth. Mice who were engineered to develop cancer showed no tumor growth when they were injected with acriflavine daily. The study showed that acriflavine inhibits the function of a protein called HIF-1, which promotes new blood vessel formation.

"Mechanistically, this is the first drug of its kind," Jun Liu, an author of the paper and a professor of pharmacology and molecular sciences, said in a news release. "It is acting in a way that is never seen for this family of proteins."

Researchers at Johns Hopkins continue to explore new uses for old drugs in the school's expansive drug library.

"The more drugs you have, the more possibilities, the higher the chance you rediscover something that will help," Liu said. "Oftentimes, we are surprised that a drug known to do something else has another hidden property."

The study is published in the Proceedings of the National Academy of Sciences.

-- Shari Roan

Photo credit: Advanced Cell Technology Inc.

Rodent of the Week: Axons regenerate long after injury

Scientists have been working for more than a decade on methods to treat spinal cord injuries by attempting to regrow injured nerves. Some success has been achieved in animals that are treated immediately after the injury.

However, new research shows it's possible to coax the regeneration of nerve axons in rats as long as a year after injury. Axons are the part of the nerve that carries signals away from the nerve body. In the experiment, researchers were able to stimulate the growth of axons in the damaged part of the spinal cord and somewhat beyond the site.

It's difficult to get injured axons to grow because of scar tissue at the injury site, inflammation and chemical processes that inhibit the growth. Thus, the treatment was dependent on a complex and sophisticated process that included a cellular bridge to the injury site, a nervous-system growth factor to guide axons to the correct target and a stimulus to the injured neurons that turns on genes to promote growth.

Using this formula, researchers were able to demonstrate successful regeneration of axons. Rats that did not receive the full combination treatment did not exhibit growth.

"The good news is that when axons have been cut due to spinal cord injury, they can be coaxed to regenerate if a combination of treatments is applied," the lead author of the study, Dr. Mark Tuszynski of UC San Diego, said in a news release. "The chronically injured axon is not dead.

"While the regenerating axons grow for relatively short distances, even this degree of growth could be useful. For example, restoration of nerve function even one level below an injury in the neck might improve movement of a wrist or hand, providing greater quality of life or independence."

The study is published in the journal Neuron.

- Shari Roan

Photo credit: Advanced Cell Technology Inc.