BioMed Radio - Washington University School of Medicine in St. Louis

Adults and teenagers with clinical depression don’t respond to rewards in a normal manner. Their moods are less enthusiastic, and their brains don’t act the same way as those in adults and adolescents who are not depressed. Although depression has been diagnosed in children as young as 3, it hasn’t been clear whether the responses of very young children to rewards also may be blunted. So Washington University researchers studied kids ages 4 to 7 and found that, like adults, when these young children were depressed, their brains were less likely to respond to rewards. The researchers say that could mean insensitivity to rewards may serve as a “red flag” for depression in young children.

PAST RESEARCH HAS FOUND THAT THE BRAINS OF DEPRESSED ADULTS AND ADOLESCENTS OFTEN DON’T RESPOND AS MUCH TO REWARDS AS THE BRAINS OF PEOPLE WHO DON’T HAVE DEPRESSION. NOW, CHILD PSYCHIATRY RESEARCHERS AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS HAVE FOUND THE SAME THING IS TRUE IN VERY YOUNG CHILDREN. JIM DRYDEN HAS MORE…

 

IT’S GETTING TO BE THE SEASON FOR PRESENTS, AND IF YOUR FOUR-YEAR-OLD DOESN’T SEEM EXCITED ABOUT THAT, IT COULD BE A PROBLEM ACCORDING TO RESEARCHERS AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS. IN OLDER ADOLESCENTS AND ADULTS, RESEARCH HAS FOUND THAT WHEN A PERSON IS DEPRESSED, THE BRAIN’S RESPONSE TO REWARDS CAN BE BLUNTED. NOW, THE FIRST AUTHOR OF A NEW STUDY OF PRESCHOOLERS SAYS THEY’VE FOUND THE SAME THING IS TRUE IN KIDS AS YOUNG AS FOUR. ANDREW BELDEN SAYS THIS IS…

 

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…frequently found in adults and adolescents, so what we were

interested in doing was to see, do, in fact, the depressed

preschoolers show this blunted response to reward doing slightly

modified, but age-appropriate tasks?

 

AGE-APPROPRIATE TASKS BECAUSE THE CHILDREN WERE PLAYING FOR TOYS. ADULTS AND ADOLESCENTS WERE STUDIED USING MONEY AS A REWARD. BELDEN SAYS FOR THIS STUDY, KIDS WERE SHOWN A COUPLE OF SETS OF TOYS THAT THEY COULD WIN. THEN THEY SAT AT A COMPUTER AND WERE ASKED TO PICK ONE OF TWO DOORS, WHICH THEN RANDOMLY GAVE THEM POINTS TOWARD A GOOD TOY OR SUBTRACTED POINTS FROM THEM, KIND OF LIKE A SLOT MACHINE FOR PRESCHOOLERS.

 

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The depressed preschoolers show a neural response very similar

to what is seen in older children, adolescents, adults.

 

THE RESEARCHERS MEASURED BRAIN ACTIVITY BY HAVING THE KIDS WEAR A SHOWER CAP-LOOKING DEVICE THAT WAS HOOKED TO ELECTRODES THAT MONITORED THEIR BRAIN ACTIVITY AS THE CHILDREN MADE CHOICES AND LEARNED WHETHER THOSE CHOICES WERE GETTING THEM CLOSER TO A TOY THEY LIKED, OR FARTHER AWAY. SENIOR INVESTIGATOR JOAN LUBY SAYS HER RESEARCH PREVIOUSLY HAD IDENTIFIED ANHEDONIA, THAT IS AN INABILITY TO EXPERIENCE JOY, FOR EXAMPLE IN ACTIVITIES AND PLAY, AS AN IMPORTANT MARKER OF DEPRESSION IN PRESCHOOLERS. AND THESE NEW FINDINGS APPEAR TO FIT WITH THOSE OLDER ONES.

 

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So this just gave us the neural validator of the behavior. An

alteration in this process this early in development is a serious

concern because it sort of sets the stage for how people approach

their interaction with rewarding tasks.

 

AND BELDEN SAYS THE DIFFERENCES WEREN’T APPARENT WHEN THE CHILDREN MADE A CHOICE THAT COST THEM POINTS. IN OTHER WORDS, IT WASN’T THAT THE BRAIN REACTED MORE NEGATIVELY TO FAILURE. IT WAS THAT IT REACTED LESS POSITIVELY TO SUCCESS AND REWARD.

 

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Vision problems can be caused by neurofibromatosis. Kids with mutations in the NF1 gene that causes neurofibromatosis often develop tumors on the optic nerve, but not all of them develop vision problems. Interestingly, Washington University researchers previously had learned that girls with tumors on the nerve were five to 10 times more likely to lose vision than boys with tumors of about the same size. Now those same researchers have found, in mice, that estrogen is the reason that females with these tumors are more likely to lose vision. Further study showed that cells called microglia are more common and more active in the tumors females develop. Those cells make substances that are more toxic to nerve cells and, therefore, damage vision. The researchers say strategies to temporarily lower estrogen levels in children with tumors on the optic nerve may make it possible to preserve vision without the need for chemotherapy to shrink such tumors.

TUMORS ON THE OPTIC NERVE ARE A COMMON FEATURE OF A GENETIC CONDITION CALLED NEUROFIBROMATOSIS TYPE 1 (NF1). ABOUT 15 TO 20 PERCENT OF YOUNG BOYS AND GIRLS WHO HAVE NF1 WILL DEVELOP THOSE TUMORS, CALLED OPTIC GLIOMAS. BUT LESS THAN HALF WILL EVER DEVELOP VISION PROBLEMS AS A RESULT. THAT’S IMPORTANT TO KNOW BECAUSE DAVID GUTMANN, DIRECTOR OF THE WASHINGTON UNIVERSITY NF CENTER, SAYS YOU DON’T WANT TO TREAT THE TUMOR WITH CHEMOTHERAPY IF IT’S NOT GOING TO THREATEN VISION.

 

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When we looked at our kids with NF1 who have these optic gliomas,

girls whose tumors were in the nerve were 5 to 10 times more

likely to lose vision than boys with tumors of about the same size.

 

IT TURNS OUT THAT FEMALE SEX HORMONES ARE PARTLY TO BLAME FOR THAT DIFFERENCE. GUTMANN AND HIS TEAM LOOKED AT MOUSE MODELS OF NF1 AND FOUND THAT ONLY FEMALE MICE WERE LOSING VISION FROM THE TUMORS. SO, THEY WORKED TO GET RID OF THE ESTROGEN IN THE FEMALE MICE TO SEE WHAT WOULD HAPPEN.

 

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If you either chemically ablate the ovaries, or remove the

ovaries, in these female mice with optic gliomas, they were

not experiencing the damage to the optic nerve that leads to

vision loss.

 

NEXT, GUTMANN’S TEAM FOUND THAT ESTROGEN WAS ASSOCIATED WITH LARGER NUMBERS OF IMMUNE SYSTEM CELLS CALLED MICROGLIA, AND THOSE MICROGLIA WERE MORE ACTIVE.

 

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And because they were numerous, and because they were changed

in a way that makes them more active, they were making compounds,

chemicals, that were damaging the nerve. And while identifying

those neurotoxins, we were able to establish a cause-and-effect

relationship between estrogen, the microglia and the “death

signals” that eventually cause the nerves to die.

 

GUTMANN SAYS ALTHOUGH THE COMPARISON FROM MOUSE TO HUMAN ISN’T PERFECT, IT IS CLEAR THAT BOYS AND GIRLS, EVEN AT VERY YOUNG AGES, HAVE HIGH ENOUGH LEVELS OF SEX HORMONES IN THEIR BRAINS TO EXPLAIN THESE DIFFERENCES IN MICROGLIA. AND GUTMANN SAYS UNDERSTANDING THE ROLE THAT SEX HORMONES PLAY IN THE DAMAGE TO VISION THAT THESE TUMORS CAN CAUSE ALSO WILL PROVIDE THE RESEARCHERS WITH NEW IDEAS ABOUT HOW TO TREAT OPTIC GLIOMAS IN KIDS WHO HAVE NF1.

 

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We can treat them with conventional therapies, but what I’d like

to see us start moving towards is not focusing on treating the tumor,

but focusing on treating those immune system cells that are damaging

the nerve itself. Because we can “win the battle,” that

Using MRIs, researchers at Washington University School of Medicine in St. Louis have identified areas in the brains of children with Tourette’s syndrome that appear markedly different from the same areas in the brains of children who don’t have the neuropsychiatric disorder.

RESEARCHERS AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS HAVE IDENTIFIED A FEW AREAS IN THE BRAINS OF CHILDREN WITH TOURETTE’S SYNDROME THAT APPEAR TO BE DIFFERENT FROM THE SAME AREAS IN THE BRAINS OF KIDS WHO DON’T HAVE THE NEUROLOGICAL DISORDER. AND THE REGIONS THAT THEY IDENTIFIED ARE ONES WHERE THEY HADN’T REALLY EXPECTED TO SEE DIFFERENCES. JIM DRYDEN HAS THE STORY…

THE RESEARCHERS USED MAGNIETIC RESONANCE IMAGING IN THE LARGEST STUDY OF ITS KIND EVER DONE ON PATIENTS WITH TOURETTE’S SYNDROME. IT INVOLVED RESEARCH TEAMS AT SEVERAL CENTERS AROUND THE UNITED STATES. PRINCIPAL INVESTIGATOR KEVIN BLACK, A PSYCHIATRIST AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS, SAYS THE RESEARCHERS ANALYZED MRI BRAIN SCANS CONDUCTED ON 103 KIDS WHO HAD TICS RELATED TO TOURETTE’S SYNDROME AND ANOTHER 103 KIDS OF THE SAME AGE AND GENDER WHO DIDN’T.

(act) :23 o/c template brain

The method that we picked is one that looks at the whole brain.

Basically, it squishes and stretches a brain until it’s the same

shape as a “standard brain,” and keeps track of how much it’s

squished, or stretched, in each spot so that you can tell what the

volume of the brain was that matches any given part of the template

brain.

IN ADDITION TO THE SQUISHING AND STRETCHING OF THE IMAGE, THE METHOD ALSO CAN DIFFERENTIATE BETWEEN GRAY MATTER AND WHITE MATTER IN THE BRAIN.

(act) :09 o/c the MRI

The method also figures how much gray matter or white matter

was in each spot based on the color, essentially, of the brain

image, of the MRI.

BLACK SAYS WHEN THE STUDY BEGAN, THE RESEARCHERS WERE FOCUSED ON PARTS OF THE BRAIN THAT ARE RELATED TO MOVEMENT BECAUSE TOURETTE’S IS CHARACTERIZED BY MOVEMENTS CALLED TICS. BUT BLACK SAYS THE STUDY DIDN’T FIND DIFFERENCES IN THOSE PARTS OF THE BRAIN. INSTEAD, THEY FOUND EXTRA GRAY MATTER IN SOME PARTS OF THE BRAIN AND REDUCED WHITE MATTER IN OTHER PARTS, AND MANY OF THOSE BRAIN REGIONS WERE RELATED TO THE PROCESSING OF SENSATION. THAT COULD MAKE SOME SENSE, BLACK SAYS, BECAUSE MANY PEOPLE WITH TOURETTE’S REPORT THAT THEY TEND TO TIC IN RESPONSE TO A SENSATION.

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Like, “Well, I’m only clearing my throat because it feels funny,”

that kind of thing. Or “I only sniff because my nose feels itchy.”

Maybe the sensory features are really the most obvious ones. Like,

if you have a cold, and somebody says, “Well, why don’t you stop

coughing?” You’re like, “Well, I’m only coughing because I’ve got

junk in my throat.” You know, that kind of sense that, really, it’s

the feelings inside that lead to the tics, rather than the tics

being their own beast.

AS TO WHETHER THE DIFFERENCES IN THE BRAINS OF KIDS WITH TOURETTE’S ARE ACTUALLY CAUSING THEM TO TIC OR ARE THE RESULT OF THOSE CHILDREN TRYING TO ADJUST TO THEIR TICS, BLACK SAYS IT’S TOO EARLY TO TELL.

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Is this something that starts early in life? Does it start

before people have tics, and that leads to their having tics?

Or, is it a healthy response to tics that helps fight them off?

Those are questions that we can best answer by trying to catch

people very early on in the course of tic disorders. That’s a

line of work that I’ve been trying to do for several years now.

HE SAYS THE SEARCH FOR A BETTER UNDERSTANDING OF WHAT TOURETTE’S IS AND HOW TO TREAT IT MORE EFFECTIVELY CAN BE A SLOW PROCESS BECAUSE THE DISEASE IS RELATIVELY RARE, AND STUDIES TAKE A LONG TIME. BUT BLACK SAYS COOPERATION BETWEEN SEVERAL CENTERS, AS OCCURRED IN THIS STUDY, COULD HELP SPEED THE PACE OF DISCOVERY. THE NEW STUDY IS PUBLISHED IN THE JOURNAL MOLECULAR PSYCHIATRY. I’M JIM DRYDEN…

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As part of the White House Brain Initiative, researchers at Washington University School of Medicine in St. Louis have received two grants to develop tools to map and activate pathways in the brain with light. With $3.8 million in funding from the National Institutes of Health (NIH), the researchers, with collaborators at the University of California, San Diego School of Medicine and the University of Illinois at Urbana-Champaign, will study how light-sensitive proteins can be used to control specific brain circuits with the goal of understanding how the brain is wired to regulate behaviors, such as stress, anxiety and depression.

THE WHITE HOUSE BRAIN INITIATIVE HELPS FUND CUTTING-EDGE PROJECTS THAT HELP SCIENTISTS BETTER UNDERSTAND THE WORKINGS OF THE BRAIN. A TEAM OF RESEARCHERS AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS HAS RECEIVED A PAIR OF GRANTS FROM THE INITIATIVE TO FUND THE DEVELOPMENT OF TOOLS ALLOWING ALLOW THEM TO USE LIGHT-SENSING PROTEINS FROM OTHER ORGANISMS, BIND THOSE PROTEINS TO RECEPTORS ON BRAIN CELLS, AND THEN USE LIGHT TO MAP AND ACTIVATE BRAIN PATHWAYS. JIM DRYDEN HAS THE STORY…

THE RESEARCHERS, FROM WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS AND THE UNIVERSITY OF CALIFORNIA, SAN DIEGO SCHOOL OF MEDICINE, WILL STUDY OPSINS. THOSE ARE LIGHT-SENSITIVE PROTEINS FROM THE EYES OF ANIMALS, AND HUMANS. IN ANIMALS, SUCH PROTEINS OFTEN ARE USED TO TELL THE ANIMAL WHEN IT’S DAYTIME, TO HELP THE ANIMAL AVOID PREDATORS, TO FIND A MATE, ETC. THE SCIENTISTS WILL USE THOSE NATURALLY OCCURING PROTEINS AND…

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Combine them with similar, related proteins that exist,

for example, dopamine receptors. In this grant, we’re going

to take proteins and combine some of their features with these

naturally-occurring proteins, that are in humans and in other

mammals, and be able to make tools that we can turn on switches

in the brain to sort of map how it’s connected.

THE BRAIN INITIATIVE GRANT WILL HELP BRUCHAS AND HIS COLLEAGUES STUDY THE STRUCTURE OF ALL KINDS OF OPSIN PROTEINS IN ANIMALS, FROM GOLDFISH TO BIRDS, AND HE SAYS CLEAVING THOSE ANIMAL PROTEINS ONTO HUMAN PROTEINS, LIKE BRAIN CELL RECEPTORS, COULD ALLOW THE SCIENTISTS TO INFLUENCE BEHAVIOR IN ANIMALS.

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It’s a three-year proposal involving everything from very

detailed structural biology of how these proteins look at

the structural level, all the way up to taking these proteins

and using genetic manipulations to get them into animals and

to do behavioral experiments to see, can we actually turn on

circuits and use this to map the brain?

MANY OF THE OPSIN PROTEINS THAT WILL BE USED IN THE STUDY ARE SUBSTANCES THAT ALREADY HAVE BEEN EXTENSIVELY STUDIED BY BIOLOGISTS.

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And that’s what’s so beautiful about it is we’re taking naturally

occurring things that many biologists have studied, and we’re

taking that knowledge, that basic knowledge, that was discovered;

and now we’re combining it with some of the mammalian biology, the

mammalian neuroscience that we do in my lab to fuse the two

disciplines in a way that allows us to sort of perturb neural

circuits in interesting ways and eventually be able to understand

how they function normally so that we can develop better treatments

for mental health disorders, including, you know, psychiatric

diseases like depression and anxiety.

BRUCHAS PREVIOUSLY WAS PART OF A TEAM THAT DEVELOPED WIRELESS, MICRO-LED DEVICES THAT CAN BE IMPLANTED INTO THE THE BODY OF A MOUSE TO TRANSMIT LIGHT. BY USING OPSIN PROTEINS FROM OTHER ORGANISMS, BRUCHAS SAYS IT SHOULD BE POSSIBLE IN THE FUTURE TO USE SEVERAL DIFFERENT WAVELENGTHS OF LIGHT IN THESE STUDIES. TYPICALLY, BRUCHAS SAYS HIS TEAM HAS ONLY USED ONE TYPE OF LIGHT.

(act) :21 o/c access previously

But now we’re going to be moving into other colors, like down into

the UV range of light, to the far-red-shifted sensitivities. Ther

Treatment-resistant depression is a big problem for older adults. More than half of seniors with clinical depression don’t get relief from standard antidepressant medications. To address that problem, psychiatrists at Washington University School of Medicine in St. Louis are helming a multicenter study to evaluate the efficacy of supplementing current therapies with additional drugs, or changing medications altogether. The study will follow 1,500 people with depression from St. Louis and rural Missouri, Los Angeles, Western Pennsylvania, New York City, Toronto and rural Ontario. Study subjects will be 60 or older, and all will have failed to respond to treatment involving at least two antidepressants. Some subjects will take additional drugs during the study, and others will be switched to different medications. After treatment, the researchers will attempt to evaluate which types of patients respond best to specific treatment strategies.

TREATMENT-RESISTANT DEPRESSION IS A PARTICULAR PROBLEM FOR OLDER ADULTS. LESS THAN HALF OF SENIORS WITH CLINICAL DEPRESSION RESPOND COMPLETELY TO THE MOST COMMONLY USED ANTIDEPRESSANT DRUGS. SO NOW, RESEARCHERS AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS ARE LEADING A STUDY TO IDENTIFY BETTER WAYS TO PROVIDE RELIEF FOR THOSE WHO DON’T CURRENTLY GET COMPLETE RELIEF FROM COMMON ANTIDEPRESSANT MEDICATIONS. JIM DRYDEN HAS THE STORY…

IT’S CALLED THE OPTIMUM STUDY — AN ACRONYM FOR OPTIMIZING OUTCOMES OF TREATMENT-RESISTANT DEPRESSION IN OLDER ADULTS — AND RESEARCHERS ARE RECRUITING 1500 PEOPLE OVER THE AGE OF 60 WHOSE DEPRESSION HASN’T RESPONDED COMPLETELY TO DRUGS CALLED SELECTIVE SEROTONIN REUPTAKE INHIBITORS, OR SSRIs. WASHINGTON UNIVERSITY PSYCHIATRIST ERIC LENZE IS LEADING THE OPTIMUM STUDY.

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Most older adults get either an incomplete benefit or an

insufficient benefit. You’ll almost always receive a medication

that we call an SSRI. These are medications like Prozac or Paxil

or Zoloft or Lexapro. Half, or more, of older adults will have, as

I said, either an incomplete or a very insufficient benefit from

these medications.

SOME PEOPLE IN THE STUDY WILL REMAIN ON WHATEVER DRUG THEY’RE CURRENTLY USING, AND A SECOND DRUG WILL BE ADDED, TOO. ADDING A SECOND DRUG IS KNOWN AS AUGMENTATION, AND LENZE SAYS IT’S A COMMON WAY TO TREAT MANY DISORDERS.

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Many people might have high blood pressure or diabetes, and

they take one medication for it. And that helps some but not

enough, so they need to take a second medication. So in

depression treatment, if one treatment isn’t enough, add a

second one that seems to work well with that first one.

OTHERS IN THE STUDY WILL GET A DIFFERENT DRUG ENTIRELY. THAT’S A STRATEGY THAT LENZE CALLS A SWITCH.

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The other line of thinking is, well if this medication isn’t

working, don’t stay on that medication because it’s not working

very well. So try switching to a different kind of medication.

THE REASON SWITCHING IS ATTRACTIVE, PARTICULARLY FOR OLDER ADULTS, IS THAT IT LIMITS THE NUMBER OF PILLS A PATIENT HAS TO TAKE.

(act) :14 o/c to do

If you get augmentation treatment, that means you’re going to

be on two medications, so you might have more side effects.

You might have more risks, simply because you’re on two

Medications, and right now, we don’t know which is the best

thing to do.

THE AUGMENTATION AND SWITCH PATIENTS WILL BE EVALUATED AFTER 10 WEEKS OF TREATMENT, AND IF SOME STILL HAVE DEPRESSION, THEY’LL BE PLACED INTO ANOTHER ARM OF THE STUDY IN WHICH OLDER, HARDER-TO-USE DRUGS MAY BE INTRODUCED AS TREATMENTS.

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You might benefit from your doctor adding lithium. And in fact,

decades ago, that’s what psychiatrists used to do. And this isn’t

done very much anymore, in part because lithium can be difficult

to prescribe. You need to check someone’s kidney function. You need

to do blood l

Children with sickle cell disease frequently have painful episodes that can require hospitalization for a few days. Physicians want to treat those episodes quickly to eliminate pain and get a child back home and back to school as quickly as possible, and now, researchers at Washington University School of Medicine in St. Louis have found that using the drug methadone might eliminate the pain more quickly. Methadone frequently is used to treat cancer pain and is a well-known treatment for addiction. But it also may be useful treating the severe pain associated with sickle cell disease.

TREATING PAIN FROM SICKLE CELL DISEASE CAN BE DIFFICULT. CHILDREN WITH THE DISEASE OFTEN HAVE SEVERE PAIN EPISODES THAT CAN REQUIRE HOSPITALIZATION. BUT NOW RESEARCHERS AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE AND ST. LOUIS CHILDREN’S HOSPITAL HAVE FOUND THAT ADDING METHADONE TO OTHER PAIN KILLERS CAN RELIVE SICKLE CELL PAIN MORE QUICKLY IN CHILDREN AND MAY BE ABLE TO HELP YOUNGER PATIENTS GET HOME FROM THE HOSPITAL SOONER. JIM DRYDEN HAS THE STORY…

IT’S NOT UNCOMMON FOR PATIENTS WITH SICKLE CELL DISEASE TO HAVE PAIN EPISODES THAT LAND THEM IN THE HOSPITAL. SIXTY PERCENT HAVE AT LEAST ONE SUCH EPISODE, CALLED A VASO-OCCLUSIVE EPISODE, EACH YEAR. ABOUT ONE IN FIVE HAVE MULTIPLE EPISODES ANNUALLY THAT REQUIRE HOSPITALIZATION. BECAUSE THE DRUG METHADONE HAS BEEN EFFECTIVE AS A TREATMENT FOR CANCER PAIN, WASHINGTON UNIVERSITY EMERGENCY MEDICINE SPECIALIST JENNIFER HORST AND HER COLLEAGUES DECIDED TO SEE HOW IT WORKED IN PATIENTS WITH PAIN FROM SICKLE CELL DISEASE.

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Methadone is a medication that is used a lot with patients with

other types of chronic pain, such as cancer patients. There are

some patients with sickle cell disease who have received methadone,

but it’s a small minority. And it’s not one of the typical pain

medications.

CHILDREN, AND ADULTS, WITH SICKLE CELL DISEASE HAVE VASO-OCCLUSIVE EPISODES WHEN THE SHAPE OF THEIR RED BLOOD CELLS BECOMES ALTERED.

(act) :25 o/c causes pain

There is a problem with their red blood cells, and under

certain circumstances – such as illness or dehydration or,

sometimes, of unknown causes – the red blood cells change

shape. And we call it sickle; they’re in a sickle shape.

And whenever the red blood cells change shape, they do not

flow through the blood vessels as well and cannot give oxygen

to the tissue as well, and that’s what causes pain.

HORST WORKED WITH WASHINGTON UNIVERSITY ANESTHESIOLOGIST EVAN KHARASCH IN TESTING METHADONE IN SICKLE CELL PATIENTS. THEY FOLLOWED 24 CHILDREN AND ANOTHER 23 ADULTS WHO HAD BEEN HOSPITALIZED FOR PAIN. EVERYONE GOT STANDARD PAIN-KILLING DRUGS, BUT HALF OF THE KIDS AND ADULTS ALSO GOT A SINGLE, LOW DOSE OF METHADONE ON THEIR FIRST DAY IN THE HOSPITAL.

(act) :21 o/c discharged home

Because this pain medication has a faster onset and lasts longer

than other, typical pain medicines, we hoped that we would be able to

either prevent them from being admitted to the hospital – which would be

the most ideal thing, that they’d be able to go home – or that if

they had to be admitted, they would be able to resolve their pain

crises more quickly and be discharged home.

IN THE CHILDREN, THE SINGLE, LOW DOSE OF METHADONE RESULTED IN BETTER PAIN RELIEF THAN THE STANDARD PAIN-KILLING DRUGS THAT KIDS NORMALLY GET.

(act) :23 o/c last longer

There is not a lot of data on how methadone works in children,

and so that was one of the things we were looking at. What we

have found is that methadone is longer lasting than other pain

medicines that would typically be used, and also has a faster

onset. And so, the pain could be treated more quickly, and the

pain relief would last longer.

BUT IN ADULTS, HORST SAYS, THERE WASN’T AS MUCH OF A DIFFERENCE BETWEEN PATIENTS WHO GOT METHADONE AND THOSE WHO DIDN’T.

(act) :15 o/c have seen

Part of the study was to make sure that we could give this

m

Researchers at Washington University School of Medicine in St. Louis will play a major role in the largest long-term study of brain development and child health in U.S. history. The landmark study will follow the biological and behavioral development of more than 10,000 children, beginning when the kids are 9 to 10 years old. Scientists studying the adolescents will use advanced brain imaging, interviews and behavioral testing to see how childhood experiences can affect a child’s changing biology, brain development and, ultimately, social, behavioral, academic and health outcomes. If the researchers can get a better understanding of the relationships between such factors, they may be able to predict and prevent, or even reverse, potential problems in development.

WE AREN’T BORN WITH FULLY-DEVELOPED BRAINS. IN FACT, BRAIN DEVELOPMENT CONTINUES FOR YEARS. AND RESEARCHERS AT WASHINGTON UNIVERSITY IN ST. LOUIS WILL PLAY A BIG ROLE IN A NEW NIH-FUNDED STUDY OF BRAIN DEVELOPMENT IN ADOLESCENTS. THE SO-CALLED ABCD STUDY WILL BE THE LARGEST OF ITS KIND EVER, FOLLOWING MORE THAN 10,000 CHILDREN FROM AGE 9 OR 10 INTO EARLY ADULTHOOD. JIM DRYDEN REPORTS…

A WHOLE LOT OF THINGS INFLUENCE BRAIN DEVELOPMENT: FAMILY BACKGROUND, SOCIO-ECONOMIC GROUP, AND A GREAT DEAL OF GROWTH AND DEVELOPMENT OCCURS DURING ADOLESCENCE. NOW, THE NIH HAS LAUNCHED AN AMBITIOUS PROJECT TO KEEP TRACK OF SOME OF THE THINGS THAT INFLUENCE HEALTHY, AND UNHEALTHY, BRAIN DEVELOPMENT. RESEARCHERS AT 19 CENTERS, INCLUDING WASHINGTON UNIVERSITY, WILL SCAN THE BRAINS OF YOUNG PEOPLE, CONDUCT INTERVIEWS AND DO BEHAVIORAL TESTING TO LEARN HOW ENVIRONMENT, BEHAVIOR AND GENETICS INTERACT TO INFLUENCE BRAIN DEVELOPMENT. WASHINGTON UNIVERSITY NEUROSCIENTIST DEANNA BARCH SAYS THEY’LL BE LOOKING AT…

(act) :14 o/c in life

Factors that promote both health brain development in children

and the factors that lead brain development to go awry and to

put kids at risk for a variety of mental health or other challenges

later in life.

AND BARCH SAYS THE RESEARCHERS WILL CONSIDER PRETTY MUCH EVERYTHING.

(act) :25 o/c and behavior

Things like peers and social supports and families, and how those

help promote healthy brain development; factors related to the

activities that kids engage in — sports and music and after-school

activities — but to also try to understand what happens when kids

engage in behaviors that may be less good for them. You know, if

they use substances or other things that might interfere with healthy

brain development and behavior.

ONE KEY PART OF THE STUDY WILL INVOLVE FOLLOWING TWINS. THE WASHINGTON UNIVERSITY TEAM IS ONE OF FOUR INVOLVED IN THIS STUDY THAT IS SPECIFICALLY RECRUITING PAIRS OF TWINS. BY STUDYING THE BRAINS AND BEHAVIOR OF THOSE TWIN PAIRS, AND BY RECRUITING TWINS OF EVERY RACE, ETHNICITY AND ECONOMIC BACKGROUND, WASHINGTON UNIVERSITY GENETICS RESEARCHER ANDREW HEATH SAYS THE PROJECT SHOULD BE ABLE TO LEARN A GREAT DEAL ABOUT HOW GENETICS INFLUENCE BRAIN DEVELOPMENT.

(act) :26 o/c diverse sample

We are going to be able to achieve a breadth of race and ethnic

diversity that has never before been possible: Hispanic pairs,

African-American pairs, Asian pairs, as well as white non-Hispanic

pairs. That’s a really exciting aspect of this study. It’s going to

allow us to look at the genetics of brain development in a truly

diverse sample.

THE IDEA, SAYS WASHINGTON UNIVERSITY RESEARCHERS PAMELA MADDEN IS TO GET A LARGE, AND REPRESENTATIVE SAMPLE OF KIDS.

(act) :13 o/c Missouri region

In addition to twins throughout the state, we are reaching more

locally to school districts. We are interested in coming up with

a representative sample of the St. Louis, and the broader

Missouri region.

BUT WHEN IT’S ALL SAID AND DONE, HEATH SAYS THE PROJECT SHOULD HELP RESEARCHERS LEARN WHAT CONSTITUTES NORMAL BRAIN DEVELOPMENT SO THAT THEY MAY BE ABLE TO SPOT AT-RISK KIDS AT VERY YOUNG AGES.

(act) :17 p/c high-r

Quitting smoking improves health and lowers odds of developing lung cancer. But a new study shows that even among smokers with a genetic predisposition to smoking heavily and developing young cancer at a young age, the benefits of quitting are significant. An international study led by researchers at Washington University School of Medicine in St. Louis and the Siteman Cancer Center indicates that in these high-risk smokers, quitting cuts lung cancer risk in half and delays the age at which the disease is diagnosed.

AN INTERNATIONAL STUDY, LED BY RESEARCHERS AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS AND THE SITEMAN CANCER CENTER, SHOWS THAT QUITTING SMOKING IMPROVES HEALTH AND LOWERS THE ODDS OF DEVELOPING LUNG CANCER, EVEN AMONG SMOKERS WHO ARE GENETICALLY PREDISPOSED TO SMOKE HEAVILY AND TO DEVELOP CANCER AT A YOUNGER AGE. JIM DRYDEN HAS THE STORY…

THE NEW FINDINGS SUGGEST THAT DOCTORS MIGHT WANT TO REQUEST DNA ANALYSIS FROM SMOKERS IN ORDER TO EMPLOY THE MOST EFFECTIVE THERAPIES TO HELP THEM QUIT, BUT THERE’S NO DOUBT, SAYS WASHINGTON UNIVERSITY RESEARCHER LI-SHIUN CHEN, THAT KICKING THE SMOKING HABIT CAN CUT CANCER RISK, EVEN IN SMOKERS WHO HAVE A GENETIC PROFILE THAT PUTS THEM AT RISK FOR HEAVY SMOKING AND FOR DEVELOPING LUNG CANCER FOUR YEARS EARLIER THAN SMOKERS WHO DON’T HAVE THAT GENETIC BURDEN. CHEN SAYS DOCTORS ALWAYS ADVISE SMOKERS THAT THEY SHOULD QUIT…

(act) :15 o/c risk anyway

The question is that quitting smoking, does that reverse the

genetic risk? Because one can argue that, “Well, I have the

high genetic risk for lung cancer. It’s too late for me to

quit. There’s no use. Why should I quit? I have high risk anyway.”

BUT, STUDYING DATA FROM MORE THAN 12,000 CURRENT AND FORMER SMOKERS, CHEN AND HER COLLEAGUES FOUND THAT QUITTING SMOKING BENEFITS BOTH THOSE AT ELEVATED GENETIC RISK, AND THOSE SMOKERS WHO DON’T HAVE SUCH A RISKY GENE PROFILE. BUT SHE SAYS THE SMOKERS WHO HAVE GENE VARIANTS THAT INCREASE THEIR RISK GET PARTICULAR HEALTH BENEFITS IF THEY CAN MANAGE TO QUIT.

(act) :14 o/c 7 years

Quitting smoking cut the risk of lung cancer in half. And

the second finding is that for those who get lung cancer,

quitting smoking delays the cancer diagnosis by 7 years.

PERHAPS EVEN MORE IMPORTANTLY, CHEN’S TEAM FOUND THAT THERE WERE BENEFITS BOTH FOR SMOKERS WITH AN ELEVATED RISK AND FOR THOSE WITHOUT THAT RISK.

(act) :18 o/c genetic risks

This is the first time that we’ve quantified the benefits of

quitting — delays cancer by 7 years — versus the genetic risk

that accelerates cancer by 4 years. We find that these benefits

of quitting are no different for people with high versus low

genetic risks.

SO CHEN SAYS THE FINDINGS DEMONSTRATE THAT A SMOKER’S GENES AREN’T THE ONLY THINGS DETERMINING WHETHER THAT INDIVIDUAL WILL DEVELOP LUNG CANCER.

(act) :15 o/c my fate

Some people believe that genes determine everything, so

there’s no use for me to promote my own health behavior.

And this is a study to really, directly fight the myth of

there’s no use. My genes determine my fate.

IN ADDITION, CHEN’S TEAM ALREADY HAD LEARNED IN A PAST STUDY THAT SMOKERS WITH ELEVATED GENETIC RISKS ARE MORE LIKELY TO RESPOND TO NICOTINE-REPLACEMENT THERAPY. SO SHE SAYS DOCTORS MAY WANT TO TAKE A LOOK AT THE DNA OF SMOKERS WHO WANT TO QUIT, IN ORDER TO TAILOR PRECISE TREATMENTS BASED ON AN INDIVIDUAL PATIENT’S RISKS.

(act) :23 o/c more precise

Another important concept that’s brought forward by the

National Cancer Institute is called “precision prevention.”

In the field of medicine, we give all kinds of medical advice.

You should quit smoking. You should eat healthy. You should

exercise. So, we’re stepping into the era where the health

advice can be personalized and be more precise.

HER TEAM REPORTED ITS FINDINGS ONLINE IN THE JOURNAL eBioMedicine. I’M JIM DRYDEN...

RUNS 2:58

In search of genetic clues regarding autism spectrum disorder, researchers at Washington University School of Medicine in St. Louis are launching a study focused on grandmothers. Autism has a strong genetic basis, and rates of the disorder may be higher in the grandchildren of women who had at least one child with an autism spectrum disorder than in the population as a whole. To test that hypothesis, the researchers plan to recruit a minimum of 500 grandmothers and soon-to-be grandmothers to complete questionnaires about their own children with autism, their other biological children and their biological grandchildren. The researchers want to better understand how to support families and help them understand the odds that some of their children may inherit the disorder.

AUTISM SPECTRUM DISORDERS HAVE A STRONG GENETIC COMPONENT, AND RESEARCHERS AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS ARE SURVEYING GRANDMOTHERS TO FIND OUT MORE ABOUT HOW IT’S PASSED DOWN IN FAMILIES. THE RESEARCHERS ARE RECRUITING WOMEN WHO HAD AT LEAST ONE CHILD WITH AUTISM, AND WHO NOW HAVE GRANDCHILDREN, TO SEE HOW RISK FOR THE DISORDER MAY BE PASSED THROUGH THE GENERATIONS. JIM DRYDEN HAS MORE…

ALTHOUGH PEOPLE WITH SERIOUS AUTISM SPECTRUM DISORDER DON’T OFTEN HAVE CHILDREN THEMSELVES, SCIENTISTS KNOW THAT GENETICS PLAYS A BIG ROLE IN THE DISORDER. CURRENTLY, EXPERTS ESTIMATE THAT ABOUT ONE IN 68 CHILDREN WILL BE BORN WITH AN AUTISM SPECTRUM DISORDER. TO LEARN ABOUT GENETIC RISKS, RESEARCHERS HAVE STUDIED PARENTS AND SIBLINGS OF THE KIDS WHO HAVE THE DISORDER, AND NOW, THEY’RE RECRUITING GRANDMOTHERS TO LEARN EVEN MORE. WASHINGTON UNIVERSITY CHILD PSYCHIATRIST NATASHA MARRUS.

(act) :18 o/c biological grandmothers

The project is called the Second Generation Survey Project. We’re

recruiting women who are the biological mothers of a child with an

autism spectrum disorder, but who also have other children, who

themselves did not necessarily have autism, and who now are

biological grandmothers.

THE HYPOTHESIS IS THAT IN FAMILIES WHERE AT LEAST ONE CHILD HAD AN AUTISM SPECTRUM DISORDER, THERE MAY BE A GREATER RISK OF AUTISM IN SUBSEQUENT GENERATIONS, EVEN IF THE PARENTS OF THOSE CHILDREN AREN’T THE FAMILY MEMBERS WHO HAD BEEN DIAGNOSED WITH AUTISM. BY SURVEYING GRANDMOTHERS ABOUT THEIR GRANDKIDS, MARRUS AND HER COLLEAGUES HOPE TO LEARN WHETHER THAT THAT’S TRUE.

(act) :11 o/c be there

We’re curious to see what is the prevalence of autism in that

next generation so that we can better understand how to support

families, so they understand the risk that may be there.

ONE KEY ASPECT OF AUTISM IS THAT ALTHOUGH THE INCIDENCE OF DISORDERS SEEMS TO BE INCREASING THROUGHOUT THE POPULATION, THE PROBLEM IS STILL MUCH MORE LIKELY TO AFFECT BOYS THAN GIRLS. HOWEVER, GIRLS WITH A FAMILY HISTORY OF AUTISM MAY STILL BE AT A HIGHER RISK OF HAVING A CHILD OF THEIR OWN WHO HAS AUTISM.

(act) :18 o/c general population

Girls, as many people know, are less likely to develop autism

themselves, however, it’s thought that they may carry the genetic

susceptibility to autism, which could then be passed on, to male

children in particular, at rates higher than would be expected in

the general population.

AND SHE SAYS ALTHOUGH THERE ARE SOME ENVIRONMENTAL RISK FACTORS, AUTISM SPECTRUM DISORDER MAINLY IS INHERITED.

(act) :12 o/c in families

So there is a strong genetic basis for autism — this isn’t to

say that the environment doesn’t matter, but a lot of what

contributes to autism is thought to be in genes — which,

therefore, means that it can run in families.

MARRUS SAYS MANY RESEARCHERS BELIEVE AUTISM RISK CAN BE MASKED, PARTICULARLY IN GIRLS, AND THEN PASSED ON WHEN THOSE GIRLS GROW UP AND HAVE KIDS OF THEIR OWN.

(act) :20 o/c as treatments

One of the very active areas of research is to figure out what

the level of this risk is and the biology that underlies this

risk because if we understand the biology t

A new study reveals that some eye specialists who receive money from pharmaceutical companies are more likely to use drugs promoted by those companies than similar drugs that are equally effective but less expensive. Although the data can’t confirm a cause and effect between money from industry and the prescribing habits of some physicians, researchers at Washington University School of Medicine in St. Louis report in the journal JAMA Ophthalmology that they have identified a “positive association between reported pharmaceutical payments and increased use” of drugs prescribed to treat several retinal problems.

AN ANALYSIS OF RECORDS MADE PUBLIC BY THE U.S. PHYSICIANS PAYMENTS SUNSHINE ACT, SHOWS THAT THERE IS AN ASSOCIATION BETWEEN REPORTED PAYMENTS FROM PHARMACEUTICAL COMPANIES AND THE DRUGS THAT SOME RETINA SPECIALISTS USE IN THEIR PATIENTS WHO HAVE MACULAR DEGENERATION AND OTHER RETINAL DISEASES. OPHTHALMOLOGY RESEARCHERS AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS IDENTIFIED THAT ASSOCIATION CRUNCHING NUMBERS FROM 2013, THE MOST RECENT YEAR FOR WHICH THE INFORMATION IS AVAILABLE. JIM DRYDEN HAS MORE…

THE ABILITY TO ASSOCIATE PAYMENTS FROM PHARMACEUTICAL COMPANIES WITH THE DRUGS THAT DOCTORS ACTUALLY PRESCRIBE PROVIDED RESEARCHERS WITH AN OPPORTUNITY TO LOOK FOR CONNECTIONS. THE RESEARCH TEAM MAKES IT CLEAR THAT THEY CAN’T IDENTIFY A CAUSE-AND-EFFECT RELATIONSHIP BETWEEN DRUG COMPANY PAYMENTS AND THE RETINAL THERAPIES SOME DOCTORS USE, BUT THEY DO FIND AN ASSOCIATION. WASHINGTON UNIVERSITY RETINA SPECIALIST RAJ APTE SAYS HISTORICALLY, DOCTORS LIKE HIM HAD ONE DRUG THAT WORKED PRETTY WELL, KNOWN AS AN ANTI-VEGF AGENT, THAT THEY COULD INJECT TO TREAT SEVERAL RETINAL DISEASES. APTE SAYS ALTHOUGH IT WORKED WELL, IT WAS NOT FDA-APPROVED FOR USE IN THE EYE. THEN, A FEW YEARS LATER, TWO OTHER DRUGS WERE INTRODUCED, AND THOSE MEDICATIONS DID GET FDA APPROVAL. ALL THREE DRUGS ARE ABOUT EQUALLY EFFECTIVE, BUT WHEN THE LATTER TWO CAME TO THE MARKET, THEY WERE HEAVILY PROMOTED. APTE SAYS THAT HISTORY ALLOWED HIS TEAM TO LOOK AT A UNIQUE INTERACTION.

(act) :15 o/c conditions, off-label

The utilization of medications that are approved by the FDA and

promoted by industry, versus a medication that is not approved

by the FDA but also used extensively for the same conditions,

off-label.

APTE’S TEAM FOUND THAT THE TWO NEWER, FDA-APPROVED DRUGS, CALLED RANIBIZUMAB AND AFLIBERCEPT, WERE USED MORE OFTEN BY DOCTORS WHO GOT PAYMENTS FROM THE DRUG COMPANIES THAN THE OLDER DRUG, BEVACIZUMAB.

(act) :15 o/c not promoted

What we found was a positive association between payments from

pharmaceutical companies and usage of the two promoted medications,

which also happen to be FDA-approved, compared to the medication,

bevacizumab, that’s not FDA-approved and not promoted.

APTE’S TEAM ALSO FOUND THAT THE DRUG COMPANIES DIDN’T HAVE TO PAY OUT VERY MUCH.

(act) :19 o/c the association

And this is not just us. It’s been shown before, in other studies,

that it’s not the dollar amount. It’s really the interaction

between the provider and the industry that influenced it. There

was an increase, but it really was the fact that there was an

interaction that would influence the association.

THE STUDY DOES NOTE THAT THE NEWER, PROMOTED DRUGS COST OVER $1900 PER DOSE, WHILE THE OLDER, OFF-LABEL DRUG COSTS ABOUT $60 PER DOSE, BUT APTE SAYS IT ISN’T POSSIBLE WITH THESE NUMBERS TO IDENTIFY A CAUSE-AND- EFFECT RELATIONSHIP BETWEEN PAYMENTS AND USE OF THE DRUGS.

(act) :28 o/c good start

And I think as we start collecting data, five and 10 years from

now, you know this is going to become more clear, and we’ll get

more sophisticated metrics and an understanding of what this means.

And so, I’m really not willing to make any conclusions about causality

because I just don’t know if our data truly says that. If five years

from now, you know, more robust data shows us that, then we would

be able to say somethi