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

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-risk kids

Who are the high-risk kids? What are the factors that identify someone, when they’re 9 or 10? I think that, in itself, is going to be very helpful to advance our understanding. Who are the high-risk kids? Because once we know that, we can do much more to understand how do we help the high-risk kids?

THE ABCD, THAT’S ADOLESCENT BRAIN COGNITIVE DEVELOPMENT, STUDY WILL FOLLOW THE CHILDREN FOR AT LEAST 10 YEARS. I’M JIM DRYDEN...

RUNS 3:00

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 that protects girls from autism, then we might get some insights and clues into markers that could help with diagnoses, as well as treatments.

ONE WAY TO FIGURE THAT OUT, SAYS MARRUS, IS TO ASK GRANDMOTHERS TO HELP EVALUATE THEIR GRANDKIDS, AND THAT’S WHAT THE RESEARCH TEAM IS DOING, RECRUITING AT LEAST 500 GRANDMOTHERS WHO HAD AT LEAST ONE CHILD WHO HAD AUTISM. I’M JIM DRYDEN...

RUNS 2:53

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 something. But I think right now, this is a good start.

APTE’S TEAM REPORTS ITS FINDINGS IN THE JOURNAL JAMA OPHTHALMOLOGY. I’M JIM DRYDEN...

RUNS 2:55

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.