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…   (act)                                                                  :14                               o/c age-appropriate tasks   …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.   (act)                                                                  :08                               o/c adolescents, adults   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.   (act)                                                                  :17                               o/c rewarding tasks   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.   (act)                                                                  :06                               o/c or reward   The difference was specific to their reactivity, their neural reaction, to winning, or reward.   LUBY AND BELDEN ARE CONTINUING TO STUDY PRESCHOOLERS WITH AND WITHOUT DEPRESSION. THEY SAY THEY PLAN TO USE MRI IMAGING TO LOOK MORE CLOSELY AT SPECIFIC BRAIN REGIONS THAT MAY BE RESPONSIBLE FOR THE DIFFERENCES THEY SAW IN THIS STUDY, AND LUBY SAYS THE RESEARCHERS ALSO PLAN TO SEE WHETHER THERAPY MIGHT CHANGE THESE PATTERNS.   (act)                                                                  :06                               o/c the treatment   With the expectation that they will have a greater response to reward after undergoing the treatment.   LUBY, BELDEN AND THEIR COLLEAGUES REPORT THEIR FINDINGS IN THE JOURNAL OF THE AMERICAN ACADEMY OF CHILD & ADOLESCENT PSYCHIATRY. I’M JIM DRYDEN…   RUNS 3:00

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.   (act)                                                                  :14                               o/c same size   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.   (act)                                                                  :15                               o/c vision loss   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.   (act)                                                                  :27                               o/c to die   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.   (act)                                                                  :26                               o/c vision loss   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 is, we can stop the tumor from growing, but over the past 30 years, we haven’t “won the war.” And the war is really to prevent further vision loss.   GUTMANN’S TEAM REPORTS ITS FINDINGS IN THE JOURNAL OF EXPERIMENTAL MEDICINE. I’M JIM DRYDEN…   RUNS 2:51

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. (act) :24 o/c own beast 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. (act) :23 o/c years now 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… RUNS 3:00

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… (act) :20 o/c it’s connected 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. (act) :18 o/c the brain 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. (act) :30 o/c and anxiety 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. There’s a whole ‘nother world out there in biology that responds to UV and responds to far-red that your eye and my eye can’t see. Some advantages of far-red are that you can penetrate tissue deeper, we can access parts of the brain that we wouldn’t be able to access previously. BRUCHAS SAYS COMBINING THE LIGHT-SENSING PARTS OF THE OPSINS TO RECEPTORS ON BRAIN CELLS SHOULD ALLOW SCIENTISTS TO ACTIVATE CELLS, TO INFLUENCE BEHAVIOR AND TO BETTER UNDERSTAND HOW THE VARIOUS CIRCUITS IN THE BRAIN ARE ORGANIZED. I’M JIM DRYDEN… RUNS 2:55

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. (act) :26 o/c these medications 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. (act) :22 o/c first one 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. (act) :13 o/c of medication 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. (act) :25 o/c like that 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 levels of the medication, instruct them on how to stay hydrated, and things like that. OTHERS IN THE STUDY WILL GET AN OLDER TYPE OF ANTIDEPRESSANT DRUG CALLED NORTRIPTYLINE. LENZE SAYS THE RESEARCHERS HOPE THAT BY STUDYING ALL OF THESE DIFFERENT COMBINATIONS OF AUGMENTATION AND SWITCHING, THEY MAY BE ABLE TO IDENTIFY EFFECTIVE THERAPIES THAT CAN BE PERSONALLY TAILORED TO INDIVIDUAL PATIENTS. I’M JIM DRYDEN... RUNS 2:56

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. (act) :16 o/c pain medications 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 medication in a safe manner, and so we used lower doses than one would probably typically give to treat pain. And so that might be why the adults did not have the improvement in pain scores that we would liked to have seen. THE NEW STUDY IS PUBLISHED IN THE JOURNAL PEDIATRIC BLOOD & CANCER. I’M JIM DRYDEN... RUNS 3:00

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

Researchers have found how sensory nerve cells work together to transmit itch signals from the skin to the spinal cord, where neurons then carry those signals to the brain. Their discovery may explain why some people experience various types of itching, including chronic itching, and help scientists find ways to make some types of itching stop. The researchers report that by interfering with the activity of sensory neurons, they may be able to inhibit multiple types of itching. THERE ARE SPECIFIC NEURONS IN THE SPINAL CORD THAT CARRY ITCH SIGNALS TO THE BRAIN, BUT BEFORE THOSE CELLS CAN BE ACTIVATED, OTHER SENSORY CELLS MUST PROCESS AND TRANSMIT ITCH SIGNALS. NOW, RESEARCHERS AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS HAVE IDENTIFIED CHANNELS IN NERVE CELLS THAT CARRY DIFFERENT TYPES OF ITCH SIGNALS TO THE SPINAL CORD. AND THE FINDINGS MAY GIVE SCIENTISTS NEW TARGETS TO HELP BLOCK OR RELIEVE ITCHING IN SOME PATIENTS. JIM DRYDEN HAS MORE… THE RESEARCHERS STUDIED HOW ITCH SIGNALS ARE PROCESSED IN THE DORSAL ROOT GANGLION. THAT’S A CLUSTER OF NERVE CELLS THAT CARRIES SIGNALS FROM THE SKIN TO THE SPINAL CORD. ZHOU-FENG CHEN, DIRECTOR OF WASHINGTON UNIVERSITY’S CENTER FOR THE STUDY OF ITCH, SAYS THERE WERE TWO CALCIUM CHANNELS IN THE CELLS IN THAT STRUCTURE THAT WERE KNOWN TO BE INVOLVED IN TRANSMITTING DIFFERENT TYPES OF ITCH — KNOWN AS HISTAMINE-INDUCED ITCH, WHICH IS THE TYPE OF ITCHING THAT CAN BE TREATED WITH ANTIHISTAMINES LIKE BENADRYL, AND CHLOROQUINE-INDUCED ITCH, WHICH OFTEN EFFECTS PEOPLE WHO TAKE THE DRUG CHLOROQUINE FOR MALARIA. CHEN SAYS CALCIUM CHANNELS IN NERVE CELLS CALLED TRPV1 AND TRPA1 PROCESS THOSE ITCH SIGNALS. (act) :20 o/c of histamine TRPV1 is required for histamine, a very important itch mediator. And TRPA1 is very important for chloroquine-mediated itch. So these two types of itch are very different because chloroquine- mediated itch is independent of histamine. MEANING THAT ANTIHISTAMINES DON’T DO MUCH FOR PATIENTS WITH CHLOROQUINE-INDUCED ITCHING. BUT, STUDYING MICE, CHEN FOUND THAT A THIRD CALCIUM CHANNEL, CALLED TRPV4, ALSO WAS REQUIRED FOR CHLOROQUINE-INDUCED ITCH. (act) :12 o/c itch sensations Not only that. We also found TRPV4 also is required for histamine. So, therefore, here you have one channel mediating two types of very distinct itch sensations. HE SAYS IT APPEARS THERE’S SOME CROSS-TALK BETWEEN THESE ITCH-PROCESSING CHANNELS IN THE NERVE CELLS. (act) :24 o/c is surprising There are so many TRP channels co-expressed in sensory neurons, and there’s lots of cross-talk, but then, there are really no studies of behavior, physiologically relevant studies to show this kind of two TRP channels in a sensory cell may cross-talk to relay each specific type of itch. So this is surprising. AND CHEN SAYS THE SURPRISING DISCOVERY OF CROSS TALK BETWEEN THE THE V4 CHANNEL AND THE OTHER, PREVIOUSLY DISCOVERED ITCH-TRANSMITTING CHANNELS MEANS THAT SCIENTISTS AND DRUG MAKERS MAY HAVE ANOTHER TARGET THAT COULD BE USED TO BLOCK MULTIPLE TYPES OF ITCH SIGNALS. (act) :13 o/c additional target V4 is an important target, for both histamine-induced itch and for chloroquine-induced itch. Our data suggest that it’s probably a very important channel for the chloroquine itch, so you have an additional target. CHEN AND HIS COLLEAGUES REPORT THEIR FINDINGS IN THE JOURNAL SCIENCE SIGNALING. I’M JIM DRYDEN... RUNS 2:38

Scientists’ understanding of the genetic roots of breast cancer is based largely on research conducted in women of European ancestry. But that knowledge does little to explain why African-American women with breast cancer are more likely to be diagnosed at younger ages and with more aggressive tumors than their white counterparts. Researchers at Washington University School of Medicine in St. Louis are launching a major study involving 600 African-American women with breast cancer to learn whether their genetic risks are influenced by the same gene mutations that affect white women or if their mutations are altogether different. Such information may lead to new ways to prevent or treat breast cancer in African-American women. AS SCIENTISTS HAVE MADE BIG ADVANCES IN GENETIC TESTING FOR BREAST CANCER, NOT ALL WOMEN HAVE GOTTEN THE BENEFITS. MOST OF THAT RESEARCH HAS BEEN DONE IN WOMEN OF EUROPEAN ANCESTRY, AND MUCH LESS IS KNOWN ABOUT THE GENETICS OF BREAST CANCER IN AFRICAN-AMERICAN WOMEN. NOW, A TEAM OF RESEARCHERS AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS IS TRYING TO CHANGE THAT. JIM DRYDEN HAS THE STORY… BEGINNING WITH BRCA1 AND 2, THE SO-CALLED BRCA GENES, DOCTORS AND SCIENTISTS HAVE BEEN LEARNING HOW TO IDENTIFY WOMEN AT RISK FOR BREAST CANCER AND, IN SOME CASES, TO PROVIDE TREATMENT BEFORE ANY SYMPTOMS ACTUALLY PRESENT THEMSELVES. WASHINGTON UNIVERSITY GENETICS RESEARCHER LAURA BIERUT SAYS THERE’S BEEN SOMETHING OF A REVOLUTION IN GENETIC TESTING OVER THE LAST DECADE OR SO. (act) :23 o/c African-American populations But as you start to look at the genetic data, you realize that these studies have been done in populations of European ancestry. One of the next areas that we need to turn to is getting a better understanding of genetic causes of cancer in other populations, and in particular, in African-American populations. SO BIERUT AND HER COLLEAGUES ARE LAUNCHING A STUDY IN AFRICAN-AMERICAN WOMEN WHO HAVE BEEN DIAGNOSED WITH BREAST CANCER. CO-INVESTIGATOR AND SITEMAN CANCER CENTER ONCOLOGIST FOLUSO ADEMUYIWA SAYS TO QUALIFY FOR THE STUDY, THE ONLY CRITERIA ARE THAT A WOMAN BE AFRICAN-AMERICAN AND THAT THAT WOMAN HAS BEEN DIAGNOSED WITH BREAST CANCER AT SOME POINT IN HER LIFE. (act) :14 o/c black women We’re inviting all women with breast cancer, who are African Americans, and the ultimate goal is to really try to understand what genetic factors drive the aggressive disease in black women. BIERUT SAYS AS GENETICISTS HAVE BEEN GAINING A BETTER UNDERSTANDING OF SOME OF THE UNDERLYING GENETIC CAUSES OF BREAST CANCER, AND DELIVERING BETTER DIAGNOSIS AND TREATMENT TO WHITE WOMEN, THE SAME THING ISN’T NECESSARILY TRUE FOR AFRICAN-AMERICAN WOMEN. (act) :18 o/c in time The African-American women with breast cancer present at a younger age. They have more aggressive types of breast cancer, and they have the characteristics of breast cancer that are often thought to have genetic underpinnings. Yet we don’t know what these genetic underpinnings are at this point in time. CO-INVESTIGATOR ADEMUYIWA SAYS IT’S A FAIRLY STRAIGHTFORWARD STUDY. WOMEN WHO PARTICIPATE NEED ONLY PROVIDE A SALIVA SAMPLE AND ANSWER SOME QUESTIONS. (act) :19 o/c these women We’re going to try to obtain a family history to see if there is a family history of breast and ovarian cancer, and then we’re going to be doing genetic testing on all these women to really see if we can build a database to find out what genes, if any, contribute to breast cancer aggressiveness in these women. AND BIERUT SAYS ALTHOUGH THIS STUDY IS BEGINNING AS A SINGLE-CENTER STUDY AT WASHINGTON UNIVERSITY AND THE SITEMAN CANCER CENTER, THE HOPE IS TO BUILD IT UP OVER TIME, TO INCLUDE AFRICAN-AMERICAN WOMEN FROM OTHER PLACES AND TO DEVELOP A VERY LARGE DATABASE OF DNA. (act) :11 o/c risks are And that’s what we want to do. We really want to improve the health of people with cancer, to prevent cancer in the future and to give people the information about what their risks are. BIERUT AND ADEMUYIWA SAY BETTER UNDERSTANDING OF GENETIC RISKS COULD HELP IMPROVE DIAGNOSIS, TREATMENT AND SURVIVAL FOR AFRICAN-AMERICAN WOMEN WITH BREAST CANCER. I’M JIM DRYDEN... RUNS 2:56

A program aimed at helping abused and neglected children and their families is improving short-term outcomes for kids and providing children with stable home environments as their cases move through the courts. The program is for children and families whose cases ended up in court. Researchers at Washington University School of Medicine in St. Louis have found that kids whose families received psychiatric help and educational support through the program have better-than-expected outcomes compared to kids comparably matched for level of risk whose cases went through the court system before the program was launched. WHEN YOUNG CHILDREN SUFFER ABUSE OR NEGLECT, THEY ARE AT RISK FOR BIG PROBLEMS LATER ON IN LIFE, SUCH AS PSYCHIATRIC DISORDERS, SUBSTANCE ABUSE AND BECOMING ABUSERS THEMSELVES AS ADULTS. BUT A PROJECT INVOLVING THE ST. LOUIS COUNTY COURTS AND WASHINGTON UNIVERSITY CHILD PSYCHIATRISTS IS WORKING TO BREAK THAT PATTERN BY OFFERING SERVICES BOTH TO CHILDREN AND TO THEIR PARENTS. JIM DRYDEN HAS MORE… ONE IN EIGHT CHILDREN IN THE UNITED STATES WILL SUFFER ABUSE OR NEGLECT, AND WHEN THAT HAPPENS, THEY OFTEN END UP IN THE COURT SYSTEM. A CHILD MAY BE REMOVED FROM THE FAMILY HOME AND PLACED IN FOSTER CARE. THE COURT OFTEN WILL LIMIT CONTACT BETWEEN THE CHILD AND THE PARENT WHO MISTREATED HIM OR HER. BUT THAT DOESN’T SOLVE UNDERLYING PROBLEMS THAT LED TO ABUSE IN THE FIRST PLACE. SO A TEAM FROM WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IS NOW WORKING WITH COURTS IN ST. LOUIS COUNTY TO TRY TO ADDRESS SOME OF THE ROOT CAUSES OF ABUSE AND NEGLECT. THE SYNCHRONY PROJECT, WHICH STANDS FOR STRENGTHENING YOUNG CHILDREN BY OPTIMIZING FAMILY SUPPORT IN INFANCY, TREATS KIDS WHO HAVE BEEN MALTREATED BY FAMILY MEMBERS. IN THE EARLY YEARS OF THE PROJECT, THOSE INVOLVED HAVE FOUND THAT KIDS REFERRED TO SYNCHRONY HAVE DONE BETTER EMOTIONALLY AND DEVELOPMENTALLY THAN ABUSED OR NEGLECTED CHILDREN WHO WENT THROUGH THE COURT SYSTEM IN THE YEARS JUST BEFORE THE SYNCHRONY PROJECT WAS LAUNCHED. WASHINGTON UNIVERSITY CHILD PSYCHIATRIST JOHN CONSTANTINO SAYS IT’S RARE TO TRY TO HELP BOTH KIDS AND THEIR PARENTS, BUT HE SAYS THAT’S WHAT THE SYNCHRONY PROJECT ATTEMPTS TO DO. (act) :24 o/c health care At risk children are medically insured, but often their parents aren’t. Systems of mental health and health care that are available to the babies are not available to the parents. You end up in the situation of trying to support an infant, or a young child, when the person that you need to support most is the parent, and yet they don’t have access to mental health care. CONSTANTINO SAYS SYNCHRONY IS BASED ON A SIMILAR PROGRAM STARTED SEVERAL YEARS AGO IN THE NEW ORLEANS AREA. AND HE SAYS THE APPROACH APPEARS TO BE PUTTING A LOT OF KIDS ON THE ROAD TO A BETTER LIFE. (act) :23 o/c SYNCHRONY project We’re recognizing unmet mental health needs, delivering them early. The interventions that were done unequivocally resulted in improved functioning of the babies, and children, and in fact, the total time that the children are in foster care was reduced within the children in the SYNCHRONY project. CONSTANTINO SAYS WHEN KIDS ARE ABUSED OR NEGLECTED, THEY END UP AT HIGH RISK FOR A LOT OF BAD THINGS LATER IN LIFE. (act) :20 o/c of childhood Psychiatric disorders, suicide, substance use impairment, or becoming an abuse perpetrator yourself when you become an adult. All of those are related, in a dose-response fashion, to the number of cases of abuse you experience over the course of childhood. IF THERE’S ONLY A SINGLE CASE, CONSTANTINO SAYS, THE CHILD MAY BE OKAY. BUT IF THERE ARE TWO OR MORE TIMES THAT A CHILD IS ABUSED OR NEGLECTED, BIG PROBLEMS ARE MUCH MORE LIKELY. (act) :18 o/c the goal For children who are lucky enough to only have one episode of abuse and no more after that in the official report records, their outcomes were not that much worse than all kids in the general population. So the idea is that if it happens once, to make sure that it never happens again. That’s the goal. CONSTANTINO’S GROUP REPORTS ON THE LAUNCH OF THE SYNCHRONY PROJECT IN THE AMERICAN JOURNAL OF PSYCHIATRY. I’M JIM DRYDEN... RUNS 3:00

As young people reach adulthood, their preferences for sweet foods typically decline. But for people with obesity, new research suggests that the drop off may not be as steep and that the brain’s reward system is operating differently in obese people than in thinner people, which may play a role in this phenomenon. AS WE GET OLDER, WE TEND TO HAVE LESS OF A PREFERENCE FOR SWEET THINGS. DURING THAT SAME TIME IN LIFE, THE NUMBER OF A PARTICULAR TYPE OF DOPAMINE RECEPTOR IN OUR BRAINS BEGINS TO DECLINE, AND THERE IS A STRONG RELATIONSHIP BETWEEN RECEPTORS, AGE AND SWEET TASTE PREFERENCES IN PEOPLE WHO DON’T HAVE OBESITY. BUT SCIENTISTS AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS HAVE FOUND THAT THINGS DON’T WORK THAT WAY IN PEOPLE WHO DO HAVE OBESITY. JIM DRYDEN HAS THE STORY… WHEN WE EAT, OUR BRAINS RELEASE CHEMICALS THAT MAKE US FEEL GOOD, AND WHEN WE EAT SOMETHING REALLY GOOD, THE SAME THING HAPPENS, ONLY MORESO. A BRAIN CHEMICAL CALLED DOPAMINE IS WHAT MAKES US FEEL GOOD, AND TO MEASURE DOPAMINE RELEASE IN RESPONSE TO FOOD, SCIENTISTS OFTEN MEASURE OUR REACTION TO SWEET THINGS BECAUSE EVERYONE TENDS TO LIKE SWEETS, WASHINGTON UNIVERSITY NUTRITION RESEARCHER YANINA PEPINO SAYS AS PEOPLE GET OLDER, A COUPLE OF THINGS HAPPEN. WE TEND TO HAVE LESS OF A PREFERENCE FOR SWEETS, AND WE TEND TO HAVE FEWER DOPAMINE D2 RECEPTORS IN A KEY BRAIN STRUCTURE CALLED THE STRIATUM. (act) :21 o/c with obesity We are using as a model sweetness because it’s the ancient food reward. Almost every other study in animals that looks for rewards uses something sweet. And we are showing that this kind of biological thing that happens — that as you age, you lose, you know, your interest for sweetness — that is also already impaired. We don’t see it in the group with obesity. IN OTHER WORDS, OBESITY MAY BE CHANGING THE WAY THE BRAIN RESPONDS TO THINGS THAT WE EAT. PEPINO’S TEAM STUDIED PEOPLE WITH AND WITHOUT OBESITY, MEASURING THEIR PREFERENCE FOR SWEETNESS AND THEN CONDUTING PET SCANS ON THEIR BRAINS TO LOOK FOR D2 RECEPTORS. IN PEOPLE WITHOUT OBESITY… (act) :28 o/c in obesity The lower the amount of D2 receptor that they had, the more concentrated sugar that the liked. And we know that this is similar to what has been shown in animals. If you give them a blocker of this receptor, the less D2 you have, the more sugar the animal will go and prefer. Now interestingly, these observations that we found in people without obesity, we didn’t find them in people with obesity. So there is a dysregulation, or there is an association with a dysfunction in obesity. CO-INVESTIGATOR TAMARA HERSHEY SAYS THAT PET SCANS ON STUDY VOLUNTEERS USED A SPECIAL BINDING MOLECULE THAT VERY ACCURATELY IDENTIFIED DOPAMINE RECEPTORS. (act) :17 o/c misidentifying it That just gives us a little more strength in our, specificity, in our conclusions about the role of D2 receptors in obesity. We’re still, like, just feeling one “leg of the elephant” here, but at least we’re sure it’s the leg, and not…we’re not misidentifying it. HERSHEY SAYS THE ASSOCIATION BETWEEN THOSE BRAIN RECEPTORS AND AGE WAS ABLE TO PREDICT THE PREFERENCE FOR SWEETNESS IN NORMAL-WEIGHT PEOPLE. (act) :22 o/c D2 receptors Some people liking it a lot, some people not liking it a lot. There’s also a lot of individual difference in D2 receptors — some people high; some people low. When we look at how those go together across all of the people, half of the variance, or the differences, between people were explained by the differences in D2 receptors. BUT PEPINO SAYS IT WAS DIFFERENT FOR PEOPLE WITH OBESITY. (act) :10 o/c no obesity In the group of people with obesity, we were unable to look at…find the same relationships between dopamine and sweetness that were so clear in the people that had no obesity. THEY REPORT THEIR FINDINGS IN THE JOURNAL DIABETES. I’M JIM DRYDEN... RUNS 2:58

With more U.S. states legalizing or decriminalizing marijuana use, the number of adults using the drug has increased. But a survey of more than 216,000 adolescents from all 50 states indicates the rates of marijuana use are falling among the young. Researchers at Washington University School of Medicine in St. Louis examined data on drug use collected from young people and found that the number of adolescents who had problems related to marijuana declined by 24 percent between 2002 and 2013. Over the same period the number of kids reporting they used marijuana at all fell by 10 percent. AS SEVERAL STATES HAVE MADE USING MARIJUANA LEGAL, AT LEAST FOR MEDICINAL PURPOSES, SOME HAVE WORRIED THAT THE NUMBER OF YOUNG PEOPLE USING MARIJUANA WILL INCREASE, BUT RESEARCHERS AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS HAVE FOUND THAT THE NUMBER OF AMERICAN KIDS BETWEEN 12 AND 17 WHO USE MARIJUANA IS ACTUALLY DECLINING. SO IS THE NUMBER OF ADOLESCENTS WHO HAVE MARIJUANA-RELATED PROBLEMS. JIM DRYDEN HAS THE STORY… AS THE NUMBER OF STATES LEGALIZING MEDICAL MARIJUANA, AND EVEN RECREATIONAL USE OF THE DRUG, HAS INCREASED IN RECENT YEARS, THE NUMBER OF AMERICAN TEENAGERS REPORTING THAT THEY USE POT HAS BEEN DECLINING. WASHINGTON UNIVERSITY RESEARCHERS LEARNED THAT WHEN THEY ANALYZED DATA ABOUT POT THAT WAS GATHERED FROM MORE THAN 200 THOUSAND KIDS, AGES 12-17, IN THE YEARS BETWEEN 2002 AND 2013. LEAD INVESTIGATOR RICHARD GRUCZA SAYS ALTHOUGH THERE WERE UPS AND DOWNS FROM YEAR TO YEAR, DURING THAT 12-YEAR PERIOD, THE NUMBER OF KIDS WHO REPORTED THAT THEY’D USED MARIJUANA DECLINED. (act) :10 o/c marijuana use That number went up and down over the 12-year period encompassed by the study, but on the whole, it went down by 10 percent. The net decline was 10 percent in marijuana use. IN ADDITION, THE NUMBER OF ADOLESCENTS WHO HAD PROBLEMS RELATED TO MARIJUANA DECLINED EVEN MORE. (act) :16 o/c with use Probably the more impressive result was the fact that we actually saw a 25 percent decrease in marijuana use disorder. So that means, not only is the number of teenagers using marijuana going down a little bit, but the number who use are also less likely to report having problems with use. AND GRUCZA SAYS TO BE CONSIDERED A MARIJUANA-USE DISORDER, THE PROBLEM HAS TO BE PRETTY SERIOUS. (act) :13 o/c of problems So the proportion of adolescents reporting problems with the law, inability to quit, interference with their social or educational functioning or similar types of problems. GRUCZA SAYS THE RESULTS WERE SURPRISING, NOT ONLY THAT PROBLEMS WITH MARIJUANA DECLINED, BUT ALSO HOW SHARP THOSE DECLINES WERE. (act) :24 o/c in life And we can’t say that the policies don’t matter because, you know, maybe we’d have seen larger declines had we kept these stricter marijuana-use policies. But I think what it does tell us is that there are other issues related to adolescent behavior that are probably contributing to marijuana-use disorder on the whole, and maybe we can address those problems earlier in life. THE RESEARCHERS ALSO NOTICED THAT SOMETHING ELSE DECLINED DURING THE YEARS OF THE STUDY: BEHAVIOR PROBLEMS. GRUCZA SAYS KIDS REPORTED THAT THEY GOT INTO FEWER FIGHTS. THEY WERE LESS LIKELY TO SELL DRUGS OR TO BRING A WEAPON TO SCHOOL. THOSE SORTS OF DELINQUENCY AND CONDUCT PROBLEMS ARE FREQUENTLY LINKED TO MARIJUANA USE AND ABUSE. BUT FOR TEENAGERS IN THE UNITED STATES, ALL OF THOSE PROBLEMS WERE DOWN DURING THE STUDY PERIOD. (act) :21 o/c pediatric population We’re seeing the prevalence of these behavior problems go down, and typically, the sorts of behaviors we’re looking at have their roots earlier in life. By mid childhood, you can really, kind of, predict who’s going to go on to have legal problems or get into a lot of fights, and things like that. One possibility is that we’re simply seeing better mental health treatments in the pediatric population. GRUCZA AND HIS COLLEAGUES REPORT THEIR FINDINGS IN THE JOURNAL OF THE AMERICAN ACADEMY OF CHILD & ADOLESCENT PSYCHIATRY. I’M JIM DRYDEN... RUNS 2:46

People who suffer itching with no clear cause may have defects in their immune systems that haven’t been recognized. In a small study of patients who struggle with itching but have no known cause, researchers from the Center for the Study of Itch at Washington University School of Medicine in St. Louis identified several immune system irregularities that may underlie the urge to scratch. The patients suffer from what doctors call chronic idiopathic pruritis. Studying blood samples and skin biopsies, the researchers have found some very unusual things in the immune systems of these patients. SOME PEOPLE SUFFER HAVE BAD PROBLEMS WITH ITCHING BECAUSE THEY HAVE A RASH OR SOME OTHER SKIN CONDITION. BUT OTHERS HAVE ITCHING PROBLEMS WITH NO KNOWN CAUSE. NOW RESEARCHERS FROM THE CENTER FOR THE STUDY OF ITCH AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS HAVE IDENTIFIED DEFECTS IN THE IMMUNE SYSTEMS OF SOME PATIENTS WITH THAT TYPE OF ITCHING THAT MAY UNDERLIE THE URGE TO SCRATCH. JIM DRYDEN HAS MORE… ALTHOUGH IT’S RELATIVELY UNCOMMON, A CONDITION CALLED CHRONIC IDIOPATHIC PRURITIS IS ONE OF THE MOST DIFFICULT TYPES OF ITCHING TO TREAT BECAUSE THE BEST TARGET FOR THERAPY REMAINS UNKNOWN. WHEN A PERSON WITH AN ITCHY RASH GOES TO THE DERMATOLOGIST, THE DOCTOR OFTEN ORDERS A SKIN BIOPSY TO SEE WHAT’S UP. BUT IN PATIENTS WITH ITCHING WITHOUT A KNOWN CAUSE, THERE’S NOTHING TO BIOPSY. WASHINGTON UNIVERSITY DERMATOLOGIST BRAIN KIM SAYS SOMETIMES PEOPLE WONDER IF THE ITCHING IS “ALL IN THEIR HEADS.” (act) :14 o/c our mission It is often viewed as a “wastebasket term” in that there’s nothing really wrong with these patients. But, you know, if it was simply, you know, a psychiatric disorder or something not otherwise specified, we should try to figure out what’s going on. And that’s, really, what we’ve taken as our mission. KIM RUNS A CLINIC FOR PEOPLE WITH CHRONIC ITCHING. AMY XU, A MEDICAL STUDENT WHO WORKS IN KIM’S LAB, SAYS SOME OF THE PATIENTS HAVE ECZEMA OR SOME OTHER KNOWN SKIN CONDITION, BUT OTHERS DON’T. (act) :16 o/c their itch So these patients have itch that is of unknown origin, meaning that we do a whole bunch of lab tests, and we get a chest X-ray and other things on them and find that they really don’t have any primary, like, skin conditions, or other medical conditions, that could be causing their itch. XU IS THE FIRST AUTHOR ON A NEW STUDY FROM KIM’S LAB THAT ANALYZED SKIN AND BLOOD SAMPLES FROM PATIENTS WITH ITCHING, BUT NO KNOWN CAUSE, TO SEE WHETHER THEY COULD FIND ANY SIMILARITIES BETWEEN THE PATIENTS. KIM SAYS THEY DID FIND ELEVATED LEVELS OF IMMUNE CELLS, CALLED EOSINOPHILS, IN THOSE SAMPLES. EOSINOPHILS USUALLY ARE MARKERS OF ALLERGIC INFLAMMATION. (act) :13 o/c the itch The thought is, could that just be secondary to scratching? It’s possible, but then you look deeper in the blood, and then you see profound immune defects in the blood. There is this immune dysregulation, and it’s very likely that this immune dysregulation is contributing to the chronicity of the itch. THE STUDY LOOKED ONLY AT A SMALL SAMPLE A PATIENTS. THERE WERE 4 IN THIS INITIAL STUDY. BUT KIM FOUND THAT CERTAIN IMMUNE SYSTEM DEFECTS WERE COMMON IN 3 OF THEM. (act) :21 o/c a rash Three of them have elevated IgE, which is a marker of allergic inflammation. Three of them have elevated eosinophils, which is another marker of allergic inflammation. What’s unique about them is that they don’t have a history of atopic dermatitis or other allergic disorders, and the other thing that’s common to all of them is they typically don’t have a rash. KIM SAYS THE EARLY FINDINGS SUGGEST THAT WHEN IT COMES TO THIS SORT OF UNEXPLAINED CHRONIC ITCHING, IT ISN’T REALLY ALL IN THEIR HEADS. (act) :21 o/c for instance We’ve now been more routinely doing these clinical tests to identify what’s going on in these patients, and, in fact, we have many more patients; and what we’re finding out is that the immune dysfunction is now stratifying across different defects. Some patients will have such profound defects that we’ve actually sent them to our colleagues in allergy and immunology, for instance. KIM’S LAB IS NOW WORKING TO MAKE MOUSE MODELS THAT HAVE SOME OF THE SAME UNDERLYING IMMUNE DEFECTS IN ORDER TO DEVELOP BETTER TREATMENTS. HIS TEAM REPORTS ON THOSE DEFECTS IN THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY. I’M JIM DRYDEN... RUNS 2:59

There is news almost every day about the epidemic of opioid drug use in the United States. Some 65 percent of heroin users report that they used prescription opioids first and then made the switch to heroin. And current estimates are that 4-20 percent of all opioid pills prescribed in the United States actually are taken for nonmedical reasons. Now, an anesthesiologist and a surgeon at Washington University School of Medicine in St. Louis are proposing ways to reduce the availability of opioid drugs by eliminating some of them from the pipeline. Among other things, they’re proposing that doctors prescribe fewer pills for patients after they undergo surgery and that pharmaceutical companies initiate turn-in programs for unused opioids. RELATED FEATURE: Inside an epidemic: Overcoming America’s opioid crisis starts with understanding abuse patterns THE U.S. CENTERS FOR DISEASE CONTROL AND PREVENTION IS RECOMMENDING THAT DOCTORS TRY TO AVOID PRESCRIBING OPIOID PAINKILLERS FOR MANY PATIENTS, AND NOW EXPERTS AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS ARE RECOMMENDING IN THE JOURNAL ANESTHESIOLOGY THAT PHYSICIANS ALSO MAY WANT TO CUT BACK ON OVER-PRESCRIBING TAKE-HOME OPIOID DRUGS FOR SURGERY PATIENTS. THEY HOPE TO LIMIT THE RESERVOIR OF UNUSED PAINKILLERS IN THE COMMUNITY. JIM DRYDEN HAS THE STORY… MORE THAN 80 PERCENT OF ALL OF THE OPIOID PRESCRIPTIONS IN THE WORLD ARE WRITTEN BY DOCTORS IN THE UNITED STATES, AND NOT ALL OF THOSE DRUGS ARE TAKEN TO TREAT PAIN. THE PROBLEM OF OPIOID PAINKILLER ABUSE HAS BEEN GETTING A LOT OF ATTENTION LATELY, BUT WASHINGTON UNIVERSITY ANESTESIOLOGIST EVAN KHARASCH SAYS MOST OF US DON’T APPRECIATE JUST HOW BIG THE PROBLEM IS. (act) :14 o/c opioid overdose There is an accidental opioid overdose in this country every 18 minutes. More than 28,000 people last year died from an accidental opioid overdose. THAT NUMBER INCLUDES BOTH PRESCRIPTION OPIOIDS AND HEROIN. RESEARCH OVER THE LAST FEW YEARS HAS FOUND THAT MANY PEOPLE START GETTING HIGH ON PRESCRIPTION DRUGS AND THEN MOVE ON TO HEROIN BECAUSE IT’S CHEAPER. KHARASCH SAYS SURGERY PATIENTS OFTEN TAKE HOME PRESCRIPTIONS FOR PAINKILLERS, BUT THEN THEY DON’T NEED ALL OF THE PILLS. (act) :21 o/c or taken There is a reservoir of unused opioids in the community. Many people may get an opioid prescription. They may not take all the opioids, and the remaining drugs sit in their medicine cabinet. What we’ve now come to learn is that sometimes those opioids are diverted or taken. ONE POTENTIAL SOLUTION, HE SAYS, WOULD BE TO SEND PATIENTS HOME AFTER SURGERY WITH FEWER PILLS. INSTEAD OF A BIG PRESCRIPTION, HE SAYS SURGEONS AND ANESTHESIOLOGISTS COULD PRESCRIBE FEWER PILLS AND THEN REFILL THE PRESCRIPTIONS AS NEEDED TO MAKE SURE PAIN NEEDS ARE ADEQUATELY ADDRESSED, WITHOUT OVERPRESCRIBING. (act) :15 o/c pain pills It is not unusual for patients to be sent home with 30, 60, 90 pills, and they may only take them for two or three days. One approach to the problem is to simply prescribe fewer pain pills. ANOTHER WAY TO REDUCE THE NUMBER OF POTENTIALLY DANGEROUS OPIOIDS SITTING IN MEDICINE CABINETS WOULD BE TO ALLOW PEOPLE TO RETURN DRUGS THEY WON’T BE NEEDING. (act) :14 o/c under-appreciated There are some pharmacies which may take unused opioids back, in return, to get the unused drugs out of the house and get them away from misuse. That’s an avenue which is under-utilized and under-appreciated. AND KHARASCH SAYS ONE MORE POTENTIAL STRATEGY INVOLVES THE WAY THAT DOCTORS EMPLOY OPIOID DRUGS WHILE SURGERY PATIENTS ARE IN THE HOSPITAL. HE SAYS IN RECENT YEARS THERE HAS BEEN A MOVEMENT TO USE SHORTER-ACTING PAINKILLERS IN THOSE PATIENTS. (act) :17 o/c home with Should we, instead of using short-duration opioids, should we be using long-duration opioids in surgery so that patients are more comfortable for a longer period of time, and they may need fewer pain pills to go home with? KHARASCH SAYS SOMETHING HAS TO BE DONE TO PREVENT OVERDOSES AND ADDICTION. IT’S ESTIMATED THAT ABOUT 5 MILLION AMERICANS USE PRESCIPTION OPIOIDS FOR NON-MEDICAL REASONS, AND THE COST TO THE U.S. ECONOMY IS ESTIMATED TO BE ABOUT $70 BILLION DOLLARS PER YEAR. I’M JIM DRYDEN... RUNS 2:58

State laws designed to help teens gradually ease into full driving privileges may have an unintended benefit: They appear to lower rates of teen alcohol consumption and binge drinking. Researchers at Washington University School of Medicine in St. Louis have found that in states with stricter graduated driver licensing laws, there not only is less drinking and driving among teens, there also is less total alcohol consumption by teenagers. MANY STATES HAVE ADOPED LAWS IN RECENT YEARS THAT ARE DESIGNED TO MAKE THE ROADS SAFER BY ALLOWING TEEN DRIVERS TO GRADUALLY EASE IN TO FULL DRIVING PRIVILEGES. BUT NEW RESEARCH FROM WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS FINDS THAT THOSE LAWS ALSO APPEAR TO BE HAVING AN UNINTENDED EFFECT: THEY APPEAR TO BE HELPING LOWER THE RATES OF TEEN ALCOHOL CONSUMPTION AND BINGE DRINKING. JIM DRYDEN REPORTS … SO-CALLED GRADUATED DRIVER LICENSING LAWS, OR GDLs, MIGHT RESTRICT THE NUMBER OF PASSENGERS A NEW DRIVER CAN HAVE IN THE CAR AT ONE TIME. SOME LAWS ALSO KEEP YOUNG DRIVERS OFF THE ROADS LATE AT NIGHT OR LIMIT FULL DRIVING PRIVILEGES IN OTHER WAYS IN AN ATTEMPT TO MAKE THE ROADS SAFER. WASHINGTON UNIVERSITY RESEARCHER PATRICIA CAVAZOS-REHG SAYS THE LAWS ARE MEANT TO EASE TEENS INTO DRIVING. (act) :11 o/c GDLs yet States have become more restrictive over time, but there is still some progress that could be made. So not, not all states have implemented fully restrictive GDLs yet. CAVAZOS-REHG HAD STUDIED THESE LAWS A FEW YEARS AGO AND FOUND THAT TEENS IN STATES WITH STRICTER GDLs TENDED TO DRINK AND DRIVE LESS. THIS TIME, TAKING ANOTHER LOOK, CAVAZOS-REHG AND HER COLLEAGUES ANALYZED INFORMATION FROM MORE THAN 129 THOUSAND HIGH SCHOOL SENIORS WHO PARTICIPATED IN THE NATIONAL “MONITORING THE FUTURE” SURVEY, AND SHE SAYS THEY FOUND THAT STRICTER GDL LAWS HAD AN EFFECT ON DRINKING ITSELF. (act) :11 o/c drink less GDLs also had an unintended effect on reducing their drinking behaviors. When the GDLs became, were, more restrictive, kids tended to drink less. THE GDL LAWS HAD A BIGGER IMPACT ON TEEN DRINKING THAN ALCOHOL TAXES, OR SO-CALLED USE-AND-LOSE LAWS. CAVAZOS-REHG SAYS THAT MAY BE PARTLY DUE TO THE FACT THAT TAXES ON ALCOHOL TEND TO BE PRETTY LOW. (act) :28 o/c be doing States do continue to drive up those prices with cigarette taxes. Unfortunately, with alcohol taxes, those don’t add a lot to the price of alcohol. And then the use-and-lose laws are different because the kid actually has to be caught engaging in the bad behavior to then lose their driver’s license. That’s different from the GDLs. So the GDL is more… there’s rules and structure, and the kids know very clearly what they should be doing. THE STATE GDL LAWS ARE SCORED ON A SYSTEM DEVELOPED BY THE INTERNATIONAL INSTITUTE FOR HIGHWAY SAFETY. ACCCORDING TO THEIR GRADING SYSTEM, 35 STATES HAD GDL LAWS RANKED AS GOOD. THOSE GOOD LAWS CUT RISK BEHAVIORS BEHIND THE WHEEL, BUT THEY ALSO MAY HAVE OTHER, MORE FAR-REACHING ADVANTAGES. (act) :15 o/c long haul There is a policy in place that clearly shows that these risk behaviors are being impacted in a way that we want to see, that not only could have short-term benefits, but really could help improve lives over the long haul. AND CAVAZOS-REHG SAYS NOT DRINKING AS MUCH DURING THE TEEN YEARS COULD PAY BIG BENEFITS LATER ON. (act) :22 o/c population level The earlier that these drinking behaviors begin, the higher the likelihood that the behaviors will transition into addiction. The more that we can implement policies that can delay these behaviors, and prevent these behaviors from happening, the better off that we are at a population level. THE NEW STUDY IS PUBLISHED IN THE JOURNAL ALCOHOLISM: CLINICAL & EXPERIMENTAL RESEARCH. I’M JIM DRYDEN... RUNS 3:00

Going to the doctor can be a frightening experience for some kids, and a visit to the psychiatrist can be even more unnerving. So a Washington University psychiatrist has written a children’s book about what happens on a visit to the psychiatrist’s office and why some kids receive psychiatric care. The idea is to make the experience of going to the psychiatrist less stressful and to inform healthy children that getting psychiatric care isn’t all that different from visiting the pediatrician or the dentist. A GOOD DEAL OF RESEARCH IS NOW SUGGESTING THAT EARLY ASSESSMENT AND DIAGNOSIS OF PSYCHIATRIC DISORDERS IS VERY IMPORTANT TO GOOD OUTCOMES IN CHILDREN, AND A WASHINGTON UNIVERSITY CHILD PSYCHIATRIST HAS WRITTEN A CHILDREN’S BOOK THAT’S DESIGNED TO HELP GET THAT WORD OUT, AS WELL AS TO MAKE KIDS MORE COMFORTABLE WITH THE IDEA OF SEEING A MENTAL HEALTH PROFESSIONAL. JIM DRYDEN HAS THE STORY… THERE ARE CHILDREN’S BOOKS ABOUT ALL KINDS OF MEDICAL EXPERIENCES: VISITING THE DOCTOR, GOING TO THE DENTIST, GETTING GLASSES, AND WASHINGTON UNIVERSITY CHILD PSYCHIATRIST MINI TANDON HAS NOW ADDED A VISIT TO A MENTAL HEALTH PROFESSIONAL TO THAT LIST. (act) :20 o/c these services I get questions from parents on how to describe to their children why they’re going to see a mental health professional, what to expect from the visit. We’re starting to realize, in psychiatry, that early assessment and diagnosis is key, and we want to destigmatize the chance and opportunity for a child to go to get these services. WITH RESEARCH POINTING TO THE IDEA THAT EARLY ASSESSMENT AND DIAGNOSIS OF PSYCHIATRIC DISORDERS IS IMPORTANT TO GOOD OUTCOMES, TANDON HOPES THE BOOK WILL HELP SPREAD THE WORD IN THE COMMUNITY. SHE’S ALSO TAKING THE BOOK TO SCHOOLS TO TRY AND TRANSMIT MORE INFORMATION ABOUT MENTAL HEALTH ISSUES IN CHILDREN, NOT JUST TO HELP KIDS WHO MAY NEED TO SEE SOMEONE, BUT TO RAISE AWARENESS AMONG ALL SCHOOLCHILDREN. (act) :17 o/c all ages But also to feel comfortable about peers and friends and colleagues and students in their classes who may have such problems so that there is a growing awareness in education, less stigma and seeking of treatment of mental health services at all ages. TANDON’S BOOK IS CALLED DR. MINI MENTAL HEALTH MEETS WILLIE WANNAKNOW. HE’S A BOY WHO HAS TO VISIT THE PSYCHIATRIST FOR TREATMENT OF ADHD AND TICS THAT OFTEN MAKE HIM DISRUPTIVE IN SCHOOL. (act) :24 o/c that rare ADHD occurs in about 5 to 8 percent of school-age children and, probably, about the same in preschool-age children, and so it is likely that people of these age bracket in schools will see and have other peers who are hyperactive, impulsive, inattentive, off task. And I wanted to start with more common disorders so that people feel like they can relate, and also to destigmatize something that’s not that rare. SHE SAYS MAY HELP SCHOOLS, NOT ONLY BY HELPING KIDS AND PARENTS RECOGNIZE THAT SEEING A MENTAL HEALTH PROFESSIONAL ISN’T ALL THAT SCARY, BUT ALSO BY HELPING OTHER KIDS UNDERSTAND MORE. (act) :15 o/c our disorders And they’re trying to help their children, and their students, understand that these disorders exist. They’re real. They affect their peers. And so I am hoping that by reaching the schools, that we are actually trying to demystify some of our disorders. AND IDEALLY, TANDON SAYS, BETTER UNDERSTANDING OF PSYCHIATRIC DISORDERS WILL NOT ONLY IMPROVE AWARENESS IN SCHOOLS, BUT ALSO COMPASSION. (act) :16 o/c early ages This person may have something that I don’t have, and that’s why they’re often getting into trouble. So the idea of the book is actually not necessarily to make a visit to the office less scary. It’s the idea of destigmatizing mental health as a whole, in early ages. IN THE FUTURE, TANDON HOPES TO WRITE MORE CHILDREN’S BOOKS ABOUT KIDS WITH OTHER PROBLEMS, SUCH AS AUTISM AND SUBSTANCE ABUSE, INCLUDING SMOKING. I’M JIM DRYDEN... RUNS 2:55

Some cases of diabetes are caused by mutations to a single gene, In studies of such cases, a team of Washington University researchers has identified the way that those genetic mutations cause problems. Although most people with the genetic form of diabetes called Mature-Onset Diabetes of the Young 1, seem to have clinical symptoms that are very close to the symptoms that affect people with type 2 diabetes, these studies show that the underlying mechanisms are very different. Most treatments for type 2 diabetes are designed to excite insulin-secreting cells into making more insulin, but that’s not the problem in the genetic form of the disorder. The study finds that insulin-secreting cells are under stress in the genetic form of diabetes, and those treatments that work in type 2 diabetes can increase stress, eventually killing the cells. So the researchers say say their findings suggest that patients with that genetic form of diabetes may need a different type of therapy. ALMOST 30 MILLION AMERICANS HAVE DIABETES, AND THE VAST MAJORITY HAVE THE NON-INSULIN-DEPENDENT FORM OF THE DISORDER, CALLED TYPE 2. BUT UP TO 5 PERCENT OF THOSE WITH DIABETES HAVE A FORM THAT’S CAUSED BY CHANGES IN A SINGLE GENE. AND NOW, RESEARCHERS AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS HAVE UNCOVERED THE MECHANISM THAT CAUSES THOSE PATIENTS TO BECOME DIABETIC, AND THEIR FINDINGS SUGGEST THAT MANY WHO HAVE THE GENETIC FORM OF DIABETES MAY NEED A DIFFERENT TYPE OF THERAPY THAN WHAT THEY’RE GETTING CURRENTLY. JIM DRYDEN HAS MORE… THE GENETIC FORM OF DIABETES IS CALLED MATURE-ONSET DIABETES OF THE YOUNG, OR MODY. PATIENTS WITH THAT FORM OF THE DISORDER OFTEN ARE NOT DIAGNOSED BECAUSE THEY HAVE SYMPTOMS THAT LOOK A LOT LIKE THOSE SEEN IN PATIENTS WITH TYPE 2 DIABETES, ACCORDING TO RESEARCHER BEN MOORE. (act) :12 o/c years old They’re really not often detected because they present a lot like type 2 diabetes. So they look like type 2 diabetes, but they happen uncharacteristically young. So they happen between 15 and 25 to 35 years old. WORKING IN THE LABORATORY OF WASHINGTON UNIVERSITY RESEARCHER JASON MILLS, MOORE DISCOVERED A PAIR OF PROTEINS THAT FUNCTION DIFFERENTLY TO GIVE PATIENTS THE MODY FORM OF DIABETES. THE GENES THAT MAKE THOSE PROTEINS ARE CALLED TRANSCRIPTION FACTORS, WHICH ARE THE SORTS OF GENES EVENTUALLY ASSOCIATED WITH MANY OTHER GENES. IN THIS CASE, MOORE SAYS, WHEN THE TRANSCRIPTION FACTORS BEHAVE A CERTAIN WAY, THE RESULT IS LOTS OF STRESS FOR INSULIN-SECRETING BETA CELLS IN THE PANCREAS. (act) :21 o/c the pancreas And the way that these transcription factors interact with each other can make…effect huge changes in the way that a cell functions and behaves. And we’ve identified a relationship between two transcription factors that is necessary for the proper function of cells that secrete insulin in the pancreas. AND UNFORTUNATELY, SINCE THE CLINICAL SYMPTOMS OF THE DISEASE LOOK SO MUCH LIKE THOSE IN TYPE 2 DIABETES, DOCTORS USUALLY TREAT PATIENTS WITH THE SAME TYPE OF MEDICATION THAT THEY GIVE TO TYPE 2 PATIENTS. THE PROBLEM WITH THAT IS THE MEDICINE IS DESIGNED TO EXCITE INSULIN-SECRETING BETA CELLS, WHICH PUTS THEM UNDER EVEN MORE STRESS AND APPARENTLY KILLS THEM OVER TIME. WHAT SHOULD BE TARGETED, SAYS SENIOR INVESTIGATOR JASON MILLS, IS THE TRANSCRIPTION FACTOR CALLED HNF4-ALPHA, A GENE THAT THEY IDENTIFIED WHILE STUDYING OF THE DEVELOPMENT OF CELLS IN THE STOMACH. MILLS SAYS IT APPEARS A LOT OF CELLS THAT SECRETE THINGS — LIKE BETA CELLS, STOMACH CELLS, AND LIVER CELLS — MAY RELY ON THE SAME HNF4-ALPHA MACHINERY. (act) :18 o/c same approach Obviously, what they secrete is incredibly important and different. The factories for building a BMW are not really that different from the factories for building a Volkswagen. The end product is, of course, incredibly important what the difference is, but actually, all the machinery you need is relatively similar. And it seems like nature has that same approach. AND MOORE SAYS AS A RESULT OF THE DISCOVERIES, IT APPEARS TO BE A GOOD IDEA FOR DOCTORS TO TEST FOR IRREGULARITIES IN HNF4-ALPHA SO THAT THEY CAN MAKE SURE THEY’RE NOT SIMPLY TREATING PATIENTS WITH THE MODY FORM OF DIABETES AS IF THEY HAD THE MORE COMMON TYPE 2 FORM. (act) :11 o/c that pathway We’ve identified a completely different pathway that is disrupted in MODY — not the same thing that is disrupted in type 2 diabetes. So hopefully this will lead to further research kind of uncovering drugs that are able to modulate that pathway. THE NEW STUDY IS PUBLISHED IN THE JOURNAL OF BIOLOGICAL CHEMISTRY. I’M JIM DRYDEN... RUNS 2:57