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Hopkins THE NEWSLETTER O F T H E J O H N S H O P K I N S D E PA RT M E N T O F P S Y C H I AT RY A N D B E H AV I O R A L S C I E N C E S summer 2014 “If we’re going to say ‘yes’ to helping the community,” says Robert Findling, “we need to collaborate.” New Professorship from Leonard and Helen R. Stulman Foundation The Leonard and Helen R. Stulman Foundation supports work in mental health, health and aging. Leonard Stulman, a Baltimore businessman, philanthropist and Johns Hopkins alumnus, died in 2000, but his legacy lives on through the foundation that he and his wife created. The foundation established the Leonard and Helen R. Stulman Professorship in Child and Adolescent Psychiatry to improve the quality of and increase access to mental health services for young people. This new professorship was dedicated and Robert Findling installed as its inaugural recipient in April 2014. Joining Hands for Child Psychiatry I n a low voice, as if he’s telling a secret, Robert Findling says, “The supply of child psychiatrists is not even close to meeting the demands that are out there. Depending on how you look at it, there’s more than a 50 percent shortage.” But Findling, who heads child and adolescent psychiatry at Johns Hopkins, isn’t deterred by these seemingly dire statistics. In fact, he’s working to meet the challenge head-on. Recently, he was named the Leonard and Helen R. Stulman Professor in Child and Adolescent Psychiatry. Thanks in part to this gift, Findling is spearheading an effort to improve access to psychiatric care for young people. “To do this, we must collaborate,” he says. “We are thinking locally and recognizing that what we do can have an impact globally.” To start, Findling has been working to build partnerships among three Baltimore entities: The Johns Hopkins Hospital, Johns Hopkins Bayview Medical Center and the Kennedy Krieger Institute (KKI), which is dedicated to helping patients with developmental, brain, spinal cord and musculoskeletal disorders. After just six months, he says, “We are referring patients between the groups in a much more facile way, so it’s better for children and families. Sometimes when you get care from two organizations, they don’t really speak to each other. Now information can more readily flow.” The three-part collaboration also supports Findling’s efforts to boost psychiatric services by increasing staff. When he needed a training director for child psychiatry residents learning about the psychiatric diagnosis and treatment of children, adolescents and their families, he identified Roma Vasa, an autism researcher and child psychiatrist at KKI. Now, Vasa pursues her educational endeavors at Johns Hopkins and clinical research at KKI. “These kinds of changes will help stabilize, build and secure a durable, clinical child psychiatry practice,” says Findling. With more personnel, there can also be an increase in research, and Findling says the area he most wants to explore is prevention. “Most psychiatric conditions develop during mid- to late-adolescence, and that tells me there is an opportunity to intervene and prevent them,” he says. Most of the early symptoms that present to a child and adolescent psychiatrist are not specific— irritability, hostility or distractibility—much like a fever, cough or abdominal pain might present to a pediatrician. “You don’t wake up one morning with a serious psychiatric illness,” Findling says. “We want to look at what’s going on and how we can intervene and prevent it. Why wait until someone is in extremis before you intercede, which is what we currently do in psychiatry.” In a tone filled with optimism, Findling says, “We have only one goal here: to help children. Our job is to serve them. That’s the privilege of having this endowed professorship.” n “The supply of child psychiatrists is not even close to meeting the demands that are out there. Depending on how you look at it, there’s more than a 50 percent shortage.” Genetic Links One Small Step for OCD Treatment, One Large Step for OCD Research C “ onsidering that obsessivecompulsive disorder is one of the world’s more disabling conditions,” says Gerald Nestadt, “we know very little about its underpinnings.” But Nestadt, who has devoted most of his career to understanding the disorder, recently came closer than ever to pinpointing a genetic cause. For the last five years, the Johns Hopkins psychiatric epidemiologist and inaugural recipient of the Rudolf and Evanne Hoehn-Saric Professorship for ObsessiveCompulsive Disorder and Anxiety Disorders Research led a group of researchers in the second-ever genome-wide association study of OCD. After scanning the genomes of more than 1,400 people with OCD and more than 1,000 close relatives of people with the disorder, Nestadt and his colleagues identified a strong signal associating OCD with a gene called protein tyrosine phosphokinase (PTPRD). While the study was not quite a “home run,” Nestadt says they got very close. Previously, PTPRD was shown in animals to possibly be involved in learning and memory, traits related to OCD in humans. Moreover, some cases of attention-deficit hyperactivity disorder (ADHD) have been associated with the gene, and OCD and ADHD have some symptoms in common. Nestadt says the gene also works with another gene family, “The cause of OCD is due to a complex pattern of genetic and environmental factors,” says Gerald Nestadt. Curbing Doubts SLITRK, which has been associated with OCD in animals. OCD affects an estimated 1 to 2 percent of the U.S. population, and the World Health Organization has called it one of the more disabling medical conditions worldwide. Some of the least disabling forms of the disorder Although Gerald Nestadt and his team are closer to understanding the genetics of obsessive-compulsive disorder, he believes that other domains are worth looking into as well. “Whatever is ultimately causing OCD is actually causing something before OCD,” he says. “My hypothesis is that one thing is the trait of doubt.” In collaboration with other Johns Hopkins faculty, Nestadt is working on imaging and neuropsychology research to identify fundamental traits of OCD, including doubt. “We are trying to define what doubt is, get measurements of it, and test it using functional magnetic resonance imaging,” he says. “We are also working on a behavioral test to see if we can identify doubt and how much of a doubter someone is” n Drug Discovery PAK Inhibitors Pack an Interesting Punch for Schizophrenia Research T he physicians who discovered the first effective medication for schizophrenia— chlorpromazine—did so by luck. The first antipsychotic, it had initially been used as an antihistamine and then as an antiseptic. Only by serendipitous observation did physicians realize that it improved hallucinations, delusions and other symptoms related to schizophrenia. Today, Johns Hopkins psychiatrist Akira Sawa aims to gain a clearer understanding of the disease’s pathways to develop drugs that specifically target its molecular pathology. To this end, he and his colleagues recently completed a study looking at a cascade of events that disrupt connections between brain cells in the schizophrenic brain. They then examined whether a unique compound could lessen the disturbing activity. Working with mice that had brain mutations involving a gene associated with schizophrenia, Sawa, Akiko Hayashi-Takagi and colleagues introduced a drug that is one of a class of compounds known as PAK inhibitors. The PAK compounds have been shown in animal studies to provide some protection during which important neural connections are unnecessarily destroyed. The researchers were also able to partially restore disabled neurons so they could connect to other nerve cells. “We hope to find drugs that reverse an existing defect as well as block future damage.” “We wish to come across drugs that are able to reverse an already existing defect as well as block future damage for good treatment,” says Sawa. “This compound might have potential to do both.” Akira Sawa aims to uncover compounds that target the Even though the results need to be validated by mechanisms at work in the schizophrenic brain. determining whether the same PAK cascade occurs in humans, the findings in “teenage” mice are an from brain damage due to Fragile X syndrome, a especially promising step because schizophrenia disease in humans marked by mental retardation. symptoms typically appear in late adolescence and Because the PAK protein can initiate cancer and cell early adulthood, says Sawa. “That we could intervene growth, PAK inhibitors have also been tested for in adolescence and still make a difference in restoring cancer. brain function in these mice is intriguing.” After the 35th and 60th days of treatment— Ultimately, Sawa hopes the compound provides equivalent to adolescence and young adulthood in an opportunity for drug discovery and development the mice—the compound, called FRAX486, appears that intentionally targets the mechanisms causing to halt an out-of-control biological “pruning” process synaptic disturbance not only in schizophrenia, but in the brain of the mouse model for schizophrenia in other brain disorders as well. n Medication Review Why We Still Use Lithium R can still add an extra hour to the day’s routine, causing distress and interfering with daily life. But some patients are so disabled that they can’t leave their homes. “OCD research has lagged behind other psychiatric disorders in terms of genetics,” Nestadt says. “We hope this finding brings us closer to making better sense of it and helps us find ways to treat it.” n ecently, a patient came to The Johns Hopkins Hospital from across the country for treatment of bipolar disorder. Expecting that there was something new he could try, he was at first surprised, and even a bit disappointed, by his prescription. But after starting two of the oldest medications around—including lithium—he reported feeling better than he had in years. “There’s always enthusiasm for new treatments for bipolar disorder in hopes they will have fewer side effects and provide additional options for treatment,” says Karen Swartz, who directs Johns Hopkins’ Mood Disorders Consultation Clinic. “But we want evidencedriven treatments, and even though lithium is the oldest treatment for bipolar disorder, it still has the strongest evidence supporting its efficacy, which is why it’s a medication we commonly use.” Although it was neither doubleblind nor placebo-controlled, the initial 1949 report by Australian psychiatrist John Cade describing lithium’s therapeutic effects in patients with acute and chronic mania has not only stood its ground ever since, but has also been well validated. Among the examples Swartz cites is the 2010 BALANCE trial, which found that lithium was more effective at preventing mood symptoms than valproate, and that the combination of lithium and valproate was better than valproate alone. In a 2013 metanalysis, lithium was more effective than a placebo in reducing the number of suicide attempts and deaths, while another study found that patients taking lithium were rehospitalized for mood symptoms less than patients taking valproate. “The caveat,” says Swartz, “is that you have to make sure patients are willing to participate in the treatment.” Because lithium’s narrow therapeutic window means patients require frequent blood level, thyroid and kidney monitoring, “sometimes that can make lithium less appealing,” says Swartz. Other issues that patients need to understand include how some medications, such as ibuprofen, or medical conditions like a urinary tract infection or dehydration can alter their lithium levels. “We’ve become pretty sophisticated on how to dose, treat and monitor lithium,” says Swartz. “We’ve come to appreciate that Karen Swartz often starts treatment of bipolar disorder with lithium because it has the most evidence behind it. lower doses can often be just as effective, so it’s a medication that more people can tolerate. If we work with patients and find that they do just as well with control of their mood at a lower dose, it can be a way to decrease their side effects.” n For information: 410-955-5212 expert opinion Answering Some Basic Questions About Medical Marijuana Whether you are for or against the use of marijuana as medicine, 21 states plus the District of Columbia have legalized the substance for medical use. The laws allow qualified individuals to purchase and use marijuana products from dispensaries to treat conditions from pain to anorexia. Here, Johns Hopkins behavioral pharmacologist and cannabis researcher Ryan Vandrey discusses some of the benefits and risks. What are the benefits of medical marijuana? Isn’t smoking bad for you? Much like any other drug, there are risks and benefits of medical marijuana, says Ryan Vandrey. Research has been done with tetrahydrocannabinol, or THC, the primary psychoactive component of marijuana, in pill form. This research finds that the medical benefits of marijuana include management of pain, nausea and spasticity. It is also good for appetite stimulation, especially for people having chemotherapy or people with AIDS wasting syndrome. And yes, many physicians have a hard time recommending a drug that is smoked. Depending on why a person is using it, though, smoking may be (continued on page 4) Medical Marijuana (continued from page 3) better than swallowing. For example, if it is being used to treat nausea, there is a chance that the person might not be able to keep the pill form down. Plus, in certain cases of acute pain, the effects from smoking are going to happen more quickly. The downside is that compared to oral administration, smoking is much shorter-acting, and of course, isn’t good for your lungs. symptoms and be unable to quit even though they want to. However, when it is used for a medical purpose as it’s prescribed and discontinued when it’s no longer needed, the risk of addiction is probably relatively low. You are among a small number of scientists who have made marijuana studies a specialty. Have your studies showed that people can become addicted to marijuana? Data show that about half of adults in the U.S. have tried marijuana at some point. Most move on and don’t have a problem with it. A subset of about 10 percent, however, try it and develop a problematic pattern of use. There is also the risk of having an acute panic or psychotic reaction to the drug, and there’s no way of knowing what kind of reaction someone is going to have. So, people have to recognize the risks associated with it. Again, it’s Yes. Just as with other kinds of drugs, such as nicotine, people can become addicted, and it can be abused. Using marijuana can affect a person’s ability to work, go to school or have relationships. When people stop using it, they can experience withdrawal What do people need to know before using medical marijuana? much like any other drug. Do you have worries about the trend to legalize marijuana? Yes. My biggest concern at the moment is the lack of oversight and regulation of the medical marijuana industry. Right now, there is no way to ensure that the marijuana being sold isn’t contaminated, and there’s no oversight making sure that the amount of THC in one product is the same as the next. In addition, there is no ceiling on the amount of drug that can be in a single product, and that can be dangerous. As medicine, the dose needs to be consistent each time it is taken. Medical marijuana needs oversight and regulation, just as food and other drugs are regulated. n Hopkins This newsletter is published for the Department of Psychiatry and Behavioral Sciences by Johns Hopkins Medicine Marketing and Communications. 901 South Bond Street, Suite 550 Baltimore, MD 21231 Some of the research in this newsletter has corporate ties. For full disclosure information, call the Office of Policy Coordination at 410-223-1608. To make a gift, contact Jessica Preiss Lunken, Director of Development Johns Hopkins Department of Psychiatry and Behavioral Sciences Fund for Johns Hopkins Medicine 550 North Broadway, Suite 914 Baltimore, MD 21205 Non-Profit Org. U.S. Postage PAID Permit No. 5415 Baltimore, MD Department of Psychiatry and Behavioral Sciences J. Raymond DePaulo Jr., M.D. Director Marketing and Communications Dalal Haldeman, Ph.D., M.B.A. Senior Vice President Lisa Rademakers, Writer Mary Ann Ayd, Managing Editor Lori Kirkpatrick, Designer Keith Weller, Photography ©2014 The Johns Hopkins University and The Johns Hopkins Health System Corporation If you no longer wish to receive this newsletter, please email [email protected] Check our departmental website for more news: www.hopkinsmedicine.org/Psychiatry/index.html Hopkins T H E NE W S L ET T ER summer 2014 O F T H E J O H N S H O P K I N S D E PA R T M E N T O F P S Y C H I AT RY A N D B E H AV I O R A L S C I E N C E S One Small Step for OCD Treatment, One Large Step for OCD Research PAGE 2 Why We Still Use Lithium PAGE 3 Answering Some Basic Questions About Medical Marijuana PAGE 3