By Pamela Linton
Dr. Rosenberg has spent his career researching and treating mental illness in child and adolescent populations.
Pediatric Psychiatrist Tackles Obsessive-Compulsive Disorder On a "Smaller" Scale
After an exhaustive and futile attempt to help their seven year old with her spelling homework, the child’s parents sank into a mood of disappointment, frustration and helplessness. The little girl had been fidgety; she continually interrupted her parents’ coaching with numerous trips to the kitchen to wash her hands. Each time, she would check the lock on the back door. Her parents could not understand why she was unable to focus and concentrate. Their assurances that the house was secure and her hands were clean fell on deaf ears.
The scene was a familiar one to this family, and one that occurs in approximately three percent of families throughout the U.S. whose children suffer from a major anxiety disorder characterized by conscious, ritualized, seemingly purposeless acts and recurrent, unwanted thoughts. When diagnosed, it is called obsessive compulsive disorder, or OCD. When treated, peace is restored to most families.
Hope begins in Wayne State University’s department of psychiatry and behavioral neurosciences (DPBN). Under the direction of pediatric OCD specialist and associate professor David Rosenberg, MD, a group of WSU researchers is uncovering information about pediatric neurobehavioral disorders more rapidly than at any point in the history of psychiatry. Dr. Rosenberg, director of both the OCD Clinical Research Program and Child and Adolescent Research Services, DPBN, is pioneering methodology that is enabling doctors to better understand not only brain activity and processes, but to locate and treat specific regions of that organ that malfunction.
One of the multiple projects Dr. Rosenberg has funded is the study of the types and the dosage of medications prescribed to children with OCD. "From everything we’re learning, the more effective and permanent treatments are behavioral rather than pharmacological," he points out. "Unfortunately when we first see the child, the stress and anxiety is so high that behavior intervention often can’t work and they sometimes need medication to facilitate the behavior therapy."
The goal, Dr. Rosenberg explains, is to target the most effective and lowest dose of medication for each child. "These are developing children with developing brains. You don’t use medication any longer than necessary, typically only until the behavior or psychosocial intervention can take over," he said.
Difficult to understand because of its limited accessibility and limitless complexities, the brain, more than any other of the body’s organs, has posed the greatest challenge to researchers. It was not until the 1950s that scientists had achieved an understanding of the molecular biology of the brain to allow for the identification of a number of new receptors and neurotransmitters involved in the actions of drugs. The most pivotal of those discoveries was the neurotransmitter serotonin.
Fueled by glucose, the brain’s diverse biochemical effects - including thought, feeling and behavior processes - are mediated by serotonin. Research showed that when malfunctions in this neurotransmitter occur, the result is mental, emotional and behavioral disorders which can often be severe. In the 1960s, specific responses of neurologic illness to medications was the key evidence confirming the existence of a biological link, and the next two decades were spent developing medications and treatments specific to serotonin irregularities.
Select serotonin re-uptake inhibitors, or SSRI’s, are a relatively new family of antidepressant medications that have proved to be a significant help for a number of neurologic illnesses, including OCD. SSRI’s, such as paroxetine, a drug Dr. Rosenberg is studying the effects of in children, target serotonin without affecting the brain’s other chemicals. Treatment with SSRIs, when combined with cognitive therapy, reduces OCD symptoms in up to 80 percent of sufferers.
On some levels the OCD traits, such as the anxiety or the obsession and compulsion are not bad, in and of themselves. "For example," Dr. Rosenberg points out, "it would be a good thing if more children washed their hands or were more aware of checking for safety precautions." The right combination of medication and behavioral therapy gives the OCD child the opportunity to conquer their extreme manifestations of these traits. "Ultimately, there is nothing wrong with OCD kids that what’s right with them can’t fix," Dr. Rosenberg believes. "So the right combination of medication and behavioral therapy gives the OCD child the opportunity to conquer their extreme manifestations of these traits." However, there is no magic bullet, and successful treatment typically involves an intense long-term process.
To achieve the right treatment combination, Dr. Rosenberg is working with neurologists, neurosurgeons, pediatricians, pharmacologists and basic scientists to unmask many of the brain’s mysteries that account for pediatric neurobehavioral disorders. The knowledge they have uncovered is leading to the development of new ways of compensating for abnormal neural activity, thereby alleviating the symptoms of OCD. Today, children are being treated in ways that were not thought possible 10, or even five, years ago. Dr. Rosenberg points out one of the changes that has occurred to move this area forward. "First, and most crucial, is that traditional pediatric medicine has become more aligned with pediatric psychiatry. Pediatricians are more knowledgeable and are responding to parents’ concerns by recognizing conditions like OCD, depression, ADD and Tourette’s syndrome earlier. They are now consulting with pediatric neuropsychiatrists the way they have always consulted with pediatric specialists such as cardiologists."
"This is one of the most gratifying aspects of my work," says Dr. Rosenberg. "Because pediatricians are recognizing the conditions earlier, we are able to begin treatment sooner."
This collaboration has led the Wayne State doctors to use positron emission tomography (PET) scans and functional magnetic resonance imaging (fMRI) to observe the interactions between the brain’s neural circuits in pediatric OCD. Where previous studies relied on spinal taps or lumbar punctures to look at cerebrospinal fluid and blood studies, the PET/MRI scans allow Dr. Rosenberg and his colleagues to measure brain activity at a particular moment in time, noninvasively and with no radiation, and to observe the brain’s complex behaviors and activity in mental disorders.
Through PET scans, which provide pictures of the brain at work by using a radioactive tracer to show the brain’s chemical activity, Dr. Rosenberg and colleagues have learned that the orbital frontal cortex and the caudate nucleus - part of the basal ganglia - are critically involved in the illness. In describing the process, Dr. Rosenberg likens OCD to Parkinson’s, in which "the caudate nucleus, being the switch that controls motor movement and cognitive processes, turns on and can’t be turned off." The result is involuntary and inappropriate movement. The results of these non-invasive tests are affording afflicted children new treatment options and the chance for a more typical childhood that a decade ago was unthinkable.
Although biologic psychiatry emerged in the 1950s, child psychiatry was not recognized as a specialty until two decades later. Early treatment of children who suffered from depression was replicated from adult treatment using antidepressants, including those from the tricyclic family such as Elevil, regularly prescribed to children in the same manner and at the same dosage as adult prescriptions. "Because of the side effects inherent with adult dosages, children literally responded better when treated with placebos," Dr. Rosenberg explains.
Today’s use of PET/MRI scans provide opportunity for more accurate diagnosis as well as a means to measure neural change subsequent to treatment. While children with OCD are in a MRI scanner, they are presented with stimuli such as pictures, words or numbers which have been predetermined to be neutral, or not distress provoking. Noxious stimuli includes any stimuli that children with OCD have obessions about and that would provoke OCD behavior. This work initiated in Pittsburgh was done with the consent of the parents and the child, and is somewhat analogous to cardiac stress tests. In comparisons between the neural activity of children with and without OCD, Dr. Rosenberg found that striking activation occurred in the inferior frontal lobe or orbital frontal cortex of the brain when children with OCD were shown the provocative, or noxious, stimuli.
MRI scans are also being used to study the chemistry of the brain, especially in such areas as the caudate nucleus, which is very rich in serotonin. Using another non-invasive technique called proton magnetic resonance spectroscopy, which relies on the brain’s own magnetism, Dr. Rosenberg has been able to study the brain’s neurochemistry and measure compounds like amino acids and GLX, or glutamate, which is a compound believed to regulate the release of serotonin. He has observed that high levels of GLX are associated with low levels of serotonin and, in OCD patients, the GLX levels are much higher.
Using the same tests to measure neural activity after treatment, Dr. Rosenberg has seen a marked response in children after 12 weeks on the SSRI medication paroxetine. In both the GLX studies and stimuli studies, the previous brain abnormalities normalize and no abnormal brain activity is seen in treatment responders.
Wayne State’s is the first group of doctors to study children who have never been medicated for their disorder, and then follow them serially as they are treated. Dr. Rosenberg has high praise for his colleagues. "The physicians here, like Alan Gruskin and Harry Chugani, are among the very best I’ve ever worked with." Dr. Thomas Uhde, chair of psychiatry and behavioral neurosciences, Dr. Gruskin, chair of pediatrics, and pediatrician-in-chief at Children’s Hospital of Michigan (CHM), and Dr. Chugani, professor of pediatrics at the School and medical director of Positron Emission Tomography at CHM, are among the reasons that WSU was attractive to Dr. Rosenberg. "Here you have these great doctors doing this milestone work, and it’s in a child-friendly environment. Other places may have the technology, but this is the only place in the world that can offer these services by a group of professionals that care only for children in an environment created just for kids."
The high caliber and dedication of the students he works with is another aspect of WSU that Dr. Rosenberg finds exciting. "Because of the exceptional department of psychiatry and behavioral neurosciences that Thomas Uhde has built as chairman, we are evoking interest much earlier in some of the brightest students in the School." Dr. Rosenberg is currently working closely with Year II student Kate Diamond on treatment resistant OCD and psychiatric conditions. "There is a population who do not respond to the standard treatment. With Kate taking the lead, we have been developing new treatment combinations such as adding Risperdone to a therapy with traditional SRIs and are seeing some very exciting results," he said.
Citing a need for 30,000 child psychiatrists in the U.S., where only about 10,000 are currently practicing, he is optimistic that student interest and response will continue. As Dr. Rosenberg points out, "working with children and their families is the window of opportunity for making a difference. Childhood is where the chances for great treatment, improvement and ultimate potential cure are the highest."
Behind the scenes, Dr. Rosenberg credits associates like his assistant, psychiatric nurse Carol Stewart, and psychologist Dr. Nili Benazon, with helping the public become more educated and helping the families of OCD children overcome the stigma of such a diagnosis. "I have the greatest respect for Carol and the dedication she brings to her job and to our patients and their families," said Dr. Rosenberg. "People come to know Carol as an ally, someone they can turn to or call upon with any type of concern."
Often the most difficult part of their work is convincing parents that OCD is not a result of bad parenting, but most likely the result of a certain area of the brain not working properly and a genetic component. "Dr. Benazon’s work with the families is likewise critical. Besides doing crisis intervention, she identifies and assesses the family’s impact on treatment," he said. With their intervention, families come to understand that getting help for a child with OCD is no different than getting help for a diabetic child. Dr. Rosenberg points out that although a stigma of sorts still exists, enormous strides have been made. "We are continually countering that stigma through public speaking and public education. In my experience I have found that it is crucial to be honest and forthright on all sides about what we know and what we don’t know."
The diagnosis and treatment methodology that Dr. Rosenberg is pioneering through his research at Wayne State is certainly closing that gap.