Researchers seek insight into disorders of mood and emotion

Researchers seek insight into disorders of mood and emotion

We don’t often think about the emotional and mental health of people with intellectual disabilities. Somehow, it seems like they should be immune to the stress and complexities of life. Yet, researchers are learning that people with mental retardation are at increased risk for emotional or behavioral problems, and even psychiatric disorders. Understanding the basis for such findings is just one of the interdisciplinary projects at the Vanderbilt Kennedy Center for Research on Human Development that fall under the umbrella of the Program on Mood and Emotion.

“Just because you have mental retardation doesn’t mean you are somehow protected against also having attention deficit hyperactivity disorder, anxiety, psychosis — any of the psychiatric or behavior problems we have in the general population,” said Elisabeth M. Dykens, Ph.D., professor of Psychology and Human Development and director of the Mood and Emotion program. “These folks are actually twice as likely to have such problems. We are trying to figure out why that is the case, what those problems are like, and how we can intervene.”

Dykens’ research focuses primarily on individuals with genetic disorders such as Williams syndrome, which results in serious cardiac problems as well as mild to severe mental retardation. Children affected by the disorder are prone to experience anxiety and phobia. One frequently seen problem is the fear of falling from high places.

Such a fear might stem from problems with gait, balance, and coordination that characterize the disorder. But, researchers suggest, the phobia may also be associated with factors that anyone in the general population might experience — a family history of anxiety, parental reinforcement of fear, or previous trauma, for instance.

Dykens believes that studying people with genetic syndromes will help sort out the relative contribution of genetic and bio-psycho-social risk factors for specific behavioral or emotional problems. “The idea is to use current findings to help families and improve interventions,” she said. “In the long term, these data should also help us find links between genes, the brain, and behavior.”

On the flip side of the issue, says Dykens, there is also a growing movement within the field to look at “positive psychology” — the idea that mental health is also a matter of things we all aspire to, such as creativity, altruism, integrity, or having meaningful relationships. “One of the novel things I’d like to do in our Mood and Emotion area is actively tackle those issues as they apply to people with mental retardation.”

Dykens moved to Vanderbilt from UCLA this past summer, drawn by the number and caliber of Vanderbilt Kennedy Center investigators in her field. “I feel like a kid in a candy store,” she said. “It’s wonderful to work with a center full of colleagues invested in learning more about people with disabilities.”

One of those colleagues is Judy Garber, Ph.D., professor of Psychology and Psychiatry, who collaborates with researchers across all campuses in her work on depression in adolescents. Garber just completed a six-year longitudinal study looking at predictors of depression in adolescents whose mothers varied in their risk for depression. An ongoing study with Dr. Richard Shelton in Psychiatry and Steve Hollon, Ph.D. in Psychology follows children who have a parent in treatment for depression. The idea is to see if improvement in a parent’s depression impacts children’s adjustment.

Garber is starting a new study, again looking at children of depressed parents, this time asking whether a cognitive-behavioral intervention can prevent depression in at-risk children 13-17 years of age. The intervention program, TEAMS (Teens Achieving Mastery over Stress) will be conducted at four different sites: Vanderbilt University, University of Pittsburgh Medical School, Harvard Medical School and Kaiser Permanente in Portland, Ore.

Garber also collaborates with Lynn Walker, Ph.D. in Pediatrics and Bruce Compas, Ph.D. in Psychology to study abdominal pain in children. Compas is co-director of the Pain and Symptom Management Program and director of Psychological Oncology at the Vanderbilt-Ingram Cancer Center.

Compas came to Vanderbilt a year ago to accept the Patricia and Rodes Hart Professor of Psychology and Human Development at Peabody College, an endowed chair created to link work done at Peabody with that done at VICC. His efforts focus on understanding how people are affected psychologically and emotionally by a diagnosis of cancer. That can mean how it affects the individual diagnosed and how it affects the family.

One collaborative project in development will look at whether chemotherapy affects a cancer patient’s cognitive function, such as memory or the ability to plan and carry out a particular behavior. Working with Laurel Brown, Ph.D. in Psychiatry and Adam Anderson, Ph.D. in the Vanderbilt University Institute of Imaging Science, Compas plans to study how specific brain regions are affected.

In addition to addressing adults and children with cancer, Compas also addresses children with chronic pain, children at risk for developing cancer, and children with sickle cell disease — a project being launched through the Meharry-Vanderbilt Alliance.

Stress can play a large role in all of these scenarios, and it is one of Compas’ major interests. In a person under stress, the brain and adrenal glands increase production of certain hormones, like cortisol, that help manage emotions. Evidence shows that being chronically stressed — elevating that system for sustained periods — can have adverse effects on brain development and function. Compas is developing a project to study cortisol levels in children living with depressed parents.

“A lot of what we are looking at across the different projects is the relationship between emotional health and physical health,” he said. “Having a physical illness affects my emotions. How I respond emotionally could affect how well I do in my illness.”

Neuroscientist probes complexity of behavior

by Bill Snyder

This summer, Science magazine published an intriguing finding about the interaction between genes and environment in depression: People who had an altered form of a gene that regulates the supply of a neurotransmitter in the brain were significantly more likely to become depressed after experiencing stressful life events than were people who had the normal gene.

"Human behavior is a complex mixture of the inherited and the learned," explains Randy Blakely, Ph.D., director of the Vanderbilt Center for Molecular Neuroscience and a Kennedy Center investigator.

To figure out how genetic and environmental factors interact, however, scientists must understand how the brain works — right on down to the molecular level. “We need some biochemical landmarks to work from,” says Blakely, who also is Allan D. Bass Professor of Pharmacology.

Those landmarks include neurotransmitters, which carry signals across the synapses, or gaps, between nerve cells, and transporters, which limit the amount of neurotransmitters that is available at the synapse.

When a transporter is blocked, neurotransmitter builds up in the synapse. By blocking the transporter for serotonin, drugs like Prozac increase the supply of serotonin at the synapse, and help elevate mood.

Ritalin is thought to relieve symptoms of hyperactivity disorder (ADHD) primarily by blocking the transporter for dopamine. But dopamine levels alone cannot explain the complexities of ADHD, says Blakely, who has made some important discoveries in the transporter field.

Blakely began studying signaling agents in the brain as a graduate student at Johns Hopkins University, where he earned his Ph.D. in neuroscience in 1987. In the early 1990s, he and his colleagues at Yale and Emory were the first to clone the genes that encode the transporters for serotonin and another neurotransmitter, norepinephrine.

Soon after coming to Vanderbilt in 1995, Blakely began collaborating with Dr. David Robertson, professor of Medicine, Pharmacology and Neurology, and an expert on heart rate and blood pressure regulation.

They suspected that a mutation in the norepinephrine transporter might be responsible for orthostatic intolerance experienced by one of Robertson’s patients and her identical twin sister. The syndrome is characterized by a racing heart, nausea and dizziness when a person stands up.

Upon testing the women and their family, the researchers found a genetic mutation that effectively disabled the transporter in five family members, including the twins and their mother. The finding, reported three years ago in The New England Journal of Medicine does not explain all cases of orthostatic intolerance, but this was the first neurotransmitter transporter mutation associated with specific symptoms of a disease, Blakely says.

Since the mutation also would be expected to affect norepinephrine levels in the brain, the researchers recently evaluated members of the same family for attention problems.

Sure enough, those who carried the mutation reported they had a hard time maintaining attention and concentration — one of the hallmarks of ADHD, says Dr. Richard Shelton, professor of Psychiatry and Pharmacology.

Currently Blakely, with lab members Maureen Hahn and Michelle Mazei, and Dr. Steve Couch, assistant professor of Pediatrics, are looking for genetic mutations that may affect the function of dopamine and norepinephrine transporters in children with ADHD and their family members.

Blakely hopes his work will lead to improvements in the diagnosis and treatment of ADHD. Ultimately, it may also help scientists understand how environmental factors affect brain function.

“It’s a challenge,” he says, “but new leads could really help clarify what's altered in the disorder and who is at risk."

Clinic brings novel approach to severe behavioral problems

by Mary Beth Gardiner

Aggression can be a frightening thing, especially when it’s physical, and especially when seen in a child. Head banging, self-biting, hitting and scratching — severe behavioral problems such as these can be common in a child with intellectual or developmental disabilities.

The natural response — to intervene — may unintentionally reinforce the behavior by giving the child the attention he wanted in the first place but wasn’t able to verbalize. The behavior becomes routine and may escalate. Consequences grow even more alarming as that child approaches adulthood; often, the only reasonable solution is institutionalization.

The new Behavior Analysis Clinic at the Vanderbilt Kennedy Center for Research on Human Development aims to teach children and adults with developmental disabilities better ways to deal with the emotions that can lead to severe behavioral problems.

“Behavior analysis is a fairly recent approach to trying to understand people’s behavior problems through recognizing the environmental causes of it,” said Craig H. Kennedy, Ph.D., associate professor of Special Education and Pediatrics and director of the clinic. “We look for events that occur in a person’s environment that might make them learn to use aggression as a tool for communication.”

Assessment at the clinic is comprehensive. A visit entails an intensive half-day evaluation by an interdisciplinary team looking at health conditions that might contribute to problem behavior, possible environmental causes, and a medication review.

“We look to Nursing to help us give the initial health exams and to Psychiatry to look at polypharmacy,” said Kennedy. “These people may be on three or four or five drugs, and the interaction of those drugs is largely unknown. We work with Psychiatry to medicate more rationally, using as few drugs as possible.”

Unlike most outpatient clinics, service at the Behavior Analysis Clinic doesn’t stop with the evaluation, says Kennedy.

“We wrap all of that information together into a treatment strategy and actually go out into the community — to schools and to homes, or wherever the person lives — and train the people who live and work with the individuals to implement the intervention.”

Kennedy and Pat R. Levitt, Ph.D., director of the Vanderbilt Kennedy Center, have been meeting with officials from the Tennessee Division of Mental Retardation and the Tennessee Council on Developmental Disabilities about treating patients from the state institution system.

“This is a huge problem for the state,” said Levitt. “They are very enthusiastic about the holistic approach we are taking, which has been missing to this point.”

The clinic is a valuable training ground for students in Peabody’s department of Special Education, one of the top-ranked programs in the country and one of only three universities to offer behavioral analysis certification. Administrators in the School of Nursing and the department of Psychiatry also recognize the unique opportunity for their trainees.

“The School of Nursing is happy to support this collaborative effort,“ said Bonnie Pilon, DSN, senior associate dean for Practice Management at VUSN. “The partnership will enhance learning opportunities for our students and offers our faculty members the chance to contribute to an important community service.”

“We will start participation in January, sending a fellow in Child and Adolescent Psychiatry to spend time in the clinic learning about behavior analysis methods and providing consultation regarding psychiatric concerns and pharmacological intervention,” said Dr. Cathy Fuchs, director of the residency training program in Psychiatry. “I’m very excited about our involvement in the clinic because we need both types of expertise to do a good job with these individuals.”

The Behavior Analysis Clinic will see only adults initially, expanding services to children over time. For more information or to request to be contacted as services expand, call 322-8185 or email bac@vanderbilt.edu.