Chicago Researchers Seek to Predict and Prevent Early-Onset Bipolar Disorder
Related Pediatric Mood Disorders Clinic Offers Multidisciplinary Treatment

The Department of Psychiatry’s Institute for Juvenile Research at the University of Illinois at Chicago (UIC) is conducting studies in genetics, brain structure, and biochemistry to search for early biological markers of bipolar disorder. These markers are physiological changes or traits that provide evidence of the illness that can be detected even before symptoms appear in at-risk children. Early intervention can greatly reduce the symptoms that occur, and it can head off other disorders, such as substance abuse, that often develop in untreated individuals. The UIC researchers are examining medication and gene therapy as preventive treatments for children who are at risk for developing the illness.

“We need to focus on neurobiology to start talking about real prevention,” says Mani Pavuluri, MD, founding director of the Institute’s Pediatric Mood Disorders Clinic, and chair of The Balanced Mind Foundation's Scientific Advisory Council. Pavuluri, UIC Assistant Professor in Child Psychiatry, received her training in mood disorders in Australia, treating prodromal (very early) symptoms of children at risk for schizophrenia and bipolar disorder. “I am particularly interested in imaging these young children’s brains using functional MRI and looking at how mood dysregulation negatively influences their problem-solving ability.” With functional MRI technology researchers can watch the brain at work, while the test subject performs different types of cognitive tasks and undergoes a variety of emotional responses. The resulting image lets scientists analyze the level of activity in the brain’s different regions and observe variations in its chemical properties as they occur.

Among the areas the UIC researchers are pursuing is an examination of the role of reelin, a newly discovered protein that is found in abnormally low levels in the brain and blood of a person with bipolar disorder or schizophrenia. Pavuluri is also collaborating with her colleague Ghanshyam Pandey, MD, an expert on serotonin function abnormalities in the brain. Together they are looking for biological markers of suicidal behavior in children and teens with bipolar disorder.

Pavuluri’s research and clinical work are closely integrated at the Institute’s Pediatric Mood Disorders Clinic, which is the first multidisciplinary clinic in the Midwest devoted to research and treatment of pediatric mood disorders. “If we are to take pride in developing a good treatment program, we must ultimately be able to show biological evidence as to what is changing,” says Pavuluri. “Conversely, we must use knowledge of pathophysiology [the anatomical manifestations of illness] to guide us in early intervention, given that it is a brain disorder.”

The mood disorders clinic offers an integrated, multifaceted, outpatient program that meets the diverse and extensive needs of children with bipolar disorder and their families. The clinic’s staff includes a doctoral nurse clinician as its administrative director, plus a clinical social worker, neuropsychologist, and fellows in child psychiatry. The clinic evaluates approximately 350 children per year, about half of whom have bipolar disorder. The mood disorders clinic provides many types of services for families, including psychiatric evaluation, medication treatment, individual and group psychotherapy for children, family education and therapy, and consultation to schools. Parents and children learn how to monitor and recognize symptoms of a change in the child’s cycling, how to minimize and manage stresses at home, and how to collaborate with schools. Parents receive parallel counseling that provides effective techniques for dealing with their children and guidance on coping with the strains that come with having an ill child. Families are also directed to community organizations such as the The Balanced Mind Foundation (The Balanced Mind Foundation) Web site, www.thebalancedmind.org, for additional support and information.

“We will not know how the treatment is changing the course of the illness, as we don’t have the long-term studies published yet that followed these children beyond two years,” according to Pavuluri. “All we are able to do now is contain the symptoms. The good news from our preliminary results is that more than 80 percent of the children can improve using systematic, protocol-based, medication therapy and psychotherapy combined.”

In one of her studies Pavuluri followed 87 preadolescent children with bipolar disorder for 18 months while treating them all with mood stabilizers and Risperdal (an atypical antipsychotic). Before they began treatment, more than 90 percent of the children experienced ultra rapid cycling. They were given mood stabilizers only, Risperdal only, or a combination of the two. After treatment was initiated, their symptoms improved to the point where the rapid cycling occurred only about 30 percent of the subjects. This progress, notes Pavuluri, makes it possible for the kids to do things other children take for granted, such as visit their grandparents and attend school. While more than 70 percent of the subjects showed improvement, using Risperdal alone produced the most rapid overall improvement. The subjects were classified as Bipolar I (73.6 percent); Bipolar II (9.2 percent); and Bipolar NOS—Not Otherwise Specified (17.2 percent.)

One of the interventions offered at the clinic is the Rainbow program, a 12-week course of individual family/group therapy for children. The program integrates cognitive behavioral therapy and interpersonal therapy and covers issues such as how to change negative thoughts, communicate with family, nurture self- esteem, stay motivated, be more social and manage school life. The Rainbow name denotes Routine, Anger control, I can do it, living in the Now and No negative thoughts, Be a good friend and Balanced life style, Oh how we can solve problems, and Ways to get support. During the children’s group therapy sessions, groups for their parents meet concurrently to learn about peer relations, school issues, discipline, medication management, family issues, and others. Some sessions combine the parents group and the children.

Current and future research studies include:

• developing a reliable rating scale for parents and teachers to identify early-onset bipolar disorder
• examining the prefrontal cortex for differences in emotion and behavior regulation in children with ADHD, bipolar disorder and major depression, using neuropsychological assessments, tracking eye movements, and functional brain imaging
• DNA studies of children with bipolar disorder and their families to identify genes associated with the illness
• examining serotonin levels in children with depressive and bipolar disorders as possible indicators of suicidality and/or clinical response to treatment with medication
• developing a treatment algorithm (a set sequence of treatment steps) for early-onset bipolar disorder

The clinic staff maintains a close relationship with The Balanced Mind Foundation, and families are routinely directed to the The Balanced Mind Foundation Web site for information and additional support. “Families who come to the clinic always tell us how very kind the The Balanced Mind Foundation staff have been to them,” says Pavuluri. “And the child psychiatry fellows and medical students who rotate through the clinic are expected to visit and be familiar with the The Balanced Mind Foundation Web site. The site helps them learn a great deal about bipolar disorder in kids and the needs of their families.”

The staff also keeps up a strong working relationship with the Josselyn Center for Mental Health in the Chicago suburb of Northfield. For more information, contact:
Pediatric Mood Disorders Clinic
University of Illinois at Chicago
Department of Psychiatry
Institute for Juvenile Research
www.psych.uic.edu/pmdc/index.htm
(312) 996-2200