Stanford study of genetics of bipolar disease may help predict disease in kids

STANFORD, Calif. ­ Parents who have bipolar disorder stand an anxious vigil over their children, wondering whether their offspring's irritability, mood swings and depression are normal childhood changes or the first sign of the disease they've been battling for years. The concerns are justified. Up to 24 percent of children of bipolar parents develop bipolar disorder, and about one in four displays some other type of mood disorder.

Kiki Chang, MD, assistant professor of psychiatry in the division of child and adolescent psychiatry at the School of Medicine, hopes that his research will one day relieve this burden of uncertainty. He and his colleague, Joachim Hallmayer, MD, PhD, associate professor of psychiatry and behavioral sciences, have received a $345,000 grant from the Heinz C. Prechter Fund for Manic Depression to study the genetic underpinnings of early onset bipolar disorder.

Bipolar disorder, which affects about 2.3 million adults in this country, is characterized by episodes of depression and mania that cause extreme shifts in mood, energy and functioning. Chang and Hallmayer hope to be able to predict which children of parents with the disease are likely to develop bipolar disorder before symptoms begin, allowing early, more effective treatment.

'There have been a lot of studies of the genetics of bipolar disorder, but no particular gene or region has been identified as the culprit,' said Chang. 'Most of these studies have concentrated solely on adults with bipolar disorder. We're hoping that by looking at the children of bipolar parents - those who already have bipolar disorder or who are exhibiting early signs - we can identify not only the genes involved, but also other contributing factors.'

These factors may help explain why children of bipolar parents often begin exhibiting earlier, more severe symptoms of the disease than their parents did - an unfortunate phenomenon called genetic anticipation that is shared with a few other inherited diseases. In addition to genetic studies, Chang is also involved in ongoing research efforts to create brain images of children with and without bipolar disorder and to identify structural and functional changes that may be the hallmark of the disease.

'We really want to identify bipolar disorder before it happens and prevent it,' said Chang. Preliminary results in Chang's lab suggest that early intervention with appropriate medications might be able to halt the progress of the disease.

Pediatric bipolar disorder can manifest itself in many ways. Children are first frequently diagnosed with attention deficit/hyperactivity disorder, or ADHD, at around 4 or 5 years of age. Mood problems typically develop later and can worsen around puberty. Other symptoms include extreme euphoria or depression, irritability, sleep disruptions, hypersexuality and severe mood swings.

'There is some variability of symptom expression and method of onset,' said Chang, 'and all sorts of overlap between bipolar disorder and other types of mood dysregulation. Sometimes the symptoms get confused with normal behaviors surrounding puberty.'

Chang and Hallmayer are looking for families in which at least one parent has suspected or confirmed bipolar disorder to participate in their genetic studies. They're especially interested in families with one or more children with early mood difficulties or full-blown bipolar disorder. Participants receive free diagnostic evaluation of the entire family and are asked to give a small amount of blood for genetic analysis. There is also some payment for participants as reimbursement for their time. To volunteer or for more information call Diana Iorgova at (650) 723-7885 or e-mail diorgova@stanford.edu.

The non-profit Prechter Fund was established by Waltraud 'Wally' Prechter in memory of her late husband, Heinz Prechter, an industrialist who suffered from intermittent bouts of manic depression for most of his adult life and fell victim to suicide in July 2001. The fund aims to advance medical research to help develop cures for bipolar disorder.

Lucile Packard Children's Hospital at Stanford is a 240-bed hospital devoted entirely to the care of children and expectant mothers. Providing pediatric medical and surgical services associated with Stanford University Medical Center, Packard offers patients locally, regionally and nationally the full range of health-care programs and services - from preventive and routine care to the diagnosis and treatment of serious illness and injury. To learn more about Lucile Packard Children's Hospital, please visit our Web site at www.lpch.org.

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