Is this child bipolar? What’s needed to improve diagnosis
With genetic and brain imaging biomarkers, early intervention could protect at-risk kids.
We’ve also seen children who start to show symptoms but don’t develop full bipolar disorder. These children have had clinical treatment, so we’re not sure if the intervention prevented full bipolar disorder or if they would not have developed it anyway. Some children have developed mood symptoms and other psychiatric problems that have resolved with early intervention.
DR. CHANG: Kindling, which originally referred to seizure disorders, also has been applied to affective disorders.5 Early stressors and triggers appear to add up over time and combine with genetic predisposition to create a full mood episode. After that break, it becomes easier and easier to have the next episode, and the disorder becomes chronic and more difficult to treat.
The goal of our work is to stop kindling in bipolar disorder—to prevent environmental or developmental “sparks” from interacting with genetic predisposition and igniting a chronic, spontaneous course of mood episodes.
Brain imaging biomarkers
DR. KOWATCH: Are researchers finding biomarkers for bipolar disorder?
DR. CHANG: The field is young but light-years ahead of where we were 10 years ago. Brain imaging has revealed consistently abnormal areas in children with bipolar disorder. These abnormalities are seen in adults with bipolar disorder as well, but chronic illness, substance abuse, and medication exposure affect the findings in adults. Children have had less exposure to these confounding variables.
We and other groups have identified areas of the prefrontal cortex, amygdala, cerebellum, and striatum that could represent biomarkers, although I wouldn’t say yet that there are any markers per se. A decrease in amygdala volume has been found consistently in children with bipolar disorder, for example, but it’s not specific to bipolar disorder. So we have a way to go before we find specific biomarkers.
In the future, clinicians will probably use a set of 10 to 20 biomarkers, and the more biomarkers a patient has, the greater the risk for bipolar disorder. Once a battery of biomarkers has been put together, the more certain a bipolar disorder diagnosis will become.
Genetic biomarkers
DR. KOWATCH: We’ve talked about high-risk families; are there genetic markers for bipolar disorder?
If you look at common polymorphisms in a set of genes, eventually you’ll be able to calculate the risk that a person will develop bipolar disorder. We’re also investigating whether genes control the age of onset.
DR. KOWATCH: How are you looking for genetic markers in the high-risk children you’re studying?
DR. CHANG: We start with the proband—the child of a bipolar parent—and then study as much of the family as we can. Approximately 50% of the probands’ first- or second-degree relatives have a mood disorder—so our samples are highly loaded.
We’re interested in the interaction between genes and brain function and structure: How do genetic predispositions lead to brain differences that create vulnerability for mood disorders—in this case, bipolar disorder?
To explore that question, we’re starting a 5-year study funded by the National Institutes of Health (NIH). We’re recruiting 50 sibling pairs in which 1 child has early bipolar symptoms and the other is healthy. We will compare these pairs’ genetic and brain imaging profiles with those of 30 healthy children with no genetic risk for bipolar disorder, as far as we can tell.
Something makes 1 child develop bipolar disorder and another child not. By matching siblings with shared environments, we’re trying to eliminate environmental factors and look at their genetic and brain function differences. We’ll use functional brain imaging to look at how children respond to mood-related tasks and standard tasks involving facial emotion exposure to activate brain areas bipolar disorder is thought to affect.
Preventing bipolar ‘kindling’
DR. KOWATCH: What interventions might interrupt kindling and help prevent bipolar I disorder from developing in high risk children?
DR. CHANG: Families affected by bipolar disorder are characterized by stress and high expressed emotion; they tend to fight a lot, and we’re trying to improve communication and their ability to work together. We think reduced stress could halt the progression of the disorder in at-risk children.
