ICBD 2009: fMRI Differentiates Bipolar from Major Depression
Mary L. Phillips, MD, professor of psychiatry and director of functional neuroimaging in emotional disorders at the University of Pittsburgh School of Medicine, in Pennsylvania, discussed the imaging research at the 8th International Conference on Bipolar Disorder.
"Bipolar disorder is difficult to diagnose if the patient presents with depression and no history of being manic or 'high.' That matters, because it leads to inappropriate treatment with antidepressants and delay in treatment with mood stabilizers, which in turn can make the risk of switching to the manic phase greater," Dr. Phillips told Medscape Psychiatry. "We have shown that neuroimaging with functional magnetic resonance imaging [fMRI] can be used to differentiate major depression from depression in bipolar disorder."
The biomarkers Dr. Phillips and colleagues identified pertain to areas in the amygdala and orbitomeatal prefrontal cortex (OMPFC) involved in the emotional dysregulation associated with bipolar disorder. When they compared scans of subjects who were asked to label the emotional intensity of happy and sad faces, the researchers found that those with bipolar disorder had brain changes that reduced left-sided regulation of the amygdala by OMPFC. This might indicate a predisposition to elevated mood and mania, they speculate.
By contrast, subjects with major depressive disorder had overregulation of the amygdala in response to positive emotional stimuli, which might cause a reduced ability to respond to positive emotions. These subjects also had an exaggerated response to negative emotional stimuli.
Dr. Phillips noted that bipolar depression is the most frequent presentation of bipolar disorder and that 35% of bipolar individuals do not receive a correct diagnosis for more than 10 years after symptoms begin, so a reliable noninvasive diagnostic test would have major clinical implications. Only 20% of bipolar-disorder cases are correctly diagnosed within the first year of the patient seeking treatment.
Children of patients who are diagnosed with bipolar disorder are at 10-fold higher risk for the disorder than the general population. Dr. Phillips said that her research team is now "working backward in time" by using fMRI to examine the offspring of bipolar-disorder patients.
"We have data showing that certain fMRI abnormalities in otherwise-healthy offspring are similar to what we see in adults with bipolar disorder," Dr. Phillips said. "We are now following these children to see which ones go on to develop bipolar disorder. If these neuroimaging markers do identify that subgroup, it might enable us to intervene early with psychotherapy and try to intervene in the abnormal developmental pathway, perhaps preventing or reducing the severity of disease."
Dr. Phillips collaborated on these neuroimaging studies with Drs. David Axelson and Boris Birmaher.
Identifying Those at Risk
Jonathan Savitz, MD, told Medscape Psychiatry that Dr. Phillips's discoveries might be very useful for researchers as well as clinicians.
"The ability to identify high-risk individuals with neuroimaging would be a wonderful advance, because it would tell us something about the underlying neuropathology of the disorder and help inform genetic studies," said Dr. Savitz, who is in the section on neuroimaging in the Mood and Anxiety Disorders Program at the National Institute of Mental Health, in Bethesda, Maryland
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