PITTSBURGH — Neuroimaging may soon become an important clinical tool for the diagnosis and treatment of mood disorders, Dr. Mary L. Phillips said at the Seventh International Conference on Bipolar Disorder.
Emerging data suggest that functional magnetic resonance imaging (fMRI) can identify specific neural biomarkers that may help distinguish patients with bipolar disorder from those with unipolar disorder. These data may also help physicians assess which patients will respond to which psychotropic medications and possibly even predict which healthy individuals at high genetic risk will go on to develop bipolar disorder, said Dr. Phillips, who is with both the University of Pittsburgh, where she is professor of psychiatry and director of the functional neuroimaging program, and the Institute of Psychiatry in London, where she is with the section of neuroscience and emotion.
“We've moved beyond blue sky high-level science for its own sake. We're now using neuroimaging to ask and answer real-life clinical problems,” she said at a press briefing held during the conference.
Improving the diagnostic capability of those who treat bipolar disorder is a research priority and is likely to be the first bedside use of the technology. Bipolar disorder is frequently misdiagnosed as unipolar depression, often for as long as 8–10 years, before patients receive a correct diagnosis and treatment.
Using fMRI to record neural responses to pictures of people with facial expressions of varying emotions, Dr. Phillips and her London associates found distinct differences between a group of 12 patients with a diagnosis of bipolar I disorder, 9 with major depressive disorder, and 11 healthy control subjects.
The bipolar group demonstrated increases in both subcortical (ventral, striatal, thalamic, and hippocampal) and ventral prefrontal cortical responses, particularly to expressions of mild and intense fear, mild happiness, and mild sadness; activity was diminished in the dorsal prefrontal cortical area to the majority of facial expressions (Biol. Psychiatry 2004;55:578–87).
The results are in line with the fact that one of the specific subcortical areas that show abnormally elevated activity, the ventral striatum, is associated with the processing of expressions of emotion and reward. Interestingly, activity in this area was most elevated by pictures of faces showing expressions of mild happiness rather than to faces showing more extreme emotions. This may be explained by the fact that mild expressions of happiness are more frequently observed in everyday life, and may be seen as especially rewarding in people with bipolar disorder, Dr. Phillips said in an interview.
The dorsal prefrontal cortical area, where the bipolar patients demonstrated reduced brain activity, comprises the regions primarily associated with regulation of emotion. Reduced activity in these regions may therefore underlie the emotional lability experienced by people with bipolar disorder, she said.
In contrast, the group with unipolar depression showed diminished neural responses to all emotional expressions except mild sadness. Severity of depression correlated positively with hippocampal response to mild sadness in both patient groups, while the healthy controls demonstrated increased subcortical responses to intense happiness and mild fear, and increased dorsal prefrontal cortical responses to intense expressions of sadness.
Dr. Phillips is now replicating these findings in Pittsburgh, with larger groups of bipolar patients. Results in the Pittsburgh patients have shown that the same patterns occur in subjects with active and with remitted disease, suggesting that the test would be specific to the disease state, regardless of current symptoms. Those data are currently being prepared for submission to a journal.
“I see in the not-too-far-distant future that we might be able to perform a brain imaging scan the same way that people get chest x-rays. It's not going to be the only tool we have, but it will be part of a battery of tests, along with blood tests and paper-and-pencil cognitive tests,” Dr. Phillips predicted.
However, she cautioned that because the use of fMRI in psychiatry is still relatively new, there are not as yet enough normative data with which to compare people with various psychiatric abnormalities. Those data are now being gathered. “So perhaps not tomorrow, but within the next 10 years, I would like to see at least a basic paradigm, such as face task,” she said at the press briefing.
“If we can do anything to identify and accurately diagnose people with bipolar disorder earlier, that has to be a good thing,” Dr. Phillips said at the conference, which was sponsored by the University of Pittsburgh.