Manic-depressive illness, also called biopolar disorder, is known best by the sharp mood swings it causes. For people with type I bipolar disorder, these moods can flip-flop quickly between dizzying manic highs and black suicidal depressions, both of which typically require hospitalization and other interventions. The available medications, such as lithium, do help many affected, but they were often found by accident and come with unpleasant side effects. So with an eye toward developing more tailored--and more effective--treatments, many scientists have focused their work on identifying neurochemical differences that set people with the disorder apart.

Jon-Kar Zubieta of the University of Michigan and his colleagues describe one such difference in the latest issue of the American Journal of Psychiatry. These scientists carefully matched 16 type I bipolar subjects with 16 controls and injected them all with a weakly radioactive tracer, DTBZ. This tracer binds only to a protein found in cells that release monoamines--neurotransmitters suspected to play a significant role in mood disorders in general. Then Zubieta took positron emission tomography (PET) scans of the subjects' brains and found a striking division between the two groups. The DTBZ density--and so the number of monamine-releasing cells--was on average 30 percent higher in the bipolar subjects.

"To put it simply, these patients' brains are wired differently, in a way that we might expect to predispose them to bouts of mania and depression," Zubieta comments. "Now we must expand and apply this knowledge to give them a treatment strategy based on solid science, not on the current method of trial and error. We should also work to find an exact genetic origin, and to relate those genetic origins to what is happening in the brain."