Brain images show structure of depression.

A preliminary investigation has identified specific parts of the brain involved in severe, or major depression. Two areas stand out: The left prefrontal cortex mallunctions only during bouts of depression, whereas the amygdala - a small, inner-brain structure thought to regulate emotional reactions -- operates abnormally both during and between depressive episodes, apparently serving as a biological marker of susceptibility to severe depression.

Psychiatrist Wayne C. Drevets of Washington University School of Medicine in St. Louis and his colleagues pinned down these regions by tracking blood flow in the brain. They present their data in the September JOURNAL OF NEUROSCIENCE.

Scientists track cerebral blood flow by injecting volunteers with a minute amount of a radioactively labeled oxygen compound. A positron emission tomography (PET) scanner picks up gamma rays emitted by the rapidly decaying compound and produces images of blood flow throughout the brain.

The bleak mood, apathy, hopelessness, and other signs of severe depression typically wax and wane. Drevets and his associates performed PET scans on 13 adults who suffered from severe depression at the time of testing and 10 others previously diagnosed with depression but showing no signs of the disorder when the study took place. All participants were right-handed and had at least one parent, sibling, or child with major depression but no family history of other

psychiatric disorders.

Depressed volunteers had not taken any psychoactive medication for at least three weeks.

Another 33 right-handed people, with no history of depression. served as controls.

In the first phase of the study, the researchers examined six currently depressed volunteers and 18 controls. PET images focused on the entire brain rather than any particular areas. A computer compared the images with the help of a program designed to minimize individual differences in anatomy and produce a composite view of blood flow for the entire group.

With the composite serving as a baseline measure, markedly increased blood flow, indicating increased brain-cell activity, appeared in the left prefrontal cortex of all the depressed individuals but none of the controls.

Drevets' group focused on that area of the brain in the remaining seven currently depressed volunteers and 15 controls. Again, the left prefrontal cortex displayed heightened blood flow only among the depressed. PET data also revealed increased blood flow in the amygdala of depressed individuals.

The investigators then compared PET images of volunteers whose depression was in remission to those of currently depressed individuals and controls. Both groups diagnosed with depression showed comparable blood-flow boosts in the amygdala, but the prefrontal cortex remained stable among those in remission.

"Excessive blood flow in the prefrontal cortex indicates that a depressive episode is in progress," Drevets contends. Elevated blood flow in the amygdala seems to signal that an individual harbors a biological propensity to severe depression, at least when such depression runs in that person's family, he adds.

The prefrontal cortex may process the constant negative thoughts that often characterize depression, Drevets theorizes. The amygdala probably plays a role in the severity of depression, he notes; those participants with the most debilitating symptoms displayed the most striking blood-flow jumps in the amygdala.

A set of chemical messengers that normally dampen the activity of the prefrontal cortex, the amygdala, and another brain structure that links the two regions may go awry in some cases of severe depression, Drevets suggests.

- B. Bower