Depression, sadness yield brain link.

Major depression includes not only feelings of intense sadness and despair but also a wandering, indecisive train of thought. Distinct brain areas involved in emotion and attention together foster both depression and ordinary bouts of sadness, according to a new study.

Specific changes in these neural regions accompany recovery from major depression, whether achieved with an antidepressant drug or placebo pills, says a team of neuroscientists led by Helen S. Mayberg of the Rotman Research Institute in Toronto.

"The negative influence of depressed mood on attention is probably due to functional connections between these two brain regions," Mayberg says. "Successful treatment, including placebo use, alters those connections."

Mayberg's group first took positron emission tomography (PET) scans of eight women resting and after recalling a sad personal experience. The PET scans measured blood-flow changes in their brains, an indirect sign of boosts or drops in brain-cell activity. None of the women or their family members had been diagnosed with mood disorders.

In a second trial, the researchers took PET scans of eight men before and after successful treatment for major depression. Over 6 weeks, four men had improved after taking the antidepressant drug fluoxetine (Prozac); the rest had rallied in response to pills that they thought might be antidepressants but that contained no active ingredients.

When the women recalled sad experiences, blood-flow surged in a pair of the inner brain structures that regulate emotional responses and declined in two parts of the brain's outer layer previously linked to attention, the team reports in the May AMERICAN JOURNAL OF PSYCHIATRY. The men who had recovered from depression showed unusually high activity in the two attention areas and low activity in the emotion areas.

Before recovery, however, the depressed men had exhibited marked overactivity in only one of the two emotion-related areas characteristic of brief sadness in the women. Further research will examine more closely the processes that occur during depression, Mayberg says.

The findings suggest that a brain circuit incorporating emotion and attention "offers a plausible converging point" for antidepressant effects of drugs and psychotherapy, remark psychiatrist Charles B. Nemeroff of Emory University School of Medicine in Atlanta and his coworkers in an accompanying editorial.

Researchers haven't yet explored brain function in the substantial minority of depressed people who don't benefit from treatment, Mayberg adds.