Newer kinds of antidepressants are supposed to work by affecting brain chemistry. They are designed to put more chemical messengers -- such as serotonin -- in the gaps across which brain cells communicate. This is supposed to improve brain function.
There's a problem with this theory, note Johns Hopkins researcher Vassilis E. Koliatsos, MD, and colleagues. SSRI (selective serotonin reuptake inhibitor) antidepressants affect brain chemistry in a matter of days. Yet every psychiatrist knows that the drugs usually take two to four weeks to start working.
Moreover, SSRI antidepressants increase serotonin levels -- yet antidepressants that decrease serotonin levels seem to work just as well. Maybe, Koliatsos and colleagues thought, drugs that directly affect serotonin make those brain cells grow.
Serotonin works as a chemical messenger by plugging into special sockets at the tip of brain cells. These serotonin receptors trigger a cascade of events. One of these events, the researchers suggest, is brain regeneration. In other words, drugs aimed at serotonin receptors make brain cells sprout.
"Serotonin terminals may be especially prone to regenerative sprouting," Koliatsos and colleagues write. "We propose that this phenomenon ... may be the key structural effect of serotonin antidepressants."
Koliatsos's team reports the findings in the January issue of the Journal of Neurochemistry.
Rats' Brains Get Bigger
Koliatsos and colleagues gave three different antidepressants to rats. One was Prozac, an SSRI drug that increases serotonin. The second was tianeptine, a drug that decreases serotonin. This drug is not available in the U.S.
The third was Norpramin, an antidepressant that affects norepinephrine, a different chemical messenger.
Despite their different actions, both Prozac and tianeptine made the rats' brains more dense. Microscopic analysis showed that selected areas of the animals' brains had more serotonin fibers after they took the drugs. Norpramin, which does not affect serotonin receptors, did not cause serotonin fibers to sprout.
The growth of serotonin-sensitive cells did not seem to result in increased production of serotonin itself.
The findings, Koliatsos and colleagues suggest, "support the idea of a structural effect of these compounds on serotonin [brain cells] -- i.e., sprouting."