In a painstaking experiment that may help revise our view of depression, a team at the Johns Hopkins University School of Medicine found that rats given Prozac did not merely experience a change in their brain chemistry but also grew new nerve fibers in mood-critical areas. This finding, which suggests that depression reflects problems of fine neural structure and not just chemistry (the prevailing model), should bolster the emerging "network hypothesis" of mood.

Over the past quarter of a century, it has become doctrine that depression is primarily a chemical issue. The prevailing model holds that depression occurs largely because shortages of the neurotransmitter serotonin in key synapses dampen mood-regulating neural signaling, opening the door to depression. But the recent results indicate that mood disorders stem at least partly from frail synaptic structures such as weak nerve endings and dead fibers, which cause signaling breakdowns.

Through intricate staining techniques, the Hopkins team found that rats treated with Prozac grew more axons--the neural branches that send messages--on serotonin-sensitive neurons in cortical and forebrain areas crucial to mood. Lijun Zhou, a researcher in neuro¿surgery, proposes that this local change is "the key structural effect of serotonin anti¿depressants" and may help explain some successful antidepressant therapy. The findings mesh with other recent human studies showing that both drug and talk therapy, when successful, raise levels of pervasive brain-growth chemicals called neurotrophins. Shortages of neurotrophins may contribute to the original structural weakening of neural-network circuits.

"This is one of the first [studies] to report anatomical changes in response to drugs," says University of Helsinki neuroscientist Eero Castr¿n, a specialist in neurotrophins and network theory. "It should help tell us where to look in humans for markers of similar change." That, in turn, could produce a richer understanding of depression, as well as more possibilities for treatment.

This article was originally published with the title Weak Nerves May Cause Depression.

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