As reported by the New Haven Register, February 5, 2006.

Scientists Discover Vagus Nerve Stimulation Relieves Depression 

By Abram Katz

An astute hotel clerk in Florida observed in the late 1990s that epilepsy patients who underwent nerve stimulation to stop stubborn seizures were among the happiest people he had ever seen.

Psychiatrists and other researchers studying depression wondered whether the same technique could alleviate the intense psychological hopelessness, despair and pain.

Scientists at the University of Texas, Columbia and Brown universities found that passing small pulses of electricity through the left vagus nerve could elevate depression that had resisted most medications.

The University of Connecticut Health Center is now offering this procedure, approved over the summer by the Food and Drug Administration and called vagus nerve stimulation (VNS).

In addition to offering relief to patients who have spent decades in the deep shadows of depression, VNS also offers intriguing clues about mood, the brain, the body and how all three interact, said Dr. Leighton Huey, chairman of psychiatry at the University of Connecticut Health Center.

The vagus nerve is among 12 sets of cranial nerves that travel from the brain stem down into the body. They are among the longest nerves, and physiologists had assumed they imparted brain signals one way to internal organs.

Huey said VNS shows that the nerve is a two-way street, terminating in the brain centers related to mood and emotions.

The left vagus nerve is chosen for stimulation because the right branch is linked to the heart and altering the neuron’s functions might have cardiac effects, Huey said. This nerve is apparently the only one suitable for stimulation, he said.

Cyberonics of Houston created a stopwatch-sized device that a surgeon implants under general anesthetic in the left chest wall. Wire electrodes are run to under the collar bone, adjacent to the left vagus nerve.

The wires are then carefully wrapped around the nerve. After two weeks of healing, a psychiatrist turns on the battery-powered device with a magnetic wand.

The unit sends 0.25 milliamperes to the vagus nerve for 30 seconds every five minutes.

Huey said most patients have no sensation. However, the left vagus is linked to the voice box and when the pulse is on, the patient’s voice may be altered.

If the patient must make a presentation or speech, he can turn the unit off with the magnet control and restart it later.

Eighty percent of patients with implants continue with the therapy, Huey said. A high percentage of patients can stop taking antidepressant medication after six months, he added.

UConn will only implant the device in people 18 and older who have tried other regimens of antidepressants without success.

Long-term studies are ongoing. A dosing study will begin soon to determine the optimum current and pulse frequency and duration, Huey said.

Meanwhile, patients with VNS have normal electro-encephalograms, and the device does not appear to alter cognition.

When the battery wears out in about eight years, a new unit is implanted.

Huey said other studies suggest that half of the implant patients experience a benefit, about one-third report an improvement in symptoms of depression and one-sixth become symptom-free. One out of 6 are free of depression after one to two years of VNS.

"The full implications of this technology are not clear yet," Huey said.

The old view of the vagus nerve is also being refined.

Rather than a one-way phone line, the nerve is more like a coaxial cable with multiple functions.

Why stimulating the vagus nerve can both alleviate seizures and lift depression is not known, said Dr. Andrew Winokur, professor of psychiatry at the UConn Health Center.

The nerve links to the a relay point in the brain called the nucleus tractus solitarius, which in turn activates neurons in the limbic system and the cortex, where higher thoughts emerge. The limbic system is involved in emotions, fear, anxiety and other moods.

This is one plausible explanation for VNS efficacy, Winokur said. VNS in animals revealed changes in chemical messengers in the brain called neurotransmitters, specifically serotonin and norepinephrine. Both have been implicated in depression.

Presumably stimulating the vagus nerve increases the amount of serotonin and norepinephrine. Antidepressants increase levels of these neurotransmitters in a completely different way.

The connection between seizures and depression poses other interesting questions. Electroconvulsive therapy, long the "gold standard" of depression treatment, stimulates seizures.

VNS inhibits seizures, and several drugs now used to treat bipolar disorder were originally introduced to control seizures.

"In the past, we saw the brain as separate domains. This is not accurate," Winokur said.

"There are important connections between the body and brain," he added, which could be another factor in VNS.

"Physiological function is integrated to psychological. Sleep is a very complex interaction between body and mind. There are some relationships between seizure activity and emotional state," Winokur said. "We need to learn about the optimal level of VNS frequency and establish refinements.

"What’s striking in VNS is the general pattern. In people who respond, the response can get better over time," he added.

At least one other method of stimulating the interior of the brain appears promising.

In repetitive transcranial magnetic stimulation, pulses of magnetic waves are aimed at specific areas. The fluctuating magnetic field should induce a weak current within the brain.

"This is conceptually similar to VNS. A cousin," Winokur said.