Depression first seized Ms. Harris 10 years ago. Since then, the former Toronto psychiatric nurse had sobbed through an entire summer on her condo balcony, spent six months in bed, shunned food and friends and fought off steady thoughts of suicide.
Nothing had worked, neither medication nor psychotherapy.
But today, two years after she agreed to take part in the landmark Canadian experiment, Ms. Harris could hardly be happier for the electrodes buried in her brain: two wires, nearly as thick as spaghetti and a foot long, pulsing 130 times per second to silence the negativity of her mind.
"It is an unbelievable, dramatic change for me," said the 50-year-old Ms. Harris. "For the first time in 10 years, I feel alive. I have energy, it's like a light bulb being turned on."
Four of the six patients who participated in the unprecedented investigation, led by scientists at the Baycrest Centre's Rotman Research Institute and the University of Toronto, report experiences similar to Ms. Harris.
The results, albeit from a small patient sample, offer the world's first new possibility of an effective therapy for treatment-resistant depression.
"Some people will say this is pretty extreme, but this condition is pretty extreme," said study leader and clinical neurologist Helen Mayberg, describing the therapy known as deep brain stimulation, or DBS. "I never could have dreamed that we'd have the kind of clinical effect that we've seen."
It's estimated that more than one million Canadians suffer from some form of depression -- the leading cause of disability in North America for people under 50 -- and the condition is resistant to treatment in roughly 20 per cent of cases.
Still, Dr. Mayberg, lead author of the study to be published this week in the journal Neuron, emphasized the research is preliminary and that she remains optimistic, but cautious.
Unlike electroconvulsive therapy (ECT), which shocks the entire brain with electricity to induce brain seizures as a treatment for severe depression, DBS is designed to electrically stimulate only the brain region known to be overactive in people with the condition.
It is part of an expanding field known as "brain pacemakers," in which doctors implant devices that electrically alter neural circuits to treat disorders such as Parkinson's disease, epilepsy and even obsessive-compulsive behaviour.
DBS is also less painful than ECT, with patients unable to feel the presence of the electrodes, or even whether they are turned on. As well, in stark contrast to other external, electrical therapies, the beneficial effects of DBS appear, so far, to be long lasting.
"The stimulation is on constantly," said Andres Lozano, co-author of the study and U of T professor of neurosurgery. Although each patient requires a slightly different level of stimulation, in each case signs of their depression returned within two weeks after the electrodes were turned off, he said.
Ms. Harris had an adjustment several months ago. She says she still suffers the occasional bout of depression, but the episodes are relatively brief and mild.
Dr. Lozano, also a neurosurgeon at Toronto Western Hospital, explained that the two electrodes were threaded through the top of the skull and down, with one on each side of the brain, using a rod and straw-like device. The electrodes are connected to wires that run from the top of the head beneath the scalp, down behind the ears, beneath the skin of the neck and then connect to a small battery pack (with an estimated five years of life) that's embedded beneath the collar bone. The pack also contains a program chip, powered by remote control, that sets the frequency and voltage of the electrodes.
"This is not like a drug that goes everywhere in the brain," Dr. Lozano said, estimating that the electrical signal hardly travels more than a few millimetres beyond its target area.
That area is the fatty, white matter that surrounds a region known as the cingulate. In her research examining the biology of sadness, Dr. Mayberg found that while the whole brain is involved in depression, the cingulate plays a crucial role. It is the c-shaped structure behind the eyes at the floor of the frontal lobe that zings into action when healthy people think of something sad. In people with treatment-resistant depression, it seems to idle in overdrive.
So it was that Dr. Mayberg, who conducted the DBS work at Baycrest before moving to Emory University in Atlanta, felt they should try "to turn this area down."
They started from the premise that electrical stimulation inhibits brain activity by jamming the signals between nerve cells. Dr. Lozano said there was already evidence the therapy worked this way in patients with Parkinson's disease.
However, researchers could not first test their hunch in any animal model; finding the rat equivalent of depression is no simple matter. And there were risks: a small chance of brain hemorrhage or seizure.
But when Ms. Harris read through all the information, she didn't hesitate to sign up: "It seemed to make sense to me. At that point, I didn't care. I didn't even care if it killed me."
Most remarkable are some of the descriptions patients offered the researchers not long after they turned on the electrodes. They described a "sudden calmness or lightness" and a "disappearance of the void."
Dr. Mayberg and Dr. Lozano are continuing to recruit new patients for the experimental therapy in Toronto.
For Ms. Harris, who now shops, throws dinner parties and visits the library, the effects of the implants were immediate: "When I first came home, I was out with a hat covering the staples on my head and cutting back the hedges that had overgrown for so long. . . . I felt that good."
"If they can refine this procedure, imagine how many could be saved."