Is depression hard-wired in our brains?

Published Mar 9, 2016

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Washington - Surgeons snaked the electrodes under the 65-year-old woman's scalp.

Thirty years of Parkinson's disease had almost frozen her limbs. The wires, connected to a kind of pacemaker under the skin, were aimed at decreasing the woman's rigidity and allowing for more fluid movement.

But five seconds after the first electrical pulse was fired into her brain, something else happened. Although awake and fully alert, she seemed to plunge into sadness, bowing her head and sobbing.

One of the doctors asked what was wrong.

“I no longer wish to live, to see anything, to hear anything, feel anything,” she said.

Was she in some kind of pain?

“No, I'm fed up with life. I've had enough,” she replied. “Everything is useless.”

The operating team turned off the current. Less than 90 seconds later, the woman was smiling and joking, even acting slightly manic. Another five minutes more, and her normal mood returned.

The patient had no history of depression. Yet in those few minutes after the electrical pulse was fired, the despair she expressed met nine of the 11 criteria for severe major depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders.

Fascinated by the anomaly, the French physicians wrote up the episode for the New England Journal of Medicine. The year was 1999, and hers was one of the first documented cases of an electrically induced, instantaneous, yet reversible depression.

Additional testing was done, including a brain scan eight months later during which the same procedure was repeated. And again, when the pulse was on, the woman said she felt as though she was being sucked into a black hole.

The scan revealed a significant increase in blood flow in several brain areas, including the left frontal cortex. The precise contact area of the electrode could not be determined, but it was located in the mid-brain's basal ganglia, which controls some limb movement and is connected to other structures implicated in unpleasant feelings.

The fact that doctors had inadvertently found a source of symptoms for one of the most pernicious of psychological maladies - and in a bit of gray matter no larger than the head of a pin - prompted a singularly bizarre question:

Why would depression, which is responsible for so much misery in the world, be hard-wired into the brain?

Two psychiatric researchers think they have an answer. Charles Raison at the University of Arizona and Andrew H. Miller at Emory University in Atlanta think depression once had an evolutionary, adaptive purpose for our primitive ancestors.

For millennia, one of the world's leading causes of death was infection. The body's natural counter to infection includes a number of genetic mutations that rachet up the immune system. Researchers now know that one of those altered genes, known as NPY, is linked to major depression.

Why would the body need to leverage depression to fight off infection? In a 2012 study, Raison and Miller contended that symptoms of depression such as social withdrawal and apathy played to the advantage of ancient humans for two important reasons: Keeping still helped their bodies fight infection, and social isolation helped prevent the spread of contagious germs.

There is no direct evidence for this theory. There are, however, additional cases of Parkinson's patients undergoing pallidotomy (the placement of electrodes in the mid-brain's globus pallidus, which plays a role in movement and co-ordination) who have also experienced instantaneous depression. Likewise, stimulation of other areas of the basal ganglia have induced spontaneous laughter in others.

Perhaps the question the French doctors needed to consider wasn't whether they had turned on depression in their patient, but whether they had turned off happiness.

 

Washington Post

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