Mapping the Blues

ON October 29, 2003, a tall, dark-haired man suffering from severe depression lay on a narrow bed in the PET scan room at the Clarke Institute of Psychiatry in Toronto while a nuclear-medicine technologist injected a small amount of radioactive sugar into a vein in his left arm. He rested quietly in the darkened room as the sugar tracer circulated through his bloodstream and accumulated in the most active regions of his brain. A white sheet of stiff plastic, softened in a steam tray, was then placed over his face and allowed to harden into a mask that would help to keep his head still during the positron emission tomography scan (PET for short) that was about to take place.

The technologist punched the remote and the bed slid back until the man’s head was properly positioned in the doughnut hole of the PET machine. His head was now encircled by a thick ring containing thousands of small crystal detectors that would measure the radiation emitted by the sugar molecules in his brain. He felt anxious and a little claustrophobic, but eventually he relaxed and signalled that the photo session could begin. During the next thirty minutes the PET camera took snapshots showing the levels of activity in different parts of his brain, a process that allows the neurologist to observe the brain in action over time. These images would highlight the most active regions in brilliant red or yellow tones, while less active areas would appear green, blue, or black. They would also reveal patterns of abnormal brain activity, a metabolic signature characteristic of major depression.

Patient X is one of about five million Canadians who will suffer from depression during their lifetimes. He is participating in a study conducted by the neurologist and world-renowned researcher Dr. Helen Mayberg. Mayberg, who was head of neuropsychiatry at Baycrest’s Rotman Research Institute and the University of Toronto until a recent move to Emory University in Atlanta, has developed an exciting new approach to an ancient problem that seems almost as perplexing and intractable today as it did to the classical Greeks. For the past fifteen years, she has been developing a map of the brain to chart the terra incognita of depression. On this odyssey into troubled moods and minds, Mayberg has looked deep inside the brain to expose and illuminate the dark, hidden pathways of depression. Through successive stages of this voyage, she has identified key landmarks that offer fresh approaches to the diagnosis and treatment of one of the commonest and most devastating forms of mental illness.

According to the World Health Organization, depression is the leading cause of disability in developed nations, and the second most cited reason for visits to family doctors in Canada. Apart from the incalculable anguish it causes in the private lives of those who suffer from it, depression also cuts productivity in the workplace and costs the Canadian economy an estimated $14 billion a year. In the past four years alone, the number of antidepressant prescriptions dispensed annually in Canada has increased by nearly fifty percent to more than thirty million, and two leading antidepressants, Paxil and Zoloft, are among the ten top-selling drugs worldwide.

Despite advances in drug treatments and the proliferation of talk therapies, only about one-third of people who suffer from depression seek treatment, and fewer than half of those who receive treatment recover. “Depression is inescapable negativity. You’re in a pit. You can see yourself, and there is no other. The outside world doesn’t exist. How you feel and your sense of self are one. There is no border. It’s all black,” says Helen Mayberg, noting that depression involves disturbances of both mind and mood. “Many people are sad. But what brings a lot of people to the doctor is the fact that they can’t think straight.”

In his depression memoir, Darkness Visible, the novelist William Styron talks about the inexplicable nature of depression and the difficulty of treating it. He recalls a clinician in the field telling him: “If you compare our knowledge with Columbus’s discovery of America, America is yet unknown; we are still down on that little island in the Bahamas.”

The quest to make the great dark mystery of depression visible and treat melancholy moods began about 2,500 years ago with the Greek physician Hippocrates, who, in the late fifth century B.C., was the first to describe a condition he called melancholia. In ancient Greece, human disease was explained in terms of an imbalance of the four humours that were thought to determine human personality. A melancholic, for instance, was considered to have an excess of black bile. Hippocrates observed that melancholics suffered from a lack of appetite, dejection, and insomnia, symptoms we would recognize today. And then, as now, treatments fell into two main categories: medical or physical procedures and therapeutic “lifestyle” prescriptions. The main physical treatments recommended were blood-letting and purgative medicines, intended to eliminate the excess of black bile. But patients were also advised to adopt a healthy regimen: nourishing food, rest, warm baths, support from friends, and amusing activities.

And that was pretty much how things remained until relatively recently. In The Anatomy of Melancholy, the classic Renaissance study of the blues published in 1621, Robert Burton was still recommending the bloodletting and purgatives, while also counselling what we would call psychological treatments: advice and comfort from friends or a doctor, soothing music, mirth, and merry company.

In the early twentieth century, melancholia was finally relabelled depression. The two main streams of therapy (the biological/physical and psychological/talk) continued to evolve, but at a more rapid rate, to become what amounts to a massive trial-and-error experiment. By the late twentieth century, this had produced a bewildering array of treatments.

Modern psychotherapy began at the turn of the century with Sigmund Freud’s development of psychoanalysis and Adolf Meyer, psychiatrist-in-chief at Johns Hopkins Hospital, who understood depression as a reactive rather than a biological disorder and trained a generation of American psychiatrists to look at patients’ life histories and experiences as the keys to understanding and modifying their behaviour. Today, patients can choose from about two hundred types of psychotherapy ranging from cognitive behaviour therapy to interpersonal therapy, which involve a commitment of time and energy.