Key to depression found
T.O. scientists discover increased activity of an obscure protein could lead to more potent medicines T.O. scientists' discovery of an elevated protein in patients may lead to better drugs
Nov. 7, 2006. 01:00 AM
Toronto researchers say they've discovered the neurological key to depression in a new study that explains how the classic "chemical imbalances" likely occur.
The discovery, made by scientists at the Centre for Addiction and Mental Health (CAMH), could lead to better, more potent medicines to combat the disorder, said lead author Dr. Jeffrey Meyer.
"This is a very crisp, clean explanation," said Meyer, head of neurochemical imaging at CAMH. "This is an explanation that makes sense and that fits with the literature." The study will be published today in the Archives of General Psychiatry.
Most researchers believe that depression, which will affect about 8 per cent of Canadians in their lifetime, occurs when neurotransmitters known as monoamines are out of whack in the brain.
Monoamines such as serotonin, norepinephrine and dopamine — which play an important role in governing emotions — are found in significantly lower levels in depressed people.
But Meyer said scientists didn't understand why until his team refined CAMH's Positron Emission Tomography scanner to the point where it could find and examine the activity of an obscure protein called monoamine oxidase A — or MAO-A for short — produced in the brain.
For two decades, researchers have known MAO-A breaks down serotonin and other monoamines.
Meyer's team found that MAO-A was elevated by a whopping 34 per cent in people suffering from depression.
"The monoamine theory is the central theory of depression," said Meyer, who notes that most depression drugs target things like serotonin and dopamine.
"And (our) hypothesis was that MAO-A would be increased because, if there is more of this protein, then you would expect that would lead to a greater breakdown of these (other) chemicals," he said.
While researchers in the past had thought about looking at the role of MAO-A, the technology wasn't available to more thoroughly study it.
Meyer said some drugs that target MAO-A have long been used to combat depression. But they were discovered by luck and no one seemed to connect the protein with the actual neurochemical chain of depression.
"It's sort of astounding when you consider how long this (monoamines) theory of depression has been around," Meyer said.
Drugs that targeted MAO-A were originally prescribed for people with tuberculosis.
"All the treatments for depression have really come about through serendipity," Meyer said. "In this case, people who got depression in sanatoriums would take an anti-tuberculosis medication, it happened to inhibit MAO-A, and people got (less depressed)."
Meyer said his team's discovery should help pharmaceutical researchers maximize their ability to target MAO-A production and bring it under control during depressive incidents.
Phil Upshall, national director of the Mood Disorder Society of Canada, welcomed the research, but cautioned: "The reality is there are a whole other array of other psychosocial factors that have to be in play to really alleviate the problems in depression," such as peer support, self-help groups and improved living environments.