Working late one night in my lab, I heard someone commit suicide.
Though I didn't realize it at the time, the sudden metallic thud outside my office window was the sound of a person ending her life.
In the morning, a few details emerged: a young scientist dealing with depression, recently stressed by family problems, jumped from a small bathroom window several floors above mine.
I was stung by the closeness of the catastrophe. And puzzled. On the surface we seemed alike: two young women spending countless hours in the lab at a top-notch university to gain our scientific chops. And yet there is a stark difference between someone like me who pulls all-nighters to complete her thesis on time, and another who jumps.
A depressed state of mind
How does a person reach a state of mind so extreme that it has the power to override the natural instinct to live? Many people contemplate suicide while in the depths of major depressive disorder (MDD). Much more than a bad day, this disabling condition is the most severe form of depression. Hounded by pervasive feelings of sadness and negativity, a person no longer wants to socialize with friends, get out of bed, or even eat.
"Why is life so tragic; so like a little strip of pavement over an abyss?" wrote the novelist Virginia Woolf, who suffered recurrent bouts of depression and ultimately took her life. "I look down; I feel giddy; I wonder how I am ever to walk to the end."
As ephemeral as our moods may seem, neuroscientists think they result from biological realities inside our brains. The wiring of connections between the cells of the brain, or neurons, the proteins that keep them healthy, and the chemicals that carry messages from neuron to neuron, all combine to produce our inner mental life.
Faulty wiring
In the case of MDD, scientists like Michael Poulter of the University of Western Ontario have been looking for clues like these that can explain why a person is depressed. "Is [the] wiring wrong?" he asks. "Is the red wire going where the green wire should go?"
Recently, Poulter and colleagues made some headway into these questions, by studying the brains of people suffering from MDD who had killed themselves. Perhaps this sounds morbid, but studying these brains can give clues to what has gone wrong in depression, and how to fix it.
His new study reports that the brains from people with MDD had abnormally high levels of a protein called DNA methyltransferase, or DNMT for short. These brains had 61 percent more of one type of DNMT than did brains from people who had died suddenly but who were not depressed.
This is intriguing because DNMT has the powerful ability to turn genes off. MDD, then, might stem from inappropriate silencing of genes inside neurons: genes that should be on are turned off instead.
In the study, it appeared that DNMT silenced DNA that helps make a protein that's integral for keeping the electrical signals in the brain flowing in the right direction. Without the right protein-making machinery, this traffic gets rerouted, resulting in the type of wiring problem Poulter refers to.
Interestingly, the overabundance of DNMT was located in the frontopolar cortex, a part of the brain involved in sizing up how good or bad something really is.
"It makes sense to study that area in depression because clearly [depressed] people are not reflecting on their experiences appropriately," says Poulter.
The sum of experiences
But why was the frontopolar cortex overloaded with DNMT? Poulter speculates that stress may raise DNMT levels, and he is doing more experiments to find out. This may seem like an important piece of the puzzle for those of you who are thinking that the events in a person's life lead them to commit suicide—not their brain.
But for neuroscientists, these are nearly one and the same. Experience—what we see, feel, hear—can literally sculpt our brains, leaving lasting marks on neurons and their connections. As we are the sum of our experiences, so are our brains.
If experiences can reprogram our genomes, then it's another reason to limit stress for the sake of our health. As for depression, "It's not a matter of splashing cold water in someone's face ... and say[ing] 'Get over it'," says Poulter. "It is a state of your biochemistry."
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