Dead people’s brains normally do not tell stories. But for scientists like Michael Poulter, they not only tell stories, they tell them eloquently. Poulter, who works at the Robarts Research Institute of the University of Western Ontario in Canada, looks at the brains of suicide victims to see whether they are any different from those of normal people. It now turns out that they indeed are, and what he and other scientists uncover in the next few years will have a bearing on ways to diagnose and treat depression and suicide.

Poutler has discovered that the brains of suicide victims — who had been known to be depressed for some time — are chemically modified through a process that is normally involved in switching genes off. What this means is that as a result of the change, the genes shut down and malfunction, inhibiting the individual’s ability to handle stress and cope with anxiety. This is probably not a surprising finding, except that this switching off is not an inherited problem. The environment of the victims — their experience in life — was somehow influencing their genes. “We do not know how this happens,” says Poulter. “But it takes a long time to reverse.” The observation correlates with clinical findings of depression, because it is known to be difficult to treat, and often results in suicide.

Scientists have been trying for a long time to get at the molecular basis of depression. But other than some teasing hints, some of which led to blind alleys, they have not been able to understand depression and suicide brains. But things have brightened in the last few years, with discoveries that point to some clear biological and molecular differences in the brains of depressed people from those who do not suffer from the problem.

Scientists also know some possible reasons for these biochemical changes, and are getting closer to developing a real drug that could treat the disease well.

This is good news for many reasons. Depression is, in many ways, a disease hidden from the mainstream public view. However, by the year 2020, it is expected to be the second leading disease in the world in terms of economic costs. This is because of the costs of treating depression and also the loss of productivity owing to depression.

Drugs for treating depression had been developed several decades ago, but they are not always effective. The standard method is to combine psychotherapy and drugs. As a last resort, short pulses of electricity — known as electro-shock or electro-convulsive therapy (ECT) — are administered on the patient’s brain under general anaesthesia. Because shock therapy does not always work, and it is not clearly understood why it works when it does, ECT has been a controversial mode of treatment. In any case, we do not know how to separate the patients who could benefit from a drug from those who may not. About half of the patients with depression recover in the long run, while many in the other half commit suicide.

So in the last decade there has been an increased effort to understand depression and its molecular basis. For the last 50 years, the dominant theory of depression was based on a class of compounds called monoamines. There are three of them that are important, and depression patients seemed to be deficient in these neurotransmitters (chemicals used to relay, amplify and modulate signals between a neuron and another cell): serotonin, noradrenaline, and dopamine. There is some evidence to support this theory. An enzyme that breaks down these monoamines is particularly high in patients with depression. However, in controlled studies, patients have been found to improve with placebos (dummy pills) as well as with drugs.

The monoamine theory is either wrong or not enough to understand depression.

In the last few years, scientists have assembled several pieces of the molecular basis of depression that help us understand depression without quite being able to fit them all together yet. Specifically, by examining the brains of suicide victims, they now know many factors that are different in their brains. For example, Yogesh Dwivedi and his colleagues at the University of Illinois, Chicago in the US, showed in a series of papers that some molecules are reduced in the brains of suicide victims. These molecules are involved in the proliferation and survival of neurons. Says Dwivedi: “All suicide victims show an increase in the molecule cortisol and a decrease in another molecule called BDNF (brain-derived neurotrophic factor).”

Cortisol is released in the brain during stress, and it is no surprise to see its levels increase in suicide victims. BDNF is a key molecule involved in the survival of neurons and the plasticity of their junctions. Once again, it is probably no accident that parts of the brain — called hippocampus — of suicide victims seem to have shrunk. It is clear that key enzymes necessary for brain health are disturbed in the brains of depressed people. Now we also know that genes that are important in the brain are switched off in their brains. Both are important steps towards understanding depression, and towards developing a drug to treat it well.