/ 29 March 2009

It runs in the blood

The early death of Sylvia Plath and Ted Hughes’s son, Nicholas, is so much more shocking because it was suicide. His mother famously gassed herself a year after he was born. And on Tuesday March 23 his sister announced that Nicholas, aged 47, had hanged himself last week at his home in Alaska.

High-profile suicides always get attention, but when there has already been one such tragedy in the family, questions about to what extent depression and suicidal tendencies are inherited are inevitably raised.

It seems that in any family where there has been a suicide it is likely that it has happened before and will happen again.
The Hemingway family has been one of the most severely affected.

Ernest’s father killed himself in 1928. In 1961, Hemingway attempted suicide in the spring, and succeeded in the summer. Two of his siblings and his granddaughter also took their own lives.

When Kurt Cobain killed himself in 1994 a lot was made of his comments that he felt he had inherited ”suicidal genes”. It is entirely possible? Two of his uncles took their own lives. As often with men, both used guns.

The apparent inheritance of depression genes has not gone unnoticed by scientists. Studies of twins have allowed researchers to tease apart how large a role is played by our genes, and what we can put down to our environment.

In this case, environment could be the state of your life, the hard knocks you have had to take, and more unusual factors, including infections.

One of the starkest insights into depression and suicide comes from scientists studying bipolar disorder, formerly known as manic depression.

People with the condition experience periods of intense mania, and will often feel themselves compelled to attempt grandiose tasks and projects, but fall into a deep depression once they are completed. The condition is thought to be strongly linked to specific genes.

”If you look at a population of people diagnosed with bipolar disorder, a fifth of them will attempt or succeed in committing suicide,” said David Porteous, professor of human molecular genetics at Edinburgh University.

”Also, if you look at families where someone has committed suicide, the chances are that you will find another case in the not-too-distant family,” he added.

Serious depression, which requires medical treatment, is thought to be 70% genetic, with the rest a hodgepodge of environmental effects. Peter McGuffin, professor of psychiatric genetics at the Institute of Psychiatry in London, is currently working through the results of a large study aimed at discovering the genetics of depression.

In the study scientists have taken genetic material from 3 500 patients, and will compare them against genetic markers from a large healthy population.

The results, which are expected within a month or so, are likely to reveal a spread of new genes that ratchet up our susceptibility to becoming depressed.

”Everybody is somewhere on a spectrum of susceptibility to depression,” says McGuffin.

One of the most interesting questions the study may answer is why twice as many women as men experience recurrent depression. So far, no genes for depression have been found on the X chromosome, of which women have two.

Once we have inherited our deck of genetic cards it is often life experience that will determine whether or not we go on to have depression.

”The most obvious non-genetic cause is just bad things happening to you, so-called severe life events,” said McGuffin. ”On average, you see that people have more severe life events before the onset of depression,” he says.

Strikingly, it could be the suicide of a family member that itself becomes a serious enough blow to nudge someone closer to depression. How Nicholas Hughes was affected by his mother’s death when he was tiny is unknown. But we do know he had had depression for a long time and had left his position as professor of fisheries and ocean sciences at the University of Alaska in Fairbanks to focus on pottery at home.

”There is a lot of controversy about the impact of very early trauma on later depression,” says McGuffin.

Some evidence of particular depression genes is already emerging. Porteous recently discovered a gene called Disc1, which is associated with schizophrenia. Subsequent studies by McGuffin show the same gene may also play a role in depression.

Understanding the underlying genetics of depression is unlikely to lead directly to new treatments, but it will shed light on the neurobiology at work.

Getting a better grasp on that may then in turn open doors to new treatments, and explain how some of today’s most popular drugs for the condition work. ­-