The Biology of Suicide

Why do people kill themselves?

“Dearest, I feel certain that I am going mad again. I feel we can’t go through another of those terrible times. And I shan’t recover this time.” So begins Virginia Woolf’s last note to her husband. A short time later she filled her overcoat pockets with stones and waded into the Ouse River near her house in Southern England.

Why do people kill themselves? The common answer: because of despair. A more nuanced answer traces environmental and genetic influences and their complex interaction.

Endangered families

Studies of twins and adopted children have shown that genes play an important role in the risk of committing suicide. A recently published study by the Karolinska Institute in Sweden involving eleven million people revealed that children of parents who had committed suicide had twice the risk of committing suicide themselves. The risk was three times as high with siblings of suicides, and with identical twins the risk was 15 times greater. When a child with no discernible genetic risk factors was adopted by a family with a high rate of suicide, there was only a slight increase in the child’s risk of committing suicide.

Ms. Danuta Wasserman, professor of psychiatry and suicidology at the Karolinska Institute, and president of the European Psychiatric Association states that, “We have found a whole series of genes that are important to the understanding of suicide. The genes that come most into question are those that influence the way stress is processed and those that regulate important chemical messengers in the brain – serotonin, GABA, and glutamate are some examples. New findings indicate that genes involved in nerve growth also play a role.” Professor Wasserman stresses that, “There is no suicide gene. However, there is a complex, jointly interacting gene network, and this can raise the risk of suicide.”

Deadlier than traffic accidents

A study by the Max Planck Institute for Psychiatry in Munich, Germany indicates the magnitude of the problem. 2,000 people who suffered from clinical depression were examined. The concurrence of three small variations in a gene that is involved in nerve growth (NTRK2) raises the risk of attempting suicide by a factor of four to five. Elisabeth Binder, the study’s co-author, stated that, “Healthy individuals also carry this genetic variation. However, when there are no stressful life situations that cause anxiety or depression, there are no negative consequences.”

Worldwide, some one million people commit suicide each year. In virtually all of the developed countries suicide causes more deaths than traffic accidents, and is one of the top ten causes of death. There is a Northeast-Southwest demarcation that splits Europe. Lithuania, Estonia, and Finland have the highest suicide rates, whereas Italy, Spain, and Greece have the lowest. Switzerland, Austria, and Germany, with 15, 13, and 9 suicides per 100,000 people, respectively, lie somewhere in the middle. In the United States suicide is one of the four leading causes of death among people under 55 years. In 2010 roughly 40,000 Americans took their life, 30,000 of them male. With 12 suicides per 100,000 people, the US has a rate that compares with mid-Western Europe and Canada.

Experiences influence genes

Whether or not a gene manifests itself to the point of influencing our behavior, and how it accomplishes this feat, is shaped in part by our environment. What happens when specific traumatic and stressful experiences collide with a particular genotype? How does a genetic trait influence the perception of an intense emotional experience?

The field of epigenetics helps in the search for answers to these questions. The epigenome is the chemical structure that encompasses the entirety of the gene. Environmental influences – food choices, smoking, stress – change the epigenome through the accumulation of methyl groups. These variations in the epigenome can cause a particular gene to be turned on or off. Prof. Gustavo Turecki, director of the McGill Group for Suicide Studies at McGill University in Montreal, Canada, explains that, “The epigenome is a mechanism that allows the organism to flexibly assimilate different environments.” More and more studies indicate that incidences in childhood – such as sexual molestation – influence genes through epigenetic changes, thus impacting on an individual’s behavior, including suicidal behavior.

The Chemistry of neglect

A gene that has been shown to influence suicide risk factors is responsible for encoding a protein known as the “brain-derived neurotropic factor” (BDNF). BDNF affects nerve growth. Some two years ago a study conducted in the USA by Tania Roth and colleagues at the University of Alabama attracted a lot of attention. The research team went about making the life of pregnant rats difficult. They gave the rats insufficient nesting material and situated them in an unfamiliar setting. The stressed-out rat mothers neglected their offspring, groomed their young less often and suckled them irregularly.

And indeed, the BDNF encoding gene in the rat pups was less active than it was in a control group that was raised under normal conditions. The restricted gene activity was accompanied by a rise in the level of methylation in the BDNF encoding gene. When the researchers placed the stressed mothers’ new-born in the care of unstressed mothers, the methylation levels were dramatically reduced.

At this juncture, suicide researchers find themselves at a dead end. There are rats and mice who suffer from diseases similar to Alzheimer, fear, alcoholism, and depression, but with one questionable exception, it seems that there are no animals other than humans who commit suicide. So instead of looking for answers within the animal research community, researchers are concentrating on biological correlations within the brains of suicide victims.

Traces in the brain

Gustavo Turecki and his colleagues examined the epigenetic status of various genes in the hippocampus of suicide victims. The hippocampus is an area of the brain that is involved in memory formation. At the same time, the researchers conducted psychological autopsies; they questioned close friends, relatives, parents, and teachers of suicides concerning the victims’ backgrounds, behavior, and problems. The researchers concentrated on incidences of violence, sexual abuse, and extreme neglect during the victims’ childhood. Gustavo Turecki reported that, “Around 30 percent of suicides were traumatized during childhood. In the general population the figure is ten percent.”

The research team examined twelve brains from suicide victims with and without incidents of abuse in their background. A control group was set up that consisted of the brains of twelve people who had also died suddenly, but had not committed suicide. The researchers’ attention was focused on the epigenetic changes occurring in the gene NR3C1, which regulates the activity of a stress hormone receptor.

They discovered that there was excess methylation in specific areas of the NR3C1 gene only when suicides with traumatic childhoods were involved. For the first time, scientists had found that an individual’s experiences could influence epigenetic processes in the brain.

Genetic predilection combined with high levels of stress is not the only indication of a higher risk of suicide. Sometimes low stress levels are enough to trigger the compulsion towards suicide. Danuta Wasserman has analyzed specific gene fragments, so-called SNPs (single-nucleotide polymorphism), in families with sons who have attempted suicide. Specific SNP variations in a gene involved in stress response (the CRHR1) were connected with a higher risk of attempted suicide by people who experienced only low levels of stress. “Because of their genetic predisposition these people are much more sensitive to low stress levels,” says Wasserman. According to her, those people who have these genetic variations could be helped by being taught stress management at an early age.

Good characteristics – bad timing

Do biological factors that promote psychological diseases or suicidal tendencies also have a positive side? Gustavo Turecki says, “Technically speaking, there isn’t one particular gene that raises the risk of suicide; rather, there are sets of genes that are involved in specific behaviors that in combination can heighten the risk of suicide.”

Impulsivity is one behavior that has been extensively studied. Turecki states, “Being impulsive is a big advantage in a job that requires quick decisions. However, for someone who is suffering from depression and contemplating suicide – which is the case with almost everyone who is afflicted with this disease – the disadvantages of acting impulsively clearly outweigh the advantages.”
There are no good and bad genes. There are genetic constellations that are advantageous under certain conditions and harmful under others. Working at the Social Neuroscience Lab at the University of California, Shelly Taylor showed that a genetic variant, the short allele of the serotonin transporter gene 5-HTTLPR, raised the risk of depression when childhood experiences were problematic. Under beneficial conditions in childhood, there was a smaller risk of depression associated with the short allele. The role of the short allele in connection with depression, suicide,  and childhood adversities was first described by Avshalom Caspi in 2002. In the light of these findings, developmental psychologist Jay Belsky from Birbeck University in London talks about plasticity genes rather than vulnerability genes. People who carry plasticity genes have stronger reactions to their environment than do those without these genes.

Glad to be alive

Can the understanding of human genetics and epigenetics help in lowering the suicide rate? Danuta Wasserman is optimistic; “Research in this area is just at the beginning. No one should expect sophisticated epigenetic tools in the near future. But by combining the newest findings in genetics and epigenetics with our clinical experiences we are already able to accomplish a lot by way of suicide prevention.”

Researchers on suicide and suicide prevention agree that the best prevention has been to erase the stigma associated with mental illness. Wasserman points out that, “Mental illness is a disease in the same sense as diabetes or heart disease. It is influenced in the same way as other diseases – by the interaction between the environment and genes – and it is controllable.”
When the depression disappears, then the compulsion to end your life also vanishes. “Today is the anniversary of my attempted suicide,” sassyg1rl, a woman around forty, wrote on an online-forum. “I am so happy to be alive.”

 

(Anyone who is suicidal may receive immediate help by logging onto Suicide.org or by calling 1-800-SUICIDE. Suicide is preventable, and if you are feeling suicidal, you must get help. So please visit Suicide.org or call 1-800-SUICIDE immediately. In Germany please dial: 0800 – 111 0 111 or 0800 – 111 0 222)

The text appeared in 2011 in the Neue Zürcher Zeitung.

Photocredit: .BJORN / photocase.de