How Genes Changes Can Lead to Suicide

Child Abuse and/or Neglect Causes DNA Changes in the Brain that may make Suicide more Likely

by Dr. Barry Starr, Stanford University

May 23, 2008

Many studies have been done that show that childhood experiences can affect mental health later in life. For example, abuse and neglect as a child increases someone's chances of committing suicide as an adult.

What these studies don't answer is how upbringing affects someone's later behavior. In other words, what are the specific brain changes caused by neglect and abuse that increase someone's risk of suicide?

A new study has found that the rRNA gene in the hippocampus of the brain in these people is different from people who do not end up committing suicide. These differences aren't the kind a person inherits though. These are changes caused by our experiences.

Methylation and Genes

Methyl groups (in green) can
hide a gene from the cell.

Changes in DNA affect how well genes work. The changes the authors found would be predicted to make rRNA genes not work as well. To understand why, we need to first understand what a gene is and how one works.

Genes are made up of DNA. And DNA is made up of four different letters—A, G, C, and T. The order of these letters is a big part of what makes each person unique.

One way to affect how a gene works is to change one of these letters. We would not predict that these are the kind of changes that would result in specific changes due to someone's upbringing.

Why not? Because changes in the letters of DNA tend to be random. A person does not get specific changes like these in response to something. In other words, neglect and abuse would not change the letters of someone's DNA in a predictable way.

A more likely way to get specific DNA changes in response to abuse and/or neglect is from something called methylation. Methylation affects the cell's ability to use a gene. And methylation can happen in a predictable way in response to outside influences.

Before the information in a gene can be used, it needs to be copied into RNA. It is the RNA that then goes on to do all the things that make us work.

An RNA can be translated and its instructions used to make a protein. Or an RNA can go on to destroy other RNAs or keep them from being translated. Or an RNA can go on to become part of a protein-making machine called a ribosome.

But to do these things, a cell needs to find the start of a gene and start reading. This is not easy because so much of our DNA is not genes.

A cell finds a gene by looking for a certain sequence of DNA letters at the start of the gene called a promoter. Think of the promoter as punctuation—like ending a sentence with a period or capitalizing the first word of a sentence.

When we see a capital letter after a period, we know a new sentence is starting. If we read something that has no capital letters, it is very hard to know when one sentence starts and another ends. Same thing in the cell.

Except of course there is no punctuation or capital letters. Instead, the promoter can become hidden through something called methylation. These methyl groups act like a sentence in which the first letter has become lower case. Since the cell can't see the start of the gene, the gene doesn't get copied into RNA. No RNA, no effect.

DNA can definitely be specifically methylated due to something in the environment. One well known example is in mice.

A mouse will end up with blonde or brown hair depending on what its mom ate while pregnant. This is the result of the methylation of the promoter of a certain gene in mice.

The new study presents evidence of another case of specific methylation. The authors found increased methylation of rRNA genes in the hippocampus of the brain of people who had been neglected and/or abused as children and who later committed suicide. The authors argue that the methylation comes from childhood neglect and/or abuse.

More Information

Hippocampus, Methylation, and Suicide

For a gene to work, it has to be
seen and read by the cell.

The study focused on looking at the rRNA genes of the hippocampus of people who committed suicide. The main reason for studying the hippocampus is that it is one of the key areas of the brain involved in mental health. The rRNA gene was selected because it has been implicated in other psychological disorders.

The authors compared two groups of people. One was a set of 18 people who were abused and/or neglected as children and committed suicide. The other was a set of 12 people not abused or neglected who died suddenly (the control group).

The authors report two major findings. The rRNA promoter in the hippocampus of the suicide group was riddled with methyl groups. The control group was much less methylated.

The second finding was that this was not true in a different part of the brain. In the cerebellum, both groups had about the same level of methylation. The authors argue that this means the methylation is due to common environmental effects and not to something else.

This study shows that one way that abuse and/or neglect might affect later behavior is through DNA changes. In response to their upbringing, these people end up with extra methylation in the DNA of cells in the hippocampus of their brain. This methylation leads to less RNA being made from the rRNA gene.

At least this is what the authors' data suggests. It is difficult to nail something like this down. Ideally a researcher would want to look at the rRNA genes before and after abuse. This is both morally wrong and impossibly difficult technically.

Another possible way to nail it down would be to come up with medicines that decrease the methylation of rRNA genes. Then a researcher could figure out if the medicine decreases the risk for suicide.

Content provided by the Department of Genetics, Stanford University.