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Post-traumatic Stress Disorder Caused by Both Genes and Environment

Both genetic and environmental factors affect people’s risk of developing post-traumatic stress, according to new research that illustrates how nature and nurture combine to shape health and behaviour.
A particular genetic variant makes people much more susceptible to post-traumatic stress disorder (PTSD) after harrowing experiences, but only if they have also had an abusive childhood, scientists in the United States have discovered.

The findings add to a growing consensus that the debate about whether mental health, personality and behaviour are driven by nature or nurture is founded on a misconception.

They indicate strongly that genes and the environment are not mutually exculsive forces, but rather work together to influence human development.

PTSD is a serious anxiety disorder that develops among people who witness or experience unpleasant events, such as war, murders, terrorist attacks or natural disasters. It commonly leads to nightmares, insomnia, flashbacks, mood swings and depression, and can severly impair people’s ability to live a normal life.

Not everybody who experiences severe trauma develops PTSD, and the risk is known to be influenced by genetics. Studies of twins who served in Vietnam showed that identical pairs, who share all their genes, are more likely both to suffer than are fraternal sets.

Genes, however, do not explain all the variability in people’s risk, and the precise genes and environmental factors that are involved have remained obscure.

A study led by Kerry Ressler, of Emory University in Atlanta, examined the effects of a gene called FKBP5, which is known to be involved in the way the human body responds to stress.

The DNA code of this gene varies at four points, which allowed the scientists to investigate whether any particular genetic profiles would either raise the risk of PTSD or protect against it.

As PTSD develops only when people have lived through traumatic events, Dr Ressler decided to study a group of 900 adults who lived in deprived urban communities, who were more likely to have had violent experiences of the sort that can provoke the disorder.

The participants, most of whom are black, were also asked to complete a questionnaire about their childhood experiences, which recorded whether they had suffered physical or sexual abuse at a young age.

When variations in the FKBP5 gene were examined on their own, the researchers found no effect on PTSD risk. A history of child abuse also made no difference when considered in isolation.

When the two factors were considered together, however, they were found to interact to raise or reduce risk. People with certain variants of FKBP5 were much more likely to develop PTSD after trauma if they had also been abused as children.

“These results are early and will need to be replicated, but they support the hypothesis that combinations of genes and environmental factors affect the risk for stress-related disorders like PTSD,” Dr Ressler said.

“Understanding how gene-environment interactions affect mental health can help us to understand the neurobiology of these illnesses.”

The results, which are published in the Journal of the American Medical Association, follow several other studies that have shown how genetic variants interact with environmental factors to affect behaviour or mental health.

A team led by Avshalom Caspi and Terrie Moffitt, of the Institute of Psychiatry in London, has found that a particular variant of a gene called MAOA predisposes to antisocial behaviour when accompanied by child abuse.

Evidence from the same research group also indicates that variation in a gene called 5HTT can influence whether people develop depression after stressful life events such as bereavement, and whether they develop psychosis after smoking cannabis.

Dr Caspi said the Emory research was exciting. “It is part of an emerging body of research that documents not so much that genes cause disease, but rather that genetic differences between people shape how people respond differently to the same experiences."

Dr Moffitt said: “This is an important insight, because it offers clues for unraveling the biology of psychiatric disorders, which will lead to new and better treatments.”

Dr Ressler said the social aspects of the research are as important as its genetic aspects, showing how important it is to understand how social deprivation contributes to PTSD.

“This finding helps us to understand the neurobiology of PTSD,” he said. “It’s equally important to understand how to decrease the high rates of childhood and adult trauma that inner-city populations suffer. PTSD rates in US inner cities are as high as among war veterans.”

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