News Release

Epigenetic changes at birth could explain later behavior problems

Peer-Reviewed Publication

King's College London

Epigenetic changes present at birth - in genes related to addiction and aggression - could be linked to conduct problems in children, according to a new study by King's College London and the University of Bristol.

Conduct problems (CP) such as fighting, lying and stealing are the most common reason for child treatment referral in the UK, costing an estimated £22 billion per year. Children who develop conduct problems before the age of 10 (known as early-onset CP) are at a much higher risk for severe and chronic antisocial behaviour across the lifespan, resulting in further social costs related to crime, welfare dependence and health-care needs.

Genetic factors are known to strongly influence conduct problems, explaining between 50-80 per cent of the differences between children who develop problems and those who do not. However, little is known about how genetic factors interact with environmental influences - especially during foetal development - to increase the risk for later conduct problems.

Understanding changes in DNA methylation, an epigenetic process that regulates how genes are 'switched on and off', could aid the development of more effective approaches to preventing later conduct problems.

The study, published today in Development & Psychopathology, used data from Bristol's Avon Longitudinal Study of Parents and Children (ALSPAC) to examine associations between DNA methylation at birth and conduct problems from the ages of four to 13.

The researchers also measured the influence of environmental factors previously linked to early onset of conduct problems, including maternal diet, smoking, alcohol use and exposure to stressful life events.

They found that at birth, epigenetic changes in seven sites across children's DNA differentiated those who went on to develop early-onset versus those who did not. Some of these epigenetic differences were associated with prenatal exposures, such as smoking and alcohol use during pregnancy.

One of the genes which showed the most significant epigenetic changes, called MGLL, is known to play a role in reward, addiction and pain perception. This is notable as previous research suggests conduct problems are often accompanied by substance abuse, and there is also evidence indicating that some people who engage in antisocial lifestyles show higher pain tolerance. The researchers also found smaller differences in a number of genes previously associated with aggression and antisocial behaviour, including MAOA.

Dr Edward Barker, senior author from King's College London, said: 'We know that children with early-onset conduct problems are much more likely to engage in antisocial behaviour as adults, so this is clearly a very important group to look at from a societal point of view.

'There is good evidence that exposure to maternal smoking and alcohol is associated with developmental problems in children, yet we don't know how increased risk for conduct problems occurs. These results suggest that epigenetic changes taking place in the womb are a good place to start.'

Dr Charlotte Cecil, first author from King's College London, said: 'Our study reveals significant epigenetic changes which differentiate children who go on to develop conduct problems and those who don't. Although these findings do not prove causation, they do highlight the neonatal period as a potentially important window of biological vulnerability, as well as pinpointing novel genes for future investigation.

'Given that the postnatal environment is also crucial for children's development, future research should examine whether positive environmental experiences can help to modify these epigenetic changes.'

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Notes to editors

For further media information please contact Jack Stonebridge, Senior Press Officer, Institute of Psychiatry, Psychology & Neuroscience, King's College London jack.stonebridge@kcl.ac.uk/ 020 7848 5377.

About King's College London - http://www.kcl.ac.uk

King's College London is one of the top 25 universities in the world (2016/17 QS World University Rankings) and among the oldest in England. King's has more than 26,500 students (of whom nearly 10,400 are graduate students) from some 150 countries worldwide, and nearly 6,900 staff. The university is in the second phase of a £1 billion redevelopment programme which is transforming its estate.

King's has an outstanding reputation for world-class teaching and cutting-edge research. In the 2014 Research Excellence Framework (REF) King's was ranked 6th nationally in the 'power' ranking, which takes into account both the quality and quantity of research activity, and 7th for quality according to Times Higher Education rankings. Eighty-four per cent of research at King's was deemed 'world-leading' or 'internationally excellent' (3* and 4*). The university is in the top seven UK universities for research earnings and has an overall annual income of more than £600 million.

King's has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine, nursing and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar.

King's College London and Guy's and St Thomas', King's College Hospital and South London and Maudsley NHS Foundation Trusts are part of King's Health Partners. King's Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world's leading research-led universities and three of London's most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit: http://www.kingshealthpartners.org.


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