Early life stress can modify DNA expression, a study finds

Researchers studied 50 children of parents with alcoholism

Updated - May 18, 2019 06:24 pm IST

Published - May 18, 2019 06:23 pm IST

Estimation:  Having all the data in the same sample set helped us gauge how adversity, HPA axis function, DNA methylation and behaviour might interact, says Meera Purushottam (left).

Estimation: Having all the data in the same sample set helped us gauge how adversity, HPA axis function, DNA methylation and behaviour might interact, says Meera Purushottam (left).

A Bengaluru-based group of researchers has discovered a link between stress during early life and problematic, externalising behaviour in the DNA of children of alcoholic parents. In particular, they have studied 50 children of parents with alcoholism who had experienced stress in early life, which includes violent behaviour by alcoholic father towards mother and family, abuse and even sometimes their having to leave the home. They also studied 50 healthy children in a control group who had no such history. The results of the study were published in the journal Progress in Neuropsychopharmacology & Biological Psychiatry.

Biology and adversity

Early adversity is known to have several biological effects. One of this is DNA methylation — a process by which chemical changes occur to the DNA molecule. It also affects the functioning of what is called the hypothalamus-pituitary axis. This is a complex set of interactions between the hypothalamus and the pituitary gland in the brain and the adrenal glands (above the kidneys). “The hypothalamus-pituitary axis is a major neuroendocrine system that controls reactions to stress, regulates digestion, the immune system, mood and emotions, sexuality and energy storage and expenditure,” explains Meera Purushottam from the Molecular Genetics Lab, Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, and an author of the paper.

The present study provides further evidence of the association of early adversity in children of alcoholics with blunted cortisol activity, increased site-specific DNA methylation in a particular gene (SLC6A4) and high externalising behaviour. “The gene codes for the serotonin transporter. Serotonin is a very important chemical produced in the body and required for communication between neurons among other things,” says Dr Purushottam. Activity of this protein is crucial for appetite, emotional well being, cognition and memory.

Stress and cortisol

In the course of the study, the children were subjected to a standard stress test, and their saliva was sampled every ten minutes and tested for levels of a chemical called cortisol. In normal individuals, it is expected that the level of cortisol spikes during stress. “We found that the children with chronic stress had a subdued rise in cortisol levels when exposed to acute stress,” says Vivek Benegal from the Centre for Addiction Medicine at NIMHANS and a co-author of the paper.

Collated data

The study is unique in that it carries out a detailed assessment of HPA axis function by cortisol estimation during stress and also estimates chemical effects due to early adversity at the DNA level. The combined approach helped the researchers estimate adversity, HPA axis function, DNA methylation and behaviour. “Having all the data in the same sample set helped us draw conclusions on how the four parameters might be interacting,” she says.

The study concludes that children of alcoholics might have a compromised HPA axis and epigenetic changes at the DNA level possibly resulting in increased externalising behaviour.

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