It has always been known that a good mother-child contact leads
to healthier and happier babies and adults. But what would happen
if we knew that early life nurturing affects our genes and can
leave life long imprints in our genome? This is a research focus of
Patrick McGowan and his colleagues at the Douglas Mental Health
University Institute in Montreal, Canada, who found that suicide
victims with a history of childhood abuse are more prone to carry
stable chemical modification on their DNA that will cause impaired
response to stress later in life, published in a recent volume of
Nature Neuroscience (McGowan et al., 2009).
A significant number of studies show that adverse early life
experiences have a profound effect on the development of the brain
and can lead to neurological disorders like depression and anxiety
(Nemeroff, 2004). Conversely, psychotherapy has been shown to
generate chemical changes in the brain that can reverse altered
neurological states to normal. It is clear that the brain structure
and connections and are modelled by the experiences we accumulate
throughout life but do these dynamic neurological states mirror as
far as in the DNA sequence? An accumulating number of studies,
including the present one, indicate that under certain
circumstances the answer could be positive.
Brain samples have been collected from the Quebec Suicide Brain
Bank 12 for each of the three groups analysed: 1) suicide victims
with a history of childhood abuse; 2) suicide victims with negative
history of childhood abuse and 3) controls (adults who died
suddenly of unrelated causes).
Individuals with a history of childhood abuse had lower amount of a
protein in the brain (the glucocorticoid receptor, NR3C1) compared
to those that also committed suicide but were not abused as
children and controls. The glucocorticoid receptor is important for
a healthy stress response by the hypothalamic-pituitary-adrenal
(HPA) activity since low amount of this protein will lead to
incapacity to react healthily to normal and stressful life
situations.
What the authors have found was that the low amount of the
glucocorticoid receptor was caused by methylation of the DNA (one
of the four letters, the cytosine, was changed to methylcytosine).
More precisely the promoter of this gene was methylated more than
normal and as a consequence it couldn't be completely functional.
If we compare the promoter to an engine of a train - when the
engine of a train is defective and the brakes are on it can't pull
the train with the normal speed of travelling.
This finding is a confirmation of a previous work where rats raised
by negligent mothers suffered changes similar changes in their DNA
leading to impaired response to stress in adulthood (Weaver et al.,
2004). DNA methylation changes have been shown for other
neurological conditions like schizophrenia and bipolar disorders.
Under which circumstances are these modifications reversible is not
clearly known, there are some indications that certain chemicals
interfering with the methylation process were able to restore the
normal stress response in rats.
An important speculation that arises from these experiments and is
supported by the authors is that epigenetics might be the interface
between social environment in the childhood and brain development
and stable epigenetic states might persist into adulthood that can
later define the individual's vulnerability to psychopathological
conditions.
For more information please read
McGowan, P. O., Sasaki, A., D'Alessio, A. C., Dymov, S., Labonte,
B., Szyf, M., Turecki, G., and Meaney, M. J. (2009). Epigenetic
regulation of the glucocorticoid receptor in human brain associates
with childhood abuse. Nat Neurosci 12, 342-348;
Nemeroff, C. (2004). Neurobiological consequences of childhood
trauma. J Clin Psychiatry 65, 18:-28;
Weaver, I. C. G., Cervoni, N., Champagne, F. A., D'Alessio, A. C.,
Sharma, S., Seckl, J. R., Dymov, S., Szyf, M., and Meaney, M. J.
(2004). Epigenetic programming by maternal behavior. Nat Neurosci
7, 847-854;
or visit the following links
http://www.nature.com/nature/supplements/insights/epigenetics/index.html
http://www.epigenome-noe.net/aboutus/epigenetics.php
Note:
Gabriella Ficz is Postdoctoral Research Scientist at Laboratory of
Developmental Genetics and Imprinting,The Babraham Institute,
Cambridge, UK.