Heavy drinking in teens causes lasting changes in emotional center of brain


Binge drinking in adolescence has been shown to have lasting effects
on the wiring of the brain and is associated with increased risk for
psychological problems and alcohol use disorder later in life.

Now, researchers at the University of Illinois at Chicago Center for
Alcohol Research in Epigenetics have shown that some of these lasting
changes are the result of epigenetic changes that alter the expression
of a protein crucial for the formation and maintenance of neural
connections in the amygdala — the part of the brain involved in emotion,
fear and anxiety. Their results, which are based on the analysis of
postmortem human brain tissue, are published in the journal Translational Psychiatry.

Epigenetics refers to chemical changes to DNA, RNA or specific
proteins associated with chromosomes that change the activity of genes
without changing the genes themselves. Epigenetic modifications are
involved in the normal development of the brain, but they can be
influenced by environmental or even social factors, such as alcohol and
stress. These kinds of epigenetic alterations have been linked to
changes in behavior and disease.

The researchers looked at postmortem human amygdala tissue obtained
from the New South Wales Brain Tissue Resource Center in Sydney,
Australia. The amygdala is the part of the brain involved in emotional
regulation. The specimens were from the brains of 11 individuals who
started drinking heavily before the age of 21 or early-onset drinkers;
11 individuals who started drinking seriously after the age of 21, known
as late-onset drinkers; and 22 individuals with no history of alcohol
use disorder. The average age of death of the individuals from whom the
samples were taken was 58 years old for those without alcohol use
disorder; 55 years old for early-onset drinkers; and 59 for late-onset

Amygdalae of individuals who were early-onset drinkers had about 30
percent more of a molecule called BDNF-AS, a large non-coding RNA.
Usually, RNA is involved in the production of proteins from DNA, but
this one is not. BDNF-AS regulates a gene that produces a protein called
BDNF. This protein is a growth factor and is crucial for the normal
formation and maintenance of synapses throughout the brain. When there
is more BDNF-AS, there is less BDNF. The brain tissue of early-onset
drinkers had 30 percent to 40 percent less BDNF compared with brain
tissue from people with no history of alcohol use disorder. This
reduction in BDNF was not seen in brain samples from late-onset drinkers
or from people with no alcohol use disorder.

Subhash Pandey, professor of psychiatry and director of the UIC
Center for Alcohol Research in Epigenetics, and corresponding author on
the paper, believes that epigenetic changes to BDNF-AS are the reason
BDNF is lower in the amygdalae from people who started drinking early in
life. In the amygdala from people who started drinking after age 21,
there were no such changes.

“BDNF is needed for normal development in the brain and for
connections to form between neurons,” said Pandey, who is also a senior
research career scientist at Jesse Brown VA Medical Center, Chicago. “If
levels are lowered due to alcohol exposure, then the brain will not
develop normally, and we see that in these brain samples where there are
abnormalities in another synaptic gene, Arc, possibly making abnormal
connections between neurons.”

Pandey and his colleagues found that the increase in BDNF-AS in the
early-onset drinkers is caused by decreased methylation of BDNF-AS.
Methylation is a type of epigenetic change where a molecule containing a
methyl group is added to another molecule and results in a change in
genetic expression. The decreased methylation of BDNF-AS is believed to
be caused by early-onset drinking and appears to be a long-lasting

“The epigenetic changes we saw in the amygdala of early-onset
drinkers can alter the normal function of the amygdala, which helps
regulate our emotions, and may cause individuals to be more susceptible
for things like anxiety, which we have shown in other studies, or the
development and maintenance of alcohol use disorder later in life,”
Pandey said.

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