36 | New Scientist | 22 February 2020
There is no doubt that upbringing plays a
part. Animal experiments demonstrate that
early trauma affects an individual’s response
to stress as an adult. Testing this link in
humans is difficult, though, given the diversity,
frequency and severity of events that can
negatively impact a child. One of the few
studies to give an insight is the Bucharest Early
Intervention Project, a one-of-a-kind study of
children raised in Romanian orphanages. In
total, 136 children were randomly chosen from
six institutions, half of whom were fostered
between the ages of 6 months and 30 months.
When the children were around 12 years old, a
team led by Katie McLaughlin at the University
of Washington, Seattle, assessed their response
to stress-inducing tasks. Analysis of their saliva
revealed that those who had been fostered had
similar cortisol levels to a control group of
children living in nearby families – but only if
they had been placed in foster care before the
age of 2. Those fostered later or who remained
in orphanages had a blunted stress response,
producing less cortisol.Sensitive period
This might seem like a good thing because it
suggests that these children were less easily
stressed. In fact, it seems to be a manifestation
of underlying damage to the normal stress
response, and is associated with long-term
behavioural problems and an increased risk
of depression. Other research hints at what
is going on, revealing that the first two years
of life are a sensitive period in which our
environment is particularly likely to cause
changes to the brain that influence the stress
response. The mechanisms are probably
numerous, but research led by Linda Chao
at the University of California, San Francisco,
suggests that trauma can trigger an increase
in myelin in the brain’s grey matter, where
the cell bodies of neurons are found. Myelin
normally forms an insulating sheath around
nerve fibres, but in grey matter it prevents
new connections forming between neurons,
and is linked with PTSD and depression.
As for which aspects of the early
environment are key to healthy development,
experiments point to social interaction,
stimulation and parental support.
Developmental psychologist Suniya Luthar
at Arizona State University identifies the single
most important factor in developing stress
resilience as a strong, supportive, dependable
relationship with your primary caregivers.
“But adults who did not have a good childhood
experience are by no means doomed,” she says.How to make a
stress vaccineWe all produce a chemical
called neuropeptide Y (NPY)
that acts like an on-off switch
to modulate our body’s stress
response. Intriguingly, a single
injection of NPY before a
stressful experience seems to
protect animals from some of
the negative consequences of
stress. This discovery inspired
James Murrough and Dennis
Charney at Mount Sinai
Hospital in New York to try a
similar approach for people
with post-traumatic stress
disorder (PTSD). Their team
gave each volunteer an
intranasal dose of NPY before
they read a story designed to
elicit their PTSD. Although only
a small pilot study, it hinted
that NPY might offer relief
from some PTSD symptoms.
There was a problem though:
it took an hour of inhalation
and a specially designed
gadget to get enough of the
chemical into people’s brains.KETAMINE SURPRISE
For this reason, Murrough and
his colleagues have turned
their attention to another
chemical. Infamous as a party
drug, ketamine may sound like
an unlikely stress buster, but
it is actually a mainstay of
modern medicine, commonly
used as an anaesthetic. It
has also been found to have
antidepressant properties.
While testing these in mice,
Rebecca Brachman, then
at Columbia University in
New York, made a surprise
discovery. As with NPY, a single
dose of ketamine can protectmice from the negative effects
of chronic stress. It seems to
work by increasing the brain’s
ability to grow new neurons
and form new connections.
Recently, Murrough’s
colleague Sara Costi began
the first human study to see if
ketamine has potential as a
human “stress vaccine”.
Her healthy volunteers receive
one dose of ketamine – less
than people tend to take for
recreational purposes – or a
placebo. A week later, the
volunteers give a presentation
to a stern-looking panel, who
provide negative feedback.
“We’re looking at whether
pretreating people with
ketamine has an effect on their
stress response,” says
Murrough. The team is also
closely monitoring for side
effects. But, he says, there are
few of these with this low,
one-off dose, and even if
ketamine is needed several
times in a year, the available
evidence suggest that the
benefits outweigh the risk.
Results are expected within
the year. “It’s very exciting,”
says Murrough. “We wouldn’t
be advocating putting it in our
drinking water, but perhaps we
could give it to soldiers about
to deploy on a mission, or to
firefighters or police.” He
acknowledges that using the
stress vaccine in a non-combat
scenario would be harder
because stress is usually
unexpected. “But there might
be a window of time after the
stress in which the drug might
still be useful,” he says.