'Fear extinction' is a phenomenon through
which animals and humans disassociate with fearful memories of a
traumatic experience, such as war, assault or a natural disaster. Most
people recover with no ill effects, but approximately one out of 10 go
on to develop post traumatic
stress disorder (PTSD).
A specific gene that helps form memories from traumatic events can be
manipulated - and in doing so may actually help prevent PTSD, according to a new study led NYU Langone
Medical Center that recently published in Neuropharmacology
‘Dexamethasone, a widely prescribed steroid for inflammatory conditions, affects the expression of fkbp5 in the brain, preventing the formation of the fearful memories that are the hallmark of post traumatic stress disorder.’
Specifically, the findings explain how a particular gene - called
fkbp5 - is involved in a phenomenon known as "fear extinction".
The new study, in collaboration with Harvard and Emory Universities
and other organizations, examined fear extinction patterns in mice and
humans. They found that dexamethasone, a widely prescribed steroid for
inflammatory conditions, affects the expression of fkbp5 in the brain,
preventing the formation of the fearful memories that are the hallmark
"The interaction between fkbp5 and dexamethasone could enable us to
enhance fear extinction," says Isaac Galatzer-Levy, a research
assistant professor in the Department of Psychiatry at NYU Langone and
its Steven and Alexandra Cohen Veterans Center, and the lead
investigator on the study. "If dexamethasone works well in humans, we
could potentially use it to prevent fearful memories in soldiers on the
battlefield, patients in emergency rooms, or anywhere else where
healthcare providers provide treatment within hours of traumatic
In a life-threatening situation, the brain launches into
"fight-or-flight," a rapid and instinctive survival mechanism during
which cortisol travels to the brain to dampen the initial response.
Versions of the fkbp5 gene, in turn, affect how well cortisol affects
memory around that event.
Galatzer-Levy analyzed data from large studies in humans and mice
that involved "fear conditioning" and "fear extinction," during which
subjects receive a mild aversive stimulus when exposed to a sound or
light, and "fear extinction learning," during which conditioning is
reversed by applying sound or light without the stimulus.
In humans, Galatzer-Levy found that different versions of the fkbp5
gene were able to predict specific differences in extinction learning
related to PTSD symptoms such as reliving or re-experiencing the
traumatic event; avoiding reminders of the event; and, in particular,
hyperarousal, or the inability to sleep or concentrate.
To further determine if manipulating fkbp5 could prevent the
abnormal paths of extinction learning, Galatzer-Levy looked at data
taken from a mouse study in which they were fear conditioned, given
doses of dexamethasone or a placebo, and then put through fear
extinction training the following day. He found that when given a dose
of dexamethasone high enough to enter the brain, the mice almost
uniformly extinguished fear. Although the change in fkbp5 expression was
temporary, the effect of high-dose dexamethasone on extinction learning
was permanent, Galatzer-Levy says.
To further this research, Galatzer-Levy recently launched a pilot
project to test whether a single oral dose of dexamethasone given in the
emergency room after a traumatic accident or injury decreases the
chances of developing PTSD.
"A treatment like dexamethasone is very appealing because it has
very few side-effects and is inexpensive," Galatzer-Levy says. "It
potentially could be an ideal preventative treatment since we know it
has effects that alter fear learning and memory."