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A study published recently in theJournal of Neuroscience points, for the first time, to
the gene trkC as a factor in susceptibility to the disease. The researchers define the specific
mechanism for the formation of fear memories which will help in the development of new
pharmacological and cognitive treatments.
Five out of every 100 people in Spain suffer from panic disorder, one of the diseases
included within the anxiety disorders, and they experience frequent and sudden attacks of
fear that may influence their everyday lives, sometimes even rendering them incapable of
things like going to the shops, driving the car or holding down a job.
It was known that this disease had a neurobiological and genetic basis and for some
time the search had been on to discover which genes were involved in its development,
with certain genes being implicated without their physiopathological contribution being
understood. Now, for the first time, researchers from the Centre for Genomic Regulation
(CRG) have revealed that the gene NTRK3, responsible for encoding a protein essential
for the formation of the brain, the survival of neurons and establishing connections between
them, is a factor in genetic susceptibility to panic disorder.
"We have observed that deregulation of NTRK3 produces changes in brain development
that lead to malfunctions in the fearrelated memory system," explains Mara Dierssen, head of the
Cellular and Systems Neurobiology group at the CRG. "In particular, this system is more efficient
at processessing information to do with fear, the thing that makes a person overestimate the risk
in a situation and therefore feel more frightened and, also, that stores that information in a more
lasting and consistent manner." Different regions of the human brain are responsible for processing
this feeling, although the hippocampus and amygdala play crucial roles. On the one hand, the
hippocampus is responsible for forming memories and processing contextual information, which means
that the person may be afraid of being in places where they could suffer a panic attack; and on the other,
the amygdala is crucial in converting this information into a physiological fear response.
Although these circuits are activated in everyone in warning situations, what the CRG researchers
have discovered is that "in those people who suffer from panic disorder there is overactivation of the
hippocampus and altered activation in the amygdala circuitry, resulting in exaggerated formation of fear
memories," explains Davide D'Amico, a PhD student at the CRG, coauthor of the work and the article
published in the Journal of Neuosciences, together with Dierssen and the researcher Mónica Santos.
They have also found that Tiagabine, a drug that modulates the brain's fear inhibition system,
is able to reverse the formation of panic memories. Although it had already been observed to alleviate
certain symptoms in some patients, "we have discovered that it specifically helps restore the fear
memory system," points out Dierssen.
Panic disorder
Panic attacks are a key symptom of panic disorder. They can last several minutes, be sudden and
repeated, and the sufferer has a physical reaction similar to the alarm response to real danger, involving
palpitations, cold sweats, dizziness, shortness of breath, tingling in the body, nausea and stomach pain.
On top of this, they feel continuously anxious when faced with the prospect of suffering another attack.
This study by the CRG researchers reveals that the way in which the memories resulting from a panic
attack are stored is what ultimately ends up producing the disorder, which usually appears between 20
and 30 years of age. Although it has a genetic basis, it is also influenced by other environmental factors,
such as accumulated stress. This is why the authors of the paper consider elevated environmental stress
in Spanish society to have led to an increase in the occurrence of these disorders.
Currently, there is no cure for this disease, which is treated with medicines that block the more
serious symptoms, as well as with cognitive therapy, which aims to help the person learn to survive the
attacks better. "The problem is that drugs have many side effects and psychotherapy is not really aimed
at specific moments in the process of forming and forgetting fear memories. In our work we have defined
a specific creation mechanism for these fear memories that could help in the development of new drugs
and, also, in identifying the key moments for applying cognitive therapy," indicates D'Amico.