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Is there a link between epilepsy and anxiety? It seems that such a
link exists. This conclusion is based on the work of a group led by Georges
Chapouthier, CNRS Research Director, and Patrice Venault, lecturer at
Paris 5 University. Their research has been carried out in the framework
of the "Vulnerabilité, adaptation et psychopathology"
(Vulnerability, adaptation and psychopathology) research unit of the CNRS
and Paris 6 and 7 Universities, located at La Pitié-Salpêtrière
Hospital.
Epilepsy is a pathological tendency to have convulsions, whose relation
to a major inhibiting brain neurotransmitter, GABA, has long been known
to scientists. It acts as a cerebral brake, which, by blocking the circulation
of nerve impulses, prevents the brain from short-circuiting. A short-circuit
of sorts is precisely what occurs in epilepsy following insufficient GABA
activity. Many treatments for epilepsy use molecules that increase GABA
activity.
Anxiety, a normal phenomenon when it is moderate, can also become pathological.
It has been shown that anxiety is also related to GABA: the very molecules
that counteract the activity of GABA produce anxiety when administered
in average doses and cause convulsions when administered in high doses.
Using one of the molecules that counteract GABA activity, beta-CCM, which,
depending on the dose, causes either anxiety or seizures, the researchers
were able to show the correlation between epilepsy and anxiety.
For their experiment, Georges Chapouthier, Patrice Venault and their team
members selected two strains of mice, one highly resistant and the other
highly sensitive to beta-CCM, a convulsant in high doses and a generator
of anxiety at lower doses. The researchers selected ten couples of mice
that convulsed rapidly after being injected with the product, and ten
couples that did not experience seizures after the same treatment.
Within a few generations, they obtained two strains of mice, one of which
was highly resistant to beta-CCM (BR), and the other highly sensitive
(BS). The two groups underwent three series of tests classically used
to measure degrees of anxiety. The tests, carried out in collaboration
with Jean Constentin's laboratory in Rouen, France, placed the mice in
the following situations:
1 - An elevated maze containing an enclosed space and a space that opens
on to a drop. The animal moves freely in the maze. If it spends more time
in the open space it is considered to be experiencing no anxiety.
2 - The "light/dark" test: the animal can choose between two
connected plexiglass boxes, one of which is clearly lit and the other,
dark. Preference for the dark area implies a state of anxiety.
3 - The staircase test: this involves a small wooden staircase with five
steps. The mouse climbs freely, and makes rearing movements as it climbs.
The number of steps climbed is compared to the number of times the mouse
rears. A significant amount of rearing behavior without any increase in
the number of steps climbed implies a high degree of anxiety.
The results of the tests showed that there are considerable differences
between the two strains but also revealed reactions that are contrary
to what could have been expected. The BR group (resistant to beta-CCM)
proved to have a higher degree of anxiety, while the BS group, with a
higher sensitivity to the convulsion-causing properties of beta-CCM, had
a lower degree of anxiety. One possible interpretation of this "inverse
correlation" is that the BR strain is more sensitive to the spontaneous
anxiety-causing effects while the BS strain is more sensitive to the convulsant
effects of beta-CCM.
Even though many issues concerning the interpretation of the details and
the analysis of the underlying mechanisms have still to be addressed,
these results nevertheless suggest that in mice there is a strong physiological
correlation between the mechanisms that control epileptic convulsions
and certain forms of anxiety. Further studies should show if this correlation
is also valid for humans.
Reference: Trends in Pharmacological Sciences, volume 22, no 10,
October 2001, pp 491-493.
Researcher
contacts:
"Vulnérabilité, adaptation et psychopathologie"
Research Unit
Georges Chapouthier
Tel: +33 1 40 77 97 05
e-mail: chapout@ext.jussieu.fr
Patrice Venault
Tel: +33 1 40 77 98 31
e-mail: venault@ext.jussieu.fr
Press contact
:
Martine Hasler
Tel : +33 1 44 96 46 35
e-mail : martine.hasler@cnrs-dir.fr
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