One of the most exciting and provocative areas of schizophrenia science
these days is to try to find a way of delaying, or even preventing, the
development of schizophrenia in individuals at high risk for it.
For example, Thomas McGlashan, M.D., a professor of psychiatry at Yale
University, and colleagues have been attempting to see whether an
antipsychotic medication might do the trick (Psychiatric News, June
21, 2002). "We are analyzing the data" and plan to submit results
to a psychiatric journal, McGlashan said in a recent interview with
Patrick McGorry, M.D., Ph.D., a professor of psychiatry at Australia's
University of Melbourne, and coworkers have been exploring whether an
antipsychotic medication and cognitive-behavioral therapy might do it
(Psychiatric News, November 15, 2002). They have followed up most of
their subjects, McGorry told Psychiatric News, but have not yet
published the results.
And now T.-U. Wilson Woo, M.D., Ph.D., an assistant professor of psychiatry
at Harvard University, and colleagues want to find out whether a medication
that increases levels of the neurotransmitter gamma-amino butyric acid (GABA)
in the brain might be effective in delaying or preventing schizophrenia.
It has been postulated that excessive pruning of nerve synapses in the
brain during adolescence and early adulthood may result in the onset of
schizophrenia. This excessive pruning in turn may be influenced by the
maturation of nerves in the prefrontal cortex that use GABA as their
neurotransmitter. The antiepilepsy medication tiagabine (Gabitril) is known to
enhance GABA availability. So Woo and his team speculated that if tiagabine
were given to young people at high risk for schizophrenia, it might enhance
GABA availability in the prefrontal cortex region of their brains. Enhanced
GABA availability might in turn halt the excessive pruning of nerve synapses
in the prefrontal cortex, and a halt of excessive pruning in the prefrontal
cortex might delay or prevent the development of schizophrenia.
Their first step is to conduct a small pilot trial to see whether tiagabine
might be able to alter late-development prefrontal nerve circuitry in 30 teens
who have recently developed schizophrenia. They will use fMRI scans to
visualize the prefrontal nerve-activation patterns of their subjects during
working memory, that is, when the prefrontal cortex is functionally
challenged. Then they will give the subjects tiagabine. After that, they will
use fMRI scans to again visualize the subjects' prefrontal nerve-activation
patterns during working memory. Finally, they will compare the subjects'
prefrontal nerve-activation patterns before getting the medication with their
prefrontal nerve-activation patterns after taking it.
"Very preliminary findings" from the first three subjects
recruited for the trial suggest that the patterns are "significantly
different before and after treatment," Woo told Psychiatric
News. In other words, it looks as if tiagabine "may be effective in
modifying the late development of prefrontal circuitry in young patients with
Several questions remain to be answered: Will more subjects from the pilot
trial also demonstrate tiagabine-induced prefrontal nerve-activation changes?
If so, can tiagabine do the same for teens at high risk for schizophrenia? And
if tiagabine can do the same for teens at high schizophrenia risk, will it in
turn delay, or even prevent, illness development?
"We are hoping," Woo said, "that positive findings from
this study will eventually justify a clinical trial in clinically high-risk
Their research is being funded by the Stanley Medical Research Institute
and the National Institute of Mental Health. More information about the
scientific rationale underlying it can be found in a review paper published in
the March Schizophrenia Research.
An abstract of "Targeting Synapses and Myelin in the
Prevention of Schizophrenia" can be accessed online at<www.sciencedirect.com>
by clicking on "Browse A-Z of journals," then "S,"
then "Schizophrenia Research." ▪