| Vol 7 n° 1 - Early stages of schizophrenia |
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dentification of the biological
concomitants of
psychiatric illnesses such
as schizophrenia is a goal that is
pursued for a variety of
purposes. First is the hope that, as
in other branches of medicine, biological
measurements
or markers will increase
the precision of diagnosis. Second
is the possible
usefulness of the markers to subtype
groups that may respond
to particular medications and to
monitor the progress of
the treatment. A third hope, the
subject of this essay, is
the possibility that a biological
process will be observable
before the onset of illness, so
that vulnerable individuals
can be identified early and
perhaps treated
before the full development of psy-
chopathology. If
there were markers that fulfilled the first
two criteria, then
it would be straightforward to consider
their use for early identification
and preventive treatment.
However, no biological
marker has yet been recognized
that definitively fulfills
any one of these criteria, so that
the application to prevention
has remained uncertain.This
paper will suggest that
the failure to find biological mark-
ers that fit the first
two criteria is a consequence of the
complex, multidetermined
pathophysiology of major
mental disorders, but
that this failure does not preclude
the possibility that biomarkers
will be helpful in design-
ing strategies for prevention
of schizophrenia.
The use of a biological
marker to identify someone as ill
prior to the onset of
clinically detectable symptoms car-
ries enormous responsibility
when the illness is expected
to be serious and not
amenable to a curative treatment.
Even if the marker has
high validity, examination of indi-
1 7
B a s i c
r e s e a r c h
I
Copyright
© 2005 LLS SAS. All rights reserved
www.dialogues-cns.org
Early
biomarkers of psychosis
Robert
Freedman, MD; Randal Ross, MD; Sherry Leonard, PhD;
Marina
Myles-Worsley, PhD; Catherine E. Adams, PhD;
Merilyne
Waldo, PhD; Jason Tregellas, PhD; Laura Martin, MD;
Ann Olincy, MD; Jody
Tanabe, MD; Michael A. Kisley, PhD;
Sharon
Hunter, PhD; Karen E. Stevens, PhD
Keywords: schizophrenia;
development; genetics; chromosome 15; nicotinic
receptor;
hippocampus; inhibition; auditory evoked potentials; eye movement
Author
affiliations: Departments of
Psychiatry (Robert Freedman, Randal
Ross,
Sherry Leonard, Catherine E. Adams, Merilyne Waldo, Jason Tregellas,
Laura
Martin, Ann Olincy, Michael A. Kisley, Sharon Hunter, Karen E. Stevens),
Pharmacology
(Robert Freedman, Sherry Leonard),
and Radiology (Jody
Tanabe),
Denver VAMC and University of
Colorado, Denver, Co; and
Department
of Psychiatry, University of Utah School
of Medicine (Merilyne
Waldo),
Utah, USA
Address
for correspondence: Robert Freedman, MD, Department
of Psychiatry
C-268-71,
University of Colorado Health Sciences Center, Denver, CO 80262 USA
(e-mail:
Robert.Freedman@UCHSC.edu)
Biological
traits that are predictive of the later develop-
ment
of psychosis have not yet been identified. The com-
plex,
multidetermined nature of schizophrenia and other
psychoses
makes it unlikely that any single biomarker will
be both
sensitive and specific enough to unambiguously
identify
individuals who will later become psychotic.
However,
current genetic research has begun to identify
genes
associated with schizophrenia, some of which have
phenotypes
that appear early in life. While these pheno-
types
have low predictive power for identifying individu-
als who
will become psychotic, they do serve as biomark-
ers for
pathophysiological processes that can become the
targets
of prevention strategies. Examples are given from
work
on the role of the 7-nicotinic
receptor and its gene
CHRNA7 on
chromosome 15 in the neurobiology and
genetic
transmission of schizophrenia.
©
2005, LLS SAS
Dialogues
Clin Neurosci. 2005;7:17-29.
