| Vol 7 n° 2 - New Psychiatric Classification based on Endophenotypes |
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he concept of endophenotypes in psychiatric dis-
orders has been developed over the last few decades. In
their 1967 paper on the genetics of schizophrenia,
Gottesman and Shields1 used the term endophenotype to
define an illness-related characteristic, observable through
biochemical testing or microscopic examination. It is
assumed that a valid and useful endophenotype is more
closely related to one or more pathophysiological genes
for the nosological category, compared with the entire
spectrum of disorders included in the nosological category.
The utility of endophenotypes in psychiatric research is
now more appreciated because we have a more accurate
understanding of the genetic complexity of operationally
defined disorders in our current psychiatric nosology.
Endophenotypes should be valid approaches to creating
more homogeneous subtypes of current diagnostic cate-
gories. If endophenotypes can create more homogeneous
subgroups of the traditional nosology of schizophrenia
and affective disorders, then more rapid advances in
understanding these disorders at the genetic, molecular
level can be made. Improved pharmacotherapy would
surely follow.
Criteria for an endophenotype
The criteria for an endophenotype have been derived
from those proposed by Gershon and Goldin2:
• The endophenotype must be associated with illness in
the general population.
• The endophenotype should be a stable, state-indepen-
dent characteristic (that is, it must be observable
despite the fact that the patient may be in partial or
complete remission).
• The endophenotype should be heritable.
• The endophenotype should segregate with illness
within families.
S t a t e
o f t h e a r t
9 5
Genetic
bases for endophenotypes
in psychiatric
disorders
Wade
H. Berrettini, MD, PhD
T
Copyright
© 2005 LLS SAS. All rights reserved
www.dialogues-cns.org
This article reviews the concept of an endophenotype,
with particular reference to heritability as well as diag-
nostic specificity. An endophenotype need not be herita-
ble, for example, the possible influence of in utero viral
infections for schizophrenia. However, heritability is a use-
ful characteristic for a potential endophenotype, as it can
be studied in relation to a plausible candidate gene. It
should be noted that the traditional methods of demon-
strating heritability, eg, twin studies, can be supplemented
with DNA sequence studies, suggesting heritability.
Endophenotypes need not be specific to a given nosolog-
ical class of psychiatric disorders, as these classes do not
reflect biological categories. Evidence for two useful schiz-
ophrenia endophenotypes, the P50 abnormalities and
cognitive deficits, is summarized.
© 2005, LLS SAS
Dialogues
Clin Neurosci. 2005;7:95-101.
Keywords: endophenotype;
schizophrenia; bipolar disorder; heritability; P50
auditory
evoked potential; cognitive deficit
Author
affiliations: Department
of Psychiatry and the
Center for
Neurobiology
and Behavior, University of Pennsylvania, Philadelphia, Pa, USA
Address
for correspondence: Wade H. Berrettini,
MD, PhD, Department of
Psychiatry
and the Center for Neurobiology
and Behavior, University of
Pennsylvania,
415 Curie Boulevard, Room 111, Philadelphia, PA 19107, USA
(e-mail:
wadeb@mail.med.upenn.edu)
