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590
Schizotypal Personality
Disorder: An Operational
Definition of Bleuler's
Latent Schizophrenia?
by Seymour S. Kety
Abstract
In spite of the pressure for consensus
that operational diagnoses exert,
there remains considerable
disagreement concerning the
marginal syndromes which may be
subtypes of schizophrenia or
phenomenologically or genetically
related. Some clarification of the
question may result by returning to
Bleuler's "latent schizophrenia,"
which he observed in the relatives of
schizophrenics. Schizotypal
personality disorder of DSM-III is
only a first approximation to this,
and its deficits in this respect are
discussed briefly.
In 1962, when we learned about our
mutual interest in the ability of
adoption to separate the usually
entangled genetic and environmental
influences which had confronted
studies on the etiology of schizophrenia, David Rosenthal, Paul
Wender, and I decided to pool our
efforts in the compilation of a total
sample of adoptions as large as we
could muster. We entered this
collaboration from different vantage
points and with different aims.
Rosenthal saw an adoption study as
a better means of evaluating a
diathesis:stress model of schizophrenia (Rosenthal 1963). Wender
recognized in the adoptive parents of
schizophrenic patients a valuable
means of testing parental schizophrenogenic hypotheses without
genetic interference. For me, it
permitted an examination of the
prevalence of schizophrenia in the
biological and adoptive families of
schizophrenic adoptees in order to
learn how much of the well-known
familial tendency of schizophrenia
might be accounted for by genetic or
environmental factors (Kety 1959).
When, with the invaluable collaboration of Fini Schulsinger, the Danish
Adoption Registers were compiled,
first for Greater Copenhagen and
more recently for all of Denmark, we
were able to pursue these aims using
the diligently maintained Danish
records, exhaustive interviews by
Danish psychiatrists, and our
research design developed to
minimize ascertainment, selective,
and subjective bias.
In the study of adoptees born of a
schizophrenic parent (Rosenthal et al.
1968), diagnosis was not an
overriding issue since the aim was to
elicit the psychological characteristics
of the inherited diathesis. In the
study of the types and prevalence of
mental illness in the relatives of
schizophrenic adoptees (Kety et al.
1968), however, the issue of
diagnosis was a major one which had
to be settled before we could select
the probands. For defining schizophrenia, which was the subject of our
study, there was no DSM-IH to
make operational diagnoses economically on the basis of a small number
of criteria. Instead, we had the
exhaustive descriptions of Kraepelin
and Bleuler of the syndrome they had
defined and the designations and
sketches in DSM-I and the International Classification of Mental
Disorders (ICD) to denote accretions
to the original concepts. Our
individual definitions of schizophrenia varied widely by virtue of
our training and experience, from a
substantial reliance on Kraepelin and
Bleuler to the broader psychodynamic concepts which were taught
in the 1950s.
Although not all of us accepted
psychoses with acute onset and
prompt remission as forms of schizo-
Reprint requests should be sent to
Dr. S.S. Kety, Intramural Research Program, NIMH, Bldg. 10, Rm. 4C-110, 9000
Rockville Pike, Bethesda, MD 20205.
VOL 11, NO. 4, 1985
phrenia, we agreed to retain the
putative subgroup "acute schizophrenia," which was listed in DSM-I
and the ICD. We readily agreed to
include a latent form of schizophrenia, which we called "latent" or
"borderline" interchangeably since
Bleuler had recognized it, and the
ICD had retained and widened it to
include latent, pseudoneurotic and
pseudopsychopathic schizophrenia.
The proband schizophrenic adoptees
represented the gamut of schizophrenia diagnoses—chronic, acute,
and latent—accepted at that time by
the profession. In the case of the
relatives, a category called "uncertain
schizophrenia" had to be added if
relatives with less certain diagnoses
were not to be lost. In addition two
nonschizophrenic disorders most
resembling schizophrenia, schizoid
and inadequate personality, were
included in the spectrum of disorders
to be examined. I doubt that any of
us believed that all of these disorders
would be found to be related to
schizophrenia, but it would have
been inappropriate to exclude any
prematurely. Furthermore, if we kept
the different components separate,
we might eventually be able to
evaluate the relationship of each to
paradigmatic schizophrenia.
The hypothesis to be tested in the
1968 study was stated as follows: "If
schizophrenia were to some extent
genetically transmitted, there should
be a higher prevalence of disorders in
the schizophrenia spectrum among
the biological relatives of the index
cases than in those of their controls."
Blind consensus diagnoses based on
detailed abstracts of hospital records
found a prevalence of that spectrum
in the biological index relatives of 8.7
percent compared to 1.9 percent in
the biological relatives of the control
adoptees (p = .0072), the prevalence
in the adoptive index relatives being
no higher than that in their controls.
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Without the inclusion of the two
personality disorders, the prevalence
of schizophrenia in the biological
index and control relatives was 7.3
percent vs. 1.9 percent (p = .022),
and the hypothesis was upheld.
Although there were insufficient
cases to permit testing individual
components of the spectrum with any
reliability, we noted an absence of
any schizophrenic disorders in the 30
biological relatives of the 7 adoptees
diagnosed as acute schizophrenia,
while 10 of the 13 spectrum disorders
in the index biological relatives were
latent or uncertain schizophrenia—
our first indication that Bleuler was
correct in rejecting acute schizophrenia but asserting the existence
and prevalence of latent or
borderline forms of schizophrenia.
To come closer to defining the
boundaries of schizophrenia, it was
necessary to enlarge the sample or
obtain more information about the
mental and behavioral states of the
relatives. We decided to do both by
extending the study to all of
Denmark and by conducting
exhaustive interviews with the
relatives. We were fortunate when
Bjorn Jacobsen joined our collaboration and spent the next 3 years
interviewing the relatives in the
Copenhagen sample. The structured
interviews were more exhaustive than
the Schedule for Affective Disorders
and Schizophrenia-Lifetime Version
(SADS-L), which was not yet
available, extending to 36 or more
pages with numerous checklists and
extensive narrative elaborations. The
interview was designed to elicit
response on a complete range of
psychiatric symptoms and manifestations, particularly those which had
been recorded in schizophrenia and
schizophrenia-like syndromes. Dr.
Jacobsen succeeded in obtaining
interviews with 90 percent of the
relatives still alive and residing in
Scandinavia and partial interviews or
pertinent information in an additional 5 percent. The two recent
reports of failure to find evidence for
genetic transmission or even familial
clustering in schizophrenia (Pope et
al. 1982; Abrams and Taylor 1983)
used such seriously inadequate means
of ascertainment that negative results
would be expected.
The interviews were obtained by
Dr. Jacobsen with minimal knowledge of the relationship of the subject
to an index or control proband and
were analyzed in the United States by
three of us who were entirely
ignorant of the relationships. In the
cases where Dr. Jacobsen developed a
hunch about that relationship, it was
possible to show that his hunch did
not influence the diagnoses made by
the raters who read the interview,
and excluding those cases entirely did
not significantly alter the results
(Kety et al. 1975).
Analysis of the interviews
amplified the results obtained in the
same sample from hospital records
alone. The original spectrum was
significantly (p = .006) concentrated
as before in the biological relatives of
the schizophrenic adoptees, but now
instead of two cases of schizoid or
inadequate personality in the hospitalized relatives, 26 instances were
found among the nonhospitalized
relatives. These were divided evenly
between index and control relatives.
When these nondiscriminating
personality disorders were excluded,
the remaining diagnoses (which were
forms of DSM-I and the new
DSM-11 schizophrenia) were highly
concentrated in the biological
relatives of the schizophrenic
adoptees (p = .0004). There were no
diagnoses of chronic schizophrenia in
the biological relatives of the controls
but five cases of this most severe
form in the biological relatives of the
schizophrenic adoptees (p = .03).
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There were, moreover, a large
number of latent and uncertain
schizophrenias among the biological
relatives, highly concentrated in the
index relatives (11.0 percent vs. 3.4
percent, p = .005). When only
biological relatives of the 23 control
adoptees who were interviewed and
found to be free of schizoid or inadequate personality disorder were
included, the preponderance of latent
and uncertain schizophrenia in the
biological relatives of schizophrenic
adoptees was even more striking
(11.0 percent vs. 0.9 percent, p =
.0004) (Kety et al. 1975). The significance of those findings was not lost
on us.
The concept of latent schizophrenia
had been vaguely defined by Bleuler,
and our criteria for uncertain schizophrenia were equally ill defined—
enough of the features of schizophrenia to make that the most likely
diagnosis but not sufficiently severe
or typical to be certain. Despite this
vagueness, which could only increase
the opportunity for error and make it
more difficult to find a significant
difference, these diagnoses, made
blindly, were almost exclusively in
the biological relatives of the schizophrenic adoptees. Bleuler's recognition of a mild form of the disorder
in the relatives of severely ill schizophrenic patients and his observation
that it was considerably more
common in the severe form was
confirmed, this time in relatives who
grew up apart from the patient and
could not have been influenced by
the patients' thought processes and
behavior.
Although global diagnoses may
have great sensitivity and even specificity as these results indicate, there
is difficulty in describing the
particular criteria used and communicating them to others. Wender
attempted to characterize the
diagnoses we used in the first study,
SCHIZOPHRENIA BULLETIN
with moderate success (Kety et al.
1968), particularly for chronic and
acute schizophrenia. In the case of
latent or borderline schizophrenia,
Kendler (this issue) points out that
we placed an emphasis on positive
manifestations with an apparent
neglect of primary or negative
symptoms. It should be pointed out,
however, that all of the diagnoses in
that study, in relatives as well as the
adoptees, were made on people
whose mental disorder was severe
enough to require hospitalization,
and in those, positive symptoms
would be expected to predominate.
For our diagnoses made from interviews in the 1975 study, no characterizations were attempted. We used
the DSM-II description of latent
schizophrenia, schizoid and inadequate personality that was then in
use and we also took into account
Bleuler's description of the symptoms
of latent schizophrenia as he
observed them in the relatives of
overt schizophrenic patients. Bleuler's
description of latent schizophrenia
actually was the most useful guide
since only those observations, like
ours, had been made on individuals
not hospitalized or seeking treatment.
Our diagnoses of latent and
uncertain schizophrenia in the
relatives, therefore, included a
majority with flat affect, bizarre
thinking, poor contact, and poor
interpersonal relationships rather
than the positive symptoms which
appeared to characterize the
hospitalized group.
An opportunity to operationalize
our diagnoses of latent and uncertain
schizophrenia presented itself when
Robert Spitzer and Jean Endicott
offered to review the interviews in
which we had made those diagnoses
along with a comparable number in
which we had not. From an original
list of 17 items, they narrowed the
list to 8 discriminators. These items
became the DSM-lll criteria for
schizotypal personality disorder, a
category that combined the characteristics of our diagnoses of latent
and uncertain schizophrenia. It is
possible that the apparent neglect of
negative symptoms in the eight
criteria for schizotypal personality
disorder arose not so much from our
failure to observe them in the interviews and use them in our diagnoses
as from a relative overemphasis on
positive symptoms of schizophrenia
on the part of Spitzer and his
associates.
The criteria for schizotypal personality disorder were based on all of
our borderline and uncertain schizophrenia diagnoses (plus six diagnoses
of schizoid personality) and
confirmed by reference to the
concepts of a large number of
psychiatrists selected randomly
(Spitzer, Endicott, and Gibbon 1979).
Thus, they were not derived solely
from the genetic relatives of schizophrenic patients, which would have
given it some independent validity. It
is, however, better able to discriminate the genotype than any previous
descriptors. When Kendler and his
associates asked to review Jacobsen's
interviews for the possible
relationship of anxiety disorder to
schizophrenia, we asked them to
include other DSM-lll diagnoses,
particularly that of schizotypal
personality disorder (Kendler,
Gruenberg, and Strauss 1981). They
found a prevalence of 13.6 percent
for this syndrome in the biological
relatives of 16 adoptees diagnosed by
us and by Spitzer and associates as
chronic schizophrenia using the
Research Diagnostic Criteria
compared to 2 percent in the
biological relatives of unscreened
control adoptees (Kety 1983). Our
less operationalized diagnoses had
given prevalence rates for latent and
uncertain schizophrenia of 17.1
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VOL. 11, NO. 4, 1985
percent and 6.1 percent, respectively,
in the same populations. In their
hands, DSM-III had greater specificity but less sensitivity than our
global diagnoses. Later, when
Kendler and Gruenberg (1984) made
DSM-I11 diagnoses on the index
probands, the difference in
prevalence rates for schizotypal
personality disorder between
biological relatives of DSM-III
schizophrenic adoptees and control
biological relatives was even sharper.
The genetic relationship of schizotypal personality disorder (or the
latent and uncertain schizophrenias
on which it was based) to paradigmatic schizophrenia is clearly demonstrated by their high prevalence in
the biological relatives of adoptees
with chronic schizophrenia. Although
it may be true, as Torgersen (this
issue) indicates, that the reverse is
not the case, i.e., rarely is chronic
schizophrenia found in the relatives
of borderline schizophrenic
probands, that is hardly a basis for
rejecting a genetic relationship
between the two. There are obvious
statistical and genetic explanations
for Torgersen's observation. If
chronic schizophrenia is considerably
more rare than schizotypal personality disorder, the likelihood of
finding it in the relatives of latent
schizophrenics is considerably
diminished. In addition, it is easy to
think of types of genetic transmission
which would produce a similar
phenomenon. It would be expected in
polygenic transmission and in
recessive forms, if monogenic. One
would find numerous heterozygotes
for phenylketonuria (PKU) in the
families of PKU patients, but
practically no PKU in the families of
heterozygotes. Stone (1980) has
reported finding an excess of chronic
schizophrenia in the families of
borderline schizophrenics, indicating
that such occurrences may be rare
but not nonexistent. The fact that
chronic schizophrenic probands do
have schizotypal twins and relatives
is further assurance that there must
be schizotypal individuals who have
chronic schizophrenia in their
families. Finally, I can think of no
other explanation for the high prevalence of schizotypal personality
disorder in the biological relatives of
adopted chronic schizophrenics than
that the two disorders are genetically
associated.
There is no reason to feel,
however, that the eight criteria for
schizotypal personality disorder in
DSM-III represent the complete or
the best possible description of
Bleuler's latent schizophrenia. There
are undoubtedly many more characteristics of the nonpsychotic
genotypes of schizophrenia which
remain to be noted and evaluated.
The criteria should have been
developed more explicitly within the
biological relatives of schizophrenics,
thus using the genetic association to
contribute to the validity of the
syndrome—an opportunity that is
still rare in psychiatric nosology. The
work of Kendler and his associates
and that of Gunderson, Siever, and
Spaulding (1983) have been
important in further defining the
syndrome and staking out its limits.
The syndrome is in need of further
improvement, however, as is the
DSM-III definition of schizophrenia
(Kety 1985). The interviews now
being completed in the adoption
sample outside of Greater Copenhagen will soon be available for
evaluating improved concepts and
operational diagnoses of the components of the schizophrenia spectrum
which can now be validated.
References
Abrams, R., and Taylor, M.A. The
genetics of schizophrenia: A
reassessment using modern criteria.
American Journal of Psychiatry,
140:171-175, 1983.
Gunderson, J.G.; Siever, L.J.; and
Spaulding, E. The search for a
schizotype. Archives of General
Psychiatry, 40:15-22, 1983.
Kendler, K.S., and Gruenberg, A.M.
An independent analysis of the
Danish Adoption Study of schizophrenia: VI. The relationship
between psychiatric disorders as
defined by DSM-III in the relatives
and adoptees. Archives of General
Psychiatry, 41:555-564, 1984.
Kendler, K.S.; Gruenberg, A.M.; and
Strauss, J.S. An independent analysis
of the Copenhagen sample of the
Danish adoption study of schizophrenia: II. The relationship between
schizotypal personality disorder and
schizophrenia. Archives of General
Psychiatry, 38:982-984, 1981.
Kety, S.S. Biochemical theories of
schizophrenia: Part 2. Science,
129:1590-1596, 1959.
Kety, S.S. Mental illness in the
biological and adoptive relatives of
schizophrenic adoptees: Findings
relevant to genetic and environmental factors in etiology. American
Journal of Psychiatry, 140:720-727,
1983.
Kety, S.S. The concept of schizophrenia. In: Alpert, M., ed.
Controversies in Schizophrenia. New
York: Guilford Press, 1985.
pp. 3-11.
Kety, S.S.; Rosenthal, D.; Wender,
P.H.; and Schulsinger, F. The types
and prevalence of mental illness in
the biological and adoptive families
of adopted schizophrenics.
In: Rosenthal, D., and Kety, S.S.,
eds. The Transmission of Schizophrenia. Oxford: Pergamon Press,
1968. pp. 345-362.
Kety, S.S.; Rosenthal, D.; Wender,
P.H.; Schulsinger, F.; and Jacobsen,
SCHIZOPHRENIA BULLETIN
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B. Mental illness in the biological
and adoptive families of adoptive
individuals who have become schizophrenic: A preliminary report based
on psychiatric interviews. In: Fieve,
R.R.; Rosenthal, D.; and Brill, H.,
eds. Genetic Research in Psychiatry.
Baltimore: Johns Hopkins University
Press, 1975. pp. 147-165.
Pope, H.G., Jr.; Jonas, J.M.; Cohen,
B.M.; and Lipinski, J.F. Failure to
find evidence of schizophrenia in
first-degree relatives of schizophrenic
probands. American Journal of
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Videotapes on
Schizophrenia
Available
Rosenthal, D., ed. The Genain
Quadruplets. New York: Basic
Books, 1963.
Rosenthal, D.; Wender, P.H.; Kety,
S.S.; Schulsinger, F.; Welner, J.; and
Ostergaard, L. Schizophrenics'
offspring reared in adoptive homes.
In: Rosenthal, D., and Kety, S.S.,
eds. The Transmission of Schizophrenia. Oxford: Pergamon Press,
1968. pp. 377-391.
Spitzer, R.L.; Endicott, J.; and
Gibbon, M. Crossing the border into
borderline personality and borderline
schizophrenia: The development of
criteria. Archives of General
Psychiatry, 36:17-24, 1979.
Stone, M.H. The Borderline
Syndromes. New York: McGraw
Hill, 1980.
The Video Center of the George
Warren Brown School of Social
Work, in cooperation with several
community and mental health organizations, has produced four videotapes on the following topics relating
to survival issues for chronically
mentally ill persons and their families
in the community.
Coping With a Chronically
Mentally 111 Relative in the
Community—The two videotapes on
this topic were produced in cooperation with the Alliance for the
Mentally 111, St. Louis Chapter. Each
videotape presents the experiences of
a family which has had some success
surviving the multiple problems
arising from caring for a mentally ill
relative in the community. The
videotapes are intended for an
audience of parents and relatives of
chronically mentally ill persons who
could benefit from a vicarious
sharing of experiences with the
families on the videotapes.
Psychosocial Rehabilitation: Two
Agencies Based on the Fountain
House Model—These two videotapes
were produced in cooperation with
the Missouri Department of Mental
Health, Independence Center, and
Places for People, St. Louis, MO.
Each videotape presents a psychosocial rehabilitation agency from the
point of view of its members. The
tapes are intended for professional
audiences as well as for families and
mentally ill persons who could
benefit from knowing what it's like
to experience psychosocial rehabilitation "from the inside."
For more information about the
rental or purchase of these videotapes, please contact: Dr. David
Katz, Video Center, Box 1196,
Washington University, St. Louis,
MO 63130.
The Author
Seymour S. Kety, M.D., is Emeritus
Professor of Neuroscience, Harvard
University, and Senior Science
Advisor, National Institute of Mental
Health, Alcohol, Drug Abuse, and
Mental Health Administration,
Rockville, MD 20857.