Eye Tracking Impairment Patients With Schizotypal
in Clinically Personality
Identified Disorder
Larry J. Siever, M.D., Richard Keefe, M.A., David P. Bernstein, M.A., Emil F. Coccaro, M.D., Howard M. Kiar, M.D., Zvi Zemishlany, M.D., Ann E. Peterson, M.A., Michael Davidson, M.D., Theresa Mahon, B.A., Thomas Horvath, M.D., and Richard Mobs, Ph.D.
Eye tracking accuracy, which has been found to be impaired in schizophrenic patients and their relatives, was assessed in 26 patients with schizotypal personality disorder, 1 7 control subjects with other non-schizophrenia-related personality disorders, 29 normal control subjects, and 44 schizophrenic patients. Both schizotypal and schizophrenic patients, but not control subjects with other personality disorders, demonstrated significantly more impaired tracking than the normal control subjects. These results suggest that patients with clinically defined schizotypal personality disorder may be biologically related to schizophrenic patients as part ofa spectrum of schizophrenia-related disorders. (Am J Psychiatry 1990; 147:740-745)
T
he identification of the boundaries nia-related disorders is an important
to genetic etiology studies unteers should
and biologic
studies
of schizophrenia.
of relatives
aimed
While
of schizophreprerequisite
at delineating
genetic
of schizophrenic
and
patients
suggest that schizotypal personality be included as a schizophrenia-related
(1), questions
have
been
raised
the
biologic
and
vol-
disorder disorder
as to whether
schizo-
typal personality disorder as diagnosed in clinical populations is related to chronic schizophrenia (2). The demonstration of a biologic correlate of chronic schizophrenia in clinically diagnosed schizotypal patients would support the existence of such a relationship.
Impaired biologic tracking
eye tracking correlates impairment
Received
March
cepted
Nov.
17,
1989.
School
of Medicine,
2,
is one
of the most
of chronic schizophrenia. has been reported
1989; From
Bronx,
consistent While eye in psychotic
revision received Oct. 23, the Department of Psychiatry,
N.Y.,
and
Bronx
Medical
1989; acMt. Sinai
Center.
patients and patients with bipolar affective disorder (3), it appears to be state-related in these patients, possibly attributable to lithium treatment (4). There is not a high prevalence of eye tracking impairment in the relatives of bipolar patients (5). In schizophrenic patients, in contrast, the impairment persists in remission (6) and is increased in prevalence among their relatives (5). These observations suggest that eye tracking impairment is a state-independent correlate of schizophrenia that may reflect a genetic diathesis to the schizophrenia-related disorders, possibly as a reflection of an underlying autosomal dominant gene (7). Volunteers selected for their impaired eye tracking performance have been reported to have a greater prevalence of schizotypal personality disorder than do control subjects from the same population with highaccuracy eye tracking (8). Conversely, volunteers selected on the basis of high scores on the Chapman anhedonia scales demonstrated a higher prevalence of poor smooth pursuit eye movement performance than control subjects (9). Low-accuracy tracking in volunteers has been associated with schizotypal characteristics, most consistently with social isolation and anhedonia (8-11), but also with psychotic-like symptoms (11-13). These volunteer studies, however, cannot directly address the relationship of eye tracking impairment to clinically identified schizotypal personality disorder.
In order pairment disorder associated
were
to test the hypotheses
that
eye tracking
im-
is more prevalent in schizotypal personality patients than in normal control subjects and is with social isolation, schizotypal patients
compared
to
normal
tracking accuracy; subsidiary patients with other personality schizophrenia were used to specificity of any impairment.
control
subjects
comparison disorders explore the
for
eye
groups of and with diagnostic
Ad-
dress
reprint requests to Dr. Siever, Bronx VA Medical Center, Psychiatry Service, 1 16A, Bronx, NY 10468. Supported in part by Schizophrenia Biologic Research Center grant 412520 from the General Medical Research Service of the VA.
Gary Hilt, measurement. assessment.
740
M.A., and Wathina Philip Holzman,
Hill, M.D., facilitated eye tracking Ph.D., consulted on eye tracking
METHOD Twenty-six patients with schizotypal personality disorder were compared to 29 normal control subjects for accuracy of eye tracking. For comparison purposes,
Am
J
Psychiatry
1 47:6,
June
1990
SIEVER,
the
eye
tracking
accuracy
schizophrenia-related
of
17 patients
with
non-
personality
disorders
(all
other
informed
consent
was
obtained.
from the inpatient Veterans Administration Medical Center. Patients meeting DSM-III criteria for bipolar disorder and drug or alcohol abuse/ dependence were excluded from the study. The normal control subjects were recruited through newspaper advertisements. In order to exclude subjects with a personal or family history of psychiatric illness, including
two
both axis I and axis II disorders, all potential normal control subjects were interviewed by a psychiatrist (E.F.C. or Z.Z.). A comprehensive medical evaluation was performed to screen out subjects with medical illBoth
patients
and
control
subjects
were
kept
free
of all medications for 2 weeks before testing, with the exception of the schizophrenic patients, who may have received chloral hydrate but not within 12 hours of testing. All outpatients and normal control subjects were instructed to abstain from alcohol for 24 hours before testing. Research Diagnostic Criteria (RDC) were evaluated in the patients, using the Schedule for Affective Disorders
and
Schizophrenia
perienced and
raters
(SADS)
who
diagnoses
from
(14),
by two
independently a single
assigned
interview
blind,
ex-
raters
and
with
an
informant
close
ular focus on schizotypal mented with all available
personality clinical
to the
pa-
Interview for with a partic-
disorder, information.
suppleInter-
rater reliability for schizotypal personality disorder in a sample of 55 patients with personality disorder was strong (kappa=0.73). Test-retest reliability (after at least a 6-month interval) disorder in a subsample
for schizotypal of 12 of these
with an initial six with other
diagnosis of schizotypal initial axis II diagnoses)
strong
=
(kappa
from
the authors
pathologic
traits,
0.8 3). Seventeen
on request) such
as low
personality patients (six
personality and was comparably
dimensions
reflecting self-esteem
(available
general and
psychohostility,
derived from the subsections of the Structured Interview for the DSM-III Personality Disorders (15), were rated in 33 of the patients to evaluate the specificity of any relationship between schizotypal traits and tracking
accuracy.
To measure eye tracking accuracy, silver-silver chloride electrodes were placed at the outer canthus of each eye as well as at the middle of the forehead for a ground, and both eye position and velocity were measured chart
by electro-oculograph dynograph (8). The
pendulum 1 m away that 0.4 Hz with an amplitude
Am
J
Psychiatry
147:6,
(EOG) subjects
and recorded on watched a swinging
a
oscillated at a frequency of of 20#{176} of the visual angle.
June
1990
standard
deviations
from
the mean
of the normal
control subjects were compared by Fisher’s exact test. Correlations of the ratings of tracking accuracy with the schizotypal criterion of social isolation and the structured interview’s personality disorder dimension
of desired
level
of social
contact
were
evaluated
by the
Pearson correlation coefficient, and the entire set of schizotypal criteria were evaluated by stepwise multipie regression. Correlations between tracking accuracy and criteria for paranoid, borderline, and avoidant personality disorder were evaluated by the Pearson correlation coefficient to examine the specificity of the finding.
RESULTS
(kappa=0.80
tient by a third rater, using the Structured the DSM-III Personality Disorders (15),
AL.
criteria
for schizophrenia). DSM-III axis II diagnoses were derived from the consensus of interviews with the patient by two
El
ratings were determined from the average rating of tracings derived from two trials with a plain stimulus and a third with numbers affixed to the target by two independent raters (interrater reliability: kappa=0.93). The final rating was arrived at by consensus of the raters, with a third rater evaluating the record if the two original ratings were discrepant by more than one point. Mean qualitative ratings were compared between groups by an analysis of variance (ANOVA) with a post hoc Scheff#{233}contrast. The number and percentage of each patient cohort greater than or equal to one or
All of the patients were identified and outpatient units of the Bronx
ness.
BERNSTEIN,
Q ualitative
personality disorders except for paranoid and schizoid personality disorders) and 44 schizophrenic patients are also reported. All subjects participated in this study after
KEEFE,
No significant differences were observed between the patient groups on demographic characteristics (table 1). The mean±SD ages of the groups were as follows: schizotypal personality disorder, 35.3 ±6.4 years; other personality disorders, 35 .2 ± 6.4 years; and schizophrenia, 33.6±7.7 years. The mean number of personality disorders for the first two groups was 3.0±0.8 and 2.1±1.3 (t=-2.S0, df=41, pother
group>other
group two
personality
groups, group
to examine
disorder
cohorts
current or past history and the proportion did groups (table 1).
Both
schizophrenic
included
patients
with
a
of major depressive episodes, not significantly differ between
and
schizotypal
patient
groups
evidenced mean qualitative ratings that were significantly greater (i.e., worse tracking) than those of the normal control subjects (by Scheff#{233}contrasts); the other personality disorder patients did not significantly differ from the control subjects (table 2). The schizophrenic and schizotypal groups also included a significantly greater proportion of subjects with impaired tracking than did the normal control group (as defined by the number of cases falling one and two standard deviations beyond the normal mean); no such differences were observed in the patients with non-schizophrenia-related personality disorders. However, mean qualitative ratings for the patients with other personality disorders were intermediate between those of the schizotypal and normal control cohorts. The schizotypal personality disorder patients significantly differed from the normal control subjects in mean tracking accuracy whether or not they had a
742
to test
the
hypothesis
that
deficits
in eye
the relationship
of social
isolation
and
eye
accuracy within the context of the other DSM-III schizotypal criteria, a stepwise regression analysis was performed in which the order of entry was determined by the magnitude of the semipartial correlation of each schizotypal criterion with eye tracking accuracy. Of the eight schizotypal criteria, only one criterion, “social isolation,” met the p
in Clinically Personality
Identified Disorder
Larry J. Siever, M.D., Richard Keefe, M.A., David P. Bernstein, M.A., Emil F. Coccaro, M.D., Howard M. Kiar, M.D., Zvi Zemishlany, M.D., Ann E. Peterson, M.A., Michael Davidson, M.D., Theresa Mahon, B.A., Thomas Horvath, M.D., and Richard Mobs, Ph.D.
Eye tracking accuracy, which has been found to be impaired in schizophrenic patients and their relatives, was assessed in 26 patients with schizotypal personality disorder, 1 7 control subjects with other non-schizophrenia-related personality disorders, 29 normal control subjects, and 44 schizophrenic patients. Both schizotypal and schizophrenic patients, but not control subjects with other personality disorders, demonstrated significantly more impaired tracking than the normal control subjects. These results suggest that patients with clinically defined schizotypal personality disorder may be biologically related to schizophrenic patients as part ofa spectrum of schizophrenia-related disorders. (Am J Psychiatry 1990; 147:740-745)
T
he identification of the boundaries nia-related disorders is an important
to genetic etiology studies unteers should
and biologic
studies
of schizophrenia.
of relatives
aimed
While
of schizophreprerequisite
at delineating
genetic
of schizophrenic
and
patients
suggest that schizotypal personality be included as a schizophrenia-related
(1), questions
have
been
raised
the
biologic
and
vol-
disorder disorder
as to whether
schizo-
typal personality disorder as diagnosed in clinical populations is related to chronic schizophrenia (2). The demonstration of a biologic correlate of chronic schizophrenia in clinically diagnosed schizotypal patients would support the existence of such a relationship.
Impaired biologic tracking
eye tracking correlates impairment
Received
March
cepted
Nov.
17,
1989.
School
of Medicine,
2,
is one
of the most
of chronic schizophrenia. has been reported
1989; From
Bronx,
consistent While eye in psychotic
revision received Oct. 23, the Department of Psychiatry,
N.Y.,
and
Bronx
Medical
1989; acMt. Sinai
Center.
patients and patients with bipolar affective disorder (3), it appears to be state-related in these patients, possibly attributable to lithium treatment (4). There is not a high prevalence of eye tracking impairment in the relatives of bipolar patients (5). In schizophrenic patients, in contrast, the impairment persists in remission (6) and is increased in prevalence among their relatives (5). These observations suggest that eye tracking impairment is a state-independent correlate of schizophrenia that may reflect a genetic diathesis to the schizophrenia-related disorders, possibly as a reflection of an underlying autosomal dominant gene (7). Volunteers selected for their impaired eye tracking performance have been reported to have a greater prevalence of schizotypal personality disorder than do control subjects from the same population with highaccuracy eye tracking (8). Conversely, volunteers selected on the basis of high scores on the Chapman anhedonia scales demonstrated a higher prevalence of poor smooth pursuit eye movement performance than control subjects (9). Low-accuracy tracking in volunteers has been associated with schizotypal characteristics, most consistently with social isolation and anhedonia (8-11), but also with psychotic-like symptoms (11-13). These volunteer studies, however, cannot directly address the relationship of eye tracking impairment to clinically identified schizotypal personality disorder.
In order pairment disorder associated
were
to test the hypotheses
that
eye tracking
im-
is more prevalent in schizotypal personality patients than in normal control subjects and is with social isolation, schizotypal patients
compared
to
normal
tracking accuracy; subsidiary patients with other personality schizophrenia were used to specificity of any impairment.
control
subjects
comparison disorders explore the
for
eye
groups of and with diagnostic
Ad-
dress
reprint requests to Dr. Siever, Bronx VA Medical Center, Psychiatry Service, 1 16A, Bronx, NY 10468. Supported in part by Schizophrenia Biologic Research Center grant 412520 from the General Medical Research Service of the VA.
Gary Hilt, measurement. assessment.
740
M.A., and Wathina Philip Holzman,
Hill, M.D., facilitated eye tracking Ph.D., consulted on eye tracking
METHOD Twenty-six patients with schizotypal personality disorder were compared to 29 normal control subjects for accuracy of eye tracking. For comparison purposes,
Am
J
Psychiatry
1 47:6,
June
1990
SIEVER,
the
eye
tracking
accuracy
schizophrenia-related
of
17 patients
with
non-
personality
disorders
(all
other
informed
consent
was
obtained.
from the inpatient Veterans Administration Medical Center. Patients meeting DSM-III criteria for bipolar disorder and drug or alcohol abuse/ dependence were excluded from the study. The normal control subjects were recruited through newspaper advertisements. In order to exclude subjects with a personal or family history of psychiatric illness, including
two
both axis I and axis II disorders, all potential normal control subjects were interviewed by a psychiatrist (E.F.C. or Z.Z.). A comprehensive medical evaluation was performed to screen out subjects with medical illBoth
patients
and
control
subjects
were
kept
free
of all medications for 2 weeks before testing, with the exception of the schizophrenic patients, who may have received chloral hydrate but not within 12 hours of testing. All outpatients and normal control subjects were instructed to abstain from alcohol for 24 hours before testing. Research Diagnostic Criteria (RDC) were evaluated in the patients, using the Schedule for Affective Disorders
and
Schizophrenia
perienced and
raters
(SADS)
who
diagnoses
from
(14),
by two
independently a single
assigned
interview
blind,
ex-
raters
and
with
an
informant
close
ular focus on schizotypal mented with all available
personality clinical
to the
pa-
Interview for with a partic-
disorder, information.
suppleInter-
rater reliability for schizotypal personality disorder in a sample of 55 patients with personality disorder was strong (kappa=0.73). Test-retest reliability (after at least a 6-month interval) disorder in a subsample
for schizotypal of 12 of these
with an initial six with other
diagnosis of schizotypal initial axis II diagnoses)
strong
=
(kappa
from
the authors
pathologic
traits,
0.8 3). Seventeen
on request) such
as low
personality patients (six
personality and was comparably
dimensions
reflecting self-esteem
(available
general and
psychohostility,
derived from the subsections of the Structured Interview for the DSM-III Personality Disorders (15), were rated in 33 of the patients to evaluate the specificity of any relationship between schizotypal traits and tracking
accuracy.
To measure eye tracking accuracy, silver-silver chloride electrodes were placed at the outer canthus of each eye as well as at the middle of the forehead for a ground, and both eye position and velocity were measured chart
by electro-oculograph dynograph (8). The
pendulum 1 m away that 0.4 Hz with an amplitude
Am
J
Psychiatry
147:6,
(EOG) subjects
and recorded on watched a swinging
a
oscillated at a frequency of of 20#{176} of the visual angle.
June
1990
standard
deviations
from
the mean
of the normal
control subjects were compared by Fisher’s exact test. Correlations of the ratings of tracking accuracy with the schizotypal criterion of social isolation and the structured interview’s personality disorder dimension
of desired
level
of social
contact
were
evaluated
by the
Pearson correlation coefficient, and the entire set of schizotypal criteria were evaluated by stepwise multipie regression. Correlations between tracking accuracy and criteria for paranoid, borderline, and avoidant personality disorder were evaluated by the Pearson correlation coefficient to examine the specificity of the finding.
RESULTS
(kappa=0.80
tient by a third rater, using the Structured the DSM-III Personality Disorders (15),
AL.
criteria
for schizophrenia). DSM-III axis II diagnoses were derived from the consensus of interviews with the patient by two
El
ratings were determined from the average rating of tracings derived from two trials with a plain stimulus and a third with numbers affixed to the target by two independent raters (interrater reliability: kappa=0.93). The final rating was arrived at by consensus of the raters, with a third rater evaluating the record if the two original ratings were discrepant by more than one point. Mean qualitative ratings were compared between groups by an analysis of variance (ANOVA) with a post hoc Scheff#{233}contrast. The number and percentage of each patient cohort greater than or equal to one or
All of the patients were identified and outpatient units of the Bronx
ness.
BERNSTEIN,
Q ualitative
personality disorders except for paranoid and schizoid personality disorders) and 44 schizophrenic patients are also reported. All subjects participated in this study after
KEEFE,
No significant differences were observed between the patient groups on demographic characteristics (table 1). The mean±SD ages of the groups were as follows: schizotypal personality disorder, 35.3 ±6.4 years; other personality disorders, 35 .2 ± 6.4 years; and schizophrenia, 33.6±7.7 years. The mean number of personality disorders for the first two groups was 3.0±0.8 and 2.1±1.3 (t=-2.S0, df=41, pother
group>other
group two
personality
groups, group
to examine
disorder
cohorts
current or past history and the proportion did groups (table 1).
Both
schizophrenic
included
patients
with
a
of major depressive episodes, not significantly differ between
and
schizotypal
patient
groups
evidenced mean qualitative ratings that were significantly greater (i.e., worse tracking) than those of the normal control subjects (by Scheff#{233}contrasts); the other personality disorder patients did not significantly differ from the control subjects (table 2). The schizophrenic and schizotypal groups also included a significantly greater proportion of subjects with impaired tracking than did the normal control group (as defined by the number of cases falling one and two standard deviations beyond the normal mean); no such differences were observed in the patients with non-schizophrenia-related personality disorders. However, mean qualitative ratings for the patients with other personality disorders were intermediate between those of the schizotypal and normal control cohorts. The schizotypal personality disorder patients significantly differed from the normal control subjects in mean tracking accuracy whether or not they had a
742
to test
the
hypothesis
that
deficits
in eye
the relationship
of social
isolation
and
eye
accuracy within the context of the other DSM-III schizotypal criteria, a stepwise regression analysis was performed in which the order of entry was determined by the magnitude of the semipartial correlation of each schizotypal criterion with eye tracking accuracy. Of the eight schizotypal criteria, only one criterion, “social isolation,” met the p
