Article

Smooth Pursuit Eye-Tracking Impairment

in Childhood-Onset Psychotic Disorders

Sanjiv Kumra, M.D., F.R.C.P. Objective: Although childhood-onset
schizophrenia is relatively rare, a sizable
group of children with severe emotional
Alexandra Sporn, M.D.
disturbances have transient psychotic
symptoms that fall outside of current syn-
Daniel W. Hommer, M.D.
drome boundaries. The relationship of this
Robert Nicolson, M.D. group of children to those with childhood-
onset schizophrenia and other childhood
psychiatric disorders is unclear. In this
Gunvant Thaker, M.D.
study, the authors compared smooth pur-
suit eye tracking, a biological trait marker
Elizabeth Israel, B.A.
associated with schizophrenia, of children
and adolescents with psychotic disorder
Marge Lenane, M.S.W.
not otherwise specified to that of children
with childhood-onset schizophrenia and
Jeffrey Bedwell, B.S.
healthy comparison subjects.
Leslie K. Jacobsen, M.D. Method: By means of infrared oculogra-
phy, smooth pursuit eye movements dur-
Peter Gochman, B.A. ing a 17°/second visual pursuit task were
quantitatively and qualitatively com-
Judith L. Rapoport, M.D. pared in 55 young adolescents (29 with
childhood-onset schizophrenia and 26
with psychotic disorder not otherwise
specified) and their respective indepen-
dent healthy comparison groups (a total
of 38 healthy subjects).
Results: Subjects with childhood-onset
schizophrenia had qualitatively poorer
eye tracking, higher root mean square er-
ror, lower gain, and a greater frequency
of catch-up saccades than healthy chil-
dren. Subjects with psychotic disorder not
otherwise specified also had qualitatively
poorer eye tracking, higher root mean
square error, and lower gain than healthy
children, but saccade frequency did not
differ significantly.
Conclusions: Children with childhood-
onset schizophrenia exhibit a pattern of
eye-tracking dysfunction similar to that
reported for adult patients. Similar abnor-
malities were seen in the subjects with
psychotic disorder not otherwise specified
except that they did not exhibit a greater
frequency of catch-up saccades. Prospec-
tive longitudinal neurobiological and clin-
ical follow-up studies of both groups are
currently underway to further validate
the distinction between these two disor-
ders. Also, family studies are planned to
establish whether eye-tracking dysfunc-
tion represents a trait- or state-related
phenomenon in subjects with psychotic
disorder not otherwise specified.

(Am J Psychiatry 2001; 158:1291–1298)

A cross all of medicine, the study of individuals with an

early onset of a multifactorial disorder has been an impor-
tant approach used to minimize heterogeneity and possi-
bly identify unique or more salient risk factors. Since 1990,
a study of childhood-onset schizophrenia (onset of psy-
chotic symptoms by age 12) has been ongoing at the Na-
tional Institute of Mental Health (NIMH) (1). These clinical
and neurobiological studies have provided support for the
continuity of childhood-onset schizophrenia with later-
onset schizophrenia (2). The fact that childhood-onset
schizophrenia is often chronic and refractory and that it
may be associated with higher rates of familial “schizo-
phrenia spectrum disorders” has led to the speculation
that this form of the disorder may represent a particularly
severe variant with a stronger genetic predisposition (2).
Perhaps because of its relative rarity, childhood-onset
schizophrenia is frequently misdiagnosed (3). As part of our
search for subjects with childhood-onset schizophrenia, it
became apparent from chart review or in-person examina-
tions that most patients with a referring diagnosis of child-
hood-onset schizophrenia had other disorders (3). Within
this group, a relatively large number of children with severe
emotional disturbances reported brief, intermittent psy-
chotic symptoms that did not meet the DSM-III-R/DSM-IV
duration or severity criteria for schizophrenia.
Children with atypical or subclinical psychotic symp-
toms have been well recognized but difficult to classify (4,
5). Because of the clinical heterogeneity of this group, a
subgroup from the larger population of children with
psychotic disorder not otherwise specified, provisionally
labeled “multidimensionally impaired,” was studied as a
parallel group to the childhood-onset schizophrenia
group (3, 6, 7). Children from this psychotic disorder not
otherwise specified subgroup shared a number of phe-
nomenological similarities with the childhood-onset
schizophrenia patients, including prepsychotic linguistic
deficits (6), higher rate of schizophrenic spectrum disor-
ders in first-degree relatives (6), a generalized pattern of
cognitive deficits (8), and quantitative structural brain ab-
normalities (e.g., enlarged lateral ventricles and smaller

Am J Psychiatry 158:8, August 2001 1291

EYE-TRACKING IMPAIRMENT IN CHILDHOOD PSYCHOSIS
total cerebral volume) seen at initial magnetic resonance
imaging (MRI) scan (9). In contrast, a 2–8 year prospective
clinical follow-up study of 27 of these subjects with this
psychotic disorder not otherwise specified subtype
showed that psychotic symptoms had been transient and
that none had progressed to schizophrenia (7). Moreover,
at follow-up about 50% of these subjects met criteria for
an affective disorder (7).
Eye-tracking dysfunction characterized by a disturbance
in the smooth pursuit system has been found in 21%–85%
of schizophrenic patients and in 8% of the normal popula-
tion (10, 11). Similar eye-tracking dysfunction has also
been observed in 19%–34% of the biological first-degree
relatives of schizophrenic patients (11–14) and in children
of schizophrenic patients (15). Studies of psychotic pa-
tients have yielded inconsistent results about whether
smooth pursuit eye-tracking dysfunction is specific to
schizophrenia (11, 12, 14) or if it is associated with other
nonaffective psychoses (11, 16–18). These discrepant find-
ings may reflect problems with sample size or varying diag-
nostic criteria or methodology across studies (11).
In a preliminary report, the oculomotor performance of
our first 17 patients with childhood-onset schizophrenia
(onset of psychotic symptoms before age 12) was charac-
terized by significantly lower gain (ratio of eye velocity to
target velocity), higher root mean square error (extent to
which eyes do not reproduce target motion), lower per-
centage of total task time engaged in tracking the target,
and a greater frequency of anticipatory saccades than
healthy comparison subjects (19). In contrast, there were
no significant differences in gain scores or any saccade
frequency between subjects with attention deficit hyper-
activity disorder (ADHD) and healthy comparison sub-
jects, although the ADHD subjects had higher root mean
square error. This study was limited, however, by the use of
two different recording systems and the lack of a qualita-
tive rating system to characterize smooth pursuit eye
tracking. More recently, similar abnormalities were found
in a separate group of 10 childhood-onset schizophrenia
subjects for whom higher rates of familial eye-tracking ab-
normalities were also seen (20).
In this report we focus on one specific neurobiological
trait—eye-tracking dysfunction—as part of a program ex-
amining the neurobiological characteristics associated
with childhood-onset schizophrenia and psychotic disor-
der not otherwise specified to help differentiate them
from each other. The present study compared the oculo-
motor performance of an expanded cohort of 29 subjects
with childhood-onset schizophrenia to that of 20 healthy
comparison subjects similar in age distribution and gen-
der proportion. In addition, the smooth pursuit eye track-
ing of a subgroup of 26 subjects with psychotic disorder
not otherwise specified was compared to a separate group
of 18 healthy subjects also matched for age and gender to
see if the between-group differences resembled those
seen with childhood-onset schizophrenia.
1292
Method
Subjects
The recruitment and diagnostic procedures have been de-
scribed previously (3). These are summarized briefly herein, and
the methods for the eye-tracking procedure are given in more de-
tail. All subjects and their parents gave informed assent/consent
before participation. This protocol was approved by the NIMH In-
ternal Review Board.
Male and female patients age 6 to 18 diagnosed with schizo-
phrenia whose onset of psychotic symptoms occurred by age 12
were recruited through national professional and patient advo-
cacy organizations for participation in an inpatient trial of an
atypical neuroleptic. A premorbid IQ of less than 70 and the pres-
ence of active medical or neurological disorders were exclusion-
ary. A primary diagnosis of pervasive developmental disorder,
dissociative disorder, mood disorder, conduct disorder, or per-
sonality disorder was also exclusionary.
From 950 referrals, over 600 charts were reviewed, and 200 pa-
tients and their families were seen in person. Admission to the
study followed a detailed screening examination, which included
a review of old charts and clinical and structural interviews with
parents and child.
Childhood-Onset Schizophrenia Subjects
Seventy children and adolescents were diagnosed at the
screening examination with childhood-onset schizophrenia, but
six patients did not participate because of clinical reasons (e.g.,
loss of residential placement, parental reluctance). Of the 64 re-
maining subjects, 34 underwent the eye-tracking task, but three
patients were subsequently excluded because of poor tracings re-
sulting from either machine failure or excessive head motion. The
records for two additional patients were excluded from this anal-
ysis because of inattention or lack of motivation during the task
determined by visual inspection of the tracing. Thus, data for 29
subjects with childhood-onset schizophrenia are included in this
report. To optimize performance, subjects were tested during the
last week of an atypical neuroleptic trial. Of these 29 patients, 15
were receiving medications known to affect eye-tracking perfor-
mance such as clozapine or a benzodiazepine (10, 21, 22). The re-
maining patients were being treated with olanzapine or a typical
neuroleptic.
Psychotic Disorder Not Otherwise Specified Subjects
Thirty-one children who were referred with a diagnosis of
childhood-onset schizophrenia for an inpatient trial of an atypi-
cal neuroleptic were felt to fall under DSM-III-R or DSM-IV crite-
ria for psychotic disorder not otherwise specified and were la-
beled by our group as being “multidimensionally impaired” (3).
Based on 71 consecutive referrals to the NIMH childhood-onset
schizophrenia study, this multidimensionally impaired subgroup
was reliably diagnosed (kappa=0.81) according to empirically
derived criteria (3) and was distinguishable from children with
overlapping clinical presentations (e.g., ADHD, bipolar disorder,
nonautistic forms of pervasive developmental disorder). This
psychotic disorder not otherwise specified subgroup reported
brief hallucinations and delusions that occurred a few times a
month, typically under stress, and showed no evidence of thought
disorder (3). Although their psychotic symptoms were ego-dys-
tonic and impaired their functioning, these intermittent prob-
lems were less the focus of concern than were their dramatic
mood outbursts and periodic aggression, which had necessitated
frequent psychiatric hospitalizations. These children lacked the
striking and pervasive disturbances in cognition, defective emo-
tional rapport, bizarre hallucinations, and delusions that charac-
terized the subjects with childhood-onset schizophrenia. They
were socially deficient but eagerly sought social interactions and
Am J Psychiatry 158:8, August 2001

were distressed by their frequent peer rejection. Although the dis-
torted reality and affective lability of this group suggested border-
line or schizotypal personality disorder, none of the children
given a diagnosis of psychotic disorder not otherwise specified
met criteria for these disorders (3, 6).
Five children with psychotic disorder not otherwise specified
did not participate in this study because of clinical considerations
(previous head trauma [N=1], age below 8 at time of testing [N=1])
or poor tracings resulting from machine failure or excessive head
motion (N=3).
Smooth pursuit eye-tracking data were obtained for 26 sub-
jects with psychotic disorder not otherwise specified (22 male,
four female). The testing for the patients was completed during
the first 2 weeks of their inpatient admission while they were on a
stable medication regimen. Of the psychotic disorder not other-
wise specified patients, two were receiving medications (lithium
or carbamazepine) known to affect eye-tracking performance
(10) as part of their medication regimen.
Healthy Volunteers
Healthy comparison subjects for both patient groups were se-
lected from an ongoing NIMH study of brain development in chil-
dren and adolescents (23). Any physical or neurological disorder, a
lifetime history of any psychiatric disorder, or a history of a major
psychiatric disorder in first-degree relatives was exclusionary. For
this carefully screened group approximately one in six contacts
were accepted for the study. From a pool of 38 healthy volunteers
who agreed to participate in this study, 18 subjects were selected
as comparison subjects for the psychotic disorder not otherwise
specified group, and 20 subjects were selected as comparison sub-
jects for the childhood-onset schizophrenia group on the basis of
age and gender. All volunteers were seen as outpatients.
Behavioral, Cognitive, and MRI Assessments
From the literature, the following clinical and neurobiological
measures were available for correlative analyses with eye-track-
ing variables: age at study (24), full-scale IQ (25), and clinical rat-
ings of symptom severity from the Scale for the Assessment of
Negative Symptoms (26, 27). Exploratory analyses of neuropsy-
chological data (tests that measured six cognitive domains:
speeded visual-motor processing and attention, abstraction-flex-
ibility, verbal intelligence and language, spatial organization, ver-
bal learning, and visual learning) (8) and eye-tracking measures
were also planned for this study.
Eye-Tracking Procedure
Eye movements were recorded in a quiet, darkened room with
an infrared limbus detection eye-tracking device (Eye Trac Model
210, Applied Science Laboratories, Waltham, Mass.). Subjects
wore goggles with infrared sources and sensors mounted on the
inside. The sensors require no mechanical calibration, making
the device convenient for use with subjects. This device has a re-
sponse time constant of 4 msec, an accuracy of better than 0.25 of
visual angle, and a range of 15° to the left and right of center. Elec-
tronic calibration was accomplished by having the subject fixate
on a series of sequentially presented white square targets (each
subtending a visual angle of less than 2.5°) displayed on a black
background for 2 seconds at 7.5° intervals horizontally across the
video monitor. This calibration procedure was run at the begin-
ning of each eye movement task. The subjects were seated 57 cm
away from a computer monitor on which a small bright white tar-
get was displayed against a black background. The subjects’
heads were secured by a biteplate. Analog output of the infrared
tracking device was sampled at 1000 Hz by using an 8-bit analog-
to-digital converter and was stored for subsequent analysis.
Before each trial, the subjects were given a verbal description
of the task followed by a demonstration on the computer monitor
Am J Psychiatry 158:8, August 2001
KUMRA, SPORN, HOMMER, ET AL.
while the procedure was described again. During this description,
subjects were instructed to keep their eyes on the target and fol-
low it as closely as possible.
Eye tracking was recorded during a smooth pursuit task in
which subjects followed a target moving horizontally across the
screen at a constant velocity of 17°/second. The target stopped
15° to the left and right of center and remained stationary for ap-
proximately 1 second at the end of each ramp. The constant hori-
zontal velocity combined with fixation points at the end of each
ramp created a trapezoidal waveform of target and eye motions.
The fixation points between each ramp were used for further cal-
ibration before data analysis.
Each trial consisted of 10 full ramps with a partial ramp before
the first full ramp and following the last full ramp. The two half-
ramps were excluded from the analysis, leaving 10 ramps for
quantitative and qualitative analysis.
Eye Movement Analysis
Eye movement data were analyzed with pattern-recognition
computer software described elsewhere (28, 29). The raw data
consisted of eye- and target-position values for each millisecond
of recorded tracking, which could be displayed on a computer
screen as a plot of eye position versus time. Since the initiation of
smooth pursuit is quite different from its maintenance, we ex-
cluded the 250 msec preceding or following changes in target di-
rection from the analysis. Sequential manipulations were per-
formed on the remaining data to isolate saccades from true
pursuit and artifacts. First, for each millisecond the velocity of the
tracking was calculated by subtracting the position value at 5
msec before the given point from the position value at 5 msec af-
ter the given point and dividing the result by 10 msec. The next
step was identifying the saccades. This was done by using an au-
tomated procedure that labeled as saccades local peaks in eye ve-
locity that were at least twice the variance of the local velocity.
This approach allows reliable identification of saccades as small
as 0.4° even during smooth pursuit. Presaccadic and postsaccadic
position errors were determined 5 msec before the beginning and
5 msec after the end of the saccade, respectively. High-velocity in-
tervals with a peak velocity greater than 850°/second or those that
were immediately followed by another high-velocity interval in
the opposite direction were discarded as artifacts. Both phases of
any biphasic pattern were discarded, since preliminary studies
(in which subjects purposely blinked) indicated that this pattern
represents eye blinks. Following this computer analysis, each file
was checked by the raters for missed blinks or artifacts or inap-
propriately labeled artifacts. Those areas determined to be head
movement or moments of inattention were manually labeled as
artifacts before the final computer calculations were completed.
All intervals of eye tracking not meeting the above criteria for be-
ing high-velocity interval or artifact were considered to be
smooth pursuit eye movement. Since we were interested in mea-
suring smooth pursuit eye movement only when actively pursued
targets were properly visualized by the fovea, we excluded from
analysis intervals in which smooth pursuit eye movement veloc-
ity was less than 5°/second or smooth pursuit eye movement po-
sition error (eye position subtracted from target position) was
greater than 2.5°, which is the radius of the fovea in humans.
Quantitative eye movement variables and saccade classifi-
cation system. Quantitative variables were defined as follows.
Smooth pursuit eye movement gain was defined as the ratio of
eye velocity to target velocity of each separate smooth pursuit eye
movement interval, averaged across intervals. Saccades were ob-
tained by tabulating the number of all intervals considered to be
saccades according to the criteria stated above (i.e., high-velocity
intervals with simple uniphasic pattern). In addition, saccades
were subclassified as catch-up and anticipatory saccades by their
direction in relation to target motion and presaccadic and post-
1293
EYE-TRACKING IMPAIRMENT IN CHILDHOOD PSYCHOSIS

TABLE 1. Demographic and Clinical Characteristics of Patients With Childhood-Onset Schizophrenia, Psychotic Disorder
Not Otherwise Specified, and Respective Healthy Comparison Groups
Childhood-Onset Schizophrenia Psychotic Disorder Not Otherwise Specified
Patient Comparison Patient Comparison
Group Group Group Group
Characteristic (N=29) (N=20) Analysis (N=26) (N=18) Analysis
N % N % χ2 df p N % N % χ2 df p

Gender 0.1 1 0.90 1.0 1 0.45

Male 16 55.2 11 55.0 22 84.6 13 72.2
Female 13 44.8 9 45.0 4 15.4 5 27.8
Ethnicity 1.7 3 0.60 2.4 3 0.51
Caucasian 16 55.2 13 65.0 21 80.8 14 77.7
African American 5 17.2 4 20.0 1 3.8 2 11.1
Hispanic 3 10.3 2 10.0 2 7.7 0 0.0
Other 5 17.2 1 5.0 2 7.7 2 11.1

Mean SD Mean SD t df p Mean SD Mean SD t df p

Age (years) 14.6 2.5 14.6 2.3 0.1 47 0.90 13.7 3.5 13.1 3.4 0.6 42 0.50
Vocabulary score (WISC-R)a 7.3 3.7 11.2 2.1 3.2 35 0.003 7.8 3.1 15.8 2.5 4.9 28 <0.001
Block design score (WISC-R)b 7.3 3.8 12.1 2.9 3.8 38 0.001 8.4 9.2 16.0 2.4 3.5 28 0.002
Reading decoding scorec 90.6 15.8 — — 83.5 24.3 — —
Age at onset of psychosis (years) 10.3 1.8 7.6 1.9
Length of neuroleptic treatment (months) 25.0 16.6 25.8 23.0
Length of psychiatric hospitalization (months) 5.5 10.9 5.4 11.8
BPRS score 40.6 10.7 — — 31.1 6.9 — —
a Schizophrenic patients, N=27; schizophrenic comparison group, N=10; comparison group for the subjects with psychotic disorder not oth-
erwise specified, N=4.
b N=11 and N=4 for the comparison groups of the subjects with schizophrenia and psychotic disorder not otherwise specified, respectively.
c From the Kaufman Test of Educational Achievement (33); for the schizophrenic patients, N=27.

saccadic position errors. Saccades in the direction of the target
motion that started and ended behind the target, and saccades
that ended ahead of the target but with at least two-thirds of their
saccadic amplitude-moving gaze toward the target, were classi-
fied as catch-up saccades. Saccades in the direction of target mo-
tion that ended ahead of the target and were followed by a 50
msec interval of eye velocity of less than 5°/second were classified
as anticipatory saccades. Anticipatory saccades that were greater
than 4° were subclassified as large anticipatory saccades. Saccade
rates were determined by dividing the number of saccades by the
pursuit duration.
Root mean square error, which provides a global measure of
the extent to which the eyes do not reproduce target motion (30),
was calculated by squaring the difference between eye position
and target position for all intervals of nonartifactual pursuit
tracking, and then obtaining the average of the square root of
these numbers. Split-half reliability (intraclass correlation coeffi-
cient [ICC]) for quantitative variables was high (ICC=0.75–0.96).
Qualitative eye movement analysis. Each ramp was scored
qualitatively by one of the authors (R.N.) blind to patient identity
on a scale of 1 (best) to 5 (worst) (31). Two of the authors (R.N.,
A.S.) rated a subset of this sample (N=10) with high reliability
(ICC=0.98). The average of 10 ramps was determined for each
subject and used as the primary qualitative measure of eye-track-
ing dysfunction. Additionally, subjects with a mean score of 2.5 or
greater were classified as having abnormal eye tracking. Qualita-
tive ratings for all 93 subjects (26 with psychotic disorder not oth-
erwise specified, 29 with childhood-onset schizophrenia, 38
healthy volunteers) were highly correlated with gain (r=0.83, df=
91, p<0.001) and with root mean square error (r=0.77, df=91, p=
0.0001).
Data Analyses
Analyses were performed with SPSS statistical analysis soft-
ware (32). To examine demographic differences between psy-
chotic disorder not otherwise specified patients and healthy
comparison subjects, t tests or chi-square analyses were used de-
pending on data distribution and type. Distributions for all eye-
tracking variables were examined within each group for signifi-
cant skew, kurtosis, and heterogeneity of variance. Because the
data for three of six eye-tracking variables from both the psy-
chotic disorder not otherwise specified patients and the healthy
volunteers were not normally distributed, data were analyzed by
using the Mann-Whitney U test.
Spearman rank correlation coefficients, with partial correction
for age, tested relationships between eye-tracking measures that
differed significantly from those of healthy volunteers and clinical
measures that might be related to eye-tracking performance.
Results
As seen in Table 1, the patients with childhood-onset
schizophrenia and psychotic disorder not otherwise spec-
ified performed more poorly on the WISC-R vocabulary
and block design subtests than did the healthy volunteers.
Because there were no significant group differences in age
or gender distribution between the two patient groups
and their respective healthy volunteers, comparative anal-
yses are unadjusted.
Eye-Tracking Performance
Significantly poorer qualitative ratings were seen among
the childhood-onset schizophrenia patients than in the
healthy volunteers (Table 2). Significantly more subjects
with childhood-onset schizophrenia (79.3%, N=23 of 29)
than the healthy volunteers (20.0%, N=4 of 20) were found
to have eye-tracking dysfunction (χ2=14.3, df=1, p<0.01).
The qualitative eye-tracking scores were also significantly
worse in the patients with psychotic disorder not otherwise

1294 Am J Psychiatry 158:8, August 2001


specified than in the healthy volunteers. Significantly more
subjects with psychotic disorder not otherwise specified
(65.4%, N=17 of 26) than healthy volunteers (11.1%, N=2 of
18) had eye-tracking dysfunction (χ2=12.77, df=1, p<0.001).
For the 17°/second visual pursuit task, the subjects
with childhood-onset schizophrenia and those with psy-
chotic disorder not otherwise specified had significantly
higher root mean square error than their respective
healthy comparison groups. Significant differences in
gain were also noted, with gain being lower in both pa-
tient groups (Table 2).
After removing the 15 patients who were being treated
with clozapine or a benzodiazepine, root mean square er-
ror remained significantly higher in the childhood-onset
schizophrenia patients relative to the healthy comparison
volunteers (U=37.0, df=32, p<0.001). Between-group sig-
nificant differences for the other eye-tracking characteris-
tics also held: gain (U=72.5, df=32, p<0.02), qualitative
score (U=14.0, df=32, p<0.001), saccade rate (U=72.0, df=
32, p<0.02), and rate of catch-up saccades (U=82.0, df=32,
p<0.05). For the subjects with psychotic disorder not other-
wise specified, after removing the two patients who were
receiving lithium or carbamazepine, between-group sig-
nificant differences in root mean square error, qualitative
score, and gain remained (U=96.0, df=40, p=0.002; U=63.0,
df=40, p<0.001; and U=111.2, df=40, p=0.008, respectively).
Relationship Between Eye Tracking, Age,
and Clinical Measures
For the entire group of healthy comparison subjects (N=
38), age was not significantly correlated with root mean
square error (rs =–0.24, p=0.15), gain (r s=0.26, p=0.11),
qualitative score (rs =–0.15, p=0.37), or rate of all saccades
(rs=–0.12, p=0.49). There was a significant correlation be-
tween age and the rate of catch-up saccades (rs=–0.33, p=
0.04). For both patient groups, after correction for multi-
ple comparisons, there were no significant correlations
between any eye-tracking measure and age, IQ, neuropsy-
chological test performance, or severity of positive or neg-
ative symptoms.
Discussion
To our knowledge, this is the first comparative study of
smooth pursuit eye tracking in pediatric patients with
contrasting childhood-onset psychotic disorders. As ex-
pected, the childhood-onset schizophrenia patients ex-
hibited a pattern of eye-tracking dysfunction character-
ized by poorer qualitative scores, lower gain, higher root
mean square error, and a greater frequency of catch-up
saccades than age-matched healthy volunteers. A similar
pattern of eye-tracking dysfunction has been consistently
reported in studies of adult schizophrenic patients unse-
lected for age at onset (11, 29, 34–42). Recently, similar
findings have also been reported (although with small an-
ticipatory saccades) for a cohort of 10 childhood-onset
Am J Psychiatry 158:8, August 2001
KUMRA, SPORN, HOMMER, ET AL.
schizophrenia subjects relative to healthy comparison
subjects (20). Together, these data support a hypothesis
that childhood-onset schizophrenia is related to later-on-
set schizophrenia and thus may be a manifestation of the
same disease process.
The main purpose of this study was to investigate
whether the pattern of smooth pursuit eye tracking in sub-
jects with psychotic disorder not otherwise specified re-
sembled that in a group with narrowly defined childhood-
onset schizophrenia. Patients with psychotic disorder not
otherwise specified were found to have poor global track-
ing performance as marked by significantly worse qualita-
tive ratings, higher root mean square error, and lower gain
but no difference in frequency of catch-up saccades rela-
tive to healthy comparison subjects. These data along with
a similar pattern of abnormalities observed in subjects
with either psychotic disorder not otherwise specified or
childhood-onset schizophrenia (prepsychotic linguistic
deficits, family history, neuropsychological test perfor-
mance, and quantitative brain MRI data) support a hy-
pothesis that the two disorders may share some risk factors
(6).
Because much remains to be known about the patho-
physiology of childhood-onset schizophrenia, it is difficult
to fully define the relationship between psychotic disorder
not otherwise specified and childhood-onset schizophre-
nia. Our initial clinical distinction, however, does appear
to have prognostic importance. The 2- to 8-year clinical
follow-up data indicate that psychotic disorder not other-
wise specified does not progress onto schizophrenia but
may instead develop into affective disorders (7). Further-
more, this psychotic disorder not otherwise specified sub-
group also differed from the childhood-onset schizophre-
nia group with respect to follow-up progression of brain
MRI abnormalities. In childhood-onset schizophrenia,
there is progressive loss of regional cortical gray during ad-
olescence (43, 44), whereas no significant loss of frontal or
other regional gray volume was seen in the subjects with
psychotic disorder not otherwise specified (45). These
data would argue for a separation of subjects with psy-
chotic disorder not otherwise specified from future ge-
netic analyses of childhood-onset schizophrenia.
It is theoretically possible that the pattern of neurobio-
logical abnormalities that we observed in this psychotic
disorder not otherwise specified subgroup might be seen
in a broad range of children and adolescents with severe
emotional disturbances. Other patient groups, such as
adult bipolar patients (17, 18), have been reported to have
smooth pursuit tracking dysfunction. However, the bio-
logical relatives of bipolar patients have not been shown to
have eye-tracking dysfunction (11), suggesting that glo-
bally assessed eye-tracking dysfunction in affective disor-
ders may be state-, rather than trait-, related (46). Our pre-
liminary data suggest that some measures of eye-tracking
dysfunction are also seen in the biological first-degree
relatives of childhood-onset schizophrenia patients (47).
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EYE-TRACKING IMPAIRMENT IN CHILDHOOD PSYCHOSIS

TABLE 2. Characteristics of Smooth Pursuit Eye Movements of Patients With Childhood-Onset Schizophrenia, Psychotic
Disorder Not Otherwise Specified, and Respective Healthy Comparison Groups
Subjects With Childhood-Onset Schizophrenia Subjects
Patient Group (N=29) Comparison Group (N=20) Analysis Patient Group (N=26)
Mann Whitney
Measure Mean SD Range Mean SD Range U (df=47) p Mean SD Range
Qualitative scorea 3.3 0.9 1.5–5.0 1.7 0.7 1.1–3.2 55.0 <0.001 3.0 0.9 1.4–4.4
Gainb 0.69 0.23 0.26–1.06 0.87 0.13 0.63–1.02 148.0 0.004 0.73 0.16 0.44–0.96
Root mean square errorc 4.13 2.04 1.30–9.37 2.12 0.17 0.85–4.59 97.0 <0.001 4.11 2.46 1.14–10.65
Frequency (saccades/second)
All saccades 3.60 1.18 1.81–6.38 2.86 0.84 1.60–4.50 183.0 0.03 3.37 1.34 1.55–7.61
Catch-up saccadesd 1.59 0.75 0.40–3.69 1.10 0.42 0.48–2.06 165.0 0.01 1.35 0.64 0.36–2.99
Anticipatory saccadese 1.28 0.56 0.29–2.21 1.32 0.54 0.42–2.43 287.0 0.95 1.29 0.50 0.45–2.60
Large anticipatory saccadesf 0.49 0.32 0.00–1.32 0.42 0.42 0.00–1.38 224.0 0.18 0.60 0.40 0.00–1.41
a Rating of smooth pursuit eye movement (1=best, 5=worst); subjects with ratings of 2.5 or greater were classified as having eye tracking dys-
function.
b Ratio of eye velocity to target velocity of each separate smooth pursuit eye movement interval, averaged across intervals.
c Global measure of extent to which eyes did not reproduce target motion.
d Saccades in the direction of the target motion that started and ended behind the target or ended ahead of the target but with at least two-
thirds of the amplitude-moving gaze heading toward the target.
e Saccades in the direction of the target motion that ended ahead of the target and were followed by a 50-msec interval of eye velocity less
than 5°/second.
f Anticipatory saccades greater than 4°.

Because eye tracking in younger children is harder to
record and therefore has greater variability (24, 48), the
psychotic disorder not otherwise specified group is being
followed longitudinally to establish the stability of the
study findings. Also, family studies of the psychotic disor-
der not otherwise specified group are currently underway
to address the question as to whether eye-tracking dys-
function in these patients may represent a state- or trait-
related phenomenon.
Various lines of evidence suggest that the eye-tracking
dysfunction of schizophrenia patients may arise from an
underlying dysfunction of the prefrontal cortex. The iden-
tification of eye-tracking dysfunction in subjects with
childhood-onset schizophrenia and their families may be
of use for future genetic studies as a potential alternative
phenotype for childhood-onset schizophrenia (46). Such
an alternative phenotype could increase the statistical
power of genetic analyses in schizophrenic pedigrees by
increasing the number of affected subjects. It is also possi-
ble that eye-tracking dysfunction may represent a biologi-
cal deficit in schizophrenia that could be more closely re-
lated to a single gene effect than schizophrenia itself (46).
Between 7 to 15 years of age, the performance of the
smooth pursuit system continues to develop in healthy
children (24, 48, 49). As seen in previous studies, the corre-
lation between age and smooth pursuit system variables
accounts for at most 20% of the variance (24), which may
reflect differential rates of brain maturation in healthy
children. In this study, age effects were dealt with by creat-
ing two healthy comparison groups matched in gender
and age to each respective patient group.
Because children described as having “multiplex devel-
opmental disorder” (5, 50) or borderline disorder (4) bear
some clinical resemblance to our psychotic disorder not
otherwise specified group, cross-center replications of
these findings and the inclusion of medication-naive pa-
tients will be necessary to define more homogeneous sub-
groups of patients.
The data from our study should be considered in light of
other methodologic issues. The children with childhood-
onset schizophrenia and psychotic disorder not otherwise
specified both differed from their healthy comparison
groups in terms of IQ and attentional disturbances. The
discrepancy in IQ between patients and normal subjects
may not be a confounding factor, since in normal children
no consistent relationship between IQ and eye movement
variables has been found (24). Also, the lower IQ scores of
the patients may not be reflective of their true abilities
based on previous IQ testing (8). Thus, we did not covary
IQ (or its surrogate, vocabulary) in primary analyses.
A major shortcoming is that a monitor condition was not
included in this protocol, which may have enhanced atten-
tion and provided a more conservative estimate of the sub-
jects’ optimal performance (15). In a study of children and
adolescents, attention facilitation effectively normalized
the high anticipatory saccade rate observed in the off-
spring of schizophrenic probands compared to commu-
nity control subjects (15). However the primary results of
the study (i.e., global eye-tracking measure) remained un-
changed such that children and adolescents who were off-
spring of depressed parents could not be distinguished
from offspring of schizophrenic parents (15). In the present
study, it is unlikely that the eye-tracking dysfunctions in
patients could be solely attributed to attentional distur-
bances. First, there was no significant correlation between
gain or root mean square error with performance on tests
of speeded visual-motor processing and attention (e.g.,
Trailmaking A and B and average of the coding and digit
symbol subtests of the WISC-R/WAIS-R). Second, all pa-
tients were carefully supervised during the task to ensure
that they were engaged in smooth pursuit and were in-
structed not to jump ahead of the target.

1296 Am J Psychiatry 158:8, August 2001

 KUMRA, SPORN, HOMMER, ET AL.

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