The relationship between smooth pursuit eye movements and tardive dyskinesia in schizophrenia

SCHIZOPHRENIA RESEARCH ELSEVIER

Schizophrenia Research 31 ( 1998 ) 141 - 150

The relationship between smooth pursuit eye movements and tardive dyskinesia in schizophrenia David E. Ross a,b,., Robert W. Buchanan a, Adrienne C. Lahti a, Deborah Medoff a, John J. Bartko a, Amelia D. C o m p t o n b, G u n v a n t K. Thaker a a Mao,land Psychiatric Research Center, Department of Psychiatry, University o[Maryland at Baltimore, Baltimore, MD, USA b Department (?fPsychiatry, Medical College qf Virginia, Virginia Commonwealth University, Richmond, VA, USA Received 25 September 1997; accepted 6 February 1998

Abstract

Objective: To examine the relationship between smooth pursuit eye movements and tardive dyskinesia (TD) in schizophrenia. Methods': Forty schizophrenic patients with TD and 25 non-TD patients had smooth pursuit eye movements tested with infrared oculography. In addition to the diagnosis of TD (present or absent), each patient had ratings of severity of TD. Results: There was no significant or strong association between TD and poor smooth pursuit eye movements. Conclusion: The results stand in contrast to those of several previous studies, which were based on limited methodology. However, this study was not able to exclude definitively the possibility that TD is associated with poor smooth pursuit, perhaps with a small to moderate effect. Furthermore, these conclusions are limited to simple eye tracking protocols in which distractions are minimized. The question of whether or not TD is associated with poor smooth pursuit in schizophrenia needs to be resurrected. © 1998 Elsevier Science B.V. All rights reserved. h'eywords: Eye movements; Schizophrenia: Smooth pursuit; Saccades; Tardive dyskinesia

I. Introduction The study of abnormal smooth pursuit eye movements in schizophrenia holds promise for shedding light on the pathophysiology of this enigmatic disorder. However, studies in this area are often confronted by methodological challenges * Corresponding author. Present address: Central Hospital, P.O. Box 4030, Petersburg, VA 23803, USA. Tel.: + 1 804 5244633; Fax: + l 804 524 4645; e-mail: [email protected]

State

0920-9964/98,/$19.00 © 1998 Elsevier Science B.V. All rights reserved. PII: S 0 9 2 0 - 9 9 6 4 ( 98 ) 0 0 0 2 7 - 9

which include the sequelae of chronic illness and treatment with antipsychotic medication. Tardive dyskinesia (TD) is a disorder caused by chronic treatment with neuroleptic medication and is characterized by abnormal, involuntary movements. The lifetime prevalence of TD for patients chronically treated with neuroleptic medication is about 25% (Kane and Smith, 1982). TD can affect the neural control of any voluntary muscle, and it is natural to wonder if it might worsen eye movement performance. Furthermore, the pathophysiology of TD is thought to involve the basal ganglia,

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which subserve eye movement control (Hikosaka et al., 1989a,b,c). It has been reported previously that T D is associated with abnormal smooth pursuit eye movements in schizophrenic patients (Spohn et al., 1985, 1988; Oepen et al., 1990; Klein and Andresen, 1991). For most of these studies, T D accounted for less than 10% of the variance in eye tracking measures. In another study, the smooth pursuit of T D patients was not significantly different from that of non-TD patients (Thaker et al., 1989a). T D also has been reported to be associated with increased error rate in response to the antisaccade task (Thaker et al., 1989b). Most of the studies of T D and smooth pursuit used electro-oculography to record eye movements. This technique is notoriously susceptible to biopotential artifact, e.g., that associated with movement of facial muscles (Iacono and Lykken, 1981 ), which could confound studies of eye movements in TD. Also, most of these studies used older measures, such as global ratings and gross measures of saccades. These measures are limited in comparison to more neuro-ophthalmologically informed measures, such as gain and catch-up saccades (Abel and Ziegler, 1988). If T D is associated with poor smooth pursuit, it would be important to know which specific measures were involved and to what extent their variance is accounted for by TD. In addition to these technical concerns, there are other reasons to reconsider the question of the relationship between T D and eye tracking. Based on these limited studies of the relationship between T D and eye tracking, most investigators of eye tracking in schizophrenia have excluded patients with T D from their studies. If T D was not associated with smooth pursuit abnormalities, such exclusion would be unnecessary. The purpose of this study was to use modern recording and analysis techniques in order to determine if poor smooth pursuit eye movements are associated with tardive dyskinesia in schizophrenia. Our laboratory has reported recently that patients with and without T D did not differ significantly with respect to several measures of smooth pursuit eye movements (Ross et al., 1996b, 1997). Relative to these studies, the current study focused more strongly on the relationship between T D and eye tracking in the following ways: (1)

the sample of patients from our earlier two studies ( N = 5 3 patients) was expanded for the current study ( N = 6 5 patients); (2) measures of intrusive saccades were added; and (3) correlations between smooth pursuit and severity of T D were examined. In summary, the current study attempted to extend our recent findings and not to replicate them, and to bring a greater focus on the question between the relationship between smooth pursuit and T D in schizophrenia. Also, our laboratory previously examined the relationship between saccadic and smooth pursuit eye movements, T D and schizophrenia (Thaker et al., 1989b); the current study used a new sample of patients.

2. Methods 2.1. Patients

Sixty-five patients with schizophrenia participated in the study. Written informed consent was obtained from all patients after the procedures had been explained fully. Patients were recruited from outpatient and inpatient programs at Maryland Psychiatric Research Center ( M R P C ) . All patients were administered the Structured Clinical Interview for DSM-III-R. All patients satisfied DSM-III-R (American Psychiatric Association, 1987) criteria for schizophrenia. Patients were screened to exclude those with medical illnesses or medications (including lithium and benzodiazepines) known to adversely affect eye movements. All patients were clinically stabilized on antipsychotic medication; some were on antiparkinsonian medication. A small minority of patients (less than 5%) were excluded due to severe dyskinetic movements (usually truncal or neck movements) which prevented them from keeping their heads stable. Therefore, inferences based on this study are limited accordingly. The eye tracking performance of a sample of 25 normal comparison subjects in response to the task used in this study has been described previously (Ross et al., 1997). Patients were assessed with the MPRC Involuntary Movement Scale (IMS) (Cassady et al., 1997). The IMS provides for ratings of severity of T D both globally and with respect to specific body regions (Table 1). The IMS has been

D.E. Ross et al. / Schizophrenia Research 31 (1998) 141 150

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Table 1 Ratings of severity of tardive dyskinesia (TD), based on the Involuntary Movement Scale (Cassady et al., 1997) a Categories

Specific items

Oro-facial

Upper extremities

Lower extremities

Truncal

Tongue Peri-oral Peri-orbital Masticatory

Fingers and wrists Elbows and arms Hypotonic arm swing during gait

Thighs and knees Legs and feet Heel walking during gait

Neck and shoulders Pelvic region Diaphragm (grunting

aThirteen ratings o f TD in specific body regions were divided into four categories. A summary score was calculated for each category by summing the scores on the specific items within that category. In addition to these four summary scores, a global item and each of the four specific items from the oro-facial category were used to examine the relationship between eye movements and severity of TD. Table 2 Demographic and clinical characteristics of patients TD patients

Non-TD patients

N

40

25

Sex Race

13 F, 27 M 25W, 13 B, 2 0 Mean

SD

7 F, 18 M 16W, TB, 2 0 Mean

SD

34.9 4.4 14.5 10.9 31.3 875

6.7 0.7 5.4 5.5 8,8 471

32.0 4.0 13.9 9.2 32.8 1061

8.3 0.9 9.2 5.9 7.0 786

Age (years) Socio-economic status of patient Duration of illness (years) a Duration of treatment with antipsychotic medication (years) b BPRS total score Mean dose antipsychotic (mg CPZ equivalents) ~

aDuration of illness was measured from onset of psychosis. bDuration of treatment with antipsychotic medication was determined by adding all the periods during which the patient received antipsychotic medication. ~CPZ equivalents (rag) were based on Gelenberg et al. (1991). W, White; B, Black; O, other: BPRS, Brief Psychiatric Rating Scale; CPZ, chlorpromazine.

shown to have good reliability and validity (Cassady et al., 1997). Most patients ( N = 4 5 ; 69% of total) had movements rated on the day of ocular motor testing. All patients had movements rated within 3 weeks of ocular motor testing (mean = 3.3 days after eye tracking, S D = 7 . 7 , m e d i a n = 0 , r a n g e = - 2 0 21), and all of these patients remained clinically stabilized without a change in medication. Patients were diagnosed according to Research Diagnostic Criteria for T D (Schooler and Kane, 1982). Forty patients were diagnosed as having T D and 25 were diagnosed as not having TD. Demographic and clinical characteristics of subjects are shown in Table 2. Socio-economic status

of patients were obtained using a scale developed previously (Hollingshead and Redlich, 1988). The Brief Psychiatric Rating Scale (BPRS) (Overall and Gorman, 1961) was administered to each patient within 1 week of eye movement testing. Comparisons were made between the TD and non-TD patients in order to assess the presence of potential confounds. Chi-square tests were used for categorical variables and independent t-tests were used for continuous variables. The TD and non-TD patients did not differ significantly with respect to age, sex, socio-economic status (SES), duration of psychotic illness, duration of treatment with antipsychotic medication or BPRS total (all ps >0.05).

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2.2. Oculographic methods 2.2.1. Data collection

Eye movements were tested and analyzed using our methods described previously (Ross et al., 1997), which will be treated here only briefly. The smooth pursuit target consisted of eight cycles of a 0.3-Hz sine wave traversing + 10 ~ of visual angle. The subject's head was restrained using a forehead rest, chin rest and strap. Eye movements were measured with infrared oculography. The data were converted from analog to digital format and stored for later interactive analysis. 2.2.2. Data analysis

F r o m the eight cycles of the sinusoidal target, three contiguous cycles (10 s) were chosen for analysis according to our method described previously (Ross et al., 1988). This method uses a smaller epoch of tracking than is typically used by other researchers in this area, and it was designed to minimize the effect of distractions and artifacts. The validity of this method has been shown previously (Ross et al., 1988, 1995, 1996a, 1997). Non-tracking periods were defined as sustained ( > 5 0 0 ms) periods during which the velocity of the eye was near zero, including no saccades. Catch-up saccades and anticipatory saccades were defined as previously (Ross et al., 1997). In addition, other saccades types were defined according to whether or not they reduced position error and were in the direction of target motion (Table 3). These criteria were chosen because they were thought to reflect fundamental aspects of the function of saccades during pursuit of a smooth moving target. By these criteria, our previous definition of catch-up saccades does not change, and anticipatory saccades are a subgroup of go-ahead saccades.

For the measurements of saccades, portions of the data in which the target was near an extremum (absolute value of target velocity less than 5 :~) were not included. Frequency (number per second) of all saccade types was measured. In addition, catch-up saccade amplitude and desired amplitude (i.e., the amplitude that would have placed the eye exactly on the target) were measured. Position RMS error was measured after excluding non-tracking epochs and anticipatory saccades, which were thought to reflect general inattention or distractibility (Levy et al., 1993). Gain was measured using a slightly modified version of the time-weighted average gain method. Variability of gain was measured as the standard deviation about the mean of the gain waveform. Gain and variability of gain were measured after having removed the saccadic components of the pursuit tracking response. Phase lag was obtained by subtracting the phase of the fundamental component (freq u e n c y = 0 . 3 Hz) of the position of the eye from that of the target, and it was measured in degrees. 2.3. Statistical ana@s'es 2.3.1. Comparisons o f ocuhlr motor measures between TD and non- T D patients

The primary analyses included comparisons of the ocular m o t o r variables between the T D and non-TD groups, hypothesized a priori to differ between groups. The distributions of the ocular m o t o r variables within each group were examined visually and tested for normality using the S h a p i r o - - W i l k s test (with alpha set at 0.05). Consistent with our previous study (Ross et al., 1997), anticipatory saccades and non-tracking epochs were rare; therefore, they were not considered further. In both groups, the distributions of

Table 3 Classification of saccades during smooth pursuita

Saccade direction same as target motion Saccade direction opposite of target motion

Corrective (decreases position error)

Intrusive (increases position error)

Catch-up saccade Back-up saccade

Go-ahead saccade Go-behind saccade

aSaccades were classified according to whether or not they reduced position error and were in the direction of target motion.

D.E. Ross et al. / Schizophrenia Research 31 (1998) 141--150

the frequencies of back-up saccades, go-ahead saccades and go-behind saccades were significant and egregiously non-normal: about half of the patients had a value of 0 and the remainder had values which caused the distribution to be positively skewed. Therefore, for comparisons involving these variables, the Wilcoxon test (a nonparametric test) was used. For the remaining variables, independent t-tests were used. 2.3.2. Correlations between ocular motor and TD severity ratings within the TD group In order to further examine the possibility that T D was associated with p o o r smooth pursuit eye movements, correlations between ocular m o t o r measures and T D severity ratings within the T D group were planned a priori. Therefore, the distributions of the T D items within the T D group were examined. All of the distributions were significantly non-normal. Attempts to transform the data to normality using c o m m o n transformations (e.g., natural log, square root, etc.) were not successful because patients frequently had values near the floor of the distribution. Therefore, Kendall's tau-b correlations (non-parametric) were used to test associations between ocular m o t o r and T D variables. Kendall's tau-b corrects for ties, and this feature was desirable for our data set.

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In addition to the a priori tests described above, additional correlations between each of the individual oro-facial items (tongue, peri-oral, periorbital and masticatory) were examined in an exploratory framework. Thus, the oro-facial region was examined more closely than the other body regions. The rationale for this decision was that the n e u r o a n a t o m y (e.g., somatic mapping) of eye movements is more similar to that of oro-facial regions than to that of other body regions. Given the exploratory nature of these correlations, Bonferroni corrections were used, setting alpha equal to 0.05/40 which approximately equals 0.001.

3. Results

Table 4 provides the means, SDs and ranges for the ratings of T D severity for the T D and n o n - T D groups. 3.1. Comparisons o f ocular motor measures between TD and non-TD patients Shown in Table 5 are means, SDs, effect sizes and results of tests of comparisons for the ocular m o t o r variables. There were no significant differences between patients with and without TD. Most

Table 4 Means, SDs and ranges for the TD severity ratings a TD patients ( N = 4 0 )

TD global Upper extremities sum Lower extremities sum Truncal sum Oro-facial sum Tongue Peri-oral Peri-ocular Masticatory

N on-TD patients (N = 25)

Mean

SD

Range

Mean

SD

Range

2.6 2.6 1.4 1.1 5.3 1.9 1.3 0.8 1.3

0.9 1.6 1.6 2.0 4.7 1.6 1.4 1.5 1.6

2 5 0 6 0 5 0 9 0-20 0 5 0 4 0-6 0 6

0.4 0.3 0.2 0.0 0.8 0.4 0.2 0.0 0.2

0.5 0.6 0.5 0.2 1.0 0.7 0.6 0.0 0.4

0-1 0--3 0 2 0-1 0 3 0 2 0 2 0 0 0 1

~Severity of TD was rated using the Involuntary Movement Scale (Cassady et al., 1997). Each individual item was rated on a scale from 0 to 7, where 0 = n o abnormal movement, 1 = q u e s t i o n a b l e a bnorma l movement, 2 or 3 = m i l d l y abnormal movement, 4 or 5 = moderately abnormal movement, and 6 or 7 - s e v e r e l y abnormal movement. Therefore, the maximum range for the individual items ( T D global and the four specific oro-facial items) was 0 to 7. The ma xi mum range for the upper extremities sum, lower extremities sum and truncal sum was 0 to 21. The m a x i m u m range for the oro-facial sum was 0 to 28.

D.E. Ross et aL / Schizophrenia Research 31 (1998) 141-150

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Table 5 Comparisons of ocular motor measures between T D and n o n - T D groups

Position R M S error (deg. of visual angle) Gain Gain SD Phase lag (deg.) CUS frequency (saccades/s) CUS amplitude (deg. of visual angle) CUS desired amplitude (deg. of visual angle) BUS frequency (saccades/s) Go-ahead saccade frequency (saccades/s) Go-behind saccade frequency (saccades/s)

TD (N=40)

Non-TD (N-25)

T D vs n o n - T D

Test of comparison ~

Mean

SD

Mean

SD

Effect size d

Test value

p

1.05 0.82 0.46 4.20 1.35 1.69 2.05 0.04 0.28 0.07

0.51 0.12 0.24 3.00 0.54 0.59 0.72 0.08 0.35 0.15

0.86 0.87 0.41 3.30 1.18 1.80 1.97 0.08 0.22 0.09

0.43 0.08 0.17 3.20 0.47 0.76 0.94 0.13 0.27 0.16

0.4 -0.5 0.2 0.3 0.3 -0.2 0.1 --0.4 0.2 0.2

1.50 - 1.86 0.85 1.14 1.32 -0.63 0.41 0.69 0.43 0.80

0.14 0.07 0.40 0.26 0.19 0.53 0.69 0.33 0.52 0.38

at values, from independent t-tests ( d f - 6 3 ) , are shown for all comparisons except frequency of back-up saccades, go-ahead saccades and go-behind saccades; for the latter comparisons, Ze approximations ( d r = 1 ) based on Wilcoxon tests are shown. There were no significant differences between groups. Also, for each comparison, Cohen's effect size d is shown (Cohen, 1988). TD, tardive dyskinesia; RMS, root mean square; gain SD, standard deviation about the mean of the gain waveform (a measure of variability of gain). Table 6 Kendall tau-b correlations between ocular motor and T D variables within the T D group ( N = 4 0 )

Position R M S error (deg. of visual angle) Gain Gain SD Phase lag (deg.) C U S freq. (saccades/s) C U S amplit (deg. of visual angle) C U S desired amplitude (deg. of visual angle) BUS freq. (saccades/s) Go-ahead saccade freq. (saccades/s) Go-behind saccade freq. (saccades/s)

TD global

Upper Lower Truncal Oroextremities extremities sum facial sum sum sum

-0.04 0.13 0.05 0.04 -0.03 -0.05 0.03 -0.08 -0.01 0.17

-0.03 0.01 -0.08 -0.04 0./16 -0.10 -0.02 0.07

0.22 0.25

0.07 -0.07 0.01 0.00 -0.02 0.07 0.06 -0.02 0.23 0.05

-0.09 0.27 0.06 -0.13 -0.19 -0.14 0.09 -0.02 -0.04 0.17

Tongue Peri- Perioral ocular

0.11 0.00 0.04 0.07 0.07 - 0 . 0 2 0.12 0.05 -0.07 -0.09 0.06 0.05 0.14 0.02 -0.02 -0.08 -0.03 0.03 0.20 0.02

0.18 0.00 0.13 0.07 0.03 0.00 0.14 0.01 0.07 0.37

-0.01 0.07 0.04 0.06 -0.10 -0.09 -0.11 0.18 0.09 0.09

Masticatory

0.13 -0.04 0.00 0.14 0.05 0.13 0.18 0.03 -0.08 0.10

None of the correlations was significant (alpha was set equal to 0.05 for the correlations involving T D global and the four sum items; for the remaining correlations, which involved individual body regions, alpha was set equal to 0.001 according to the Bonferonni correction (see text). freq., frequency; other abbreviations as for previous tables. of the associated effect sizes were small, although some were moderate,

the correlations significant.

3.2. Correlations between ocular m o t o r m e a s u r e s and T D items within the T D group

4. Discussion

were

small,

and

none

were

4.1. M a i n f i n d i n g s Shown

in Table 6 are the Kendall

tions between TD

the ocular

severity items within

motor the TD

tau-b correla-

measures group.

and Most

the of

This study found no significant or strong evid e n c e t h a t T D is a s s o c i a t e d w i t h p o o r s m o o t h

D.E. Ross et al. / Schi:ophrenia Research 31 (1998) 141-150

pursuit eye movements in schizophrenia. More specifically, T D and non-TD patients did not differ significantly with respect to any of the ocular motor variables. Furthermore, within the T D group, there were no significant correlations between ocular motor measures and ratings of severity of TD. For the comparisons and correlations, most of the effect sizes were small, although some were moderate. However, this study had several limitations. It was not able to definitively exclude the possibility that T D is associated with poor smooth pursuit, perhaps with a small to moderate effect. If the sample effect sizes accurately reflect the population effect sizes, then the power for detecting betweengroup differences was quite modest (<0.50). Furthermore, these conclusions may be limited to patients with mild to moderate TD, given the fact that we excluded patients with severe TD. Also, these conclusions are limited to simple eye tracking protocols in which distractions are minimized.

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4.2. Previous studies oJ'srnooth pursuit and TD in schizophrenia Several previous studies have reported that poor smooth pursuit eye movements were associated with TD, as summarized in Table 7. Each of these studies had methodological problems which limit their interpretation. Most of these studies used electro-oculography ( E O G ) to collect the eye movement data. EOG is notoriously susceptible to artifacts associated with muscle movement (Iacono and Lykken, 1981), which would be particularly problematic in patients with abnormal facial movements. This type of artifact would contribute to worse global ratings of smooth pursuit, but it probably would not interfere with ratings of large saccades. Several studies used qualitative ratings of smooth pursuit, which are more subjective than quantitative ratings and which suffer from the often-discussed limitations of global ratings (Abel and Ziegler, 1988; Ross et al., 1997).

Table 7 Summary of previous studies of smooth pursuit eye movements and tardive dyskinesia in patients with schizophrenia Ocular motor methods Authors

TD methods

Recording Measures

Spohn et al. (1985)

RDC Dx, AIMS

EOG

Spohn et al. (1988)

AIMS

EOG

Thaker et al. (1989a,c)

RDC Dx

IR

Oepen et al. (1990)

AIMS

EOG

Klein and Andresen (1991)

No standardized scale reported

EOG

Comments

Ln S/N, qualitative rating Significant correlations between TD ratings and poor smooth pursuit may have been due to muscle artifact associated with EOG Ln S/N, qualitative rating, TD associated with large non-tracking sacrating of small and large cades, thought to reflect increased distractibilsaccades ity of TD patients TD and non-TD patients did not differ sigQualitative rating nificantly with respect to qualitative rating of SPEM; effect size d=0.5 TD and non-TD patients differed significantly Little detail regarding with respect to "percentage of saccadic purscoring methods suit'. Lack of detail of scoring methods limits interpretation Frequency of 'small" Facial dyskinesia correlated with frequency of (4 6 ) and q a r g e ' ( > 6 ) saccades, but type of correlational tests and saccades statistical significance of these results were not reported. The saccades measured were probably anticipatory saccades

TD, tardive dyskinesia; RDC Dx, diagnosis of TD according to Research Diagnostic Criteria (Schooler and Kane, 1982); AIMS, Abnormal Involuntary Movement Scale (US Public Health Service, 1974); EOG, electro-oculography: IR, infared oculography: Ln S/N, natural log of the signal to noise ratio.

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Furthermore, in many of the previous studies, poor global pursuit and increased saccadic frequency may have been due to an increase in distractibility of the TD patients. This point was made clearly by Spohn et al. (1988), who found that enhancing the attention of the target resulted in a significant reduction of the frequency of large saccades in both the TD and non-TD patients, although the frequency in the TD patients remained somewhat elevated. Consistent with this idea, a previous study using the antisaccade task found that TD patients, in comparison with non-TD patients and normal controls, had significantly increased distractibility (inappropriate reflexive glances toward the target) (Thaker et al., 1989b). The current study was designed to minimize the effect of distractibility as follows: (1) the subject was in a quiet and dark room and therefore had few auditory or visual distractions; and (2) the methods of data analysis tended to minimize inclusion of non-tracking epochs and anticipatory saccades, which may reflect general inattention or distractibility (Levy et al., 1993). The conclusions of our study may not apply to other types of smooth pursuit protocols, for example, those which include distractors, or those having longer testing intervals during which a patient would be more likely to become bored or fatigued and, therefore, more distractible. To summarize these issues, the effect of distractibility in TD patients during eye movement tasks appears to be small if the task involves simply watching a target and if distractions are minimized or attention to the target is enhanced. This conclusion is consistent with the commonly recognized clinical phenomenon in which TD patients perform voluntary movement tasks fairly normally and have abnormal involuntary movements elicited by distracting tasks. 4.3. Dyskinesia may reflect an important aspect ~?] schizophrenia independently o f medication ~fffi~cts

Even if dyskinesia is associated with poor smooth pursuit eye movements in schizophrenia, it is possible that it reflects an important aspect of schizophrenia independently of medication effects. This idea is supported by the following observa-

tions: (1) previous studies have found that dyskinetic movements are sometimes associated with schizophrenia and related disorders independently of a medication effect (Reiter, 1926); Hertzig and Birch, 1968; Yarden and Discipio, 1971; Casey, 1985; Marcus et al., 1985; Caligiuri, 1994; Fenton et al., 1994; Walker et al., 1994; Hoffman et al., 1995; Chakos et al., 1996); (2) one of these studies (Fenton et al., 1994) found that dyskinesia developed more often in patients with the deficit syndrome, which has been found to be associated with eye tracking disorder in schizophrenia (for discussion, see Ross et al., 1997); and (3) vulnerability to develop TD in schizophrenia may be associated with a positive family history of psychiatric illness (O'Callahan et al., 1990; Richardson et al., 1991; McCreadie et al., 1992; but see Roy et al., 1994.

5. Conclusion In contrast with previous studies, which had important methodological limitations, this study found no significant or strong association between TD and poor smooth pursuit eye movements. However, this study was not able to definitively exclude the possibility that TD is associated with poor smooth pursuit, perhaps with a small to moderate effect. We conclude that the question of whether or not TD is associated with poor smooth pursuit in schizophrenia needs to be resurrected. Optimally, future studies which address this question would include the following elements of design: ( 1 ) longitudinal evaluation of the development of smooth pursuit dysfunction and dyskinesia, before and after initiation of treatment with medication; (2) oculographic data collection methods which are not susceptible to bioelectric artifact; and (3) quantitative and specific measures of ocular motor performance.

Acknowledgment Gratitude is expressed to Kirsten Hahn and Ashton Morgan for their assistance in collection and analysis of the data.

D.E. Ross et al. / Schizophrenia Research 31 (1998) 141 150

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