Elsevier

Brain and Cognition

Volume 68, Issue 3, December 2008, Pages 359-370
Brain and Cognition

Smooth pursuit in schizophrenia: A meta-analytic review of research since 1993

https://doi.org/10.1016/j.bandc.2008.08.023Get rights and content

Abstract

Abnormal smooth pursuit eye-tracking is one of the most replicated deficits in the psychophysiological literature in schizophrenia [Levy, D. L., Holzman, P. S., Matthysse, S., & Mendell, N. R. (1993). Eye tracking dysfunction and schizophrenia: A critical perspective. Schizophrenia Bulletin, 19, 461–505]. We used meta-analytic procedures to quantify patient-control differences in eye-tracking and to evaluate potential moderators of effect size including patient and target characteristics and characteristics of the control population (matched or not). The magnitude of patient-control differences in pursuit depended on the measure. Global measures had large effect sizes. Among specific measures, maintenance gain and leading saccades yielded large effect sizes, with gain also yielding the narrowest confidence interval. Effect sizes associated with specific measures of smooth pursuit vs. specific measures of intrusive saccades did not clearly implicate one system over the other. Patient demographics and target characteristics generally had little influence on effect sizes. However, studies that failed to sex-match patients and controls tended to have smaller effect sizes for maintenance gain and catch-up saccade rate. Average effect sizes and confidence limits for global measures of pursuit and for maintenance gain place these measures alongside the very strongest neurocognitive measures in the literature [Heinrichs, R. W. (2004). Meta-analysis, and the science of schizophrenia: Variant evidence or evidence of variants? Neuroscience and Biobehavioral Reviews, 28, 379–394] for distinguishing between patients with schizophrenia and controls.

Introduction

One hundred years ago, Diefendorf and Dodge (1908) published the earliest known report of abnormal smooth pursuit in schizophrenia. What they observed, long before the introduction of neuroleptic medication, was an excess of jerky eye movements, or saccades, in what should have been a smooth oculomotor response. The finding received little additional investigation until 1973 when Holzman and colleagues, in the course of investigating the vestibular ocular reflex (VOR; see glossary) in schizophrenia made the serendipitous observation that while the VOR seemed to be normal in schizophrenic patients, smooth pursuit was not (Holzman, Proctor, & Hughes, 1973).

In the last 35 years, there have been several lines of investigation of smooth pursuit eye movements in schizophrenia, focusing variously on: (1) establishing the presence of the deficit in patients and in high-risk populations (e.g. first-degree relatives, psychometric schizotypes); (2) characterizing the deficit in terms of specific quantitative measures that reflect specific physiological processes; (3) identifying the neural correlates of abnormal pursuit; and (4) examining the clinical and neuropsychological traits associated with the abnormality. Levy et al. (1993) Levy, Holzman, Matthysse, and Mendell, published a comprehensive review of the literature (more than 80 articles) on smooth pursuit to that time. Since 1993, more than 120 additional articles have appeared on eye tracking in schizophrenia, including one review devoted to the findings in patients (Hutton & Kennard, 1998). In addition, smooth pursuit has been investigated in other psychiatric disorders (see Section 5). However, to date there has been only one meta-analytic review of the literature on smooth pursuit in schizophrenia (Heinrichs, 2004). Because that review was part of a much larger meta-analysis, it provided a single effect size and included only a small minority of published studies, i.e., those that measured total saccade rate (n = 14). Moreover, questions of potential interest to researchers in the field, for example, whether features of the patient population, study design or choice of dependent variable influence effect size, were not addressed.

The current paper builds on aspects of Levy’s qualitative review, by evaluating research post-1993, and on Heinrich’s meta-analytic review, by evaluating other pursuit variables as well as potential moderators of effect size. During the last fifteen years global measures of pursuit, such as qualitative ratings, RMS error and log signal/noise, have been largely replaced by more specific measures such as maintenance gain and intrusive saccade rates. Indeed, studies reporting only specific measures have significantly later publication dates than those reporting global measures (t55 = 2.93, p < .005). In the last 15 years, new measures for characterizing the smooth pursuit response have also emerged. These include leading saccades, predictive pursuit gain and open-loop gain, which have been postulated to increase sensitivity to the smooth pursuit deficits observed in schizophrenia.

The goals of the current paper are to evaluate quantitatively what has been learned since 1993 with regard to the following questions:

  • 1.

    What is the size of the difference in eye tracking performance between patients with schizophrenia and nonpsychiatric controls, averaging across all the different measures of pursuit?

  • 2.

    Do some specific measures of smooth pursuit yield larger effect sizes than others, suggesting a greater sensitivity to schizophrenia-related deficits, or do all measures yield effects of essentially equal magnitude?

  • 3.

    Does effect size vary with major demographic or clinical characteristics of the population (e.g. age, duration of illness, symptom severity etc.)?

  • 4.

    Do characteristics of the target movement influence the effect size of the differences between patients and controls?

  • 5.

    Do characteristics of the control population—matched or not on various demographic variables—influence the effect size?

Other articles in this volume will consider: eye movement endophenotypes; the effect of medications on smooth pursuit, and; the possible neural bases of pursuit deficits. Thus these topics will not be considered here.

The meta-analytic methods used here have two advantages over traditional review approaches. First, rather than assigning each study a binary vote based on whether between-group differences reach a p of <0.05 (regardless of the individual study’s power), the evidence from each study is evaluated on a continuous measure, i.e. effect size. Second, the moderator variable analyses allow testing for an association between aspects of study design and the magnitude of the observed effect. For comparison’s sake, we include a table summarizing the literature using the traditional vote-count method (Table 1).

Section snippets

Literature search

We searched PubMed, Medline and PsychInfo databases using combinations of the search terms “smooth pursuit,” “eye tracking” “eye and pursuit,” “schizophrenia” and “schizophrenic.” Studies were considered for inclusion if they appeared between January 1, 1994 and January 1, 2008 and were available in English. Indexed dissertations were included if copies could be obtained. As there is sometimes a delay between the article’s publication date and its appearance in electronic databases, coverage of

Analyses

Data were analyzed using SPSS 16.0.2. We conducted a number of preliminary analyses prior to evaluating our main research questions. Descriptive data were calculated for the entire set of studies included in the vote-count and the meta-analyses. All data were checked for statistical outliers and for normality. We evaluated the data for evidence of publication bias using a funnel plot (Light & Pillemer, 1984), and evaluated the correlation between effect size and sample size using Pearson’s r.

Results

Fifty-nine studies were included in the vote-count involving a total of 2107 patients and 1965 controls (Table 1). All were peer-reviewed publications except two which were doctoral dissertations. Of the 59 studies, 57 provided sufficient statistical data to calculate d for at least one variable. The meta-analysis is based on these 57 studies involving 2049 patients and 1927 controls (Table 2 and Appendix A).

Out of 527 data points (across continuous variables from each study), 5 (1%) were

Discussion

There are robust differences between the pursuit quality of patients with schizophrenia and that of nonpsychiatric controls. Effect sizes for global measures of pursuit were large. Among specific measures of pursuit, large effect sizes were found for maintenance gain and leading saccade rate, with gain also having the narrowest confidence interval. Other specific measures fell in the medium to small range, with only square-wave jerk rate and back-up saccade rate yielding ds smaller than 0.2.

The

Acknowledgments

We thank Dr. Deborah L. Levy for valuable comments on an earlier version of the manuscript. Funding from the Canadian Institutes of Health Research, the GW Stairs Memorial Foundation and a William Dawson Scholar Award contributed to the support of this work.

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