Elsevier

Schizophrenia Research

Volume 52, Issue 3, 1 December 2001, Pages 203-213
Schizophrenia Research

Stability of exploratory eye movements as a marker of schizophrenia — a WHO multi-center study

https://doi.org/10.1016/S0920-9964(00)00181-XGet rights and content

Abstract

The exploratory eye movements of patients with schizophrenia reportedly differ from those of patients without schizophrenia and healthy controls. In an attempt to determine whether exploratory eye movements provide valid markers for schizophrenia, the present collaborative study was conducted in six countries to analyze the stability of and variation in the following parameters of exploratory eye movements: the number of eye fixations (NEFs) and mean eye scanning length (MESL) in a retention task; the cognitive search score (CSS) that indicates how frequently the eye focused on each important area of a figure in order to recognize it in a comparison task; and the responsive search score (RSS), which reflects the frequency of eye fixations on each section of a figure in response to questioning in a comparison task. In addition, we investigated the validity of the currently employed discriminant function to extract a common feature of schizophrenia by applying it to the findings of the present study. The exploratory eye movements of 145 patients with schizophrenia, 116 depressed patients and 124 healthy controls at seven WHO collaborative centers in six countries were measured using eye mark recorders during viewing of stationary S-shaped figures in two sequential tasks. The RSSs of patients with schizophrenia were found to be significantly lower than those of depressed patients or healthy controls irrespective of geographical location, with no significant difference existing between the RSSs for depressed patients and those for healthy controls. By inserting the RSS and NEF data for each subject into the formula used to calculate discriminant function, patients with schizophrenia could be discriminated from depressed patients and healthy controls with a sensitivity of 89.0% and a specificity of 86.7%. The RSS is an exploratory eye movement parameter that detected schizophrenia irrespective of culture, race and various other subject variables. Furthermore, it is indicative of the stable, significant difference that exists between subjects with and without schizophrenia. The results of discriminant analysis confirm the previously reported validity of discriminant function.

Introduction

The underlying disability in schizophrenia is widely believed to involve cognitive dysfunction. Numerous neurophysiological markers (galvanic skin response and event-related potentials (P50 and P300)) and psychological markers (errors in continuous performance test, simple reaction time, smooth pursuit eye movement, closed-eye eye movement and exploratory eye movement) can detect this disability. There is strong support for some of these markers, such as pursuit eye movement (Holzman et al., 1974) and errors in the continuous performance test (Rutschmann et al., 1977), to be biological markers of schizophrenia, with the former believed to reflect the hereditability of the schizophrenic disposition because, although a number of patients with schizophrenia show normal eye movements, many of the first-degree relatives show abnormal responses (Holzman et al., 1988). However, the validity of using these markers to extract a common feature of schizophrenia has not been reported to date. The exploratory eye movements of patients with schizophrenia when shown static horizontal S-shaped figures reflect visuocognitive dysfunction (Kojima et al., 1990, Matsushima et al., 1992). Among exploratory eye movements, those made directly after repeated questioning as part of a comparison task (responsive search score (RSS)) have been reported to reflect the interpersonal response (Kojima et al., 1986). This score and the number of eye fixations (NEFs) made during a retention task were reported to discriminate patients with schizophrenia from patients without schizophrenia and healthy controls with a sensitivity of 76.7% and a specificity of 81.4% (Matsushima et al., 1998). In the present study, exploratory eye movements were recorded using the same method at seven centers in six countries as part of a WHO collaborative study to: (1) confirm the patterns of exploratory eye movements made by patients with schizophrenia and determine whether they differ from those made by depressed patients and healthy controls; (2) analyze the stability of and variation in each marker of exploratory eye movements at all centers; (3) determine the validity of the RSS as a specific marker for vulnerability to schizophrenia; (4) clarify whether exploratory eye movements made by patients with schizophrenia are influenced by racial or cultural factors; and (5) determine the validity of the currently employed discriminant function to extract a common feature of schizophrenia.

Section snippets

Background to the commencement of the present study

This WHO collaborative study was proposed by the Tokyo Center in 1989 at the 15th WHO Researchers’ Conference in Athens and its protocol was revised at the 16th WHO Researchers’ Conference held in Tokyo in 1990 (Kojima et al., 1992a, Kojima et al., 1992b). A training session was held at the Tokyo Center in 1992. Here the use of the eye mark recorder was demonstrated to participants and the assessment of symptoms was standardized. Each center participating in the study was supplied with the

Number of eye fixations and mean eye scanning length in retention task (Table 3)

Table 3 shows the NEFs made during the retention task for all subjects. A two-way ANOVA (Table 2) indicated a significant main effect of diagnosis [F(2,364)=42.75, p<0.001]; the NEFs made by patients with schizophrenia were fewer than those made by depressed patients and healthy controls, and the NEFs for depressed patients were significantly fewer than those for the healthy controls (Scheffe F-test). A significant main effect of center [F(6,364)=6.37, p<0.001] was also found. However, there

Features of exploratory eye movement parameters

Although two-way ANOVAs on the NEFs in the retention task and the RSS of the parameters of exploratory eye movements following repeated questioning in the comparison task showed significant differences among centers, interactions between center and diagnosis were not significant. The NEFs and the RSS for schizophrenia might be affected by some conditions at the nations, although no significant correlation was obtained between these two indicators and any condition in the present study.

Since

Acknowledgements

The authors are grateful to Prof. Philip S Holzman for reviewing this paper and for his valuable comments. We also thank Emeritus Prof. Yasuo Shimazono, Prof. Katsumi Ando and Dr. Harunob Ando for their suggestions.

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