Is eye movement dysfunction a biological marker for schizophrenia? A methodological review.

Clementz, Brett A.; Sweeney, John A.

doi:10.1037/0033-2909.108.1.77

Cited by 170 publications

(93 citation statements)

References 128 publications

(288 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Baron, 1994;Holzman, 1992;19941. Eye tracking dysfunction (ETD) has been discussed as one of the most promising phenotypic markers for a genetic predisposition to this disease [recent reviews : Clementz and Sweeney, 1990;Holzman, 1992;Levy et al, 19931, Inspired by the recent reports on linkage of schizophrenia to markers on 6p and by our own collaboration with Moises et al [1995] we conducted a search for linkage of ETD as well as different diagnostic categories of schizophrenia to markers of the p21-23 region of chromosome 6.…”

Section: Introductionmentioning

confidence: 99%

Eye tracking dysfunction is a putative phenotypic susceptibility marker of schizophrenia and maps to a locus on chromosome 6p in families with multiple occurrence of the disease

et al. 1996

View full text Add to dashboard Cite

The difficulties in defining the borders of the schizophrenia spectrum is one major source of variance in linkage studies of schizophrenia. The employment of biological markers may prove advantageous. Due to empirical evidence, eye tracking dysfunction (ETD) has been discussed to be the most promising marker for genetic liability to schizophrenia. With respect to the recent progress in genomic scans, which have pointed to the short arm of chromosome 6, we carried out a scan of the 6p21-23 region with 16 microsatellite markers to test for linkage between chromosomal markers and ETD as well as schizophrenia. We tested 5 models of inheritance of ETD and found maximum two-point lod scores of 3.51 for D6S271 and 3.44 for D6S282. By including these markers in a multipoint analysis, a lod score of 4.02 was obtained. In the case of schizophrenia, 7 models were tested; however, with non-significant results. Our findings, together with another recent linkage report, point to the possibility of a second susceptibility locus for schizophrenia which may be located centromeric to the HLA region. Also, the evidence of ETD being a susceptibility marker for schizophrenia receives further support.

show abstract

Section: Introductionmentioning

confidence: 99%

Eye tracking dysfunction is a putative phenotypic susceptibility marker of schizophrenia and maps to a locus on chromosome 6p in families with multiple occurrence of the disease

et al. 1996

View full text Add to dashboard Cite

show abstract

“…Smooth pursuit eye movements; Schizophrenia; Predictive pursuit; Extra-retinal processing; Smooth pursuit initiation A wealth of evidence, including a recent preliminary report citing linkage of pursuit abnormality to chromosome 6p21 in relatives of schizophrenic patients, suggests that the smooth pursuit deficit marks the genetic liability to schizophrenia (Arolt et al, 1996;Clementz & Sweeney, 1990;Levy, Holzman, Matthysse, & Mendell, 1994). Although many aspects of the smooth pursuit deficit associated with the schizophrenia phenotype(s) have been well described, only recently have investigators focused on understanding the underlying neuronal mechanisms of these eye movement abnormalities (Clementz & McDowell, 1994;Ross et al, 1995;Sweeney et al, 1998).…”

Section: Descriptorsmentioning

confidence: 99%

A model of smooth pursuit eye movement deficit associated with the schizophrenia phenotype

Thaker¹,

Avila²,

Hong³

et al. 2003

Psychophysiology

View full text Add to dashboard Cite

Smooth pursuit eye movement (SPEM) abnormalities in schizophrenia, although well described, are poorly understood. SPEMs are initiated by motion of an object image on the retina. During initiation, the eyes accelerate until they approximate target velocity and a state of minimal retinal motion is achieved. Pursuit is maintained through predictive eye movements based on extraretinal signals and corrections based on deviations from the fovea. Here, initiation and predictive pursuit responses were used to estimate the contributions of retinal and extraretinal signals to pursuit maintenance in schizophrenia patients' relatives. Relatives exhibited normal initiation, but had lower predictive pursuit gain compared with controls. Relatives had normal gain during pursuit maintenance, presumably by greater reliance on retinal error. This was confirmed by group differences in regression coefficients for retinal and extraretinal measures, and suggests that schizophrenia SPEM deficits involve reduced ability to maintain or integrate extraretinal signals, and that retinal error may be used to compensate. DescriptorsSmooth pursuit eye movements; Schizophrenia; Predictive pursuit; Extra-retinal processing; Smooth pursuit initiation A wealth of evidence, including a recent preliminary report citing linkage of pursuit abnormality to chromosome 6p21 in relatives of schizophrenic patients, suggests that the smooth pursuit deficit marks the genetic liability to schizophrenia (Arolt et al., 1996;Clementz & Sweeney, 1990;Levy, Holzman, Matthysse, & Mendell, 1994). Although many aspects of the smooth pursuit deficit associated with the schizophrenia phenotype(s) have been well described, only recently have investigators focused on understanding the underlying neuronal mechanisms of these eye movement abnormalities (Clementz & McDowell, 1994;Ross et al., 1995;Sweeney et al., 1998). The smooth pursuit function is a highly developed and complex system served by a widely distributed neuronal network (Leigh & Zee, 1991). In recent years, many of the normal functions of the component processes of the smooth pursuit system in humans, and the underlying neurophysiological substrates in monkeys, have become known (Assad & Maunsell, 1995;Barnes, Barnes, & Chakraborti, 2000;Barton et al., 1996;Komatsu & Wurtz, 1989;Krauzlis, 2001; MacAvoy, Gottlib, & Bruce, 1991; Newsome, Wurtz, Dersteler, & Mikami, 1985;Newsome, Wurtz, & Komatsu, 1988;Schmid, Rees, Frith, & Barnes, 2001;Suh, Leung, & Kettner, 2000). Examination of smooth pursuit in schizophrenia within a neurophysiology-based framework has an advantage over traditional methods, in that it is likely to identify specific brain regions that are associated with observed deficits. In addition, the identification of a functionally specific deficit is likely to be more sensitive and specific in identifying the phenotype compared with traditional global measures.Normally, the pursuit system needs motion information to generate smooth pursuit eye movements. During initiation of smooth pursuit, ...

show abstract

“…Certain physiological traits, however, although uncommon in the general population, occur more frequently than the clinical syndrome in first-degree relatives and suggest themselves as more penetrant alternative phenotypes for the study of the genetics and pathophysiology of schizophrenia (4). One of the more widely studied of these cofamilial traits is eye tracking dysfunction (5)(6)(7).…”

mentioning

confidence: 99%

Psychophysical isolation of a motion-processing deficit in schizophrenics and their relatives and its association with impaired smooth pursuit

Chen

Nakayama

Levy

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

153

102

View full text Add to dashboard Cite

Schizophrenia patients and many of their relatives show impaired smooth pursuit eye tracking. The brain mechanisms underlying this impairment are not yet known, but because reduced open-loop acceleration and closed-loop gain accompany it, compromised perceptual processing of motion signals is implicated. A previous study showed that motion discrimination is impaired in schizophrenia patients. Motion discrimination can make use of position and contrast as well as velocity cues. Here, we report that the motion discrimination deficit, which occurs in both schizophrenic patients and in their first-degree relatives, involves a failure of velocity detection, which appears when judging intermediate target velocities. At slower and faster velocities, judgments of velocity discrimination seemed normal until we experimentally disentangled velocity cues from nonmotion cues. We further report that compromised velocity discrimination is associated with sluggish initiation of smooth pursuit. These findings point to specific central nervous system correlates of schizophrenic pathophysiology.Although schizophrenia is significantly influenced by genetic factors (1, 2), the clinical disorder occurs relatively infrequently; estimates vary from 3.5% to Ϸ8% in the nuclear families of schizophrenic probands (3). This low intrafamilial prevalence poses difficulties for studies of genetic linkage in schizophrenia. Certain physiological traits, however, although uncommon in the general population, occur more frequently than the clinical syndrome in first-degree relatives and suggest themselves as more penetrant alternative phenotypes for the study of the genetics and pathophysiology of schizophrenia (4). One of the more widely studied of these cofamilial traits is eye tracking dysfunction (5-7).Eye tracking dysfunction shows itself specifically in smooth pursuit eye movements, a tracking response to moving visual targets. Other kinds of eye movements, such as voluntary saccades (8, 9), vestibularly controlled eye movements (10), and the oculocephalic reflex (11), are normal in both patients and relatives. This set of findings indicates that the eye tracking dysfunction is specific to the smooth pursuit system and that its neuroanatomical substrate is above the brain stem.Several investigators have characterized the nature of the eye tracking dysfunction in schizophrenia as low closed-loop gain (the ratio of eye velocity to target velocity) with frequent compensatory catch-up saccades and low initial acceleration of the eye, both of which indicate that eye velocity lags behind target velocity (12-15). There may be two explanations for these findings: (i) Processing of velocity signals during target movement is deficient (16, 17); and (ii) general performance is inefficient when processing external signals (18).As evidence to support the hypothesis that deficient velocity processing is involved in eye tracking dysfunction, it is necessary to show that velocity discrimination is compromised in schizophrenic patients and that the sa...

show abstract

Is eye movement dysfunction a biological marker for schizophrenia? A methodological review.

Cited by 170 publications

References 128 publications

Eye tracking dysfunction is a putative phenotypic susceptibility marker of schizophrenia and maps to a locus on chromosome 6p in families with multiple occurrence of the disease

Eye tracking dysfunction is a putative phenotypic susceptibility marker of schizophrenia and maps to a locus on chromosome 6p in families with multiple occurrence of the disease

A model of smooth pursuit eye movement deficit associated with the schizophrenia phenotype

Psychophysical isolation of a motion-processing deficit in schizophrenics and their relatives and its association with impaired smooth pursuit

Contact Info

Product

Resources

About