Familial Aggregation of Eye-Tracking Endophenotypes in Families of Schizophrenic Patients

Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, USA.
Archives of General Psychiatry (Impact Factor: 14.48). 03/2006; 63(3):259-64. DOI: 10.1001/archpsyc.63.3.259
Source: PubMed


Abnormal smooth pursuit eye movements (SPEMs) are some of the most reproducible biological changes associated with the susceptibility for schizophrenia. Recent studies have suggested that deficit in predictive pursuit, a specific component of the SPEMs, marks schizophrenia susceptibility.
To test whether predictive pursuit contains less extraneous noise and may be under more direct genetic control than the traditional measure of overall pursuit performance using maintenance pursuit gain.
Familial aggregation estimation of the predictive pursuit measure and the traditional maintenance pursuit measure in sibling pairs from families of schizophrenic patients.
Outpatient clinics.
Patients with schizophrenia and their full siblings were recruited, provided that at least 1 sibling pair could be formed per family. Ninety-two siblings were recruited into the study. They formed 70 sibling pairs. Ninety healthy control subjects were also recruited using targeted local community advertisements based on patients' county of residence, aiming to capture the basic demographics of the regions from which the patients were recruited.
Familial correlations and heritability estimates of 2 SPEM measures: maintenance pursuit gain and predictive pursuit gain.
The sibling intraclass correlation coefficient of the predictive pursuit gain (r = 0.45-0.48) was significantly higher than that of maintenance pursuit gain (r = 0.02-0.20) (P = .005-.007). Variance component analysis suggested a high genetic loading for predictive pursuit (heritability = 0.90, SE = 0.22; P<.001) but relatively low heritability in the traditional maintenance pursuit measure (heritability = 0.27, SE = 0.21; P = .08).
These results suggest that predictive pursuit may index stronger genetic effect and may be better suited for genetic studies than the traditional SPEM measure of maintenance pursuit gain.

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    • "A relatively low familiality estimate for sustained maintenance pursuit has previously been reported in schizophrenia (Hong et al., 2006). Lower familiality estimates for predictive than early maintenance gain highlight the potential of sensorimotor vs. predictive pursuit impairments for family genetic research. "
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    ABSTRACT: Smooth pursuit eye tracking deficits are a promising intermediate phenotype for schizophrenia and possibly for psychotic disorders more broadly. The Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium investigated the severity and familiality of different pursuit parameters across psychotic disorders. Probands with schizophrenia (N=265), schizoaffective disorder (N=178), psychotic bipolar disorder (N=231), their first-degree relatives (N=306, N=217, N=273, respectively) and healthy controls (N=305) performed pursuit tracking tasks designed to evaluate sensorimotor and cognitive/predictive aspects of pursuit. Probands from all diagnostic groups were impaired on all pursuit measures of interest compared to controls (p<0.001). Schizophrenia probands were more impaired than other proband groups on both early pursuit gain and predictive gain. Relatives with and without enhanced psychosis spectrum personality traits were impaired on initial eye acceleration, the most direct sensorimotor pursuit measure, but not on pursuit gain measures. This suggests that alterations in early sensorimotor function may track susceptibility to psychosis even in the absence of psychosis related personality traits. There were no differences in pursuit measures between relatives of the three proband groups. Familiality estimates of pursuit deficits indicate that early pursuit gain was more familial than predictive gain, which has been the most widely used measure in previous family studies of psychotic disorders. Thus, while disease-related factors may induce significant impairments of pursuit gain, especially in schizophrenia, the pattern of deficits in relatives and their familiality estimates suggest that alterations in sensorimotor function at pursuit onset may indicate increased susceptibility across psychotic disorders.
    Schizophrenia Research 10/2015; DOI:10.1016/j.schres.2015.09.032 · 3.92 Impact Factor
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    • "While the findings of impaired eye tracking in patients with schizophrenia are rather consistent across the literature, studies are difficult to compare as stimulus presentation parameters and operational definitions vary widely between research groups. For example, studies have used outcome measures such as initiation of smooth pursuit eye tracking (Clementz et al., 1994; Sweeney et al., 2008), predictive pursuit measures (Thaker et al., 1996, 1998, 1999), i.e. anticipatory, catch up saccades, refixation saccades (McDowell et al., 2002), saccadic intrusions (Friedman et al., 1992), pursuit gain (Ross et al., 2002; Kathmann et al., 2003; Hong et al., 2006), quality of tracking performance (Shagass et al., 1974; Siever et al., 1994; Keefe et al., 2008), as well as low (i.e. 5°/s—Friedman et al., 1991) and high velocity target speeds (i.e. "
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    ABSTRACT: In order to investigate the nature of the eye tracking impairment in schizophrenia spectrum we measured pursuit gain with a constant velocity target using a quantitative (RMS error in pursuit gain) and, on an exploratory basis, a qualitative (quality of tracking) measure. We utilized a sample consisting of three clinically characterized groups: patients with schizophrenia (SZ), their first degree non-psychotic relatives, subjects with schizotypal personality disorder (SPD), and healthy volunteers (HV). Thirty three SZ patients, 19 SPD subjects, 66 non-psychotic relatives (all clinically assessed for schizophrenia spectrum psychopathology--DSM-IIIR) and 18 HV were evaluated using an infrared eye tracking system. Targets were constant velocity trapezoids at 5°/s (slow) and 16°/s (fast). The quality of the eye tracking was independently evaluated by at least two raters (ICC: 0.92). The RMS measures at the two velocities (quantitative measure) and the quality of the tracking obtained for each velocity were entered separately into a two factor repeated measures ANOVA, with velocity and diagnosis as the independent measures. For the quantitative ratings (RMS error), a significant effect for velocity was found, with all subjects performing worse at the higher velocity, but there was no significant velocity by diagnosis interaction. In addition, an overall significant effect for diagnosis was found in the four-group ANOVA. In post hoc multiple comparison tests, SZ subjects performed significantly worse from the HV and the relatives. SPD subjects were not different from patients with schizophrenia (or from any group--and their performance was intermediate between the HV and the SZ). Relatives of the patients with schizophrenia were different from SZ subjects, but not different from SPD or HV subjects. Similar results were obtained in the exploratory qualitative ratings. Clinical symptoms did not correlate significantly with quantitative or qualitative performance in any group. We have found that the performance of SPD subjects is intermediate between that of patients with schizophrenia and the healthy volunteers in both qualitative and quantitative (exploratory) measures. Indeed, SPD subjects comprise the only group not statistically different from schizophrenic patients in quantitative or qualitative ratings.
    Psychiatry Research 03/2011; 186(1):18-22. DOI:10.1016/j.psychres.2010.08.004 · 2.47 Impact Factor
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    • "The findings in Thaker's study suggest that extra-retinal SPEM processes may be more sensitive to differences in prefrontal dopamine levels. A recent study found that predictive pursuit had stronger sibling-pair correlations and larger heritability estimates than the steady-state SPEM task (Hong et al., 2006). Predictive pursuit deficits may therefore represent a more refined endophenotype with a less complicated genetic basis than steady-state pursuit deficits. "
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    ABSTRACT: The association between the catechol-O-methyltransferase (COMT) val(158)met polymorphism (rs4680) and smooth pursuit eye movements (SPEM) was investigated in 110 schizophrenia patients and 96 controls. Patients had lower steady-state pursuit gain and made more frequent saccades than controls. Genotype was not associated with schizophrenia or SPEM, in either group or the combined sample. SPEM deficits in schizophrenia appear to be determined by genotypes other than rs4680, although the study may have lacked power to detect small effects.
    Psychiatry Research 08/2009; 169(2):173-5. DOI:10.1016/j.psychres.2008.10.003 · 2.47 Impact Factor
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