Testing for linkage of eye tracking dysfunction and schizophrenia to markers on chromosomes 6, 8, 9, 20, and 22 in families multiply affected with schizophrenia

Arolt, Volker; Lencer, Rebekka; Purmann, Sabine; Schürmann, Manfred; Müller‐Myhsok, Bertram; Krecker, Katja; Schwinger, E.

doi:10.1002/(sici)1096-8628(19991215)88:6<603::aid-ajmg5>3.0.co;2-x

Cited by 43 publications

(13 citation statements)

References 19 publications

(17 reference statements)

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“…The anatomical and neurochemical basis of leading saccades remains largely unexplored, although antagonism of the N-methyl-D-aspartate receptor with ketamine can produce leading saccade abnormalities in normal individuals~Avila, Weiler, Lahti, Tamminga, Radant, Bowdle, Cowley, Kharasch, & Roy-Byrne, 1998;Thaker et al, 2001!. Despite the strong evidence supporting SPEM abnormalities as a potential marker of genetic risk for schizophrenia, smooth pursuit performance has rarely been utilized in linkage studies. Arolt and colleagues~Arolt, Lencer, Nolte, & Muller-Myhsok, 1996;Arolt et al, 1999!, using a combination score of global eye movement dysfunction, linked smooth pursuit dysfunction to chromosomes 6 and 8 with LOD scores of 2.73 and 1.66, respectively. It is uncertain whether different components of smooth pursuit performance represent different genetic risk factors or different expressions of the same genetic risk factor.…”

Section: Discussionmentioning

confidence: 99%

“…The difference in gain scores across definitions varies by less than 2% with a greater than .95 correlation~Ross et al, 1997!. For this report, we include all segments of smooth pursuit and present gain as a measure of Arolt et al, 1999;Arolt, Lencer, Nolte, Muller-Myhsok et al, 1996;Lencer et al, 1999!. Catch-up saccades were used as the dependent measure of smooth pursuit system performance. Catch-up saccades function to significantly reduce error between foveal gaze and target location and compensate for poor smooth pursuit system performance~eye velocity below that of target velocity!.…”

Section: Smooth Pursuit Eye Movementsmentioning

confidence: 99%

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Admixture analysis of smooth pursuit eye movements in probands with schizophrenia and their relatives suggests gain and leading saccades are potential endophenotypes

et al. 2002

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Abnormalities during a smooth pursuit eye movement task (SPEM) are common in schizophrenic patients and their relatives. This study assessed various components of SPEM performance in first-degree unaffected relatives of schizophrenic patients. One hundred individuals with schizophrenia, 137 unaffected first-degree relatives, and 69 normal controls completed a 16.7 degrees/s SPEM task. Smooth pursuit gain, catch-up saccades (CUS), large anticipatory saccades, and leading saccades (LS) were identified. Groups were compared with parametric and admixture analyses. Schizophrenic patients performed more poorly than unaffected relatives and normals on gain, CUS, and LS. Unaffected relatives were more frequently impaired than normals only on gain and LS. Relatives of childhood-onset and adult-onset probands had similar impairments. Gain and frequency of leading saccades may be genetic endophenotypes in childhood-onset and adult-onset schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Section: Smooth Pursuit Eye Movementsmentioning

confidence: 99%

Admixture analysis of smooth pursuit eye movements in probands with schizophrenia and their relatives suggests gain and leading saccades are potential endophenotypes

et al. 2002

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“…The first effort to examine the usefulness of ETD measures in linkage studies was conducted by Arolt and colleagues (Arolt et al 1996, 1999). Using a gain score dichotomized into normal or abnormal pursuit, they calculated two point linkage analyses between ETD and 16 microsatellite markers on chromosome 6p21–23.…”

Section: Association Between Genetic Polymorphisms and Etdmentioning

confidence: 99%

Eye Tracking Dysfunction in Schizophrenia: Characterization and Pathophysiology

Levy

Sereno

Gooding

et al. 2010

Current Topics in Behavioral Neurosciences

120

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Eye tracking dysfunction (ETD) is one of the most widely replicated behavioral deficits in schizophrenia and is over-represented in clinically unaffected first-degree relatives of schizophrenia patients. Here, we provide an overview of research relevant to the characterization and pathophysiology of this impairment. Deficits are most robust in the maintenance phase of pursuit, particularly during the tracking of predictable target movement. Impairments are also found in pursuit initiation and correlate with performance on tests of motion processing, implicating early sensory processing of motion signals. Taken together, the evidence suggests that ETD involves higher-order structures, including the frontal eye fields, which adjust the gain of the pursuit response to visual and anticipated target movement, as well as early parts of the pursuit pathway, including motion areas (the middle temporal area and the adjacent medial superior temporal area). Broader application of localizing behavioral paradigms in patient and family studies would be advantageous for refining the eye tracking phenotype for genetic studies.

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“…SPEM has been linked to 6p21 in 2 schizophrenia samples. 43 , 44 PPI has shown associations with NRG1 rs3924999, 45 COMT Val(158)/Met, 46 and PRODH 47 in both SZP and HC. Disrupted P50 suppression has been linked to 15q13-14 alpha-7-nicotinic acetylcholine receptor 48 and 22qD22s315 49 markers in SZP.…”

mentioning

confidence: 99%

Smooth Pursuit Eye Movement, Prepulse Inhibition, and Auditory Paired Stimuli Processing Endophenotypes Across the Schizophrenia-Bipolar Disorder Psychosis Dimension

Ivleva

Moates

Hamm

et al. 2013

Schizophrenia Bulletin

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Background: This study examined smooth pursuit eye movement (SPEM), prepulse inhibition (PPI), and auditory event-related potentials (ERP) to paired stimuli as putative endophenotypes of psychosis across the schizophrenia-bipolar disorder dimension. Methods: Sixty-four schizophrenia probands (SZP), 40 psychotic bipolar I disorder probands (BDP), 31 relatives of SZP (SZR), 26 relatives of BDP (BDR), and 53 healthy controls (HC) were tested. Standard clinical characterization, SPEM, PPI, and ERP measures were administered. Results: There were no differences between either SZP and BDP or SZR and BDR on any of the SPEM, PPI, or ERP measure. Compared with HC, SZP and BDP had lower SPEM maintenance and predictive pursuit gain and ERP theta/ alpha and beta magnitudes to the initial stimulus. PPI did not differ between the psychosis probands and HC. Compared with HC, SZR and BDR had lower predictive pursuit gain and ERP theta/alpha and beta magnitudes to the first stimulus with differences ranging from a significant to a trend level. Neither active symptoms severity nor concomitant medications were associated with neurophysiological outcomes. SPEM, PPI, and ERP scores had low intercorrelations. Conclusion: These findings support SPEM predictive pursuit and lower frequency auditory ERP activity in a paired stimuli paradigm as putative endophenotypes of psychosis common to SZ and BD probands and relatives. PPI did not differ between the psychosis probands and HC. Future studies in larger scale psychosis family samples targeting putative psychosis endophenotypes and underlying molecular and genetic mediators may aid in the development of biology-based diagnostic definitions.

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Testing for linkage of eye tracking dysfunction and schizophrenia to markers on chromosomes 6, 8, 9, 20, and 22 in families multiply affected with schizophrenia

Cited by 43 publications

References 19 publications

Admixture analysis of smooth pursuit eye movements in probands with schizophrenia and their relatives suggests gain and leading saccades are potential endophenotypes

Admixture analysis of smooth pursuit eye movements in probands with schizophrenia and their relatives suggests gain and leading saccades are potential endophenotypes

Eye Tracking Dysfunction in Schizophrenia: Characterization and Pathophysiology

Smooth Pursuit Eye Movement, Prepulse Inhibition, and Auditory Paired Stimuli Processing Endophenotypes Across the Schizophrenia-Bipolar Disorder Psychosis Dimension

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