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

Abstract

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.

Phenotype of schizophrenia: a review and formulation

“…Several phenotypic expressions of provoked behaviors are known to be altered in the illness, including smooth and saccadic eye movements, 38,39 prepulse inhibition, 40,41 and P50 after auditory evoked potential. 42 These are spontaneous behaviors of the brain occurring in response to external cues that have known neural anatomies, and hence may be more direct reflections of neural pathology.…”

“…[50][51][52][53][54]39,45 These deficits include predominately impairments in different dimensions of attention, language comprehension, verbal fluency, verbal memory, and spatial working memory, as well as abnormalities of eye tracking, PPI and P50. This has recently been documented by two comprehensive studies of schizophrenia relatives.…”

Smooth pursuit eye movement (SPEM) in patients with multiple complex developmental disorder (MCDD), a subtype of the pervasive developmental disorder

“…There have been two studies of SPEM in children with autism, and in, neither study were abnormalities of pursuit gain found (Kemner et al 2004;Takarea et al 2004), which contrasts with findings reported in the schizophrenia literature (Jacobsen et al 1996;Ross et al 1999aRoss et al , 2002Ross et al , 2003Kumra et al 2001). Therefore, SPEM parameters could be used to determine whether subjects with MCDD have neurobiological characteristics resembling those of subjects with autism (i.e.…”

“…Because both age (Ross et al 1999b(Ross et al , 2002(Ross et al , 2003Kumra et al 2001) and medication status (Litman et al 1994;Hutton et al 2001) affect SPEM performance, we age-matched the control subjects to the MCDD patients to minimize this effect and performed analyses including and excluding subjects on medication. For patients with schizophrenia the analysis was rerun excluding patients (four) using lithium or benzodiazepine because this is likely to have an effect on SPEM (Holzman et al 1991;Radant et al 1997).…”

“…Several psychophysiological markers of schizophrenia have been validated, of which abnormalities of smooth pursuit eye movements (SPEM), such as reduced gain and increased frequency of saccades, are among the most consistent and reproducible (Jacobsen et al 1996;Ross et al 1999aRoss et al , 2002Ross et al , 2003Kumra et al 2001). Indeed, global SPEM dysfunction is significantly associated with the disorganization dimension (defined primarily by thought disorder) of schizophrenia (Lee et al 2000).…”