Smooth Pursuit Eye Movement Dysfunction Research Articles

Genome-Wide Association Studies Of Smooth Pursuit Eye Movements Across Psychotic Disorders: Preliminary Findings From The B-Snip Sample

Background Smooth pursuit eye movement dysfunctions are regarded as intermediate phenotypes for psychotic disorders. They include first, impairments of sensorimotor processing during pursuit initiation and second, deficits of sustained pursuit maintenance implicating different functional brain systems. Here we were interested in genetic alterations specifically related to these pursuit deficits. Methods Pursuit performance was assessed in 849 participants (schizophrenia N=230, schizoaffective disorder N=155, psychotic bipolar disorder N=206, and healthy controls N=258) of the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study. Participants were 18-65 years of age and without significant neurological disorder, recent substance abuse or dependence. A mixed modeling GWAS approach (EMMAX) was performed using genotyping assessed with the PsychChip (287,637 SNPs with MAF>0.01 passing standard GWAS QC criteria). Eye acceleration (measure of sensorimotor processing) and sustained maintenance gain (measure of cognitive control) were modeled as quantitative trait phenotypes in relation to genetic data while controlling for genetically-derived ancestry measures, age, and sex. Probands and controls were grouped together for primary analyses stratified by the top two genetically-derived ancestry groups with follow-up studies in proband or control categories. Results Genome-wide associations (p Discussion Protocadherin 12 (PCDH12) encodes a member of the cadherin family of proteins previously identified for involvement in neurodevelopment and brain morphology in both schizophrenia and bipolar disorder. By disturbing fast axonal guidance and synaptic specificity, variation in this gene may impact neuronal signaling needed for sensorimotor processing. CABLES1 encodes a protein involved in cell cycle regulation and has been identified as an important component of neural development and interhemispheric connections needed for predictive control of sustained pursuit. Relationships between neurodevelopment related genes and smooth pursuit genotypes represent novel findings that may give insights into the behavioral/neurophysiological consequences of genetic variation in these systems and its alterations in severe mental illness. Other genes implicated in our association studies represent novel relationships requiring further study.

Predictive smooth eye pursuit in a population of young men: II. Effects of schizotypy, anxiety and depression

Smooth pursuit eye movement dysfunction is considered to be a valid schizophrenia endophenotype. Recent studies have tried to refine the phenotype in order to identify the specific neurophysiological deficits associated with schizophrenia. We used a variation of the smooth eye pursuit paradigm, during which the moving target is occluded for a short period of time and subjects are asked to continue tracking. This is designed to isolate the predictive processes that drive the extraretinal signal, a process previously reported to be defective in schizophrenia patients as well as their healthy relatives. In the current study, we investigated the relationship between predictive pursuit performance indices and age, education, non-verbal IQ, schizotypy and state anxiety, depression in 795 young Greek military conscripts. State anxiety was related to better predictive pursuit performance (increase in residual pursuit gain), while disorganized schizotypy was related to deficient predictive pursuit performance (decreased residual gain). This effect was independent of the effect of disorganized schizotypy on other oculomotor functions supporting the hypothesis that predictive pursuit might be specifically affected in schizophrenia spectrum disorders and could be considered as a distinct oculomotor endophenotype.

Is Persistent Ketamine Use a Valid Model of the Cognitive and Oculomotor Deficits in Schizophrenia?

BackgroundAcute ketamine has been shown to model features of schizophrenia such as psychotic symptoms, cognitive deficits and smooth pursuit eye movement dysfunction. There have been suggestions that chronic ketamine may also produce an analogue of the disorder. In this study, we investigated the effect of persistent recreational ketamine use on tests of episodic and working memory and on oculomotor tasks of smooth pursuit and pro- and antisaccades.MethodsTwenty ketamine users were compared with 1) 20 first-episode schizophrenia patients, 2) 17 polydrug control subjects who did not use ketamine but were matched to the ketamine users for other drug use, and 3) 20 non-drug-using control subjects. All groups were matched for estimated premorbid IQ.ResultsKetamine users made more antisaccade errors than both control groups but did not differ from patients. Ketamine users performed better than schizophrenia patients on smooth pursuit, antisaccade metrics, and both memory tasks but did not differ from control groups.ConclusionsProblems inhibiting reflexive eye movements may be a consequence of repeated ketamine self-administration. The absence of any other oculomotor or cognitive deficit present in schizophrenia suggests that chronic self-administration of ketamine may not be a good model of these aspects of the disorder.

Differential effects of cigarette smoking on performance of a smooth pursuit and a saccadic eye movement task in schizophrenia

Schizophrenic patients demonstrate a number of physiological defects including smooth pursuit eye movement dysfunction (SPEM), involuntary reflexive saccades to a prepotent stimulus during saccadic tasks, and increased response to the second of two identical auditory stimuli, the P50 evoked potential response. The P50 deficit appears to be mediated by the α7 nicotinic cholinergic receptor. This study compared the failure of saccadic inhibition demonstrated in two different eye movement tasks, to see if either deficit, like the P50 inhibitory deficit, was normalized by nicotine. Fifteen smoking schizophrenic patients and 15 smoking non-schizophrenic subjects were compared on the percentage of premature saccades in a memory-guided saccadic task, and the frequency of intrusive small and large anticipatory saccades during a SPEM task. No significant effects or interactions of smoking, group or time on premature or large anticipatory saccades were detected. However, leading saccades demonstrated a significant group × time × smoking interaction. Leading saccades may therefore be a measure of cholinergic inactivity and thus part of the α7 nicotinic receptor dysfunction observed in schizophrenia. However, premature saccades and large anticipatory saccades, although measures of inhibitory dysfunction in schizophrenia, appear to be unrelated to the nicotinic system.

Smooth pursuit eye movements of patients with schizophrenia and affective disorder during clinical treatment.

Smooth pursuit eye movement dysfunctions are considered a biological indicator for vulnerability to schizophrenia. This study examines test-retest stability of specific eye movement variables such as velocity gain and different saccadic categories. Smooth pursuit eye movements of 27 schizophrenic patients and 30 patients with major depression were examined three times during clinical treatment using high-resolution infrared oculography. Forty-one normal controls were retested after four weeks. Intraclass correlation coefficients as a measure for retest-stability were highly significant in each group for all time-points, except for anticipatory saccades in schizophrenics. No significant correlations were found between psychopathological status, neuroleptic medication and eye movement variables. Our results indicate that the most important measures of eye tracking performance in psychiatric patients are not significantly influenced by neuroleptic medication or clinical state and are stable across time.

Syndromes of schizophrenia and smooth-pursuit eye movement dysfunction

There have been a number of studies on smooth pursuit eye movement (SPEM) dysfunction in schizophrenia. However, the association between SPEM dysfunction and particular clinical symptoms remains unclear. We examined SPEM dysfunction in relation to schizophrenic symptoms using both the positive/negative dichotomy and the three-syndrome model. Subjects included 78 patients with schizophrenia and 60 healthy control subjects. SPEM performance was indexed by root mean square error. Symptom profiles were assessed using the Positive and Negative Syndrome Scale (PANSS), and the three-primary syndromes were identified by factor analysis of PANSS ratings (Psychomotor poverty: deficit negative symptoms; Disorganization: defined primarily by thought disorder; and Reality distortion: hallucinations and delusions). Compared with controls, the schizophrenia group showed significant impairment in global SPEM function. The three-syndrome approach produced more specific findings than the dichotomous model. Of the three syndromes, only the Disorganization dimension showed a significant association with increased global SPEM dysfunction. The specificity of SPEM dysfunction to Disorganization was verified in comparisons among schizophrenia subgroups and the control group. By contrast, the general domains of positive and negative symptoms were both found to be modestly associated with SPEM dysfunction. The separation of positive and negative symptoms that contribute to Disorganization from those that define Reality Distortion and Psychomotor Poverty has revealed significant new associations between SPEM and schizophrenic symptoms. These findings are interpreted in light of the proposal that the Disorganization syndrome is the central form of pathology in schizophrenia.

Eye movement dysfunction as a biological marker of risk for schizophrenia.

Our aim was to review smooth pursuit eye movement (SPEM) studies in schizophrenia and groups at high risk for schizophrenia, with a view to evaluating the utility of SPEM dysfunction as a biological marker of risk for schizophrenia. Smooth pursuit eye movement studies, related saccade function and the unresolved issues in this area of schizophrenia research were addressed. The different perspectives on the trait marker status of SPEM dysfunction, provided by both high-risk studies and related developmental research were considered. Attention was also given to the relationship between eye movement dysfunction and symptom profiles. Converging evidence points to the robust and specific nature of SPEM dysfunction in schizophrenia, and highlights the role of frontal lobe and a related network dysfunction. The vast majority of 'high risk' studies support the view that SPEM dysfunction is also genetically specific to schizophrenia, and is not simply due to the overt expression of this illness. Studies assessing SPEM in relation to symptomatology show an association with the Disorganisation syndrome in particular. Evidence for the specificity of SPEM dysfunction to diagnosed schizophrenia, as well as to healthy individuals with a genetic vulnerability to schizophrenia, suggests that the SPEM task has efficacy as a test of gene carrier status in schizophrenia, and therefore as a trait marker of risk for schizophrenia. Future studies should seek to explore the relationships between SPEM and other eye movement dysfunctions (antisaccades, express saccades), in view of evidence that some of these dysfunctions also show specificity for schizophrenia.

Heritability of different measures of smooth pursuit eye tracking dysfunction: A study of normal twins

Research studies have found that smooth pursuit eye movement dysfunction may serve as an index of genetic liability to develop schizophrenia. The heritability of various measures of smooth pursuit eye tracking proficiency and the saccades that occur during smooth pursuit was examined in 64 monozygotic (MZ) and 48 dizygotic (DZ) twin pairs. Two age cohorts were assessed (11–12 and 17–18 years of age). Intraclass correlations indicated significant similarity in the MZ twins for almost all measures in both age cohorts, whereas few of the DZ twin correlations attained significance. Biometrical modeling indicated that genetic mechanisms influence performance on both global and specific eye tracking measures, accounting for about 40% to 60% of the variance. These findings suggest that the underlying brain systems responsible for smooth pursuit and saccade generation during pursuit are under partial genetic control.

Heritability of different measures of smooth pursuit eye tracking dysfunction: A study of normal twins

Research studies have found that smooth pursuit eye movement dysfunction may serve as an index of genetic liability to develop schizophrenia. The heritability of various measures of smooth pursuit eye tracking proficiency and the saccades that occur during smooth pursuit was examined in 64 monozygotic (MZ) and 48 dizygotic (DZ) twin pairs. Two age cohorts were assessed (11-12 and 17-18 years of age). Intraclass correlations indicated significant similarity in the MZ twins for almost all measures in both age cohorts, whereas few of the DZ twin correlations attained significance. Biometrical modeling indicated that genetic mechanisms influence performance on both global and specific eye tracking measures, accounting for about 40% to 60% of the variance. These findings suggest that the underlying brain systems responsible for smooth pursuit and saccade generation during pursuit are under partial genetic control.

95. Smooth pursuit eye movement dysfunction in patients at clinical risk for schizophrenia

95. Smooth pursuit eye movement dysfunction in patients at clinical risk for schizophrenia

Eye Movement Dysfunction as a Biological Marker of Risk for Schizophrenia

Objective Our aim was to review smooth pursuit eye movement (SPEM) studies in schizophrenia and groups at high risk for schizophrenia, with a view to evaluating the utility of SPEM dysfunction as a biological marker of risk for schizophrenia. Method Smooth pursuit eye movement studies, related saccade function and the unresolved issues in this area of schizophrenia research were addressed. The different perspectives on the trait marker status of SPEM dysfunction, provided by both high-risk studies and related developmental research were considered. Attention was also given to the relationship between eye movement dysfunction and symptom profiles. Results Converging evidence points to the robust and specific nature of SPEM dysfunction in schizophrenia, and highlights the role of frontal lobe and a related network dysfunction. The vast majority of ‘high risk’ studies support the view that SPEM dysfunction is also genetically specific to schizophrenia, and is not simply due to the overt expression of this illness. Studies assessing SPEM in relation to symptomatology show an association with the Disorganisation syndrome in particular. Conclusions Evidence for the specificity of SPEM dysfunction to diagnosed schizophrenia, as well as to healthy individuals with a genetic vulnerability to schizophrenia, suggests that the SPEM task has efficacy as a test of gene carrier status in schizophrenia, and therefore as a trait marker of risk for schizophrenia. Future studies should seek to explore the relationships between SPEM and other eye movement dysfunctions (antisaccades, express saccades), in view of evidence that some of these dysfunctions also show specificity for schizophrenia.

Anticipatory saccades during smooth pursuit eye movements and familial transmission of schizophrenia

Background: Smooth pursuit eye movement (SPEM) abnormalities are a putative marker of genetic risk for schizophrenia. Accurate SPEM performance requires the subject to activate neural systems responsible for smooth pursuit tracking, while simultaneously suppressing activity of neurons responsible for saccadic movements that would move the eye ahead of the target. This study examined whether specific aspects of SPEM dysfunction cosegregate with genetic risk in parents of schizophrenic probands. Methods: Eighteen probands and their parents had SPEM recorded. Parents with an ancestral history of schizophrenia were hypothesized to be more likely than their spouses without such a history to carry a genetic risk for schizophrenia. Results: Ten families had a single parent with a positive ancestral history for schizophrenia. The frequency of anticipatory saccades, which were mostly small, and the fraction of total eye movement that they represented were the only measures that differentiated the more likely genetic carrier parents in these families from their spouses and age-matched normals. Conclusions: Failure to suppress saccadic anticipation of target motion during smooth pursuit appears an aspect of SPEM dysfunction related to presumed genetic risk for schizophrenia.

Smooth pursuit eye movements in schizophrenia and affective disorder.

Smooth pursuit eye movement (SPEM) dysfunction is considered to be a promising candidate for a biological marker for genetic vulnerability to schizophrenia. There are conflicting findings regarding the question of what is exactly dysfunctional in SPEM dysfunction and what component of eye movements is really specific to schizophrenia. The purpose of the current study was to help to clarify the nature of (SPEM) dysfunction and its specificity to schizophrenia. Smooth pursuit eye movements of 43 schizophrenic patients, 34 patients with major depression and 42 normal controls were examined using high resolution infrared oculography. These groups were compared on several indices of oculomotor functioning (gain, different saccadic categories). Schizophrenics had a significantly higher catch-up saccade rate than depressed patients and normals. The percentage of subjects with an abnormally high catch-up saccade rate defined as beyond the mean plus 2 S.D. of the normal control group was significantly higher in schizophrenics (27.9%) than in depressed patients (8.8%) and normal controls (0%). Low gain and higher numbers of intrusive saccades tended to be more prevalent in both patient groups but did not distinguish schizophrenics from depressed patients. Low gain and high rates of intrusive saccades contribute to SPEM dysfunction in major depression. Abnormally high rates of catch-up saccades seem to be the oculomotor component in smooth pursuit, that is specific to schizophrenia.

Smooth-pursuit eye movement dysfunction in schizophrenia: the role of attention and general psychomotor dysfunctions.

Smooth-pursuit eye-tracking performance was examined in 100 schizophrenic patients and various control groups under both attention-enhancing and attention-distracting conditions. The level of attentional demand was varied by introducing a secondary reaction time task that directed attention either toward or away from the visual-tracking target. Distraction from the target led to a significant deterioration of tracking performance in all subjects, which was most pronounced in the group of schizophrenic patients. Attention-enhancement, on the other hand, did not normalize performance in this group. In schizophrenic patients, mainly in the distraction condition, there was a moderate association between performance in tracking and tests presumably measuring prefrontal functions. Tracking accuracy from both conditions was related to general motor performance as measured by the Neurological Evaluation Scale. It was concluded that in schizophrenic patients attentional factors (distraction) may contribute to eye-tracking impairment, and that the impairment may be viewed as an aspect of general motor dysfunctions.

Smooth pursuit eye movements and express saccades in schizophrenic patients

Abnormalities of saccades such as disinhibition have been hypothesized as one cause of smooth pursuit eye movement (SPEM) dysfunctions in schizophrenia. Thus, we studied saccadic eye movements in schizophrenics with SPEM dysfunction. Subjects were divided into three groups: 10 normal control subjects, 10 schizophrenic subjects without SPEM dysfunction and 10 schizophrenic subjects with SPEM dysfunction characterized by a cogwheel appearance. Visually guided saccades in gap and overlap paradigms (Saslow, 1967) were examined and saccadic reaction times (SRTs) were measured in all subjects. Only schizophrenics with SPEM dysfunctions tended to manifest exessive reflexive saccades, named express saccades (Fischer, 1987), in the gap paradigm. Moreover, most of them were also found to have express saccades in the overlap paradigm, whereas normal subjects and schizophrenic subjects without SPEM dysfunction did not show such phenomena under the same conditions. In particular, most express saccades in the overlap paradigm in schizophrenics with SPEM dysfunction, were found in movements to the right.

Smooth Pursuit Eye Movement Dysfunction as a Biological Marker for Prediction of Disease Courses of Schizophrenia: A Preliminary Report

We investigated the relationship between a smooth pursuit eye movement (SPEM) dysfunction and long-term disease courses of schizophrenia. Many schizophrenic patients without the SPEM dysfunction tended to show an acute onset of illness, undulating courses and relatively good outcomes. On the other hand, patients with cogwheel-like SPEM dysfunction tended to show a chronic onset, simple courses, relatively severe outcomes and negative symptoms.

Smooth-pursuit eye movement dysfunction and liability for schizophrenia: Implications for genetic modeling.

Forty-one nonpsychiatric subjects, 38 probands with schizophrenia, and 99 of their relatives were studied. Oculomotor functioning was bimodally distributed for probands and relatives. Oculomotor dysfunction was not present in all families with a schizophrenic proband. In those families in which it was present, there were significant phenotypic correlations between oculomotor functioning and schizophrenia-related characteristics. The patterns of familial resemblance in the families in whom oculomotor dysfunction was present were consistent with nonadditive genetic variance contributing both to oculomotor dysfunction and to the relationship between oculomotor dysfunction and clinical symptoms. These results suggest that schizophrenia may be etiologically heterogeneous and that oculomotor dysfunction may help to identify nonadditive genetic variance for this disorder.

Smooth-pursuit eye movement dysfunction and liability for schizophrenia: implications for genetic modeling.

Forty-one nonpsychiatric subjects, 38 probands with schizophrenia, and 99 of their relatives were studied. Oculomotor functioning was bimodally distributed for probands and relatives. Oculomotor dysfunction was not present in all families with a schizophrenic proband. In those families in which it was present, there were significant phenotypic correlations between oculomotor functioning and schizophrenia-related characteristics. The patterns of familial resemblance in the families in whom oculomotor dysfunction was present were consistent with nonadditive genetic variance contributing both to oculomotor dysfunction and to the relationship between oculomotor dysfunction and clinical symptoms. These results suggest that schizophrenia may be etiologically heterogeneous and that oculomotor dysfunction may help to identify nonadditive genetic variance for this disorder.

Familial prevalence and coaggregation of schizotypy indicators: A multitrait family study.

Schizophrenic probands (n = 17), their first-degree relatives (n = 61), and medically and psychiatrically screened normal control subjects (n = 18) were studied with structured interviews for DSM-III Axis I disorders and schizotypal personality disorder, questionnaire measures of schizotypy, measures of smooth-pursuit eye movement dysfunction, and attention dysfunction. Schizophrenic subjects scored abnormally on essentially all measures. Relatives differed significantly from control subjects on most measures. Correlational analyses indicate that many characteristics tested in these measures run together in families. The data are consistent with the hypothesis that a single vulnerability dimension or typology, presumably in part genetically transmitted, may account for phenotypically distinct abnormalities. These traits, taken together, may have joint usefulness for identifying persons with a predisposition to schizophrenia.

High-risk research in schizophrenia: A summary of what has been learned

High-risk research on schizophrenia has been concerned chiefly with two types of issues: (1) description of background factors in the early lives of high-risk subjects; and (2) identification of biological variables that may be markers of the genetic liability to schizophrenic disorders. It is concluded that efforts to describe background factors have led to some conflicting results, have shown little evidence of specificity of the factors under study to risk for schizophrenia, and may not be generalizable to most individuals who develop schizophrenia. Results of research focusing on biological variables are summarized under the headings of attention and information processing (AIP), smooth pursuit eye movement (SPEM), neurological signs, electrodermal responding, event related potentials, and ventricular size. Of these, certain AIP and SPEM dysfunctions show substantial evidence of serving as biological markers, certain other AIP impairments are promising in this regard, electrodermal responsivity is not, and the other three categories present uncertain or conflicting results. Several methodological issues that have hampered the first generation of high-risk research are discussed.