Childhood-onset psychotic disorders: magnetic resonance imaging of volumetric differences in brain structure

OBJECTIVE: Although childhood-onset schizophrenia is rare, children with brief psychotic symptoms and prominent emotional disturbances commonly present diagnostic and treatment problems. Quantitative anatomic brain magnetic resonance images (MRIs) of a subgroup of children with psychotic disorder not otherwise specified were compared with those of children with childhood-onset schizophrenia and healthy comparison subjects. METHOD: Anatomic MRIs were obtained for 71 patients (44 with childhood-onset schizophrenia and 27 with psychotic disorder not otherwise specified) and 106 healthy volunteers. Most patients had been treated with neuroleptics. Volumetric measurements for the cerebrum, anterior frontal region, lateral ventricles, corpus callosum, caudate, putamen, globus pallidus, and midsagittal thalamic area were obtained. RESULTS: Patients had a smaller total cerebral volume than healthy comparison subjects. Analysis of covariance for total cerebral volume and age found that lateral ventricles were larger in both patient groups than in healthy comparison subjects and that schizophrenia patients had a smaller midsagittal thalamic area than both subjects with psychotic disorder not otherwise specified and healthy comparison subjects. CONCLUSIONS: Pediatric patients with psychotic disorder not otherwise specified showed a pattern of brain volumes similar to those found in childhood-onset schizophrenia. Neither group showed a decrease in volumes of temporal lobe structures. Prospective longitudinal magnetic resonance imaging and clinical follow-up studies of both groups are currently underway to further validate the distinction between these two disorders.     

Pursuit tracking impairments in schizophrenia and mood disorders: step-ramp studies with unmedicated patients.

BACKGROUND: Eye tracking abnormalities are highly prevalent in schizophrenia, and are among the most promising phenotypic familial markers for the disorder. The neurophysiologic mechanisms underlying these disturbances and their diagnostic specificity for schizophrenia are not yet well characterized. METHODS: This study assessed eye tracking deficits using foveopetal and foveofugal step-ramp tasks (ramps moving toward and away from central fixation after an initial step respectively) across a range of target velocities in anti-psychotic-naive schizophrenia patients, previously treated but currently unmedicated chronic schizophrenia patients, unmedicated patients with either bipolar or unipolar mood disorders, and healthy volunteers. RESULTS: All patient groups demonstrated reduced pursuit gain in open loop and closed loop visual tracking conditions. There were no significant group differences in the latency or accuracy of catch-up saccades on foveofugal ramp tasks. CONCLUSIONS: These findings indicate that open and closed loop pursuit eye movements are impaired during acute episodes of schizophrenia and mood disorders. The intact accuracy of saccades to moving targets in all patient groups indicates that an adequate representation of motion information is available to the saccade system. Therefore, pursuit disturbances in mood disorders and schizophrenia seem to result, at least in part, from a disturbance in sensorimotor integration in the pursuit system after the initial extraction of sensory motion information. No eye movement abnormalities observed during performance of step ramp tasks were specific to schizophrenia.     

Looking for childhood schizophrenia: case series of false positives

Extensive experience with the diagnosis of childhood-onset schizophrenia indicates a high rate of false positives. Most mislabeled patients have chronic disabling, affective, or behavioral disorders. The authors report the cases of three children who passed stringent initial childhood-onset schizophrenia "screens" but had no chronic psychotic disorder. For two, the European literature yielded more fitting diagnoses: psychosis not otherwise specified (e.g., reactive or psychogenic psychosis, paranoid schizophrenia), single episode in full remission (e.g., anxiety psychosis), and factitious disorder (DSM-IV 300.16). These cases illustrate that transient psychotic illnesses can be misdiagnosed as childhood-onset schizophrenia. Proper identification can prevent years of inappropriate therapies.     

Deficits in gain of smooth pursuit eye movements in schizophrenia and affective disorder patients and their unaffected relatives

OBJECTIVE: Disturbance of smooth pursuit eye movements has been discussed as marking a putative endophenotype closely associated with the genetic basis of schizophrenia. Previous studies are not conclusive in regard to the specificity of this marker. Therefore, oculomotor pursuit was evaluated in unaffected family members of index probands diagnosed as having either schizophrenia or affective disorders. METHOD: A series of eye tracking tasks were performed by 54 patients with schizophrenia or schizoaffective disorder, 46 patients with an affective disorder, 43 unaffected first-degree relatives of the schizophrenia patients, 36 unaffected first-degree relatives of the affective disorder patients, and 84 healthy comparison subjects. The gain, which relates the velocity of the eye movement to the velocity of the target, was determined to index the intactness of the oculomotor pursuit system. RESULTS: Mean pursuit gain was significantly lower in the schizophrenia and affective disorder patients than in the healthy comparison subjects. Moreover, the relatives of both the schizophrenia and affective disorder patients showed significant gain deficits of about one-half the size of those observed in the patients. CONCLUSIONS: Gain deficits are present in psychotic patients and in their unaffected biological relatives. This finding supports a genetic origin of eye tracking disturbances in major psychotic disorders. There is no evidence for diagnostic or familial specificity. The weak sensitivity of the marker suggests that it refers to a nonnecessary genetic factor in schizophrenic and affective disorders.     

Effect of typical antipsychotic medications and clozapine on smooth pursuit performance in patients with schizophrenia.

The effect of typical neuroleptic drugs or clozapine on smooth pursuit eye movements was tested in 13 patients with schizophrenia or schizoaffective disorder with a repeated measures design. Nineteen normal control subjects were also studied. Compared with controls, patients in the unmedicated state had low smooth pursuit gain, had a higher rate of corrective catch-up saccades, and tended to spend less time engaged in the tracking task. The patients did not significantly differ from controls on catch-up saccade amplitude, square wave jerk rate, or anticipatory saccade rate. Medication with clozapine, but not typical neuroleptics, was associated with an increase in median catch-up saccade amplitude. Number of days on clozapine and clozapine dose both correlated significantly with a worsening of oculomotor performance. No effect of medication with typical neuroleptics was found, although there was some evidence suggesting that such an affect may occur after more prolonged treatment.     

The effects of age on a smooth pursuit tracking task in adults with schizophrenia and normal subjects.

BACKGROUND: Performance during a smooth pursuit eye movement (SPEM) task has been proposed as a marker of genetic risk for schizophrenia, although the precise component of SPEM tracking most associated with genetic risk remains undetermined. Normal adult aging is associated with deterioration on SPEM tasks; it remains unclear whether investigations of SPEM abnormalities will allow inclusion of older subjects in genetic studies. This study examines 1) the effect of normal aging on several components of SPEM performance; and 2) whether schizophrenic-normal differences found in young adults continue over a broad adult age span. METHODS: SPEM was recorded during a 16.7 degrees per sec constant velocity task in 64 normal adults, ages 18 to 79 years, and 58 schizophrenic subjects, ages 18 to 70 years. RESULTS: Smooth pursuit gain, the percent of total eye movements due to catch-up saccades, the frequency of large anticipatory saccades, and the frequency of leading saccades all deteriorate with increasing age. After correction for age, schizophrenic to control differences persist on most eye movement variables with the largest effect sizes for leading saccades (1.56) and smooth pursuit gain (1.17). CONCLUSIONS: The tendency to use saccades to anticipate target motion, even in small steps (leading saccades), deserves further attention as a potential marker useful in genetic analyses.     

Quantitative characterization of eye tracking dysfunction in schizophrenia

The purpose of this study was to characterize the nature of the processes that are involved in eye tracking dysfunction (ETD). We identified a combination of quantitative measures that best distinguished qualitatively normal eye tracking from qualitatively abnormal eye tracking, using discriminant analysis. Discriminant scores distinguished schizophrenics with ETD from both schizophrenics with normal eye tracking and normal controls, but did not distinguish schizophrenics with normal eye tracking from normal controls, underscoring the heterogeneity of schizophrenic patients with respect to eye tracking. The results of the discriminant analysis indicated that ETD is a multivariate process involving a primary impairment in the smooth pursuit system characterized by increased catch-up saccades and reduced gain, and, secondarily, disinhibition of intrusive saccades, especially square-wave jerks. Quantitative characterization of ETD makes it possible to consider eye tracking as a quantitative trait in genetic investigations of a multidimensional phenotype.     

What is deviant about deviant smooth pursuit eye movements in schizophrenia?

Smooth pursuit eye movements of schizophrenic, hospitalized nonpsychotic, and normal control subjects (18 per group) were measured in low and high target information conditions. A computer method for measuring saccade frequency and velocity was used. The results indicated that the frequency of saccades was significantly greater in both tracking conditions for schizophrenic than for hospitalized nonpsychotic or normal subjects. Consistent with our earlier finding, the reduction in saccade frequency with high information was greatest for schizophrenic subjects. The results also yielded a unique finding: the velocity of saccades within smooth pursuit records was significantly greater for schizophrenic than for hospitalized nonpsychotic or normal subjects. Greater saccade velocity was not a result of increased saccade size; there was no significant difference in the size of saccades for normal and schizophrenic subjects. Yet, the duration of saccades was significantly less for schizophrenics than for other subjects. Target information affected the frequency, duration and size, yet not the velocity of saccades emitted by all subjects. In contrast to earlier interpretations of deviant smooth pursuit eye movements in schizophrenia, the results may provide the first evidence of differences in the functioning of the saccadic eye movement systems of schizophrenic and normal subjects.     

Smooth pursuit performance in families with multiple occurrence of schizophrenia and nonpsychotic families.

BACKGROUND: Eye tracking dysfunction (ETD) has been put forward as a trait marker for biological susceptibility to schizophrenia with the hope of identifying a link to specific cerebral lesions. METHODS: Eye movements were recorded using infrared oculography in 8 families (67 members) showing multiple occurrence of schizophrenia and in 9 nonpsychotic families (80 members). Triangle wave stimuli at 15 degrees/s and 30 degrees/s were used and gains (eye velocity/target velocity), rates and amplitudes of different saccade categories (catch-up, back-up, anticipatory saccades, and squarewave-jerks) were determined. RESULTS: In the relatives, the same deficit in maintenance of smooth pursuit performance was found as was seen in the schizophrenic patients. This deficit, which was not observed in the nonpsychotic families, consisted of lower gains for leftward as compared to rightward pursuit. This was emphasized most clearly at 30 degrees/s and was associated with an excess of catch-up saccades in the schizophrenic patients, whereas in the relatives a tendency to exhibit more and larger anticipatory saccades was observed. CONCLUSIONS: The results confirm the hypothesis that eye-tracking dysfunction is a phenotypic marker for genetic liability to schizophrenia. Neurophysiologically, a cerebral dysfunction which includes one or more of the oculomotor centers can be assumed in subjects who carry a genetic susceptibility to schizophrenia.     

Clozapine and obsessions in patients with recent-onset schizophrenia and other psychotic disorders.

BACKGROUND: The increase or emergence of obsessions was compared in young patients with recent-onset schizophrenia or other psychotic disorders taking clozapine and other antipsychotic drugs. METHOD: We conducted a retrospective cohort study. Subjects were 121 consecutively admitted patients diagnosed with DSM-III-R schizophrenia, schizoaffective disorder, schizophreniform disorder, or psychotic disorder not otherwise specified. Obsessions were diagnosed according to DSM-IV criteria. RESULTS: More clozapine-treated subjects (20.6%) than subjects treated with other antipsychotic drugs (1.3%) experienced an emergence or increase of obsessions (p<.01). CONCLUSION: Use of clozapine is associated with the emergence or increase of obsessions in early-phase schizophrenia.     

Ocular motor responses to unpredictable and predictable smooth pursuit stimuli among patients with obsessive-compulsive disorder.

This study was conducted to evaluate the smooth pursuit system functioning of patients with obsessive-compulsive disorder (OCD). For Study 1, 12 subjects with OCD and 12 nonpsychiatric subjects were administered 9-deg-per-sec ramp stimuli to elicit smooth pursuit eye movements. Consistent with a previous report, patients with OCD did not significantly differ from nonpsychiatric subjects on pursuit gain, or frequency of corrective and intrusive saccades. Patients with OCD, however, had smaller catch-up saccades during smooth pursuit than nonpsychiatric subjects. For Study 2, 12 subjects with OCD and 12 nonpsychiatric subjects were administered 2 different triangle wave stimuli with target velocities of 12 (0.2 Hz) deg per sec and 24 (0.4 Hz) deg per sec. Subjects with OCD and nonpsychiatric subjects did not significantly differ on any variable in the slow target velocity condition. When following 24-deg-per-sec targets, however, patients with OCD had significantly lower pursuit gain than the nonpsychiatric subjects. Results from Study 1 and 2 are consistent with the hypothesis that patients with OCD have a modest smooth pursuit deficit that is elicited only while following faster velocity targets.     

Eye tracking disorders in schizophrenic patients and their parents

Several studies have confirmed the existence of genetic factors in schizophrenia. However, the genotype predisposing for the disease is not known yet. Nevertheless, those genetic factors in the families of schizophrenic patients urge us to search for genetic vulnerability markers of schizophrenia. Ocular pursuit disorders, in particular, could be one of those vulnerability markers. Eye movements have been often tested in schizophrenia. Most of the schizophrenic patients have eye-tracking disorders and their biological relatives demonstrate an increased prevalence of eye-tracking impairments. The aim of the study was to research if smooth pursuit eye movements could be a vulnerability marker of schizophrenia. In order to have an indication about this hypothesis, impairments of smooth pursuit eye movements were researched in both schizophrenics and their parents. METHODS: Fifteen DSM IV schizophrenic patients stabilized at the time of the inclusion and not treated with lithium, benzodiazepines, barbiturates, or chloral hydrate; 19 parents without history of schizophrenic spectrum disorders (SADSLA and IPDE), and 2 groups of healthy subjects matched in age and sex with probands and with the parents, were included in the study. Parents only were included (fathers or mothers) in order to have an homogeneous population for the genetic risk and age. The eye-tracking paradigm used was a smooth pursuit task. The stimulus was a sinusoidal wave form moving on a horizontal line, with a frequency of 0.4 Hz and an amplitude of 30 degrees. Different parameters were measured: gain (ratio between the eye velocity and the target velocity) and saccades frequencies (catch-up saccades, back-up saccades, anticipatory saccades and square-wave-jerks). For each parameter, analysis of covariance (ANCOVA) with age as covariable was carried out. For the results reaching the significance of 0.05, the Bonferroni correction was applied (level of significance 0.016). The effect size of the parameter was calculated ((the mean of the subjects minus the mean of the matched controls) divided by standard deviation of the two groups). According to Cohen, 0.20 indicates a small effect size, 0.50 indicates a medium effect size and 0.80 indicates a large effect size. RESULTS: Comparison between patients and matched controls: the means of global gain, of gain for the movements to the left and of gain for the movements to the right did not differ significantly between patients and their matched controls. The size effects are 0.31 for the global gain, 0.20 for the movements to the left and 0.41 for the movements to the right. The frequencies of total saccades, catch-up saccades, back-up saccades, anticipatory saccades and square-wave-jerks did not differ significantly between patients and their controls. The size effects for those parameters were 0.09, 0.03, 0.00, 0.39 and 0.63 respectively. Comparison between parents and matched controls: the means of global gain, of gain for the movements to the left and of gain for the movements to the right did not differ significantly between the two groups. The size effects for those parameters were 0.00, 0.05 and 0.17 respectively. The frequency of total saccades did not differ significantly between the groups whereas the size effect was 0.63. The frequency of catch-up saccades was significantly more important in parents than in controls (p = 0.006) and the size effect was 0.80. The other saccadic parameters did not differ significantly between groups, their size effects were 0.24 for the back-up saccades, 0.21 for the anticipatory saccades and 0.00 for the square-wave-jerks. Whereas the gain of the patients had a tendency to be lower than the gain of their controls, no significant difference was observed between patients and their controls. Only a size effect of 0.63 for the frequency of square-wave-jerks was obtained. This large effect size suggests that the difference between patients and controls might be significant in a larger sample. The catch-up saccades frequency between parents and controls was significant. The differences between our study and the previous studies could be due to several factors. The paradigms used were different between the studies and our sample was small (only 15 patients and 19 relatives). Moreover, some patients in the previous studies were treated by lithium, drug well known to modify ocular pursuit and, finally the relatives in the other studies were 10 years older than ours and age is known to alter ocular pursuit. Since an impairment of the smooth pursuit was observed in the relatives of schizophrenic patients but not in the probands, this study does not support the hypothesis that eye-tracking disorders could be considered as a marker of vulnerability of schizophrenia.     

Differences in smooth pursuit eye movement between posttraumatic stress disorder with secondary psychotic symptoms and schizophrenia

Studies show high comorbidity between post-traumatic stress disorder and psychotic symptoms. Despite this fact, there has been only one published study of the neurobiology of this enigmatic disorder. This preliminary study examines the relationship between psychotic symptoms in post-traumatic stress disorder (PTSD) and schizophrenia by measuring smooth pursuit eye movement (SPEM) in subjects with PTSD and secondary psychotic symptoms, schizophrenia, and healthy controls. The results show that PTSD with secondary psychotic symptoms is associated with a SPEM deficit that is different from the SPEM deficit associated with schizophrenia.     

Physiology of schizophrenia, bipolar disorder, and schizoaffective disorder

OBJECTIVE: Endophenotypes have been proposed to identify the genetic and biological substrates of complex disorders. Three physiological inhibitory endophenotypes of large effect size in schizophrenia include suppression of P50 auditory evoked responses, inhibition of leading (small anticipatory) saccades during smooth pursuit eye movements, and cancellation of reflexive saccades in the antisaccade eye movement task. The aim of this study was to determine if the pattern of endophenotype abnormalities within individuals with schizophrenia differed from that within individuals with bipolar disorder. A second aim was to determine whether subjects with schizoaffective disorder, bipolar type, were neurophysiologically more similar to subjects with schizophrenia or subjects with bipolar disorder. METHOD: Endophenotypes were recorded for subjects diagnosed with schizophrenia (N=29), bipolar disorder (DSM-IV-TR) (N=40), and schizoaffective disorder, bipolar type (N=18). Data from normal comparison subjects were used to establish normal performance. RESULTS: Logistic regression determined that P50 ratio and frequency of leading saccades identified subjects with schizophrenia and bipolar disorder with a sensitivity of 95% and a specificity of 83%. The schizoaffective disorder group was split, with six subjects physiologically classified as schizophrenia-like and 12 subjects as bipolar-like. Those classified as schizophrenia-like were significantly younger at illness onset and had higher symptom ratings. CONCLUSION: A composite endophenotype of P50 ratio and frequency of leading saccades is consistent with the current clinical nosology of schizophrenia and bipolar disorder and parses patients with schizoaffective disorder, bipolar type, into two subgroups.     

Confirmatory factor analysis in neurophysiological and neuropsychological dimensions of schizophrenia

This study applied confirmatory factor analysis (CFA) to examine the construct of smooth pursuit eye movements (SPEM) and the Wisconsin Card Sorting Test (WCST) in schizophrenia. Participants were assigned to two groups: Group 1 included 27 probands chosen from families with schizophrenia in first-degree relatives, and Group 2 included 54 schizophrenics who had no families with schizophrenia spectrum disorders. There were no differences in the eye tracking pursuit and the WCST between the sporadic and familial schizophrenics. Gender impacted the catch-up saccades (CUS) and anticipatory saccades (AS) indices of the SPEM, and the conceptual level responses (CLR) index of the WCST. Education impacted the CLR and perseverative errors of the WCST. Although there were no correlation between the SPEM and the WCST, but the two instruments showed good content validity, which might be useful in the subtyping of schizophrenia.     

Changes in eye tracking during clinical stabilization in schizophrenia

Eye tracking abnormalities have been proposed as a trait marker for schizophrenia on the basis of their familial prevalence and the consistency of tracking over time in clinically stable patients. However, few studies have examined stability through acute episodes of illness, and most studies have not analyzed changes in different forms of eye movements. Therefore, the authors examined eye tracking, clinical state, and neuroleptic dose during 4 consecutive weeks in nine recently hospitalized schizophrenic patients. For the patients and controls, qualitative ratings of pursuit accuracy remained relatively stable over time. In contrast, saccade frequency increased significantly, with a 57% increase in small saccades and a 77% reduction in larger saccades. In comparison with cross-sectional studies which have found no correlation between neuroleptic dose and tracking performance, a reduction in large saccades was strongly correlated with increase in neuroleptic dose. The findings suggest that pursuit accuracy may be a trait characteristic of schizophrenia, while the frequency and size of saccades are state dependent characteristics.     

Altered transfer of visual motion information to parietal association cortex in untreated first-episode psychosis: implications for pursuit eye tracking

Visual motion processing and its use for pursuit eye movement control represent a valuable model for studying the use of sensory input for action planning. In psychotic disorders, alterations of visual motion perception have been suggested to cause pursuit eye tracking deficits. We evaluated this system in functional neuroimaging studies of untreated first-episode schizophrenia (N=24), psychotic bipolar disorder patients (N=13) and healthy controls (N=20). During a passive visual motion processing task, both patient groups showed reduced activation in the posterior parietal projection fields of motion-sensitive extrastriate area V5, but not in V5 itself. This suggests reduced bottom-up transfer of visual motion information from extrastriate cortex to perceptual systems in parietal association cortex. During active pursuit, activation was enhanced in anterior intraparietal sulcus and insula in both patient groups, and in dorsolateral prefrontal cortex and dorsomedial thalamus in schizophrenia patients. This may result from increased demands on sensorimotor systems for pursuit control due to the limited availability of perceptual motion information about target speed and tracking error. Visual motion information transfer deficits to higher-level association cortex may contribute to well-established pursuit tracking abnormalities, and perhaps to a wider array of alterations in perception and action planning in psychotic disorders.     

A quantitative analysis of saccades and smooth pursuit during visual pursuit tracking. A comparison of schizophrenics with normals and substance abusing controls.

The eye movements of schizophrenic patients are characterized by decreased smooth pursuit gain and an increased frequency of saccades. However, the nature of these saccades and their function during smooth pursuit has not been clearly defined. To address this issue we examined the eye movements of 22 schizophrenic patients, 20 substance abusing patients (primarily alcohol; some with concomitant cocaine and/or cannabis abuse), and 17 normal controls during a visual pursuit task using infra-red oculography. A computerized pattern recognition algorithm divided pursuit eye movements into two basic components: smooth pursuit and saccadic eye movements. The algorithm also determined eye position error and velocity error before and after each saccade. Schizophrenic patients had lower smooth pursuit gain (p less than 0.02) and made more saccades during smooth pursuit (p less than 0.02) than either comparison group. When saccades were assigned to subcategories based on direction and position error, only the frequency of 'catch-up' saccades differentiated schizophrenic patients from the comparison groups (p less than 0.05). Smooth pursuit gain was negatively correlated with saccadic frequency among all three subject groups. Eye velocity preceding saccades was significantly lower among the schizophrenic patients, but pre or post saccadic position error did not differ among the three groups. Discrete analysis of the fine structure of visual pursuit tracking may lead to a better understanding of eye movement abnormalities in schizophrenia.     

Evidence from increased anticipation of predictive saccades for a dysfunction of fronto-striatal circuits in obsessive-compulsive disorder

In obsessive-compulsive disorder (OCD), a dysfunction of neuronal circuits involving prefrontal areas and the basal ganglia is discussed that implies specific oculomotor deficits. Performance during reflexive and predictive saccades, antisaccades and predictive smooth pursuit was compared between patients with OCD (n=22), patients with schizophrenia (n=21) and healthy subjects (n=24). Eye movements were recorded by infrared reflection oculography. In both patient groups, higher frequencies of anticipatory saccades with reduced amplitudes in the predictive saccade task were observed. Additionally, reduced smooth pursuit eye velocity and increased frequencies of saccadic intrusions during smooth pursuit as well as increased error rates in the antisaccade task were demonstrated for patients suffering from schizophrenia. Patients with OCD and schizophrenia revealed different patterns of oculomotor impairment: whereas increased anticipation of predictive saccades provides evidence for a dysfunction of the circuit between the frontal eye field and the basal ganglia in both groups, results from the antisaccade task imply additional deficits involving the dorsolateral prefrontal cortex in schizophrenic patients. Furthermore, the cortical network for smooth pursuit (especially the frontal eye field) is also assumed to be disturbed in schizophrenia.     

Catechol O-methyltransferase polymorphism and eye tracking in schizophrenia: a preliminary report

OBJECTIVE: This study examined associations between functional polymorphism (Val(108/158) Met) in the catechol O-methyltransferase (COMT) gene and eye tracking measures in schizophrenia. METHOD: Predictive pursuit and closed-loop gains of 62 patients with schizophrenia and 53 healthy comparison subjects with Val-Val, Val-Met, and Met-Met genotypes were compared. RESULTS: There was a significant diagnosis-by-genotype interaction: patients with the Met-Met genotype showed poor predictive pursuit. The Met-Met genotype in healthy subjects was associated with significantly higher predictive pursuit gain values than the Val-Val genotype in healthy subjects. The COMT genotype explained about 10% of the variance in each group's predictive pursuit performance. DISCUSSION: These preliminary data suggest that the COMT gene is associated with predictive eye tracking performance in healthy subjects. Predictive pursuit abnormality in schizophrenia is not attributable to the Val allele. These findings suggest a complex interaction with other etiological factors (e.g., another gene), and/or with prefrontal cortical dopaminergic activity.