Eye Tracking Abnormalities Research Articles

Antisaccade and memory-guided saccade in individuals at ultra-high-risk for bipolar disorder

BackgroundUltra-high-risk for bipolar disorder (UHR-BD) is an important paradigm to investigate the potential early-stage biomarkers of bipolar disorder, including eye-tracking abnormalities and cognitive functions. Antisaccade (AS) described as looking in the opposite direction of the target, and memory-guided saccade (MGS), identified as maintaining fixation, and remembering the location of the target, were used in this study. The aim of this study was to evaluate the differences in saccadic eye movements between UHR-BD and healthy controls (HCs) via AS-MGS. MethodsThe study included 28 UHR-BD and 29 HCs. Participants were selected using a structured clinical interview for prodromal symptoms of BD. AS-MGS were measured with parameters like uncorrected errors, anticipatory saccades, and latency. Eye movements were recorded with the EyeLink 1000-Plus eye-tracker. ResultsIn the AS, the number of correct saccades was significantly decreased in UHR-BD (p = 0.020). Anticipatory (p = 0.009) and express saccades (p = 0.040) were increased in UHR-BD. In the MGS paradigm, the correct saccades were reduced in UHR-BD (p = 0.031). In addition, anticipatory (p = 0.004) and express saccades (p = 0.012) were significantly increased in cue-screen in UHR-BD. ConclusionsTo our knowledge, this is the first study to evaluate cognitive functions with eye movements in individuals at UHR-BD. The current findings showed that eye movement functions, particularly in saccadic parameters related to inhibition and spatial perception, may be affected in the UHR-BD group. Therefore, assessment of oculomotor functions may provide observation of clinical and cognitive functions in the early-stage of bipolar disorder. However, further research is needed because the potential effects of medication may affect saccadic results.

Effects of hyperbaric oxygen on eye tracking abnormalities in males after mild traumatic brain injury.

The effects of hyperbaric oxygen (HBO2) on eye movement abnormalities in 60 military servicemembers with at least one mild traumatic brain injury (TBI) from combat were examined in a single-center, randomized, double-blind, sham-controlled, prospective study at the Naval Medicine Operational Training Center. During the 10 wk of the study, each subject was delivered a series of 40, once a day, hyperbaric chamber compressions at a pressure of 2.0 atmospheres absolute (ATA). At each session, subjects breathed one of three preassigned oxygen fractions (10.5%, 75%, or 100%) for 1 h, resulting in an oxygen exposure equivalent to breathing either surface air, 100% oxygen at 1.5 ATA, or 100% oxygen at 2.0 ATA, respectively. Using a standardized, validated, computerized eye tracking protocol, fixation, saccades, and smooth pursuit eye movements were measured just prior to intervention and immediately postintervention. Between and within groups testing of pre- and postintervention means revealed no significant differences on eye movement abnormalities and no significant main effect for HBO2 at either 1.5 ATA or 2.0 ATA equivalent compared with the sham-control. This study demonstrated that neither 1.5 nor 2.0 ATA equivalent HBO2 had an effect on postconcussive eye movement abnormalities after mild TBI when compared with a sham-control.

Is Motion Perception Deficit in Schizophrenia a Consequence of Eye-Tracking Abnormality?

Studies have shown that schizophrenia patients have motion perception deficit, which was thought to cause eye-tracking abnormality in schizophrenia. However, eye movement closely interacts with motion perception. The known eye-tracking difficulties in schizophrenia patients may interact with their motion perception. Two speed discrimination experiments were conducted in a within-subject design. In experiment 1, the stimulus duration was 150 msec to minimize the chance of eye-tracking occurrence. In experiment 2, the duration was increased to 300 msec, increasing the possibility of eye movement intrusion. Regular eye-tracking performance was evaluated in a third experiment. At 150 msec, speed discrimination thresholds did not differ between schizophrenia patients (n = 38) and control subjects (n = 33). At 300 msec, patients had significantly higher thresholds than control subjects (p = .03). Furthermore, frequencies of eye tracking during the 300 msec stimulus were significantly correlated with speed discrimination in control subjects (p = .01) but not in patients, suggesting that eye-tracking initiation may benefit control subjects but not patients. The frequency of eye tracking during speed discrimination was not significantly related to regular eye-tracking performance. Speed discrimination, per se, is not impaired in schizophrenia patients. The observed abnormality appears to be a consequence of impairment in generating or integrating the feedback information from eye movements. This study introduces a novel approach to motion perception studies and highlights the importance of concurrently measuring eye movements to understand interactions between these two systems; the results argue for a conceptual revision regarding motion perception abnormality in schizophrenia.

Eye tracking in schizophrenia: Does the antisaccade task measure anything that the smooth pursuit task does not?

Smooth pursuit and antisaccade eye-tracking abnormalities have been proposed as endophenotypes for schizophrenia. However, it is not clear whether these tasks measure the same underlying abnormality. We hypothesised that these measures would be correlated. The association between smooth pursuit and antisaccade task performance was assessed in 50 schizophrenic patients, 80 unaffected first-degree relatives and 40 unaffected controls. Smooth pursuit measures included gain, number of saccades and a qualitative measure of smooth pursuit. The antisaccade distractibility error (ADE) score was the only measure of the antisaccade task. A significant correlation was found between reduced gain and an increased ADE score for all the subjects in the three groups combined. The total number of saccades was negatively correlated with the ADE score in the schizophrenic group, but positively in the relative group. Qualitative ratings of smooth pursuit correlated with the ADE score. Our results suggest that the antisaccade distractibility error score is related to gain and qualitative measures of smooth pursuit, although the relationship with number of saccades did not conform to this pattern. The finding may reflect a shared genetic liability, that affects both eye-tracking phenotypes. It is likely that both measures reflect frontal cortical dysfunction.

Childhood-onset schizophrenia: smooth pursuit eye-tracking dysfunction in family members

Background Childhood-onset schizophrenia (COS), a severe form of the disorder, is of interest for etiologic studies. Smooth pursuit eye-tracking dysfunction (ETD) is a biological marker for schizophrenia. Aims To compare familial eye-tracking abnormalities for COS and adult-onset schizophrenia (AOS). Method Eye-tracking performance for 70 COS parents, 64 AOS parents and 20 COS siblings was compared to their respective age-matched control groups. Results COS and AOS parents had higher rate of dichotomously rated eye-tracking dysfunction than their respective controls (16% vs. 1% and 22% vs. 4%, respectively). COS parents and siblings also differed from controls on several continuous measures. However, scores for COS, AOS and control groups overlapped extensively. Conclusions Genetic factors underlying eye-tracking dysfunction appear more salient for COS. However, eye-tracking measures have to be used with caution for endophenotypic definition due to low predictive power. Declaration of interest The study was done at the National Institutes of Health.

Substance abuse (including nicotine) in schizophrenic patients

Comorbid substance-use disorders are present in at least 25% of patients with schizophrenia, and 70-80% of these patients smoke. It is important to understand how substance-use disorders affect outcomes in this already impaired population. Substance-use disorders occur most commonly in males, and are most prevalent in the young. Substance-use disorders are associated with bad outcomes, including medication non-compliance, rehospitalization, homelessness, contact with the criminal justice system, medical morbidity and suicide, and these bad outcomes seem to be more likely among those patients who utilize multiple drugs rather than alcohol alone. Psychosocial and behavioral treatments produce few successes. Early indications suggest that clozapine may reduce substance-use disorders. Nicotine corrects certain neurophysiological deficits (e.g. eye-tracking abnormalities) in patients with schizophrenia. Maternal smoking during pregnancy may increase the likelihood of antisocial behavior and substance-use disorder in the offspring. Atypical antipsychotics plus bupropion increase the likelihood of smoking reduction/cessation in patients with schizophrenia. The recent literature clearly documents the devastating effects of comorbid substance-use disorders in schizophrenia. Promising new treatment options will require further study.

Effects of ketamine on leading saccades during smooth-pursuit eye movements may implicate cerebellar dysfunction in schizophrenia.

Ketamine has proved a useful probe in the study of schizophrenia. Recent studies have shown that ketamine causes abnormalities in eye tracking similar to those seen in patients with schizophrenia. The authors examined the effects of ketamine on leading saccadic eye movements, a specific component of the smooth-pursuit response shown to be abnormal in schizophrenia patients and their relatives. Twelve normal healthy volunteers received a 0.1 mg/kg bolus injection of ketamine or placebo in double-blind fashion during a smooth-pursuit eye-movement task. The number of leading saccades and the ratios of leading saccades to smooth-pursuit response time and to total saccadic eye-movement time were measured. Ketamine significantly increased the number of leading saccades and increased the leading saccade ratios for more slowly moving targets. Similar nonsignificant effects were noted at higher target speeds. Ketamine-induced abnormalities were similar to those observed in relatives of schizophrenia patients under drug-free conditions. These results suggest that neurotransmission mediated by N-methyl-D-aspartate (NMDA) is involved in eye-tracking abnormalities. The generation of disruptive leading saccades during smooth pursuit is thought to be mediated by frontal-thalamic-cerebellar circuitry. Evidence that the locus of this and other ketamine-induced smooth-pursuit eye-movement deficits involves NMDA receptor functioning in the cerebellum is suggested.

Progress toward discovery of susceptibility genes for bipolar manic-depressive illness and schizophrenia.

The inconsistency in linkage results that has bedeviled psychiatric genetics has been observed to occur regularly in common diseases with complex inheritance. Nonetheless, in two such instances--noninsulin-dependent diabetes mellitus (NIDDM) and inflammatory bowel disease (IBD)--susceptibility genes have been discovered based on the follow-ups of linkage findings. In bipolar illness disorder (BPD) and schizophrenia (SZ), there are some linkage reports with replication of other studies similar to the situation in NIDDM and IBD before the successful positional cloning efforts. Two of the regions with linkage reports, BPD and SZ, on the long arms of chromosomes 13 and 22, show linkage to the same markers in both diseases. This lends some plausibility to the hypothesis of some shared genetic predispositions for both disorders. Cytogenetic evidence offers another positional approach to susceptibility genes. The velocardiofacial syndrome is associated with deletions very close to the linkage region on chromosome 22, and with psychiatric manifestations of both BPD and SZ. Endophenotypes of SZ, previously demonstrated to the be heritable, have been found to have chromosomal linkage in at least one study. These include eye-tracking abnormalities linked to 6p, and an abnormality of the P50 cortical evoked potential linked to chromosome 15. Variants in specific genes have been associated with susceptibility to the psychiatric illnesses. These genetic findings may contribute to etiologic subcategorization of BPD and SZ, and the development of new treatment approaches. A table of genetic terms is included for review

Incorporation of molecular data and redefinition of phenotype: new approaches to genetic epidemiology of bipolar manic depressive illness and schizophrenia

Considerable advances have been made in identifying specific genetic components of bipolar manic depressive illness (BP) and schizophrenia (SZ), despite their complex inheritance. Meta-analysis of all published whole-genome linkage scans reveals overall support for illness genes in several chromosomal regions. In two of these regions, on the lonq arm of chromosome 13 and on the long arm of chromosome 22, the combined studies of BP and SZ are consistent with a common susceptibility locus for the two disorders. This lends some plausibility to the hypothesis of some shared genetic predispositions for BP and SZ. Other linkages are supported by multiple studies of specific chromosomal regions, most notably two regions on chromosome 6 in SZ. The velocardiofacial syndrome is associated with deletions very close to the linkage region on chromosome 22, and with psychiatric manifestations of both BP and SZ. Endophenotypes of SZ, previously demonstrated to be heritable, have been found to have chromosomal linkage in at least one study. These include eye-tracking abnormalities linked to the short arm of chromosome 6, and abnormality of the P50 cortical evoked potential linked to chromosome 15. Variants in specific genes have been associated with susceptibility to illness, and other genes have been associated with susceptibility to side effects of pharmacological treatment. These genetic findings may eventually be part of an integrated genetic, environmental, and interactive-factor epidemiology of the major mental illnesses.

Eye tracking abnormalities in schizophrenia: evidence for dysfunction in the frontal eye fields

Background: Eye tracking deficits are robust abnormalities in schizophrenia, but the neurobiological disturbance underlying these deficits is not known. Methods: To clarify the pathophysiology of eye tracking disturbances in schizophrenia, we tested 12 first-episode treatment-naive schizophrenic patients and 10 matched healthy individuals on foveofugal and foveopetal step-ramp pursuit tasks. Results: On foveopetal tasks, the initiation of pursuit eye movements was delayed in schizophrenic patients, and their steady-state pursuit gain was reduced particularly at slower target speeds (8 and 16 deg/sec). In foveofugal step-ramp tasks, their primary catch-up saccades were normal in latency and accuracy, but their postsaccadic pursuit in the first 100 msec after the primary catch-up saccade was significantly reduced even relative to their slow steady-state pursuit, especially during and immediately after an acute episode of illness. Conclusions: These observations indicate that motion-sensitive areas in posterior temporal cortex provide sufficiently intact information about moving targets to guide accurate catch-up saccades, but that the sensory processing of motion information is not being used effectively for pursuit eye movements. Low-gain pursuit after the early stage of pursuit initiation suggests that the use of extraretinal signals about target motion (e.g., anticipatory prediction) only partially compensates for this deficit. The pattern of low-gain pursuit, impaired pursuit initiation, and intact processing of motion information for catch-up saccades but not pursuit eye movements, was consistent in the schizophrenic patients tested at five time points over a 2-year follow-up period, and implicates the frontal eye fields or their efferent or afferent pathways in the pathophysiology of eye tracking abnormalities in schizophrenia.

Schizophrenia research: a biennium of progress. Proceedings from the Sixth International Congress on Schizophrenia Research. Colorado Springs, CO, April 12-16, 1997.

The Sixth International Congress on Schizophrenia Research (ICOSR) took place in Colorado Springs, Colorado, April 12-16, 1997, where over 1,000 scientists presented and listened to the latest developments in the search for the cause and treatment of schizophrenia. The ICOSR is sponsored by Maryland Psychiatric Research Center, Case Western Reserve University, and the William K. Warren Foundation. The National Institute of Mental Health and several pharmaceutical companies contributed generously to the meeting. The ICOSR is co-organized by Dr. Carol A. Tamminga, Maryland Psychiatric Research Center, University of Maryland at Baltimore, and Dr. S. Charles Schulz, Case Western Reserve University, Cleveland, Ohio. The William K. Warren Research Award is given to a senior investigator, who has made outstanding contributions to our understanding of schizophrenia. The fifth William K. Warren Research Award was presented to Dr. Philip S. Holzman in recognition of his contributions to the identification of eye-tracking abnormalities as a potential phenotypic marker of the illness and also in recognition of his work as a lifelong mentor for schizophrenia researchers. The ICOSR Young Investigator Awards are presented to junior investigators who have demonstrated the potential to make significant contributions to research on schizophrenia. These awards promote scientific development by enabling these young researchers to attend the meeting. There were 30 Young Investigator Award winners. The ICOSR meeting is organized into four sessions: (1) a morning plenary session; (2) a plenary lecture; (3) a poster session; and (4) concurrent afternoon oral sessions. The morning plenary sessions are comprised of a set of 30-minute lectures, which provide an overview of a particular topic area relevant to schizophrenia research. The plenary lecture is an invited lecture on a basic topic related to current research efforts in schizophrenia. The poster sessions provide a forum for the presentation of prepublication reports of basic and clinical science projects. The afternoon sessions are a collection of approximately 10 focused presentations on current research projects related to a specific topic area. The purpose of this report is to provide an account of the proceedings from the plenary and afternoon oral sessions.

Eye-tracking dysfunction in offspring from the New York High-Risk Project: diagnostic specificity and the role of attention

Eye tracking abnormalities were studied in the offspring of schizophrenic, unipolar depressed and bipolar probands from the New York High-Risk Project to examine their familial specificity. Offspring of schizophrenic and depressed probands both had significant global performance deficits based on spectral purity measurements, but only the offspring of schizophrenic probands had an increased rate of intrusive anticipatory saccades. The greater specificity of high anticipatory saccade rate than global performance impairment suggests that this eye movement abnormality may provide a more specific biological marker of risk for schizophrenia than the global measure of eye tracking performance used in this study. Attention facilitation effectively normalized all performance deficits in the offspring of schizophrenic patients, suggesting that a problem sustaining focused visual attention may contribute to eye tracking deficits observed in the relatives of schizophrenic probands.

Implications of Comorbidity for Genetic Studies of Bipolar Disorder: P300 and Eye Tracking as Biological Markers for Illness

In large families with affective illness, identification of a biological variable is needed that reflects brain dysfunction at an earlier point than symptom development. Eye movement disorder, a possible vulnerability marker in schizophrenia, is less clearly associated with affective illness, although a subgroup of affective disorders shows smooth-pursuit eye movement disorder. The auditory P300 event-related potential may be a useful marker for risk to schizophrenia, but a role in bipolar illness is less certain. The distribution of these two biological variables and their association with symptoms in two multiply affected bipolar families is described. In a single, five-generation family identified for linkage studies through two bipolar I (BPI) probands, 128 members (including 20 spouses) were interviewed. The 108 related individuals had diagnoses of BPI (7), bipolar II (2), cyclothymia (3), or major depressive disorder (19). Eight others had generalised anxiety (1), minor depression (5), intermittent depression (1), or alcoholism (1). Sixty-nine subjects had no psychiatric diagnosis. P300 latency (81) and eye tracking (71) were recorded from a subgroup of relatives within the pedigree. Eye tracking was abnormal in 11 of 71 relatives (15.5%) and was bimodally distributed. In these 11 relatives, clinical diagnoses included minor depression (1), alcoholism (1) and generalised anxiety disorder (1). P300 latency was normally distributed and did not differ from controls. In a second family in which five of seven siblings have BPI illness, P300 latency and eye movement disorder were found in affected relatives and in some unaffected offspring. In these large families, clinical diagnoses of general anxiety, alcoholism and minor depression, when associated with eye tracking abnormality, may be considered alternative clinical manifestations of the same trait that in other relatives is expressed as bipolar illness.

The construct validity of root-mean-square error for quantifying smooth-pursuit eye tracking abnormalities in schizophrenia

Smooth-pursuit eye tracking abnormalities have been consistently observed among schizophrenia patients and their relatives (Iacono and Clementz 1993; Levy et al 1993). Using a statistical technique called mixture analysis, recent studies have demonstrated that distributions of both the patients' and their relatives' ocular motor data are best characterized by two distinct components (Blackwood et al 1991; Clementz et al 1992; Gibbons et al 1984; Iacono et al 1992; Ross et al in press; Sweeney et al 1993). One component overlaps the scoring distribution of normal subjects fairly closely, whereas the other component captures subjects with poor eye tracking performance. The pattern of results suggests that ocular motor measures are capturing differences in kind among schizophrenia subjects, and that these differences are indexing biologically distinct subgroups of patients in whose families ocular motor abnormalities are an indicator of vulnerability for some form of this illness. This conclusion is consistent with a report suggesting linkage between eye tracking abnormalities and markers on chromosome 6 (Arolt et al 1995; see also Wang et al 1995). The above results, which rely primarily on global measures of eye tracking performance, should be considered in light of current trends to use specific measures, such as saccadic performance and the calculation of smooth pursuit gain, to

Eye movements in spectrum personality disorders: comparison of community subjects and relatives of schizophrenic patients

The purpose of the current study was to test the specificity of an association between eye tracking abnormality and schizophrenia spectrum personality symptoms in the family members of schizophrenic patients. The studies of biological markers for genetic vulnerability to schizophrenia, which test an association between a biological measure and schizophrenia spectrum personality symptoms, are constrained, since these personality symptoms may lack the specificity for a schizophrenic phenotype. An association between a behavioral measure and these personality symptoms in general can easily be false (i.e., not related to schizophrenic vulnerability). In contrast, a strong deviant finding in the relatives of schizophrenic patients with spectrum personality symptoms, in the presence of a relatively normal finding in spectrum subjects without a known history of schizophrenia, makes the biobehavioral measure an interesting candidate for such investigations. Seventy-five subjects recruited from the community who did not have a family history of psychosis completed the study (24 of the 75 had significant schizophrenia spectrum personality symptoms). Thirty-two first-degree relatives of schizophrenic patients (13 with spectrum symptoms) completed the study. Subjects were 18-45 years old and had no DSM-III-R axis I diagnosis. Qualitative smooth pursuit eye movement score was significantly worse in relatives with the spectrum symptoms than in spectrum subjects without a family history of schizophrenia and the nonspectrum relatives. Schizotypal and schizoid symptoms explained a significant amount of the variance in the eye tracking measure in the relatives (31% and 20%, respectively) but not in the community subjects (less than 2%). Relatives of schizophrenic patients with and without the spectrum symptoms had significantly longer antisaccade latency, in spite of comparable latency for visually guided saccades, than the community subjects. Smooth pursuit abnormality in subjects with schizophrenia spectrum personality disorders is specifically associated with a family history of schizophrenia.

Smooth pursuit eye movement differences between familial and non-familial schizophrenia

Disrupted smooth pursuit eye tracking characterizes a greater proportion of individuals with schizophrenia than in the normal population. The finding of a similar increased incidence of eye tracking abnormality in first degree relatives of schizophrenics implicates this disorder as a potential biological marker for schizophrenia. To test the assumption that the eye tracking dysfunction of schizophrenics is genetically related, left and right smooth pursuit gain and phase shift were compared between 20 schizophrenics with a family history of schizophrenia or schizophrenia-related disorders, 18 schizophrenics without a family history, as well as for 18 normal controls. Subjects tracked pendular targets on an LED light bar moving at frequencies of 0.2 and 0.7 Hz. Horizontal eye movements were recorded using DC-electro-oculography. Results indicate that schizophrenics with a positive family history had significantly reduced right pursuit gain compared with controls, while right gain for negative family history schizophrenics did not differ from either group. Schizophrenic subjects also were administered neuropsychological tests. Linear regression by groups analyses reveal that neuropsychological measures significantly predicted right gain to slower targets (0.2 Hz) for the positive family history schizophrenics, but not for negative family history schizophrenics.

Correlation of regional cerebral blood flow equivalents measured by single photon emission computerized tomography with P300 latency and eye movement abnormality in schizophrenia

Single photon emission tomography with the intravenous blood flow marker 99mTc-exametazime was carried out in 14 acutely ill drug-free schizophrenic patients from whom P300 event-related potential, smooth eye pursuit eye tracking and verbal fluency were measured within a few days of scanning. Smooth pursuit eye movement abnormality correlated significantly with abnormal tracer uptake in superior pre-frontal cortex on the right and left and inferior pre-frontal cortex on the left. Abnormal eye movement was also associated with higher tracer uptake in left anterior cingulate and left posterior cingulate. P300 latency was significantly correlated with higher tracer uptake in left superior pre-frontal and left parietal regions. Verbal fluency performance was negatively correlated with tracer uptake in left frontal region. Eye tracking abnormality in schizophrenia is associated with bilateral frontal lobe disturbance and P300 latency increase with left-sided frontal and temporoparietal dysfunction. There was, however, a significant inverse relation between eye tracking abnormalities and abnormal perfusion in the left anterior cingulate region.

Eye tracking dysfunction in schizophrenia: characterization of component eye movement abnormalities, diagnostic specificity, and the role of attention.

To characterize oculomotor components and diagnostic specificity of eye tracking abnormalities in schizophrenia, we examined a large consecutively admitted series of psychotic patients and matched controls. The most common abnormality in schizophrenic patients was low gain (slow) pursuit eye movements (47% of cases). Pursuit and saccadic eye movement abnormalities were no more severe in schizophrenic Ss than in those with affective psychoses, except that high rates of catch-up saccades were unique to schizophrenic Ss (17% of cases). These findings indicate that impaired pursuit eye movements are a major cause of eye tracking impairments in schizophrenia, that tracking dysfunctions commonly occur in affective psychoses, and that markedly high rates of catch-up saccades during eye tracking may be specific to schizophrenia.

Brain morphology, dopamine, and eye-tracking abnormalities in first-episode schizophrenia. Prevalence and clinical correlates.

To characterize the pathophysiology of schizophrenia and to identify biologic markers in first-episode patients with no or little prior treatment exposure. Prospective study of an inception cohort. Psychiatric division of an academic medical center with a suburban metropolitan catchment area. 70 patients in their first episode of schizophrenia (77%) or schizoaffective disorder (23%) with no (70%) or limited prior neuroleptic exposure (30%), and 50 healthy volunteer control subjects. ASSESSMENT MEASURES: Demographic and clinical evaluations of natural history and psychopathology; methylphenidate hydrochloride and apomorphine hydrochloride stimulation tests as measures of central nervous system dopamine activity; brain magnetic resonance imaging; eye-tracking examinations. Preliminary analyses demonstrate that pathobiologic features previously identified in heterogeneous and primarily chronically ill patients are also present in subgroups during their first episode. These include psychotogenic response to methylphenidate (59%), abnormal growth hormone (GH) secretion (50%), abnormal brain morphology (31%), and eye-tracking dysfunction (51%). An association of pathobiologic variables with increased symptom severity and earlier age of onset was observed but not statistically significant. The strongest associations among biologic variables were for the following: GH secretion and psychotogenic response to methylphenidate, which may reflect increased dopamine agonist neural activity; decreased GH response to apomorphine and third-ventricle enlargement, which may represent a neuropathologic correlate of anterior pituitary abnormalities; and morphologic abnormalities of the medial temporal lobe and third ventricle were associated with normal eye tracking, suggesting that these pathobiologic features are mediated by distinct processes. These phenomena appear to be a consequence of the disease rather than the effects of chronicity, drug treatment, or institutionalization. It remains to be determined if these biologic phenomena will remain stable over time or change with disease progression. A companion article examines the clinical significance of these findings.

Eye Tracking Abnormalities in Two Micronesian Families with Schizophrenia

Smooth pursuit eye movement (SPEM) was examined in members of two Palauan families, one with eight cases and the other with six cases of schizophrenia. Abnormal eye-tracking was present in 63% of the schizophrenic patients studied and in 53% of the first-degree relatives studied. These proportions correspond closely to those found in studies of Caucasian families with multiple incidence of schizophrenia.