Seymour S. Kety and the genetics of schizophrenia.
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History, 20th Century↗
Biomedical subjects
P S Holzman
Publications and source records attributed to P S Holzman.
A new look at reaction time in schizophrenia.
Schizophrenia patients demonstrate impaired manual reaction time (RT), but not saccadic RT, when given traditional tasks. To determine whether the manual RT time impairment could be eliminated by providing imperative stimuli to the finger (thus providing stimulus-response compatibility), we tested 28 chronic schizophrenic patients on finger-lift RT to visual (VIS), tactile plus visual (TAC+VIS), and auditory plus tactile plus visual (AUD+TAC+VIS) stimuli. The patients (a) were significantly slower than controls (n=28) in all three tasks, (b) showed bimodality, with 43% of patients having means and variances nearly identical to control values, and (c) had RTs significantly closer to control values in the TAC+VIS and AUD+TAC+VIS tasks than in the VIS task. The inability to normalize finger-lift RT in schizophrenia represents a genuine slowing of this response system regardless of stimulus-response compatibility. We consider other possible explanations for the differences between manual and saccadic RT, including the notion that excess processing capacity for saccadic RT may be masking possible deficits in that system.
Acoustic Stimulation↗
Eye movements and the search for the essence of schizophrenia.
Clinical Schizophrenia has eluded precise description because of its protean phenotypic manifestations and variable clinical course, a variability that also makes it difficult to discover genetic linkages. Co-familial traits have higher recurrence risk rates than schizophrenia itself and might serve as pointers to the underlying physiology of schizophrenic illness. A dysfunction of smooth pursuit eye movements is one such co-familial trait that occurs in about 40 to 80% of schizophrenic patients and about 25 to 40% of their first degree relatives. The eye movement abnormality appears only when the subject tracks a moving target. We have traced this abnormality to a deficit in velocity sensitivity, a function that is regulated by a specific central nervous system network that includes the middle temporal and medial superior temporal areas of the extra-striate cortex. The higher familial recurrence risk of abnormal eye tracking, compared with that of clinical schizophrenia (about 5 to 8%), suggests that schizophrenic psychosis may be the rare form of a more prevalent disorder whose symptoms are much milder and more benign than the cognitive and behavioral disturbances of the clinical psychosis. From this vantage point, abnormal eye tracking can be viewed as one pleiotropic manifestation of schizophrenia, considered broadly, just as the café-au-lait spots of neurofibromatosis are a more benign and more frequent manifestation of that disease than are the neurofibromata.
Animals↗
Contextual insensitivity in schizophrenic language processing: evidence from lexical ambiguity.
The authors investigated whether contextual failures in schizophrenia are due to deficits in the detection of context or the inhibition of contextually irrelevant information. Eighteen schizophrenia patients and 24 nonpsychiatric controls were tested via a cross-modal semantic priming task. Participants heard sentences containing homonyms and made lexical decisions about visual targets related to the homonyms' dominant or subordinate meanings. When sentences moderately biased subordinate meanings (e.g., the animal enclosure meaning of pen), schizophrenia patients showed priming of dominant targets (e.g., paper) and subordinate targets (e.g., pig). In contrast, controls showed priming only of subordinate targets. When contexts strongly biased subordinate meanings, both groups showed priming only of subordinate targets. The results suggest that inhibitory deficits rather than context detection deficits underlie contextual failures in schizophrenia.
Adult↗
Psychophysical isolation of a motion-processing deficit in schizophrenics and their relatives and its association with impaired smooth pursuit.
Schizophrenia patients and many of their relatives show impaired smooth pursuit eye tracking. The brain mechanisms underlying this impairment are not yet known, but because reduced open-loop acceleration and closed-loop gain accompany it, compromised perceptual processing of motion signals is implicated. A previous study showed that motion discrimination is impaired in schizophrenia patients. Motion discrimination can make use of position and contrast as well as velocity cues. Here, we report that the motion discrimination deficit, which occurs in both schizophrenic patients and in their first-degree relatives, involves a failure of velocity detection, which appears when judging intermediate target velocities. At slower and faster velocities, judgments of velocity discrimination seemed normal until we experimentally disentangled velocity cues from nonmotion cues. We further report that compromised velocity discrimination is associated with sluggish initiation of smooth pursuit. These findings point to specific central nervous system correlates of schizophrenic pathophysiology.
Adult↗
Motion perception in schizophrenia.
BACKGROUND: Eye-tracking dysfunction has been found in many patients with schizophrenia and in about 40% of their first-degree biological relatives. We hypothesized that a deficit in motion processing is associated with eye-tracking dysfunction because both motion signals and the brain regions responsible for processing motion signals are implicated in the generation of smooth pursuit. We examined several aspects of visual perception, including motion perception, in patients with schizophrenia. METHODS: To evaluate motion perception, contrast sensitivity for velocity discrimination was measured in patients with schizophrenia (n=15) and normal control subjects (n=18). Contrast sensitivities for orientation discrimination and contrast detection were measured as control tasks. RESULTS: Patients with schizophrenia showed significantly lower contrast sensitivity (ie, higher thresholds) than normal controls for the discrimination of small velocity differences (eg, 11 vs 9 degrees/s). This reduction in contrast sensitivity was severe (up to 10-fold) in about 40% of the patients. No group differences were found on the other tasks. CONCLUSION: The discrimination of small velocity differences is impaired in a subgroup of patients with schizophrenia.
Brain↗
Dependence of impaired eye tracking on deficient velocity discrimination in schizophrenia.
BACKGROUND: Abnormal smooth pursuit eye movements have been found in many schizophrenic patients and in about 40% of their first-degree biological relatives. A velocity discrimination deficit has also been demonstrated in schizophrenic patients. In this study, we address the relation between deficient velocity discrimination and impaired smooth pursuit eye movements, inasmuch as the brain regions responsible for processing velocity signals are implicated in generating and maintaining smooth pursuit. METHODS: Horizontal eye movements of 15 schizophrenic patients and 8 normal controls were recorded in response to sine wave (predictable) and step-ramp (nonpredictable) targets. Smooth pursuit eye movements were assessed during both the initiation and maintenance periods. Correlations were computed between measures of smooth pursuit (qualitative rating, peak gain, saccade frequency, and initial acceleration) and contrast sensitivity for velocity discrimination. RESULTS: Contrast sensitivity for fine velocity discrimination was significantly correlated both with initial acceleration of smooth pursuit and with peak gain, but was not significantly correlated with saccade frequency and qualitative ratings of pursuit integrity. No significant correlations were found within the normal control group. CONCLUSION: Deficient processing of velocity information seems to be one component that contributes to a dysfunction in the initiation and maintenance of smooth pursuit in schizophrenia.
Brain↗
Eye-tracking dysfunction and birth-month weather in schizophrenia.
The prevalence of eye-tracking dysfunction (ETD) is significantly elevated in individuals with a diagnosis of schizophrenia and in their nonschizophrenic relatives, suggesting that ETD marks a familial (most likely genetic) risk factor for schizophrenia. Birth in a season with intemperate weather is also a widely reported risk factor for schizophrenia and is particularly marked for the subgroup with no family history of the disorder. This study examined how these two risk factors covaried in 78 patients with a Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; American Psychiatric Association, 1987) diagnosis of schizophrenia. Eye tracking and birth-month weather were independently assessed. As hypothesized, patients without ETD were significantly more likely to be born in months with intemperate weather (both hot and cold) than either patients with ETD or people in the general population. Etiologic factors associated with severe weather near birth may be important sources of nonfamilial schizophrenia.
Adult↗
Differences in cerebral activation during smooth pursuit and saccadic eye movements using positron-emission tomography.
BACKGROUND: Abnormalities of smooth pursuit eye movements occur commonly in schizophrenia, but the pathophysiological significance of these abnormalities is unknown. To address this, the authors conducted a pilot study in which we examined differences in regional cerebral activation using positron-emission tomography (PET) in normal volunteers as they performed two types of eye movements. METHODS: Cerebral activation in 10 normal volunteers was studied using C15O2 PET while subjects tracked a visual target using smooth pursuit and saccadic eye movements. A left-hand movement comparison task provided a physiologic landmark for verification of the location of the frontal eye fields (FEFs). RESULTS: Subjects exhibited FEF activation during both smooth pursuit and saccadic eye movements, which was greater in the latter. During smooth pursuit, subjects also exhibited increased cerebral activation in the left temporal-occipital border and left superior frontal cortex and decreased activation in medial superior parietal and insular regions relative to saccades. Other cortical visual and eye-movement brain regions also demonstrated differences in activation between the two visual tasks. CONCLUSIONS: Significant fEF activation appears to underlie both smooth pursuit and saccadic eye movements but may be more critical in the former. Dysfunction of the frontal lobe, and possibly of other areas in the pursuit pathway such as the temporo-occipital motion area, may contribute to observed eye-movement abnormalities in patients with schizophrenia.
Adolescent↗
On preserving the National Institute of Mental Health Career Scientist Award.
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Career Mobility↗
Antisaccades and smooth pursuit eye tracking and schizotypy.
BACKGROUND: Eye tracking deficits are one of a few widely validated behavioral markers of risk for schizophrenia. Recently, it has been proposed that antisaccade performance may also constitute a marker of schizophrenia risk. This study investigated whether eye tracking and antisaccade deficits could be found in another population with putative liability to schizophrenia-nonclinical subjects with elevated scores on a psychometric index of perceptual aberrations. METHODS: Subjects were 55 university students who received either high or normal scores on the Perceptual Aberration Scale, a measure of schizotypy indexing body image and perceptual distortions. Subjects completed a smooth pursuit eye tracking task and an antisaccade task. Eye movements were monitored using an infrared limbus tracker. RESULTS: Subjects with high Perceptual Aberration Scale scores (putative "schizotypes") had lower pursuit quality and a lower percentage correct on the antisaccade task than the controls. The 2 groups did not differ in antisaccade or error latencies. The increase in antisaccade errors in the schizotypes was accounted for almost entirely by an increase in perseverative errors, but virtually no difference between groups on random errors. Antisaccade performance was significantly related to pursuit quality. CONCLUSIONS: Subjects with elevated Perceptual Aberration Scale scores have performance deficits on oculomotor tasks that have been linked to latent liability to schizophrenia, namely, smooth pursuit and antisaccade performance. The antisaccade errors in the schizotype group were primarily perseverations, a behavioral pattern often associated with frontal lobe dysfunction and observed in the performance of schizophrenic patients.
Adult↗
Inverse relationship of perinatal complications and eye tracking dysfunction in relatives of patients with schizophrenia: evidence for a two-factor model.
OBJECTIVE: Because both smooth pursuit eye tracking dysfunction and obstetrical complications are significant risk factors for schizophrenia, the authors tested the predictions of a two-factor model of how eye tracking dysfunction and obstetrical complications covary in patients with schizophrenia, their siblings, and comparison subjects. METHOD: Psychiatric diagnoses, eye tracking dysfunction, and obstetrical complications noted in birth records were independently assessed in 18 patients with schizophrenia, 16 of their siblings without schizophrenia, and 49 comparison subjects with neither personal nor family histories of schizophrenia. RESULTS: As hypothesized, 1) the combination of eye tracking dysfunction and perinatal obstetrical complications discriminated patients with schizophrenia significantly from subjects without schizophrenia, including siblings of patients with schizophrenia, and 2) eye tracking dysfunction and perinatal obstetrical complications manifested a significant inverse association in the nonschizophrenic siblings of patients with schizophrenia. CONCLUSIONS: These results support a two-factor model in which obstetrical complications often interact with genetic liability, indicated by eye tracking dysfunction, to produce schizophrenia.
Adult↗
Detection of a large CTG/CAG trinucleotide repeat expansion in a Danish schizophrenia kindred.
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Alleles↗
Smooth pursuit eye tracking in twins. A critical commentary.
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Data Interpretation, Statistical↗
Thought disorder in schizophrenic and control adoptees and their relatives.
BACKGROUND: Previous research showed significantly elevated levels of thought disorder in the relatives of persons with schizophrenia, as well as in the persons with schizophrenia themselves. Comparisons of schizophrenic and control adoptees and their respective relatives provide a method for minimizing the confounding of genetic and environmental sources of familial resemblance and for elucidating whether the elevated levels of thought disorder in persons with schizophrenia and their relatives reflect the influence of shared genetic factors, shared environmental factors, or both. The present study provides the first such adoption-sample data on an operationally defined measure of thought disorder. METHODS: Speech samples elicited by standard interview questions from schizophrenic and control adoptees and their respective biological and adoptive relatives were tape-recorded. Verbatim transcripts of these speech samples were scored, while unaware of the personal or family diagnoses of the subjects, using the Thought Disorder Index (TDI). RESULTS: The mean TDI scores were significantly higher in schizophrenic than in control adoptees and in biological relatives of the schizophrenic adoptees than in the biological relatives of the control adoptees, whereas the respective groups of adoptive relatives did not differ significantly. The differences were most marked for the samples of biological sibs and half sibs, which were larger and more representative than the samples of parents. CONCLUSION: Results suggest that the elevated TDI scores in the relatives of persons with schizophrenia that have been found in other studies reflect the operation of genes increasing the liability for schizophrenia, rather than the rearing experiences that were shared in common with schizophrenic probands.
Adolescent↗
Perceptual organization in schizophrenia: utilization of the Gestalt principles.
In 2 experiments, the authors investigated perceptual organization in schizophrenia to determine whether patients with schizophrenia used the Gestalt principles. In the visual embedded figures task (Experiment 1), the authors examined the principles of proximity and collinearity, whereas in the similarity task (Experiment 2), the authors examined similarity. Forty-three people participated in the study: patients diagnosed with schizophrenia (14) or with bipolar disorder (15), and "normal" participants (14). All 3 groups of participants showed performance superiority in the condition that was facilitated by the use of the Gestalt principles in both tasks. This study supports the hypothesis that visual perceptual organization, in terms of utilizing the Gestalt principles, is relatively intact in people with schizophrenia.
Adult↗
Spatial selective attention in schizophrenic, affective disorder, and normal subjects.
Schizophrenic, affective disorder, and normal subjects performed tasks involving exogenous (automatic) and endogenous (voluntary) attention. In the exogenous attention task, schizophrenic subjects demonstrated a greater benefit in response time than did normal subjects. In the endogenous attention task, however, schizophrenic subjects showed a smaller benefit in response time than did normal subjects. These results are consistent with a model of schizophrenia that predicts a deficit in voluntary (endogenous) control, and a disinhibition and therefore enhancement of the automatic (exogenous) processes of spatial selective attention. Affective disorder subjects did not demonstrate a greater benefit in response time than normal subjects in the exogenous attention task, but did show a smaller benefit in response time than normal subjects in the endogenous attention task. The somewhat similar pattern of behavior of schizophrenic and affective disorder subjects suggests that abnormal spatial selective attentional processes may not be specific to schizophrenia.
Adult↗
Thought disorder, perceptual aberrations, and schizotypy.
Empirical links between schizophrenia and schizotypic psychopathology were examined. The Perceptual Aberration Scale (PerAb; L. J. Chapman, J. O. Chapman, & M. L. Raulin, 1978) was used to identify putative schizotypic individuals and a contrast group of nonschizotypic controls. The Thought Disorder Index (TDI; M. J. Coleman et al., 1993) was used to quantify and classify thought disorder in these individuals. High PerAb participants, selected for having an increased number of self-reported perceptual and body image aberrations, showed an elevation in the amount and frequency of thought disorder as well as an increased number of idiosyncratic verbalizations. This supports the hypothesis that psychometrically identified schizotypic individuals display thought disorder similar to that shown by schizophrenic patients and some of their 1st-degree relatives, suggesting that there is a relation between schizotypic psychopathology, as tapped by the PerAb scale, and clinical schizophrenia.
Adolescent↗