Saccadic eye movements in families multiply affected with schizophrenia: the Maudsley Family Study.

OBJECTIVE Family studies have shown that abnormalities of smooth pursuit eye movement are increased in the adult relatives of schizophrenic probands as well as in the probands themselves. More recently, an inability of schizophrenic subjects to inhibit reflexive saccades reliably has been shown. This study aimed to test the hypothesis that the latter dysfunction is part of the extended schizophrenia phenotype. METHOD With the use of infrared oculography, measurements of reflexive saccades and antisaccades were undertaken in 29 probands with schizophrenia, 50 of their nonpsychotic first-degree relatives, and 38 unrelated healthy volunteers. RESULTS Probands, relatives, and healthy subjects showed no overall differences in the generation of reflexive saccades. However, in the antisaccade task, probands showed more saccadic distractibility when they were required to inhibit reflexive saccades. Analysis of corrective saccades showed that this was not due to failed comprehension or motivation. Relatives of the probands with high saccadic distractibility showed a higher distractibility rate than relatives of the probands with normal distractibility. Across all subjects, females showed a higher rate of distractibility errors than males. CONCLUSIONS The ability to suppress reflexive saccades is an objective neurocognitive measure that is impaired in schizophrenic patients and in a proportion of their biological relatives. This antisaccade abnormality may be a vulnerability marker in a subset of schizophrenic patients and their families.

[1]  R. Dodge,et al.  AN EXPERIMENTAL STUDY OF THE OCULAR REACTIONS OF THE INSANE FROM PHOTOGRAPHIC RECORDS. , 1908 .

[2]  Dominic W. Hughes,et al.  Eye-Tracking Patterns in Schizophrenia , 1973, Science.

[3]  D. Levy,et al.  Eye-tracking dysfunctions in schizophrenic patients and their relatives. , 1974, Archives of general psychiatry.

[4]  J. Endicott,et al.  A diagnostic interview: the schedule for affective disorders and schizophrenia. , 1978, Archives of general psychiatry.

[5]  J. Sweeney,et al.  Eye movements in schizophrenia: a quantitative analysis. , 1979, Biological psychiatry.

[6]  D. Lykken,et al.  Electro-oculographic recording and scoring of smooth pursuit and saccadic eye tracking: a parametric study using monozygotic twins. , 1979, Psychophysiology.

[7]  J. L. Conway,et al.  Deficits in eye movements following frontal eye-field and superior colliculus ablations. , 1980, Journal of neurophysiology.

[8]  P. Pichot,et al.  Eye-tracking patterns in schizophrenia. An analysis based on the incidence of saccades. , 1981, Archives of general psychiatry.

[9]  M. Baron,et al.  The Schedule for Schizotypal Personalities (SSP): A diagnostic interview for schizotypal features , 1981, Psychiatry Research.

[10]  P. Holzman Methodological Consensus in Smooth Pursuit Eye Movements: Workshop Contributions Smooth Pursuit Eye Movements in Psychopathology , 1983 .

[11]  S. Levin,et al.  Frontal lobe dysfunctions in schizophrenia--I. Eye movement impairments. , 1984, Journal of psychiatric research.

[12]  C. Bruce,et al.  Primate frontal eye fields. I. Single neurons discharging before saccades. , 1985, Journal of neurophysiology.

[13]  M. Schlag-Rey,et al.  Evidence for a supplementary eye field. , 1987, Journal of neurophysiology.

[14]  M. Goldberg,et al.  Functional properties of corticotectal neurons in the monkey's frontal eye field. , 1987, Journal of neurophysiology.

[15]  H. Goldstein Multilevel Statistical Models , 2006 .

[16]  D. Levy,et al.  A single dominant gene can account for eye tracking dysfunctions and schizophrenia in offspring of discordant twins. , 1988, Archives of general psychiatry.

[17]  L. Henderson,et al.  Predictive responses in Parkinson's disease: manual keypresses and saccadic eye movements to regular stimulus events. , 1989, Journal of neurology, neurosurgery, and psychiatry.

[18]  L. Henderson,et al.  Abnormalities of nonvisually-guided eye movements in Parkinson's disease. , 1989, Brain : a journal of neurology.

[19]  J. Sweeney,et al.  Pursuit gain and saccadic intrusions in first-degree relatives of probands with schizophrenia. , 1990, Journal of abnormal psychology.

[20]  K. Fukushima,et al.  Further analysis of the control of voluntary saccadic eye movements in schizophrenic patients , 1990, Biological Psychiatry.

[21]  J Fukushima,et al.  Voluntary control of saccadic eye movements in patients with schizophrenic and affective disorders. , 1990, Journal of psychiatric research.

[22]  L. A. Abel,et al.  Quantitative assessment of smooth pursuit gain and catch-up saccades in schizophrenia and affective disorders , 1991, Biological Psychiatry.

[23]  J. Jesberger,et al.  A model of smooth pursuit performance illustrates the relationship between gain, catch-up saccade rate, and catch-up saccade amplitude in normal controls and patients with schizophrenia , 1991, Biological Psychiatry.

[24]  Sohee Park,et al.  Schizophrenics show spatial working memory deficits. , 1992, Archives of general psychiatry.

[25]  J. Jesberger,et al.  Saccadic intrusions into smooth pursuit in patients with schizophrenia or affective disorder and normal controls , 1992, Biological Psychiatry.

[26]  Anne B. Sereno,et al.  Express Saccades and Smooth Pursuit Eye Movement Function in Schizophrenic, Affective Disorder, and Normal Subjects , 1993, Journal of Cognitive Neuroscience.

[27]  S. Deutsch,et al.  Correlation between antisaccade and Wisconsin Card Sorting Test performance in schizophrenia. , 1993 .

[28]  N. Mendell,et al.  Eye tracking and schizophrenia: a selective review. , 1994, Schizophrenia bulletin.

[29]  Yoshihiko Matsue,et al.  Smooth pursuit eye movements and express saccades in schizophrenic patients , 1994, Schizophrenia Research.

[30]  Y. Matsue,et al.  Smooth Pursuit Eye Movements and Voluntary Control of Saccades in the Antisaccade Task in Schizophrenic Patients , 1994, The Japanese journal of psychiatry and neurology.

[31]  P. Weiden,et al.  Selective effects of antipsychotic medications on eye-tracking performance in schizophrenia , 1994, Psychiatry Research.

[32]  S Zisook,et al.  Saccadic system functioning among schizophrenia patients and their first-degree biological relatives. , 1994, Journal of abnormal psychology.

[33]  Impaired frontal lobe function in schizophrenia is familial , 1995, Schizophrenia Research.

[34]  P. Goldman-Rakic,et al.  Modulation of memory fields by dopamine Dl receptors in prefrontal cortex , 1995, Nature.

[35]  L. Henderson,et al.  Saccadic abnormalities in psychotic patients. II. The role of neuroleptic treatment , 1995, Psychological Medicine.

[36]  Anne B. Sereno,et al.  Antisaccades and smooth pursuit eye movements in schizophrenia , 1995, Biological Psychiatry.

[37]  J. Sweeney,et al.  Eye tracking dysfunctions in offspring from the new york high risk project: Diagnostic specificity and the role of attention , 1995, Schizophrenia Research.

[38]  L. Henderson,et al.  Smooth Pursuit Eye Movement Abnormalities in Patients with Schizophrenia and Focal Cortical Lesions , 1995 .

[39]  L. Henderson,et al.  The functional anatomy of remembered saccades: a PET study. , 1995, Neuroreport.

[40]  D. Hommer,et al.  Early expression of smooth-pursuit eye movement abnormalities in children of schizophrenic parents. , 1996, Journal of the American Academy of Child and Adolescent Psychiatry.

[41]  G. Pearlson,et al.  Eye Movements and Psychopathology in Schizophrenia and Bipolar Disorder , 1996, The Journal of nervous and mental disease.

[42]  C Kennard,et al.  Abnormal saccadic distractibility in patients with schizophrenia: a 99mTc-HMPAO SPET study , 1996, Psychological Medicine.

[43]  A. Lambert,et al.  Antisaccadic eye movements and attentional asymmetry in schizophrenia in three Pacific populations , 1996, Acta psychiatrica Scandinavica.

[44]  J. Rapoport,et al.  Smooth pursuit eye movements in childhood-onset schizophrenia: Comparison with attention-deficit hyperactivity disorder and normal controls , 1996, Biological Psychiatry.

[45]  R. M. Murray,et al.  The Maudsley Family Study, II: Endogenous event-related potentials in familial schizophrenia , 1997, Schizophrenia Research.

[46]  A. Radant,et al.  Relationships between Neuropsychological and Oculomotor Measures in Schizophrenia Patients and Normal Controls , 1997, Biological Psychiatry.

[47]  B. Clementz,et al.  The effect of fixation condition manipulations on antisaccade performance in schizophrenia: studies of diagnostic specificity , 1997, Experimental Brain Research.

[48]  Philip D. Harvey,et al.  Eye tracking, attention, and schizotypal symptoms in nonpsychotic relatives of patients with schizophrenia. , 1997, Archives of general psychiatry.

[49]  John A. Sweeney,et al.  Eye-tracking dysfunction in offspring from the New York High-Risk Project: diagnostic specificity and the role of attention , 1997, Psychiatry Research.

[50]  W. Iacono,et al.  Antisaccade performance in patients with schizophrenia and affective disorder. , 1997, Journal of abnormal psychology.

[51]  R. Freedman,et al.  Familial transmission of two independent saccadic abnormalities in schizophrenia , 1998, Schizophrenia Research.

[52]  Thierry d'Amato,et al.  Saccadic eye movements in schizophrenic patients , 1998, Psychiatry Research.