Eye movement dysfunction in first-degree relatives of patients with schizophrenia: A meta-analytic evaluation of candidate endophenotypes

Monica E. Calkins, William G. Iacono, Deniz S. Ones

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96 Scopus citations

Abstract

Several forms of eye movement dysfunction (EMD) are regarded as promising candidate endophenotypes of schizophrenia. Discrepancies in individual study results have led to inconsistent conclusions regarding particular aspects of EMD in relatives of schizophrenia patients. To quantitatively evaluate and compare the candidacy of smooth pursuit, saccade and fixation deficits in first-degree biological relatives, we conducted a set of meta-analytic investigations. Among 18 measures of EMD, memory-guided saccade accuracy and error rate, global smooth pursuit dysfunction, intrusive saccades during fixation, antisaccade error rate and smooth pursuit closed-loop gain emerged as best differentiating relatives from controls (standardized mean differences ranged from .46 to .66), with no significant differences among these measures. Anticipatory saccades, but no other smooth pursuit component measures were also increased in relatives. Visually-guided reflexive saccades were largely normal. Moderator analyses examining design characteristics revealed few variables affecting the magnitude of the meta-analytically observed effects. Moderate effect sizes of relatives v. controls in selective aspects of EMD supports their endophenotype potential. Future work should focus on facilitating endophenotype utility through attention to heterogeneity of EMD performance, relationships among forms of EMD, and application in molecular genetics studies.

Original languageEnglish (US)
Pages (from-to)436-461
Number of pages26
JournalBrain and Cognition
Volume68
Issue number3
DOIs
StatePublished - Dec 2008

Bibliographical note

Funding Information:
Author note: This research was supported by R01’s MH49738, MH65578, a Neurobehavioral Traineeship (MH17069), a University of Minnesota Graduate School Doctoral Dissertation Fellowship, a Neuropsychiatry Post-Doctoral Traineeship (MH19112), a Scottish Rite Schizophrenia Research Fellowship, and a Mentored Clinical Scientist K Award (K08MH79364). Earlier datasets appearing in this paper were presented at the Society of Biological Psychiatry Annual Meeting, Toronto, Canada, May 1998 (Biological Psychiatry, 43, 126s) and at the Biennial meeting of the International Congress on Schizophrenia Research, Whistler, British Columbia, April 2001 (Schizophrenia Research, 49, s212–s213). We thank the hundreds of researchers and thousands of research participants whose efforts made this work possible, and gratefully acknowledge the effort made by the researchers whom we contacted for additional information about their work.

Keywords

  • Endophenotype
  • Eye movement dysfunction
  • Fixation
  • Genetics
  • Relative
  • Saccade
  • Schizophrenia
  • Smooth pursuit

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