Experimental Brain Research

, Volume 215, Issue 3–4, pp 219–226

Predictive smooth eye pursuit in a population of young men: II. Effects of schizotypy, anxiety and depression

  • Emmanouil Kattoulas
  • Ioannis Evdokimidis
  • Nicholas C. Stefanis
  • Dimitrios Avramopoulos
  • Costas N. Stefanis
  • Nikolaos Smyrnis
Research Article


Smooth pursuit eye movement dysfunction is considered to be a valid schizophrenia endophenotype. Recent studies have tried to refine the phenotype in order to identify the specific neurophysiological deficits associated with schizophrenia. We used a variation of the smooth eye pursuit paradigm, during which the moving target is occluded for a short period of time and subjects are asked to continue tracking. This is designed to isolate the predictive processes that drive the extraretinal signal, a process previously reported to be defective in schizophrenia patients as well as their healthy relatives. In the current study, we investigated the relationship between predictive pursuit performance indices and age, education, non-verbal IQ, schizotypy and state anxiety, depression in 795 young Greek military conscripts. State anxiety was related to better predictive pursuit performance (increase in residual pursuit gain), while disorganized schizotypy was related to deficient predictive pursuit performance (decreased residual gain). This effect was independent of the effect of disorganized schizotypy on other oculomotor functions supporting the hypothesis that predictive pursuit might be specifically affected in schizophrenia spectrum disorders and could be considered as a distinct oculomotor endophenotype.


Schizophrenia Endophenotype Psychometric Oculomotor Mask pursuit 


  1. Amador XF, Malaspina D, Sackeim HA, Coleman EA, Kaufmann CA, Hasan A, Gorman JM (1995) Visual fixation and smooth pursuit eye movement abnormalities in patients with schizophrenia and their relatives. J Neuropsychiatry Clin Neurosci 7(2):197–206PubMedGoogle Scholar
  2. Becker W, Fuchs AF (1985) Prediction in the oculomotor system: smooth pursuit during transient disappearance of a visual target. Exp Brain Res 57:562–575PubMedCrossRefGoogle Scholar
  3. Berman RA, Colby CL, Genovese CR, Voyovodic JD, Luna B, Thulborn KR, Sweeney JA (1999) Cortical networks subserving pursuit and saccadic eye movements in humans: an fMRI study. Hum Brain Map 8:209–225CrossRefGoogle Scholar
  4. Braff DL, Freedman R, Schork NJ, Gottesman II (2007) Deconstructing schizophrenia: an overview of the use of endophenotypes in order to understand a complex disorder. Schizophr Bull 33(1):21–32PubMedCrossRefGoogle Scholar
  5. Calkins ME, Iacono WG (2000) Eye movement dysfunction in schizophrenia: a heritable characteristic for enhancing phenotype definition. Am J Med Genet 97:72–76PubMedCrossRefGoogle Scholar
  6. Calkins ME, Iacono WG, Curtis CE (2003) Smooth Pursuit and antisaccade performance evidence trait stability in schizophrenia patients and their relatives. Int J Psychophysiol 49:139–146PubMedCrossRefGoogle Scholar
  7. Calkins ME, Iacono WG, Ones DS (2008) Eye movement dysfunction in first-degree relatives of patients with schizophrenia: a meta-analytic evaluation of candidate endophenotypes. Brain Cogn 68(3):436–461PubMedCrossRefGoogle Scholar
  8. Campion D, Thibaut F, Pierre D, Courtin P, Pottier M, Levillain D (1992) SPEM impairment in drug naive schizophrenic patients: evidence for a trait marker. Biol Psychiatry 32:891–902PubMedCrossRefGoogle Scholar
  9. Chapman LJ, Chapman JP, Raulin ML (1978) Body image aberration in schizophrenia. J Abnorm Psychol 87:399–407PubMedCrossRefGoogle Scholar
  10. Clementz BA, McDowell JE (1994) Smooth pursuit in schizophrenia: abnormalities of open- and closed-loop responses. Psychophysiology 31:79–86PubMedCrossRefGoogle Scholar
  11. Derogatis LR, Lipman RS, Rickels K, Uhlenhuth EH, Covi L (1974) The Hopkins symptom checklist (HSCL): a self-report symptom inventory. Behav Sci 19:1–15PubMedCrossRefGoogle Scholar
  12. Diefendorf AR, Dodge R (1908) An experimental study of the ocular reactions of the insane from photographic records. Brain 31:451–489CrossRefGoogle Scholar
  13. Ettinger U, Kumari V, Crawford TJ, Davis RE, Sharma T, Corr PJ (2003) Reliability of smooth pursuit, fixation, and saccadic eye movements. Psychophysiology 40:620–628PubMedCrossRefGoogle Scholar
  14. Ettinger U, Kumari V, Crawford TJ, Corr PJ, Das M, Zachariah E, Hughes C, Sumich AL, Rabe-Hesketh S, Sharma T (2004) Smooth pursuit and antisaccade eye movements in siblings discordant for schizophrenia. J Psychiatry Res 38(2):177–184CrossRefGoogle Scholar
  15. Gooding DC, Basso MA (2008) The tell-tale tasks: a review of saccadic research in psychiatric patient populations. Brain Cogn 68(3):371–390PubMedCrossRefGoogle Scholar
  16. Gottesman II, Gould TD (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 160(4):636–645PubMedCrossRefGoogle Scholar
  17. Gottesman II, Shields J (1973) Genetic theorizing and schizophrenia. Br J Psychiatry 122:15–30PubMedCrossRefGoogle Scholar
  18. Holahan AV, O’Driscoll GA (2005) Antisaccade and smooth pursuit performance in positive- and negative-symptom schizotypy. Schizophr Res 76:43–54PubMedCrossRefGoogle Scholar
  19. Holzman PS, Levy DL (1977) Smooth pursuit eye movements and functional psychoses: a review. Schizophr Bull 3:15–27PubMedGoogle Scholar
  20. Holzman PS, Matthysse S (1990) The genetics of schizophrenia: a review. Psychol Sci 1:279–286CrossRefGoogle Scholar
  21. Holzman PS, Proctor LR, Hughes DW (1973) Eye-tracking patterns in schizophrenia. Science 181:179–181PubMedCrossRefGoogle Scholar
  22. Holzman PS, Proctor LR, Levy DL, Yasillo NJ, Meltzer HY, Hurt SW (1974) Eye-tracking dysfunctions in schizophrenic patients and their relatives. Arch Gen Psychiatry 31:143–151PubMedGoogle Scholar
  23. Hong LE, Avila MT, Adami H, Elliot A, Thaker GK (2003) Components of the smooth pursuit function in deficit and nondeficit schizophrenia. Schizophr Res 63(1–2):39–48PubMedCrossRefGoogle Scholar
  24. Hong LE, Tagamets M, Avila M, Wonodi I, Holcomb H, Thaker GK (2005) Specific motion processing pathway deficit during eye tracking in schizophrenia: a performance-matched functional magnetic resonance imaging study. Biol Psychiatry 57(7):726–732PubMedCrossRefGoogle Scholar
  25. Ilg UJ, Thier P (2008) The neural basis of smooth pursuit eye movements in the rhesus monkey brain. Brain Cogn 68(3):229–240PubMedCrossRefGoogle Scholar
  26. Kallimani D, Theleritis C, Evdokimidis I, Stefanis NC, Chatzimanolis I, Smyrnis N (2009) The effect of change in clinical state on eye movement dysfunction in schizophrenia. Eur Psychiatry 24(1):17–26PubMedCrossRefGoogle Scholar
  27. Karoumi B, Saoud M, d’Amato T, Rosenfeld F, Denise P, Gutknecht C, Gaveau V, Beaulieu FE, Daléry J, Rochet T (2001) Poor performance in smooth pursuit and antisaccadic eye-movement tasks in healthy siblings of patients with schizophrenia. Psychiatry Res 101(3):209–219PubMedCrossRefGoogle Scholar
  28. Kattoulas E, Smyrnis N, Stefanis NC, Avramopoulos D, Stefanis CN, Evdokimidis I (2011) Predictive smooth eye pursuit in a population of young men: I. Effects of age, IQ, oculomotor and cognitive tasks. Exp Brain Res. doi:10.1007/s00221-011-2887-5
  29. Kay SR, Fiszbein A, Opler LA (1987) The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 13(2):261–276PubMedGoogle Scholar
  30. Lencer R, Trillenberg P (2008) Neurophysiology and neuroanatomy of smooth pursuit in humans. Brain Cogn 68(3):219–228PubMedCrossRefGoogle Scholar
  31. Levy DL, Holzman PS, Matthysse S, Mendell N (1993) Eye tracking dysfunction and schizophrenia: a critical perspective. Schizophr Bull 19:461–536PubMedGoogle Scholar
  32. Lisberger SG, Westbrook LE (1985) Properties of visual inputs that initiate horizontal smooth pursuit eye movements in monkeys. J Neurosci 5:1662–1673PubMedGoogle Scholar
  33. Lykouras L, Botsis A, Oulis P (1997) Positive and negative syndrome scale (PANSS). Multi-Health Systems, AthensGoogle Scholar
  34. Nkam I, Thibaut F, Denise P, Van Der Elst A, Ségard L, Brazo P, Ménard J, Théry S, Halbeck I, Delamilleure P, Vasse T, Etard O, Dollfus S, Champion D, Levillain D, Petit M (2001) Saccadic and smooth-pursuit eye movements in deficit and non-deficit schizophrenia. Schizophr Res 48(1):145–153PubMedCrossRefGoogle Scholar
  35. Ntonias S, Karastergiou A, Manos N (1990) Standardization of the symptom checklist 90-R rating scale in a Greek population. Psychiatriki 2:42–48Google Scholar
  36. O’Driscoll GA, Callahan BL (2008) Smooth pursuit in schizophrenia: a meta-analytic review of research since 1993. Brain Cogn 68(3):359–370PubMedCrossRefGoogle Scholar
  37. O’Driscoll GA, Benkelfat C, Florencio PS, WolV AL, Joober R, Lal S, Evans AC (1999) Neural correlates of eye tracking deficits in first-degree relatives of schizophrenic patients: a positron emission tomography study. Arch Gen Psychiatry 56:1127–1134PubMedCrossRefGoogle Scholar
  38. O’Driscoll GA, Wolf AL, Benkelfat C, Florencio PS, Lal S, Evans AC (2000) Functional neuroanatomy of smooth pursuit and predictive saccades. Neuroreport 11:1335–1340PubMedCrossRefGoogle Scholar
  39. Raine A (1991) The SPQ: a scale for the assessment of schizotypal personality in a non-clinical sample-the role of task demand. Schizophr Bull 17:555–564PubMedGoogle Scholar
  40. Roy-Byrne P, Radant A, Wingerson D, Cowley D (1995) Human oculomotor function: reliability and diurnal variation. Biol Psychiatry 38:92–97PubMedCrossRefGoogle Scholar
  41. Sharpe JA (2008) Neurophysiology and neuroanatomy of smooth pursuit: lesion studies. Brain Cogn 68(3):241–254PubMedCrossRefGoogle Scholar
  42. Siever LJ, Friedman L, Moskowitz J, Mitropoulou V, Keefe R, Roitman SL, Merhige D, Trestman R, Silverman J, Mohs R (1994) Eye movement impairment and schizotypal psychopathology. Am J Psychiatry 151:1209–1215PubMedGoogle Scholar
  43. Smyrnis N, Evdokimidis I, Stefanis NC, Avramopoulos D, Costantinidis TS, Stavropoulos A, Stefanis CN (2003) Antisaccade performance of 1,273 men: effects of schizotypy, anxiety, and depression. J Abnorm Psychol 112:403–414PubMedCrossRefGoogle Scholar
  44. Smyrnis N, Kattoulas E, Evdokimidis I, Stefanis NC, Avramopoulos D, Pantes G, Theleritis C, Stefanis CN (2004) Active eye fixation performance in 940 young men: effects of IQ, schizotypy, anxiety and depression. Exp Brain Res 156(1):1–10PubMedCrossRefGoogle Scholar
  45. Smyrnis N, Evdokimidis I, Mantas A, Kattoulas E, Stefanis NC, Constantinidis TS, Avramopoulos D, Stefanis CN (2007) Smooth pursuit eye movements in 1,087 men: effects of schizotypy, anxiety, and depression. Exp Brain Res 179(3):397–408PubMedCrossRefGoogle Scholar
  46. Stefanis NC, Smyrnis N, Avramopoulos D, Evdokimidis I, Ntzoufras I, Stefanis CN (2004) Factorial composition of self-rated schizotypal traits among young males undergoing military training. Schizophr Bull 30(2):335–350PubMedGoogle Scholar
  47. Sweeney JA, Haas GL, Li S, Weiden PJ (1994) Selective effects of antipsychotic medications on eye-tracking performance in schizophrenia. Psychiatry Res 54:185–198PubMedCrossRefGoogle Scholar
  48. Thaker GK (2008) Neurophysiological endophenotypes across bipolar and schizophrenia psychosis. Schizophr Bull 34(4):760–773PubMedCrossRefGoogle Scholar
  49. Thaker GK, Ross DE, Cassady SL, Adami HM, LaPorte D, Medoff DR, Lahti A (1998) Smooth pursuit eye movements to extraretinal motion signals: deficits in relatives of patients with schizophrenia. Arch Gen Psychiatry 55:830–836PubMedCrossRefGoogle Scholar
  50. Thaker GK, Ross DE, Buchanan RW, Adami HM, Medoff DR (1999) Smooth pursuit eye movements to extraretinal motion signals: deficits in patients with schizophrenia. Psychiatry Res 59:221–237CrossRefGoogle Scholar
  51. Thaker GK, Avila MT, Hong EL, Medoff DR, Ross DE, Adami HM (2003) A model of smooth pursuit eye movement deficit associated with the schizophrenia phenotype. Psychophysiology 40(2):277–284PubMedCrossRefGoogle Scholar
  52. Tregellas JR, Tanabe JL, Miller DE, Ross RG, Olincy A, Freedman R (2004) Neurobiology of smooth pursuit eye movement deficits in schizophrenia: an fMRI study. Am J Psychiatry 161:315–321PubMedCrossRefGoogle Scholar
  53. Weinberger DR (1988) Schizophrenia and the frontal lobe. Trends Neurosci 11:367–370PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Emmanouil Kattoulas
    • 1
    • 2
    • 3
  • Ioannis Evdokimidis
    • 1
  • Nicholas C. Stefanis
    • 2
    • 3
  • Dimitrios Avramopoulos
    • 4
  • Costas N. Stefanis
    • 2
  • Nikolaos Smyrnis
    • 1
    • 2
    • 3
  1. 1.Cognition and Action Group, Neurology Department, Medical School, Aeginition HospitalNational and Kapodistrian University of AthensAthensGreece
  2. 2.University Mental Health Research InstituteNational and Kapodistrian University of AthensAthensGreece
  3. 3.Psychiatry Department, Medical School, Aeginition HospitalNational and Kapodistrian University of AthensAthensGreece
  4. 4.McKusick–Nathans Institute of Genetic MedicineJohns Hopkins UniversityBaltimoreUSA

Personalised recommendations