Advertisement

Antisaccade and prosaccade eye movements in individuals clinically at risk for psychosis: comparison with first-episode schizophrenia and prediction of conversion

  • Luca Kleineidam
  • Ingo Frommann
  • Stephan Ruhrmann
  • Joachim Klosterkötter
  • Anke Brockhaus-Dumke
  • Wolfgang Wölwer
  • Wolfgang Gaebel
  • Wolfgang Maier
  • Michael WagnerEmail author
  • Ulrich Ettinger
Original Paper
  • 41 Downloads

Abstract

Saccadic eye movements are well-described markers of cerebral function and have been widely studied in schizophrenia spectrum populations. However, less is known about saccades in individuals clinically at risk for schizophrenia. Therefore, we studied individuals in an at-risk mental state (ARMS) (N = 160), patients in their first episode of schizophrenia (N = 32) and healthy controls (N = 75). N = 88 ARMS participants showed an early at-risk mental state (E-ARMS), defined by cognitive-perceptive basic symptoms (COPER) or a combination of risk and loss of function, whereas N = 72 were in a late at-risk mental state (L-ARMS), defined by attenuated psychotic symptoms or brief limited intermittent psychotic symptoms. We examined prosaccades, reflecting overt attentional shifts, and antisaccades, measuring inhibitory control, as well as their relationship as an indicator of the interplay of bottom–up and top–down influences. L-ARMS but not E-ARMS participants had increased antisaccade latencies compared to controls. First-episode patients had higher antisaccade error rates compared to E-ARMS participants and controls, and increased latencies compared to all other groups. Prosaccade latencies did not differ between groups. We observed the expected negative correlation between prosaccade latency and antisaccade error rate, indicating that individuals with shorter prosaccade latencies made more antisaccade errors. The magnitude of the association did not differ between groups. No saccadic measure predicted conversion to psychosis within 2 years. These findings confirm the existence of antisaccade impairments in patients with schizophrenia and provide evidence that volitional response generation in the antisaccade task may be affected even before onset of clinically overt psychosis.

Keywords

Antisaccade Prosaccade Clinical high risk Prognostic biomarkers 

Notes

Acknowledgements

This work was supported by the German Federal Ministry for Education and Research (BMBF) (Grant numbers BMBF 01GI 9934, 01GI 0234, 01GI9932, 01GI0232, 01GI0532). The funding source had no further role in the study design; the collection, analysis, and interpretation of data; the writing of the report; and the decision to submit the paper for publication.

Author contributions

MW, WW, WM, SR and JK conceived the study and obtained funding. MW designed the study and wrote the protocol. IF, WW, and ADB were responsible for data recording and management. LK and UE performed the analysis and wrote the first draft of the manuscript. All authors have contributed to data acquisition and to revising the manuscript and have approved the final manuscript. Luca Kleineidam (LK), Ingo Frommann (IF), Stephan Ruhrmann (SR), Joachim Klosterkötter (JK), Anke Brockhaus-Dumke (ABD) Wolfgang Wölwer (WW), Wolfgang Gaebel (WG), Wolfgang Maier (WM), Michael Wagner (MW), Ulrich Ettinger (UE).

Compliance with ethical standards

Conflict of interest

All authors report no biomedical financial interests or potential conflicts of interest.

Supplementary material

406_2018_973_MOESM1_ESM.docx (27 kb)
Supplementary material 1 (DOCX 26 KB)

References

  1. 1.
    Nieman DH, McGorry PD (2015) Detection and treatment of at-risk mental state for developing a first psychosis: making up the balance. Lancet Psychiatry 2:825–834.  https://doi.org/10.1016/S2215-0366(15)00221-7 CrossRefPubMedGoogle Scholar
  2. 2.
    Schultze-Lutter F, Michel C, Schmidt SJ et al (2015) EPA guidance on the early detection of clinical high risk states of psychoses. Eur Psychiatry 30:405–416.  https://doi.org/10.1016/j.eurpsy.2015.01.010 CrossRefPubMedGoogle Scholar
  3. 3.
    de Paula ALD, Hallak JEC, Maia-de-Oliveira JP et al (2015) Cognition in at-risk mental states for psychosis. Neurosci Biobehav Rev 57:199–208.  https://doi.org/10.1016/j.neubiorev.2015.09.006 CrossRefPubMedGoogle Scholar
  4. 4.
    Bodatsch M, Brockhaus-Dumke A, Klosterkötter J, Ruhrmann S (2015) Forecasting psychosis by event-related potentials-systematic review and specific meta-analysis. Biol Psychiatry 77:951–958.  https://doi.org/10.1016/j.biopsych.2014.09.025 CrossRefPubMedGoogle Scholar
  5. 5.
    Wood SJ, Reniers RLEP, Heinze K (2013) Neuroimaging findings in the at-risk mental state: a review of recent literature. Can J Psychiatry 58:13–18.  https://doi.org/10.1177/070674371305800104 CrossRefPubMedGoogle Scholar
  6. 6.
    Hutton SB, Ettinger U (2006) The antisaccade task as a research tool in psychopathology: a critical review. Psychophysiology 43:302–313.  https://doi.org/10.1111/j.1469-8986.2006.00403.x CrossRefPubMedGoogle Scholar
  7. 7.
    Munoz DP, Everling S (2004) Look away: the anti-saccade task and the voluntary control of eye movement. Nat Rev Neurosci 5:218–228.  https://doi.org/10.1038/nrn1345 CrossRefPubMedGoogle Scholar
  8. 8.
    Gooding DC, Basso MA (2008) The tell-tale tasks: a review of saccadic research in psychiatric patient populations. Brain Cogn 68:371–390.  https://doi.org/10.1016/j.bandc.2008.08.024 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    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 68:436–461.  https://doi.org/10.1016/j.bandc.2008.09.001 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Ettinger U, Meyhöfer I, Steffens M et al (2014) Genetics, cognition, and neurobiology of schizotypal personality: A review of the overlap with schizophrenia. Frontiers Media SAGoogle Scholar
  11. 11.
    Gooding DC (1999) Antisaccade task performance in questionnaire-identified schizotypes. Schizophrenia Res 35:157–166CrossRefGoogle Scholar
  12. 12.
    O’Driscoll GA, Lenzenweger MF, Holzman PS (1998) Antisaccades and smooth pursuit eye tracking and schizotypy. Arch Gen Psychiatry 55:837–843CrossRefGoogle Scholar
  13. 13.
    Nieman D, Becker H, van de Fliert R et al (2007) Antisaccade task performance in patients at ultra high risk for developing psychosis. Schizophr Res 95:54–60.  https://doi.org/10.1016/j.schres.2007.06.022 CrossRefPubMedGoogle Scholar
  14. 14.
    Caldani S, Bucci MP, Lamy J-C et al (2017) Saccadic eye movements as markers of schizophrenia spectrum: exploration in at-risk mental states. Schizophrenia Res 181:30–37.  https://doi.org/10.1016/j.schres.2016.09.003 CrossRefGoogle Scholar
  15. 15.
    Talanow T, Kasparbauer A-M, Steffens M et al (2016) Facing competition: neural mechanisms underlying parallel programming of antisaccades and prosaccades. Brain Cognit 107:37–47.  https://doi.org/10.1016/j.bandc.2016.05.006 CrossRefGoogle Scholar
  16. 16.
    Reilly JL, Frankovich K, Hill S et al (2014) Elevated antisaccade error rate as an intermediate phenotype for psychosis across diagnostic categories. Schizophr Bull 40:1011–1021.  https://doi.org/10.1093/schbul/sbt132 CrossRefPubMedGoogle Scholar
  17. 17.
    Fusar-Poli P, Cappucciati M, Borgwardt S et al (2016) Heterogeneity of psychosis risk within individuals at clinical high risk: a meta-analytical stratification. JAMA Psychiatry 73:113–120.  https://doi.org/10.1001/jamapsychiatry.2015.2324 CrossRefPubMedGoogle Scholar
  18. 18.
    Häfner H, Maurer K, Ruhrmann S et al (2004) Early detection and secondary prevention of psychosis: facts and visions. Eur Arch Psychiatry Clin Neurosci 254:117–128.  https://doi.org/10.1007/s00406-004-0508-z CrossRefPubMedGoogle Scholar
  19. 19.
    Frommann I, Pukrop R, Brinkmeyer J et al (2011) Neuropsychological profiles in different at-risk states of psychosis: executive control impairment in the early—and additional memory dysfunction in the late—prodromal state. Schizophr Bull 37:861–873.  https://doi.org/10.1093/schbul/sbp155 CrossRefPubMedGoogle Scholar
  20. 20.
    Quednow BB, Frommann I, Berning J et al (2008) Impaired sensorimotor gating of the acoustic startle response in the prodrome of schizophrenia. Biol Psychiat 64:766–773.  https://doi.org/10.1016/j.biopsych.2008.04.019 CrossRefPubMedGoogle Scholar
  21. 21.
    Frommann I, Brinkmeyer J, Ruhrmann S et al (2008) Auditory P300 in individuals clinically at risk for psychosis. Int J Psychophysiol 70:192–205.  https://doi.org/10.1016/j.ijpsycho.2008.07.003 CrossRefPubMedGoogle Scholar
  22. 22.
    Wölwer W, Brinkmeyer J, Stroth S et al (2012) Neurophysiological correlates of impaired facial affect recognition in individuals at risk for schizophrenia. Schizophr Bull 38:1021–1029.  https://doi.org/10.1093/schbul/sbr013 CrossRefPubMedGoogle Scholar
  23. 23.
    First MB, Spitzer RL, Gibbon M, Williams JBW (1997) Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version (SCID-CV)Google Scholar
  24. 24.
    Maurer K, Hörrmann F, Trendler G et al (2006) Früherkennung des Psychoserisikos mit dem Early Recognition Inventory (ERIraos) Beschreibung des Verfahrens und erste Ergebnisse zur Reliabilität und Validität der Checkliste. Nervenheilkunde 25:11–16CrossRefGoogle Scholar
  25. 25.
    American Psychiatric Association (2000) DSM-IVGoogle Scholar
  26. 26.
    Möller HJ, Riedel M, Jäger M et al (2008) Short-term treatment with risperidone or haloperidol in first-episode schizophrenia: 8-week results of a randomized controlled trial within the German research network on Schizophrenia. Int J Neuropsychopharmacol 11(7):985–997.  https://doi.org/10.1017/S1461145708008791 CrossRefPubMedGoogle Scholar
  27. 27.
    Kay SR, Fiszbein A, Opler LA (1987) The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bull 13:261–276CrossRefGoogle Scholar
  28. 28.
    Montgomery SA, Asberg M (1979) A new depression scale designed to be sensitive to chnage. Br J Psychiatry 134:382–389CrossRefGoogle Scholar
  29. 29.
    Addington D, Addington J, Maticka-Tyndale E (1993) Assessing depression in schizophrenia: the Calgary depression scale. Br J Psychiatry 163(S22):39–44CrossRefGoogle Scholar
  30. 30.
    Lehrl S, Triebig G, Fischer B (1995) Multiple choice vocabulary test MWT as a valid and short test to estimate premorbid intelligence. Acta Neurol Scand 91:335–345CrossRefGoogle Scholar
  31. 31.
    Maurer K, Häfner H (1995) Methodological aspects of onset assessment in schizophrenia. Schizophr Res 15:265–276.  https://doi.org/10.1016/0920-9964(94)00051-9 CrossRefPubMedGoogle Scholar
  32. 32.
    Stoline MR (1981) The status of multiple comparisons: simultaneous estimation of all pairwise comparisons in one-way ANOVA designs. Am Stat 35:134–141.  https://doi.org/10.2307/2683979 CrossRefGoogle Scholar
  33. 33.
    Harris MSH, Reilly JL, Thase ME et al (2009) Response suppression deficits in treatment-naïve first-episode patients with schizophrenia, psychotic bipolar disorder and psychotic major depression. Psychiatry Res 170:150–156.  https://doi.org/10.1016/j.psychres.2008.10.031 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Hutton SB, Crawford TJ, Puri BK et al (1998) Smooth pursuit and saccadic abnormalities in first-episode schizophrenia. Psychol Med 28:685–692CrossRefGoogle Scholar
  35. 35.
    Ettinger U, Kumari V, Chitnis XA et al (2004) Volumetric neural correlates of antisaccade eye movements in first-episode psychosis. Am J Psychiatry 161:1918–1921.  https://doi.org/10.1176/ajp.161.10.1918 CrossRefPubMedGoogle Scholar
  36. 36.
    Massen C (2004) Parallel programming of exogenous and endogenous components in the antisaccade task. The quarterly journal of experimental psychology A. Hum Exp Psychol 57:475–498.  https://doi.org/10.1080/02724980343000341 CrossRefGoogle Scholar
  37. 37.
    Bechdolf A, Wagner M, Ruhrmann S et al (2012) Preventing progression to first-episode psychosis in early initial prodromal states. Br J Psychiatry 200:22–29.  https://doi.org/10.1192/bjp.bp.109.066357 CrossRefPubMedGoogle Scholar
  38. 38.
    Fusar-Poli P, Bonoldi I, Yung AR et al (2012) Predicting psychosis: meta-analysis of transition outcomes in individuals at high clinical risk. Arch Gen Psychiatry 69(3):220–229.  https://doi.org/10.1001/archgenpsychiatry.2011.1472 CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Fischer B, Weber H (1997) Effects of stimulus conditions on the performance of antisaccades in man. Exp Brain Res 116:191–200.  https://doi.org/10.1007/PL00005749 CrossRefPubMedGoogle Scholar
  40. 40.
    McDowell JE, Myles-Worsley M, Coon H et al (1999) Measuring liability for schizophrenia using optimized antisaccade stimulus parameters. Psychophysiology 36:138–141.  https://doi.org/10.1017/S0048577299980836 CrossRefPubMedGoogle Scholar
  41. 41.
    Seidman LJ, Shapiro DI, Stone WS et al (2016) Association of neurocognition with transition to psychosis. JAMA Psychiatry 73:1239.  https://doi.org/10.1001/jamapsychiatry.2016.2479 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Allott KA, Schäfer MR, Thompson A et al (2014) Emotion recognition as a predictor of transition to a psychotic disorder in ultra-high risk participants. Schizophr Res 153:25–31.  https://doi.org/10.1016/j.schres.2014.01.037 CrossRefPubMedGoogle Scholar
  43. 43.
    Calkins ME, Iacono WG, Curtis CE (2003) Smooth pursuit and antisaccade performance evidence trait stability in schizophrenia patients and their relatives. Int J Psychophysiol 49:139–146CrossRefGoogle Scholar
  44. 44.
    Gooding DC, Shea HB, Matts CW (2005) Saccadic performance in questionnaire-identified schizotypes over time. Psychiatry Res 133:173–186.  https://doi.org/10.1016/j.psychres.2003.12.029 CrossRefPubMedGoogle Scholar
  45. 45.
    Gooding DC, Mohapatra L, Shea HB (2004) Temporal stability of saccadic task performance in schizophrenia and bipolar patients. Psychol Med 34:921–932CrossRefGoogle Scholar
  46. 46.
    Ettinger U, Kumari V, Crawford TJ et al (2003) Reliability of smooth pursuit, fixation, and saccadic eye movements. Psychophysiology 40:620–628CrossRefGoogle Scholar
  47. 47.
    Meyhöfer I, Bertsch K, Esser M, Ettinger U (2016) Variance in saccadic eye movements reflects stable traits. Psychophysiology 53:566–578.  https://doi.org/10.1111/psyp.12592 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Luca Kleineidam
    • 1
    • 2
  • Ingo Frommann
    • 1
    • 2
  • Stephan Ruhrmann
    • 3
  • Joachim Klosterkötter
    • 3
  • Anke Brockhaus-Dumke
    • 4
  • Wolfgang Wölwer
    • 5
  • Wolfgang Gaebel
    • 5
  • Wolfgang Maier
    • 1
    • 2
  • Michael Wagner
    • 1
    • 2
    Email author
  • Ulrich Ettinger
    • 6
  1. 1.Department of Psychiatry and PsychotherapyUniversity of BonnBonnGermany
  2. 2.Department for Neurodegenerative Diseases and Geriatric PsychiatryUniversity of BonnBonnGermany
  3. 3.Department of Psychiatry and PsychotherapyUniversity of CologneCologneGermany
  4. 4.Department of Psychiatry, Psychotherapy and Psychosomatic MedicineRheinhessen-Fachklinik AlzeyAlzeyGermany
  5. 5.Department of Psychiatry and Psychotherapy, Medical FacultyHeinrich-Heine-UniversityDüsseldorfGermany
  6. 6.Department of PsychologyUniversity of BonnBonnGermany

Personalised recommendations