Skip to main content

Advertisement

SpringerLink
Log in

Exploratory eye movement dysfunction as a discriminator for schizophrenia

A large sample study using a newly developed digital computerized system

  • ORIGINAL PAPER
  • Published:
European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

Abstract

In our previous studies, we identified that exploratory eye movement (EEM) dysfunction appears to be specific to schizophrenia. The availability of a biological marker specific to schizophrenia would be useful for clinical diagnosis of schizophrenia. Consequently, we performed the discriminant analysis between schizophrenics and non-schizophrenics on a large sample using the EEM test data and examined an application of the EEM for clinical diagnosis of schizophrenia. EEM performances were recorded in 251 schizophrenics and 389 non-schizophrenics (111 patients with mood disorders, 28 patients with neurotic disorders and 250 normal controls). The patients were recruited from eight university hospitals and three affiliated hospitals. For this study with a large sample, we developed a new digital computerized version of the EEM test, which automatically handled large amounts of data. We measured four parameters: number of eye fixations (NEF), total eye scanning length (TESL), mean eye scanning length (MESL) and responsive search score (RSS). These parameters of schizophrenics differed significantly from those of the other three groups. The stepwise regression analysis selected the TESL and the RSS as the valid parameters for discriminating between schizophrenics and non-schizophrenics. In the discriminant analysis using the RSS and TESL as prediction parameters, 184 of the 251 clinically diagnosed schizophrenics were discriminated as having schizophrenia (sensitivity 73.3%); and 308 of the 389 clinically diagnosed non-schizophrenic subjects were discriminated as non-schizophrenics (specificity 79.2%). Based on our findings we believe that the EEM measures may be useful for the clinical diagnosis of schizophrenia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Arolt V, Lencer R, Nolte A, Muller-Myhsok B, Purmann S, Schurmann M, Leutelt J, Pinnow M, Schwinger E (1996) Eye tracking dysfunction is a putative phenotypic susceptibility marker of schizophrenia and maps to a locus on chromosome 6p in families with multiple occurrence of the disease. Am J Med Genet 67:564–579

    Article  PubMed  CAS  Google Scholar 

  2. Arolt V, Lencer R, Purmann S, Schurmann M, Muller-Myhsok B, Krecker K, Schwinger E (1999) Testing for linkage of eye tracking dysfunction and schizophrenia to markers on chromosomes 6, 8, 9, 20, and 22 in families multiply affected with schizophrenia. Am J Med Genet 88:603–606

    Article  PubMed  CAS  Google Scholar 

  3. Barrantes-Vidal N, Aguilera M, Campanera S, Fatjo-Vilas M, Guitart M, Miret S, Valero S, Fananas L (2007) Working memory in siblings of schizophrenia patients. Schizophr Res 95:70–75

    Article  PubMed  Google Scholar 

  4. Bharath S, Gangadhar BN, Janakiramaiah N (2000) P300 in family studies of schizophrenia: review and critique. Int J Psychophysiol 38:43–54

    Article  PubMed  CAS  Google Scholar 

  5. Braff DL (1993) Information processing and attention dysfunctions in schizophrenia. Schizophr Bull 19:233–259

    PubMed  CAS  Google Scholar 

  6. Devrim-Ucok M, Keskin-Ergen HY, Ucok A (2007) Mismatch negativity at acute and post-acute phases of first-episode schizophrenia. Eur Arch Psychiatry Clin Neurosci 258:179–185

    Article  Google Scholar 

  7. Freedman R, Coon H, Myles-Worsley M, Orr-Urtreger A, Olincy A, Davis A, Polymeropoulos M, Holik J, Hopkins J, Hoff M, Rosenthal J, Waldo MC, Reimherr F, Wender P, Yaw J, Young DA, Breese CR, Adams C, Patterson D, Adler LE, Kruglyak L, Leonard S, Byerley W (1997) Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. Proc Natl Acad Sci USA 94:587–592

    Article  PubMed  CAS  Google Scholar 

  8. Fukushima J, Fukushima K, Chiba T, Tanaka S, Yamashita I, Kato M (1988) Disturbances of voluntary control of saccadic eye movements in schizophrenic patients. Biol psychiatry 23:670–677

    Article  PubMed  CAS  Google Scholar 

  9. Gooding DC, Tallent KA (2001) The association between antisaccade task and working memory task performance in schizophrenia and bipolar disorder. J Nerv Ment Dis 189:8–16

    Article  PubMed  CAS  Google Scholar 

  10. Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62

    Article  PubMed  CAS  Google Scholar 

  11. Haraldsson HM, Ettinger U, Magnusdottir BB, Sigmundsson T, Sigurdsson E, Petursson H (2008) Eye movement deficits in schizophrenia: investigation of a genetically homogenous Icelandic sample. Eur Arch Psychiatry Clin Neurosci 258:373–383

    Article  PubMed  Google Scholar 

  12. Holzman PS, O’Brian C, Waternaux C (1991) Effects of lithium treatment on eye movements. Biol Psychiatry 29:1001–1015

    Article  PubMed  CAS  Google Scholar 

  13. Inagaki A, Inada T (2006) Dose equivalence of psychotropic drugs. Part 18: dose equivalence of psychotropic drugs: 2006-version. Jpn J Clin Psychopharmacol 9:1443–1447 (in Japanese)

    Google Scholar 

  14. Katsanis J, Kortenkamp S, Iacono WG, Grove WM (1997) Antisaccade performance in patients with schizophrenia and affective disorder. J Abnorm Psychol 106:468–472

    Article  PubMed  CAS  Google Scholar 

  15. Kirov G, O’Donovan MC, Owen MJ (2005) Finding schizophrenia genes. J Clin Invest 115:1440–1448

    Article  PubMed  CAS  Google Scholar 

  16. Kojima T, Matsushima E, Ando K, Ando H, Sakurada M, Ohta K, Moriya H, Shimazono Y (1992) Exploratory eye movements and neuropsychological tests in schizophrenic patients. Schizophr Bull 18:85–94

    PubMed  CAS  Google Scholar 

  17. Kojima T, Matsushima E, Iwama H, Ando H, Moriya H, Ando K, Takahashi R, Shimazono Y (1986) Visual perception process in amphetamine psychosis and schizophrenia. Psychopharmacol Bull 22:768–773

    PubMed  CAS  Google Scholar 

  18. Kojima T, Matsushima E, Nakajima K, Shiraishi H, Ando K, Ando H, Shimazono Y (1990) Eye movements in acute, chronic, and remitted schizophrenics. Biol Psychiatry 27:975–989

    Article  PubMed  CAS  Google Scholar 

  19. Kojima T, Matsushima E, Ohta K, Toru M, Han YH, Shen YC, Moussaoui D, David I, Sato K, Yamashita I, Kathmann N, Hippius H, Thavundayil JX, Lal S, Vasavan Nair NP, Potkin SG, Prilipko L (2001) Stability of exploratory eye movements as a marker of schizophrenia—a WHO multi-center study. Schizophr Res 52:203–213

    Article  PubMed  CAS  Google Scholar 

  20. Kojima T, Potkin SG, Kharazmi M, Matsushima E, Herrera J, Shimazono Y (1989) Limited eye movement patterns in chronic schizophrenic patients. Psychiatry Res 28:307–314

    Article  PubMed  CAS  Google Scholar 

  21. Levy DL, Holzman PS, Matthysse S, Mendell NR (1994) Eye tracking and schizophrenia: a selective review. Schizophr Bull 20:47–62

    PubMed  CAS  Google Scholar 

  22. Malaspina D, Amador XF, Coleman EA, Mayr TL, Friedman JH, Sackeim HA (1994) Smooth pursuit eye movement abnormality in severe major depression: effects of ECT and clinical recovery. J Neuropsychiatry Clin Neurosci 6:36–42

    PubMed  CAS  Google Scholar 

  23. Mather JA, Neufeld RW, Merskey H, Russell NC (1992) Disruption of saccade production during oculomotor tracking in schizophrenia and the use of its changes across target velocity as a discriminator of the disorder. Psychiatry Res 43:93–109

    Article  PubMed  CAS  Google Scholar 

  24. Matsukawa Y, Takahashi S, Aoki M, Yamakami K, Nishinarita S, Horie T, Fukura Y, Tanabe E, Yara K, Matsuura M, Kojima T (2002) Patients with systemic lupus erythematosus show a normal responsive search score in exploratory eye movement analysis: comparison with schizophrenia. Ann Rheum Dis 61:748–750

    Article  PubMed  CAS  Google Scholar 

  25. Matsushima E, Kojima T, Ohbayashi S, Ando H, Ando K, Shimazono Y (1992) Exploratory eye movements in schizophrenic patients and patients with frontal lobe lesions. Eur Arch Psychiatry Clin Neurosci 241:210–214

    Article  PubMed  CAS  Google Scholar 

  26. Matsushima E, Kojima T, Ohta K, Obayashi S, Nakajima K, Kakuma T, Ando H, Ando K, Toru M (1998) Exploratory eye movement dysfunctions in patients with schizophrenia: possibility as a discriminator for schizophrenia. J Psychiatr Res 32:289–295

    Article  PubMed  CAS  Google Scholar 

  27. Michie PT (2001) What has MMN revealed about the auditory system in schizophrenia? Int J Psychophysiol 42:177–194

    Article  PubMed  CAS  Google Scholar 

  28. Myles-Worsley M, Coon H, McDowell J, Brenner C, Hoff M, Lind B, Bennett P, Freedman R, Clementz B, Byerley W (1999) Linkage of a composite inhibitory phenotype to a chromosome 22q locus in eight Utah families. Am J Med Genet 88:544–550

    Article  PubMed  CAS  Google Scholar 

  29. Nemoto Y, Matsuda T, Matsuura M, Motoshita M, Ohkubo T, Ohkubo H, Suzuki M, Kanaka N, Matsushima E, Kojima T (2004) Neural circuits of eye movements during performance of visual exploration task, which is similar to responsive search score task, in schizophrenia patients and normal subjects. J Nihon Univ Med Ass 63:352–359 (in Japanese)

    Google Scholar 

  30. Obayashi S, Matsushima E, Okubo Y, Ohkura T, Kojima T, Kakuma T (2001) Relationship between exploratory eye movements and clinical course in schizophrenic patients. Eur Arch Psychiatry Clin Neurosci 251:211–216

    Article  PubMed  CAS  Google Scholar 

  31. Ogura C, Nageishi Y, Matsubayashi M, Omura F, Kobayashi T, Shimokochi M (1985) Event-related potentials in patients with schizophrenia and depression, and their application to clinical diagnosis. Psychiatr Neurol Jpn 87:944–951 (in Japanese)

    Google Scholar 

  32. Overall JE, Gorham DR (1962) The brief psychiatric rating scale. Psychol Rep 10:799–812

    Article  Google Scholar 

  33. Parwani A, Duncan EJ, Bartlett E, Madonick SH, Efferen TR, Rajan R, Sanfilipo M, Chappell PB, Chakravorty S, Gonzenbach S, Ko GN, Rotrosen JP (2000) Impaired prepulse inhibition of acoustic startle in schizophrenia. Biol Psychiatry 47:662–669

    Article  PubMed  CAS  Google Scholar 

  34. Pfefferbaum A, Wenegrat BG, Ford JM, Roth WT, Kopell BS (1984) Clinical application of the P3 component of event-related potentials. II. Dementia, depression and schizophrenia. Electroencephalogr Clin Neurophysiol 59:104–124

    Article  PubMed  CAS  Google Scholar 

  35. Potter D, Summerfelt A, Gold J, Buchanan RW (2006) Review of clinical correlates of P50 sensory gating abnormalities in patients with schizophrenia. Schizophr Bull 32:692–700

    Article  PubMed  Google Scholar 

  36. Price GW, Michie PT, Johnston J, Innes-Brown H, Kent A, Clissa P, Jablensky AV (2006) A multivariate electrophysiological endophenotype, from a unitary cohort, shows greater research utility than any single feature in the Western Australian family study of schizophrenia. Biol Psychiatry 60:1–10

    Article  PubMed  Google Scholar 

  37. Sereno AB, Holzman PS (1995) Antisaccades and smooth pursuit eye movements in schizophrenia. Biol Psychiatry 37:394–401

    Article  PubMed  CAS  Google Scholar 

  38. Shagass C, Roemer RA, Straumanis JJ, Josiassen RC (1984) Psychiatric diagnostic discriminations with combinations of quantitative EEG variables. Br J Psychiatry 144:581–592

    Article  PubMed  CAS  Google Scholar 

  39. Sweeney JA, Strojwas MH, Mann JJ, Thase ME (1998) Prefrontal and cerebellar abnormalities in major depression: evidence from oculomotor studies. Biol Psychiatry 43:584–594

    Article  PubMed  CAS  Google Scholar 

  40. Szymanski S, Kane JM, Lieberman JA (1991) A selective review of biological markers in schizophrenia. Schizophr Bull 17:99–111

    PubMed  CAS  Google Scholar 

  41. Takahashi S, Matsushima E, Kojima T, Tanabe E, Yara K, Hagiwara M (2000) Study of the families and twins of schizophrenics. In: Kojima T, Matsushima E, Ando K (eds) Eyes and the mind. Karger, Basel, pp 75–79

    Google Scholar 

  42. Takahashi S, Ohtsuki T, Yu SY, Tanabe E, Yara K, Kamioka M, Matsushima E, Matsuura M, Ishikawa K, Minowa Y, Noguchi E, Nakayama J, Yamakawa-Kobayashi K, Arinami T, Kojima T (2003) Significant linkage to chromosome 22q for exploratory eye movement dysfunction in schizophrenia. Am J Med Genet B Neuropsychiatr Genet 123:27–32

    Article  Google Scholar 

  43. Tonoya Y, Matsui M, Kurachi M, Kurokawa K, Sumiyoshi T (2002) Exploratory eye movements in schizophrenia: effects of figure size and the instruction on visual search. Eur Arch Psychiatry Clin Neurosci 252:255–261

    Article  PubMed  Google Scholar 

  44. Weike AI, Bauer U, Hamm AO (2000) Effective neuroleptic medication removes prepulse inhibition deficits in schizophrenia patients. Biol Psychiatry 47:61–70

    Article  PubMed  CAS  Google Scholar 

  45. World Health Organization (1993) The international classification of mental and behavioural disorders: diagnostic criteria for research. WHO, Geneva

    Google Scholar 

Download references

Acknowledgments

The present study was supported by a Health and Labor Sciences Research Grant for Research on Psychiatric and Neurological Diseases and Mental Health (H16-KOKORO-003) from the Ministry of Health, Labor and Welfare, Japan.

Author information

Authors and Affiliations

  1. Dept. of Neuropsychiatry, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo, 173-8610, Japan

    Masahiro Suzuki, Sakae Takahashi, Makoto Uchiyama & Takuya Kojima

  2. Section of Liaison Psychiatry and Palliative Medicine, Graduate School of Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan

    Eisuke Matsushima, Mai Motoshita & Katsuya Ohta

  3. Dept. of Neuropsychiatry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan

    Masahiko Tsunoda & Masayoshi Kurachi

  4. Dept. of Neuropsychiatry, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan

    Takashi Okada & Takuji Hayashi

  5. Cognitive and Molecular Research Institute of Brain Diseases, Kurume University, 67 Asahi-machi, Kurume, 830-0011, Japan

    Yohei Ishii & Kiichiro Morita

  6. Wakahisa Hospital, Wakahisa 5-3-1, Minami-ku, Fukuoka, 815-0042, Japan

    Hisao Maeda

  7. Faculty of Medicine, Dept. of Neuropsychiatry, Tottori University, 36-1 Nishi-machi, Yonago, Tottori, 683-8504, Japan

    Seiji Katayama

  8. Midorigaoka Mental Clinic, 2793-1 Okazaki, Kushira-cho, Kanoya, Kagoshima, 893-1603, Japan

    Ryuzou Kawahara

  9. Dept. of Psychiatry, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan

    Tatsui Otsuka & Yoshio Hirayasu

  10. Dept. of Neuropsychiatry, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan

    Mizuho Sekine & Yoshiro Okubo

  11. Ohmiya-Kosei Hospital, 1 Katayanagi, Minuma-ku, Saitama, Saitama, 337-0024, Japan

    Takuya Kojima

Authors
  1. Masahiro Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sakae Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eisuke Matsushima
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Masahiko Tsunoda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Masayoshi Kurachi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takashi Okada
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Takuji Hayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yohei Ishii
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kiichiro Morita
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hisao Maeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Seiji Katayama
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Ryuzou Kawahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Tatsui Otsuka
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Yoshio Hirayasu
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Mizuho Sekine
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Yoshiro Okubo
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Mai Motoshita
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Katsuya Ohta
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Makoto Uchiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Takuya Kojima
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sakae Takahashi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Suzuki, M., Takahashi, S., Matsushima, E. et al. Exploratory eye movement dysfunction as a discriminator for schizophrenia. Eur Arch Psychiatry Clin Neurosci 259, 186–194 (2009). https://doi.org/10.1007/s00406-008-0850-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00406-008-0850-7

Keywords

Search

Navigation