Exploratory eye movement dysfunction as a discriminator for schizophrenia

A large sample study using a newly developed digital computerized system
  • Masahiro Suzuki
  • Sakae Takahashi
  • Eisuke Matsushima
  • Masahiko Tsunoda
  • Masayoshi Kurachi
  • Takashi Okada
  • Takuji Hayashi
  • Yohei Ishii
  • Kiichiro Morita
  • Hisao Maeda
  • Seiji Katayama
  • Ryuzou Kawahara
  • Tatsui Otsuka
  • Yoshio Hirayasu
  • Mizuho Sekine
  • Yoshiro Okubo
  • Mai Motoshita
  • Katsuya Ohta
  • Makoto Uchiyama
  • Takuya Kojima
ORIGINAL PAPER

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.

Keywords

schizophrenia exploratory eye movement (EEM) biological marker digital computerized system of the EEM test discriminant analysis 

References

  1. 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 67:564–579PubMedCrossRefGoogle Scholar
  2. 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 88:603–606PubMedCrossRefGoogle Scholar
  3. 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 95:70–75PubMedCrossRefGoogle Scholar
  4. 4.
    Bharath S, Gangadhar BN, Janakiramaiah N (2000) P300 in family studies of schizophrenia: review and critique. Int J Psychophysiol 38:43–54PubMedCrossRefGoogle Scholar
  5. 5.
    Braff DL (1993) Information processing and attention dysfunctions in schizophrenia. Schizophr Bull 19:233–259PubMedGoogle Scholar
  6. 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 258:179–185CrossRefGoogle Scholar
  7. 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 94:587–592PubMedCrossRefGoogle Scholar
  8. 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 23:670–677PubMedCrossRefGoogle Scholar
  9. 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 189:8–16PubMedCrossRefGoogle Scholar
  10. 10.
    Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62PubMedCrossRefGoogle Scholar
  11. 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 258:373–383PubMedCrossRefGoogle Scholar
  12. 12.
    Holzman PS, O’Brian C, Waternaux C (1991) Effects of lithium treatment on eye movements. Biol Psychiatry 29:1001–1015PubMedCrossRefGoogle Scholar
  13. 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. 14.
    Katsanis J, Kortenkamp S, Iacono WG, Grove WM (1997) Antisaccade performance in patients with schizophrenia and affective disorder. J Abnorm Psychol 106:468–472PubMedCrossRefGoogle Scholar
  15. 15.
    Kirov G, O’Donovan MC, Owen MJ (2005) Finding schizophrenia genes. J Clin Invest 115:1440–1448PubMedCrossRefGoogle Scholar
  16. 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 18:85–94PubMedGoogle Scholar
  17. 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 22:768–773PubMedGoogle Scholar
  18. 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 27:975–989PubMedCrossRefGoogle Scholar
  19. 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 52:203–213PubMedCrossRefGoogle Scholar
  20. 20.
    Kojima T, Potkin SG, Kharazmi M, Matsushima E, Herrera J, Shimazono Y (1989) Limited eye movement patterns in chronic schizophrenic patients. Psychiatry Res 28:307–314PubMedCrossRefGoogle Scholar
  21. 21.
    Levy DL, Holzman PS, Matthysse S, Mendell NR (1994) Eye tracking and schizophrenia: a selective review. Schizophr Bull 20:47–62PubMedGoogle Scholar
  22. 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 6:36–42PubMedGoogle Scholar
  23. 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 43:93–109PubMedCrossRefGoogle Scholar
  24. 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 61:748–750PubMedCrossRefGoogle Scholar
  25. 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 241:210–214PubMedCrossRefGoogle Scholar
  26. 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 32:289–295PubMedCrossRefGoogle Scholar
  27. 27.
    Michie PT (2001) What has MMN revealed about the auditory system in schizophrenia? Int J Psychophysiol 42:177–194PubMedCrossRefGoogle Scholar
  28. 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 88:544–550PubMedCrossRefGoogle Scholar
  29. 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. 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 251:211–216PubMedCrossRefGoogle Scholar
  31. 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. 32.
    Overall JE, Gorham DR (1962) The brief psychiatric rating scale. Psychol Rep 10:799–812CrossRefGoogle Scholar
  33. 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 47:662–669PubMedCrossRefGoogle Scholar
  34. 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 59:104–124PubMedCrossRefGoogle Scholar
  35. 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 32:692–700PubMedCrossRefGoogle Scholar
  36. 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 60:1–10PubMedCrossRefGoogle Scholar
  37. 37.
    Sereno AB, Holzman PS (1995) Antisaccades and smooth pursuit eye movements in schizophrenia. Biol Psychiatry 37:394–401PubMedCrossRefGoogle Scholar
  38. 38.
    Shagass C, Roemer RA, Straumanis JJ, Josiassen RC (1984) Psychiatric diagnostic discriminations with combinations of quantitative EEG variables. Br J Psychiatry 144:581–592PubMedCrossRefGoogle Scholar
  39. 39.
    Sweeney JA, Strojwas MH, Mann JJ, Thase ME (1998) Prefrontal and cerebellar abnormalities in major depression: evidence from oculomotor studies. Biol Psychiatry 43:584–594PubMedCrossRefGoogle Scholar
  40. 40.
    Szymanski S, Kane JM, Lieberman JA (1991) A selective review of biological markers in schizophrenia. Schizophr Bull 17:99–111PubMedGoogle Scholar
  41. 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 75–79Google Scholar
  42. 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 123:27–32CrossRefGoogle Scholar
  43. 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 252:255–261PubMedCrossRefGoogle Scholar
  44. 44.
    Weike AI, Bauer U, Hamm AO (2000) Effective neuroleptic medication removes prepulse inhibition deficits in schizophrenia patients. Biol Psychiatry 47:61–70PubMedCrossRefGoogle Scholar
  45. 45.
    World Health Organization (1993) The international classification of mental and behavioural disorders: diagnostic criteria for research. WHO, GenevaGoogle Scholar

Copyright information

© Steinkopff Verlag Darmstadt 2009

Authors and Affiliations

  • Masahiro Suzuki
    • 1
  • Sakae Takahashi
    • 1
  • Eisuke Matsushima
    • 2
  • Masahiko Tsunoda
    • 3
  • Masayoshi Kurachi
    • 3
  • Takashi Okada
    • 4
  • Takuji Hayashi
    • 4
  • Yohei Ishii
    • 5
  • Kiichiro Morita
    • 5
  • Hisao Maeda
    • 6
  • Seiji Katayama
    • 7
  • Ryuzou Kawahara
    • 8
  • Tatsui Otsuka
    • 9
  • Yoshio Hirayasu
    • 9
  • Mizuho Sekine
    • 10
  • Yoshiro Okubo
    • 10
  • Mai Motoshita
    • 2
  • Katsuya Ohta
    • 2
  • Makoto Uchiyama
    • 1
  • Takuya Kojima
    • 1
    • 11
  1. 1.Dept. of NeuropsychiatryNihon University School of MedicineItabashi-kuJapan
  2. 2.Section of Liaison Psychiatry and Palliative MedicineGraduate School of Tokyo Medical and Dental UniversityBunkyo-kuJapan
  3. 3.Dept. of Neuropsychiatry, Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
  4. 4.Dept. of Neuropsychiatry, Graduate School of MedicineKyoto UniversityKyotoJapan
  5. 5.Cognitive and Molecular Research Institute of Brain DiseasesKurume UniversityKurumeJapan
  6. 6.Wakahisa HospitalMinami-kuJapan
  7. 7.Faculty of Medicine, Dept. of NeuropsychiatryTottori UniversityYonagoJapan
  8. 8.Midorigaoka Mental ClinicKanoyaJapan
  9. 9.Dept. of PsychiatryYokohama City University School of MedicineYokohamaJapan
  10. 10.Dept. of NeuropsychiatryNippon Medical SchoolBunkyo-kuJapan
  11. 11.Ohmiya-Kosei HospitalSaitamaJapan

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