Hostname: page-component-cd9895bd7-jn8rn Total loading time: 0 Render date: 2024-12-26T07:30:24.337Z Has data issue: false hasContentIssue false
  • English
  • Français

Memory-guided saccade abnormalities in schizophrenic patients and their healthy, full biological siblings

Published online by Cambridge University Press:  02 November 2007

S. Landgraf ,
I. Amado ,
M.-C. Bourdel ,
S. Leonardi  and
M.-O. Krebs
S. Landgraf*
Affiliation:
INSERM U796, Physiopathology of Psychiatric Diseases, University Paris René Descartes, Faculty of Medicine, Sainte Anne Hospital, Paris, France Humboldt University Berlin, Institute of Psychology, Berlin, Germany
I. Amado
Affiliation:
INSERM U796, Physiopathology of Psychiatric Diseases, University Paris René Descartes, Faculty of Medicine, Sainte Anne Hospital, Paris, France
M.-C. Bourdel
Affiliation:
INSERM U796, Physiopathology of Psychiatric Diseases, University Paris René Descartes, Faculty of Medicine, Sainte Anne Hospital, Paris, France
S. Leonardi
Affiliation:
INSERM U796, Physiopathology of Psychiatric Diseases, University Paris René Descartes, Faculty of Medicine, Sainte Anne Hospital, Paris, France
M.-O. Krebs
Affiliation:
INSERM U796, Physiopathology of Psychiatric Diseases, University Paris René Descartes, Faculty of Medicine, Sainte Anne Hospital, Paris, France
*
*Address for correspondence: S. Landgraf, M.A., Service Hospitalo Universitaire, Hôpital Sainte-Anne, 7 rue Cabanis, 75014 Paris, France. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Ocular-motor inhibition errors and saccadic hypometria occur at elevated rates in biological relatives of schizophrenic patients. The memory-guided saccade (MS) paradigm requires a subject to inhibit reflexive saccades (RSs) and to programme a delayed saccade towards a remembered target.

Method

MS, RS, and central fixation (CF) tasks were administered to 16 patients who met the criteria for DSM-IV schizophrenia, 19 of their psychiatrically healthy siblings, and 18 controls.

Results

Patients and siblings showed elevated MS error rates reflecting a failure to inhibit RSs to a visible target, as required by the task. In contrast to controls, prior errors did not improve MS accuracy in patients and siblings.

Conclusions

The specific characteristics of the elevated MS error rate help to clarify the nature of the disinhibition impairment found in schizophrenics and their healthy siblings. Failure to inhibit premature saccades and to improve the accuracy of subsequent volitional saccades implicates a deficit in spatial working-memory integration, mental representation and/or motor learning processes in schizophrenia.

Keywords

Error ratememory-guidedsaccadesschizophreniasiblingsworking memory
Type
Original Articles
Information
Psychological Medicine , Volume 38 , Issue 6 , June 2008 , pp. 861 - 870
Copyright
Copyright © Cambridge University Press 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abel, LA, Douglas, J (2006). Effects of age on latency and error generation in internally mediated saccades. Neurobiological Aging 28, 627–637.CrossRefGoogle ScholarPubMed
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. Journal of Neuropsychiatry and Clinical Neurosciences 7, 197–206.Google ScholarPubMed
APA (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th edn. American Psychiatric Press: Washington, DC.Google Scholar
Boudet, C, Bocca, ML, Chabot, B, Delamillieure, P, Brazo, P, Denise, P, Dollfus, S (2005). Are eye movement abnormalities indicators of genetic vulnerability to schizophrenia? European Psychiatry 20, 339–345.CrossRefGoogle ScholarPubMed
Broerse, A, Crawford, T, den Boer, J (2001). Parsing cognition in schizophrenia using saccadic eye movements: a selective overview. Neuropsychologia 39, 742–756.CrossRefGoogle ScholarPubMed
Brownstein, J, Krastoshevsky, O, McCollum, C, Kundamal, S, Matthysse, S, Holzman, PS, Mendell, NR, Levy, DL (2003). Antisaccade performance is abnormal in schizophrenia patients but not in their biological relatives. Schizophrenia Research 63, 13–25.CrossRefGoogle Scholar
Calkins, ME, Curtis, CE, Iacono, WG, Grove, WM (2004). Antisaccade performance is impaired in medically and psychiatrically healthy biological relatives of schizophrenia patients. Schizophrenia Research 71, 167–178.CrossRefGoogle ScholarPubMed
Calkins, ME, Iacono, WG (2000). Eye movement dysfunction in schizophrenia: a heritable characteristic for enhancing phenotype definition. American Journal of Medical Genetics 97, 72–76.3.0.CO;2-L>CrossRefGoogle ScholarPubMed
Chafee, MV, Goldman-Rakic, PS (1998). Matching patterns of activity in primate prefrontal area 8a and parietal area 7ip neurons during a spatial working memory task. Journal of Neurophysiology 79, 2919–2940.CrossRefGoogle ScholarPubMed
Clementz, BA, McDowell, JE, Zisook, S (1994). Saccadic system functioning among schizophrenia patients and their first-degree biological relatives. Journal of Abnormal Psychology 103, 277–287.CrossRefGoogle ScholarPubMed
Crawford, TJ, Haeger, B, Kennard, C, Reveley, MA, Henderson, L (1995). Saccadic abnormalities in psychotic patients. I. Neuroleptic-free psychotic patients. Psychological Medicine 25, 461–471.CrossRefGoogle ScholarPubMed
Crawford, TJ, Sharma, T, Puri, BK, Murray, RM, Berridge, DM, Lewis, SW (1998). Saccadic eye movements in families multiply affected with schizophrenia: the Maudsley family study. American Journal of Psychiatry 155, 1703–1710.CrossRefGoogle ScholarPubMed
Curtis, CE, Calkins, ME, Grove, WM, Feil, KJ, Iacono, WG (2001 a). Saccadic disinhibition in patients with acute and remitted schizophrenia and their first-degree biological relatives. American Journal of Psychiatry 158, 100–106.CrossRefGoogle ScholarPubMed
Curtis, CE, Calkins, ME, Iacono, WG (2001 b). Saccadic disinhibition in schizophrenia patients and their first-degree biological relatives. Experimental Brain Research 137, 228–236.CrossRefGoogle ScholarPubMed
Dayen, P, Abbott, LF (2001). Theoretical Neuroscience: Computational and Mathematical Modeling of Neural Systems. MIT Press: Cambridge, MA.Google Scholar
Diwadkar, VA, Sweeney, JA, Boarts, D, Montrose, DM, Keshavan, MS (2001). Oculomotor delayed response abnormalities in young offspring and siblings at risk for schizophrenia. CNS Spectrums 6, 899–903.CrossRefGoogle ScholarPubMed
Ettinger, U, Kumari, V, Crawford, TJ, Corr, PJ, Das, M, Zachariah, E, Hughes, C, Sumich, AL, Rabe-Heskethe, S, Sharmaf, T (2004). Smooth pursuit and antisaccade eye movements in siblings discordant for schizophrenia. Journal of Psychiatric Research 38, 177–184.CrossRefGoogle ScholarPubMed
Ettinger, U, Piccioni, M, Hall, MH, Schulze, K, Toulopoulou, T, Landau, S, Crawford, TJ, Murray, RM (2006). Antisaccade performance in monozygotic twins discordant for schizophrenia: the Maudsley twin study. American Journal of Psychiatry 163, 543–545.CrossRefGoogle ScholarPubMed
Fischer, B (1987). The preparation of visually guided saccades. Reviews of Physiology, Biochemistry and Pharmacology 106, 1–35.Google ScholarPubMed
Frith, CD (1992). The Cognitive Neuropsychology of Schizophrenia. Erlbaum: East Sussex, UK.Google Scholar
Fukushima, J, Fukushima, K, Chiba, T, Tanaka, S, Yamashita, I, Kato, M (1988). Disturbances of voluntary control of saccadic eye movements in schizophrenic patients. Biological Psychiatry 23, 670–677.CrossRefGoogle ScholarPubMed
Fukushima, J, Fukushima, K, Miyasaka, K, Yamashita, I (1994). Voluntary control of saccadic eye movement in patients with frontal cortical lesions and parkinsonian patients in comparison with that in schizophrenics. Biological Psychiatry 36, 21–30.CrossRefGoogle ScholarPubMed
Fukushima, J, Fukushima, K, Morita, N, Yamashita, I (1990 a). Further analysis of the control of voluntary saccadic eye movements in schizophrenic patients. Biological Psychiatry 28, 943–958.CrossRefGoogle ScholarPubMed
Fukushima, J, Morita, N, Fukushima, K, Chiba, T, Tanaka, S, Yamashita, I (1990 b). Voluntary control of saccadic eye movements in patients with schizophrenic and affective disorders. Journal of Psychiatric Research 24, 9–24.CrossRefGoogle ScholarPubMed
Gottesman, II, Gould, TD (2003). The endophenotype concept in psychiatry: etymology and strategic intentions. American Journal of Psychiatry 160, 636–645.CrossRefGoogle ScholarPubMed
Gould, TD, Gottesman, II (2005). Psychiatric endophenotypes and the development of valid animal models. Genes, Brain, and Behavior 5, 113–119.CrossRefGoogle Scholar
Hutton, SB, Cutherbert, I, Crawford, TJ, Kennard, C, Barnes, TRE, Joyce, EM (2001). Saccadic hypometria in drug-naïve and drug-treated schizophrenic patients: a working memory deficit? Psychophysiology 38, 125–132.CrossRefGoogle ScholarPubMed
Karoumi, B, Saoud, M, d'Amato, T, Rosenfeld, F, Denise, P, Gutknecht, C, Gaveau, V, Beaulieu, F-E, Dalery, J, Rochet, T (2001). Poor performance in smooth pursuit and antisaccadic eye-movement tasks in healthy siblings of patients with schizophrenia. Psychiatry Research 101, 209–219.CrossRefGoogle ScholarPubMed
Karoumi, B, Ventre-Dominey, J, Vighetto, A, Dalery, J, d'Amato, T (1998). Saccadic eye movements in schizophrenic patients. Psychiatry Research 77, 9–19.CrossRefGoogle ScholarPubMed
Korn, H (2000). Schizophrenic vulnerability: a deficiency of the correlation between foveal perception and oculomotor proprioception? Medical Hypotheses 55, 245–252.CrossRefGoogle ScholarPubMed
Krebs, M-O, Gut-Fayand, A, Amado, I, Daban, C, Bourdel, M-C, Poirier, M-F, Berthoz, A (2001). Impairment of predictive saccades in schizophrenia. Neuroreport 12, 465–469.CrossRefGoogle ScholarPubMed
Krebs, M-O, Gut-Fayand, A, Bourdel, M-C, Dischamp, J, Olie, J-P (2000). Validation and factorial structure of a standardized neurological examination assessing neurological soft signs in schizophrenia. Schizophrenia Research 45, 245–260.CrossRefGoogle ScholarPubMed
Levy, DL, O'Driscoll, G, Matthysse, S, Cook, SR, Holzman, PS, Mendell, NR (2004). Antisaccade performance in biological relatives of schizophrenia patients: a meta-analysis. Schizophrenia Research 71, 113–125.CrossRefGoogle ScholarPubMed
McDowell, JE, Brenner, CA, Myles-Worseley, M, Coon, H, Byerley, W, Clementz, BA (2001). Ocular motor delayed-response task performance among patients with schizophrenia and their biological relatives. Psychophysiology 38, 153–156.Google ScholarPubMed
McDowell, JE, Clementz, BA (1996). Ocular-motor delayed-response task performance among schizophrenia patients. Neuropsychobiology 34, 67–71.CrossRefGoogle ScholarPubMed
McDowell, JE, Clementz, BA (2001). Behavioral and brain imaging studies of saccadic performance in schizophrenia. Biological Psychology 57, 5–22.CrossRefGoogle ScholarPubMed
Müller, N, Riedel, M, Eggert, T, Straube, A (1999). Internally and externally guided voluntary saccades in unmedicated and medicated schizophrenic patients. Part II. Saccadic latency, gain, and fixation suppression errors. European Archives of Psychiatry and Clinical Neuroscience 249, 7–14.Google ScholarPubMed
Nürnberger, JI, Blehar, MC, Kaufmann, CA, York-Cooler, C, Simpson, SG, Harkavy-Friedman, J, Severe, JB, Malaspina, D, Reich, R (1994). Diagnostic Interview for Genetic Studies: rationale, unique features and training. Archives of General Psychiatry 51, 849–859.CrossRefGoogle ScholarPubMed
Park, S, Holzman, PS, Goldman-Rakic, PS (1995). Spatial working memory deficits in the relatives of schizophrenic patients. Archives of General Psychiatry 52, 821–828.CrossRefGoogle ScholarPubMed
Pierrot-Deseilligny, C (1994). Saccade and smooth-pursuit impairment after cerebral hemispheric lesions. European Journal of Neurology 34, 121–134.CrossRefGoogle ScholarPubMed
Pierrot-Deseilligny, C, Muri, RM, Ploner, CJ, Gaymard, B, Demeret, T, Rivaud-Pechoux, S (2003). Decisional role of the dorsolateral prefrontal cortex in ocular motor behaviour. Brain 126, 1460–1473.CrossRefGoogle ScholarPubMed
Ploner, CJ, Gaymard, BM, Rivaud-Péchoux, S, Pierrot-Deseilligny, C (2005). The prefrontal substrate of reflexive saccade inhibition in humans. Biological Psychiatry 57, 1159–1165.CrossRefGoogle ScholarPubMed
Radant, AD, Claypoole, K, Wingerson, DK, Cowley, DS, Roy-Byrne, PP (1997). Relationship between neuropsychological and oculomotor measures in schizophrenia patients and normal controls. Biological Psychiatry 42, 797–805.CrossRefGoogle ScholarPubMed
Raemaekers, M, Jansma, JM, Cahn, W, Van der Geest, JN, van der Linden, JA, Kahn, RS, Ramsey, NF (2002). Neuronal substrate of the saccadic inhibition deficit in schizophrenia investigated with 3-dimensional event-related functional magnetic resonance imaging. Archives of General Psychiatry 59, 313–320.CrossRefGoogle ScholarPubMed
Raemaekers, M, Ramsey, NF, Vink, M, van den Heuvel, MP, Kahn, RS (2006). Brain activation during antisaccades in unaffected relatives of schizophrenic patients. Biological Psychiatry 59, 530–535.CrossRefGoogle ScholarPubMed
Reilly, J, Harris, M, Keshavan, M, Sweeney, JA (2005). Abnormalities in visually guided saccades suggest corticofugal dysregulation in never-treated schizophrenia. Biological Psychiatry 57, 145–154.CrossRefGoogle ScholarPubMed
Reulen, J, Marcus, J, Koops, D, de Vries, FR, Tiesinga, G, Boshuizen, K, Bos, JE (1988). Precise recording of eye movement: the IRIS technique, Part 1. Medical and Biological Engineering and Computers 26, 20–26.CrossRefGoogle ScholarPubMed
Reuter, B, Herzog, E, Kathmann, N (2006). Antisaccade performance of schizophrenia patients: evidence of reduced task-set activation and impaired error detection. Journal of Psychiatric Research 40, 122–130.CrossRefGoogle ScholarPubMed
Rijcken, C, Monster, T, Brouwers, J, Lolkje, T, de Jong-van den Berg, W (2003). Chlorpromazine equivalents versus defined daily doses: how to compare antipsychotic drug doses? Journal of Clinical Psychopharmacology 23, 657–659.CrossRefGoogle ScholarPubMed
Ross, RG, Harris, JG, Olincy, A, Radant, A, Adler, LE, Freedman, R (1998). Familial transmission of two independent saccadic abnormalities in schizophrenia. Schizophrenia Research 30, 59–70.CrossRefGoogle ScholarPubMed
Schwartz, BD, O'Brien, BA, Evans, WJ, McDermott, DE, Sautter, FJ, Winstead, DK (1995). Abnormal saccadic eye movements associated with positive family history of schizophrenics. Biological Psychiatry 38, 487–491.CrossRefGoogle ScholarPubMed
Sereno, AB, Holzman, PS (1995). Antisaccades and smooth pursuit eye movements in schizophrenia. Biological Psychiatry 37, 394–401.CrossRefGoogle ScholarPubMed
Spitzer, RL, Williams, JBW, Gibbon, M, First, MB (1990). Structured Clinical Interview for DSM-III-R – Non-Patient Edition, Version 1.0. American Psychiatric Press: Washington, DC.Google Scholar