Hostname: page-component-76fb5796d-2lccl Total loading time: 0 Render date: 2024-04-25T14:00:21.823Z Has data issue: false hasContentIssue false

Specific cognitive deficits in a group at genetic high risk of schizophrenia

Published online by Cambridge University Press:  06 March 2009

M. O'Connor*
Affiliation:
University of Edinburgh, Division of Psychiatry, Edinburgh, UK
J. M. Harris
Affiliation:
University of Edinburgh, Division of Psychiatry, Edinburgh, UK
A. M. McIntosh
Affiliation:
University of Edinburgh, Division of Psychiatry, Edinburgh, UK
D. G. C. Owens
Affiliation:
University of Edinburgh, Division of Psychiatry, Edinburgh, UK
S. M. Lawrie
Affiliation:
University of Edinburgh, Division of Psychiatry, Edinburgh, UK
E. C. Johnstone
Affiliation:
University of Edinburgh, Division of Psychiatry, Edinburgh, UK
*
*Address for correspondence: M. O'Connor, University of Edinburgh, Division of Psychiatry, Edinburgh, UK. (Email: m.oconnor@doctors.org.uk, mark.o'connor@uun.ed.ac.uk)

Abstract

Background

Neuropsychological deficits in schizophrenia patients and their relatives have been thought to represent possible genetic vulnerability markers or endophenotypes of the disorder. The present study describes results from the Edinburgh High Risk Study of computerized testing using the Cambridge Neuropsychological Test Automated Battery (CANTAB) on a group at genetic high risk (HR) of schizophrenia and a control group.

Method

A total of 97 HR and 25 control participants were assessed on three tests from the CANTAB – spatial span, spatial working memory, and Stockings of Cambridge. Analyses of covariance were used to compare the HR and control groups on the main outcome measures whilst controlling for intelligence quotient (IQ). Subsequent analysis examined the effects of the presence of symptoms on group differences.

Results

HR participants had significantly reduced spatial memory capacity [F(1, 118)=4.06, p=0.046] and significantly reduced planning processing speed [F(1, 116)=4.16, p=0.044] compared with controls even after controlling for general intelligence (IQ). Although HR individuals made more errors and showed poorer problem-solving and strategy performance compared with controls, these differences were not significant after controlling for IQ. Subsequent analysis indicated that the presence or absence of psychotic symptoms in the HR group did not influence these specific cognitive deficits.

Conclusions

Spatial memory capacity and planning processing speed may represent cognitive endophenotypes characterising the genetic predisposition to schizophrenia in this HR group.

Type
Original Articles
Copyright
Copyright © 2009 Cambridge University Press

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

Badcock, JC, Michiel, PT, Rock, D (2005). Spatial working memory and planning ability: contrasts between schizophrenia and bipolar 1 disorder. Cortex 41, 753763.Google Scholar
Barnes, TR, Hutton, SB, Chapman, MJ, Mutsatsa, S, Puri, BK, Joyce, EM (2000). West London first-episode study of schizophrenia. Clinical correlates of duration of untreated psychosis. British Journal of Psychiatry 177, 207211.CrossRefGoogle ScholarPubMed
Bartok, E, Berecz, R, Glaub, T, Degrell, I (2005). Cognitive functions in prepsychotic patients. Progress in Neuro-Psychopharmacology and Biological Psychiatry 29, 621624.CrossRefGoogle ScholarPubMed
Brewer, WJ, Wood, SJ, Phillips, LJ, Francey, SM, Pantelis, C, Yung, AR, Cornblatt, B, McGorry, PD (2006). Generalized and specific cognitive performance in clinical high-risk cohorts: a review highlighting potential vulnerability markers for psychosis. Schizophrenia Bulletin 32, 538555.CrossRefGoogle ScholarPubMed
Byrne, M, Clafferty, BA, Cosway, R, Grant, E, Hodges, A, Whalley, HC, Lawrie, SM, Cunningham Owens, DG, Johnstone, EC (2003). Neuropsychology, genetic liability, and psychotic symptoms in those at high risk of schizophrenia. Journal of Abnormal Psychology 112, 3848.Google Scholar
Byrne, M, Hodges, A, Grant, E, Owens, DC, Johnstone, EC (1999). Neuropsychological assessment of young people at high genetic risk for developing schizophrenia compared with controls: preliminary findings of the Edinburgh High Risk Study (EHRS). Psychological Medicine 29, 11611173.CrossRefGoogle ScholarPubMed
Cannon, TD, Huttunen, MO, Lonnqvist, J, Tuulio-Henriksson, A, Pirkola, T, Glahn, D, Finkelstein, J, Hietanen, M, Kaprio, J, Koskenvuo, M (2000). The inheritance of neuropsychological dysfunction in twins discordant for schizophrenia. American Journal of Human Genetics 67, 369382.CrossRefGoogle ScholarPubMed
Cannon, TD, Zorrilla, LE, Shtasel, D, Gur, RE, Gur, RC, Marco, EJ, Moberg, P, Price, RA (1994). Neuropsychological functioning in siblings discordant for schizophrenia and healthy volunteers. Archives of General Psychiatry 51, 651661.CrossRefGoogle ScholarPubMed
Cornblatt, BA, Keilp, JG (1994). Impaired attention, genetics, and the pathophysiology of schizophrenia. Schizophrenia Bulletin 20, 3146.Google Scholar
Cosway, R, Byrne, M, Clafferty, R, Hodges, A, Grant, E, Abukmeil, SS, Lawrie, SM, Miller, P, Johnstone, EC (2000). Neuropsychological change in young people at high risk for schizophrenia: results from the first two neuropsychological assessments of the Edinburgh High Risk Study. Psychological Medicine 30, 11111121.Google Scholar
Cosway, R, Byrne, M, Clafferty, R, Hodges, A, Grant, E, Morris, J, Abukmeil, SS, Lawrie, SM, Miller, P, Owens, DG, Johnstone, EC (2002). Sustained attention in young people at high risk for schizophrenia. Psychological Medicine 32, 277286.CrossRefGoogle ScholarPubMed
Dickinson, D, Ragland, JD, Gold, JM, Gur, RC (2008). General and specific cognitive deficits in schizophrenia: Goliath defeats David? Biological Psychiatry 64, 823827.Google Scholar
Donohoe, G, Clarke, S, Morris, D, Nangle, J, Schwaiger, S, Gill, M, Corvin, A, Robertson, IH (2006). Are deficits in executive sub-processes simply reflecting more general cognitive decline in schizophrenia? Schizophrenia Research 85, 168173.Google Scholar
Faraone, SV, Seidman, LJ, Kremen, WS, Pepple, JR, Lyons, MJ, Tsuang, MT (1995). Neuropsychological functioning among the nonpsychotic relatives of schizophrenic patients: a diagnostic efficiency analysis. Journal of Abnormal Psychology 104, 286304.CrossRefGoogle ScholarPubMed
Glahn, DC, Therman, S, Manninen, M, Kaprio, J, Lonnqvist, J, Cannon, TD (2003). Spatial working memory as an endophenotype for schizophrenia. Biological Psychiatry 53, 624626.CrossRefGoogle ScholarPubMed
Goldberg, TE, Ragland, JD, Torrey, EF, Gold, JM, Bigelow, LB, Weinberger, DR (1990). Neuropsychological assessment of monozygotic twins discordant for schizophrenia. Archives of General Psychiatry 47, 10661072.Google Scholar
Gottesman, II, Gould, TD (2003). The endophenotype concept in psychiatry: etymology and strategic intentions. American Journal of Psychiatry 160, 636645.Google Scholar
Hall, J, Whalley, HC, Job, DE, Baig, BJ, McIntosh, AM, Evans, KL, Thomson, PA, Porteous, DJ, Cunningham-Owens, DG, Johnstone, EC, Lawrie, SM (2006). A neuregulin 1 variant associated with abnormal cortical function and psychotic symptoms. Nature Neuroscience 9, 14771478.CrossRefGoogle ScholarPubMed
Heinrichs, RW, Zakzanis, KK (1998). Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. Neuropsychology 12, 426445.Google Scholar
Hodges, A, Byrne, M, Grant, E, Johnstone, E (1999). People at risk of schizophrenia: sample characteristics of the first 100 cases in the Edinburgh High-Risk Study. British Journal of Psychiatry 174, 547553.CrossRefGoogle ScholarPubMed
Johnstone, EC, Abukmeil, SS, Byrne, M, Clafferty, R, Grant, E, Hodges, A, Lawrie, SM, Owens, DG (2000). Edinburgh high-risk study – findings after four years: demographic, attainment and psychopathological issues. Schizophrenia Research 46, 115.CrossRefGoogle ScholarPubMed
Johnstone, EC, Ebmeier, KP, Miller, P, Owens, DGC, Lawrie, SM (2005). Predicting schizophrenia: findings from the Edinburgh High-Risk Study. British Journal of Psychiatry 186, 1825.Google Scholar
Kremen, WS, Seidman, LJ, Pepple, JR, Lyons, MJ, Tsuang, MT, Faraone, SV (1994). Neuropsychological risk indicators for schizophrenia: a review of family studies. Schizophrenia Bulletin 20, 103119.CrossRefGoogle ScholarPubMed
Levaux, M-N, Potvin, S, Sepehry, AA, Sablier, J, Mendrek, A, Stip, E (2007). Computerized assessment of cognition in schizophrenia: promises and pitfalls of CANTAB. European Psychiatry 22, 104115.CrossRefGoogle ScholarPubMed
McGuffin, P, Farmer, A, Harvey, I (1991). A polydiagnostic application of operational criteria in studies of psychotic illness. Development and reliability of the OPCRIT system. Archives of General Psychiatry 48, 764770.Google Scholar
OPCS (1991). Standard Occupational Classification, volume 3. HMSO: London.Google Scholar
Perneger, TV (1998). What's wrong with Bonferroni adjustments? British Medical Journal 316, 12361238.CrossRefGoogle ScholarPubMed
Rey, A (1964). L'examen clinique en psychologie. Presses Universitaires de France: Paris.Google Scholar
Robbins, TW, James, M, Owen, AM, Sahakian, BJ, Lawrence, AD, McInnes, L, Rabbitt, PMA (1998). A study of performance on tests from the CANTAB battery sensitive to frontal lobe dysfunction in a large sample of normal volunteers: implications for theories of executive functioning and cognitive aging. Journal of the International Neuropsychological Society 4, 474490.Google Scholar
Saperstein, AM, Fuller, RL, Avila, MT, Adami, H, McMahon, RP, Thaker, GK, Gold, JM (2006). Spatial working memory as a cognitive endophenotype of schizophrenia: assessing risk for pathophysiological dysfunction. Schizophrenia Bulletin 32, 498506.Google Scholar
Schatz, P, Browndyke, J (2002). Applications of computer-based neuropsychological assessment. Journal of Head Trauma Rehabilitation 17, 395410.CrossRefGoogle ScholarPubMed
Sitskoorn, MM, Aleman, A, Ebisch, SJ, Appels, MC, Kahn, RS (2004). Cognitive deficits in relatives of patients with schizophrenia: a meta-analysis. Schizophrenia Research 71, 285295.Google Scholar
Snitz, BE, MacDonald, AW III, Carter, CS (2006). Cognitive deficits in unaffected first-degree relatives of schizophrenia patients: a meta-analytic review of putative endophenotypes. Schizophrenia Bulletin 32, 179194.Google Scholar
Toomey, R, Faraone, SV, Seidman, LJ, Kremen, WS, Pepple, JR, Tsuang, MT (1998). Association of neuropsychological vulnerability markers in relatives of schizophrenic patients. Schizophrenia Research 31, 8998.Google Scholar
Whalley, HC, Simonotto, E, Flett, S, Marshall, I, Ebmeier, KP, Owens, DG, Goddard, NH, Johnstone, EC, Lawrie, SM (2004). fMRI correlates of state and trait effects in subjects at genetically enhanced risk of schizophrenia. Brain 127, 478490.CrossRefGoogle ScholarPubMed
Whalley, HC, Simonotto, E, Marshall, I, Owens, DG, Goddard, NH, Johnstone, EC, Lawrie, SM (2005). Functional disconnectivity in subjects at high genetic risk of schizophrenia. Brain 128, 20972108.Google Scholar
Whalley, HC, Simonotto, E, Moorhead, W, McIntosh, A, Marshall, I, Ebmeier, KP, Owens, DG, Goddard, NH, Johnstone, EC, Lawrie, SM (2006). Functional imaging as a predictor of schizophrenia. Biological Psychiatry 60, 454462.Google Scholar
Wood, SJ, Pantelis, C, Proffitt, T, Philips, LJ, Stuart, GW, Buchanan, J, Mahony, K, Brewer, W, Smith, DJ, McGorry, PD (2003). Spatial working memory ability is a marker of risk-for-psychosis. Psychological Medicine 33, 12391247.Google Scholar