Hostname: page-component-586b7cd67f-vdxz6 Total loading time: 0 Render date: 2024-11-23T21:41:05.711Z Has data issue: false hasContentIssue false
  • English
  • Français

Genetic overlap between episodic memory deficits and schizophrenia: results from The Maudsley Twin Study

Published online by Cambridge University Press:  12 May 2010

S. F. Owens ,
M. M. Picchioni ,
F. V. Rijsdijk ,
D. Stahl ,
E. Vassos ,
A. K. Rodger ,
D. A. Collier ,
R. M. Murray  and
T. Toulopoulou
S. F. Owens*
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, King's Health Partners, UK
M. M. Picchioni
Affiliation:
St Andrew's Academic Centre, King's College London, Institute of Psychiatry, Northampton, UK
F. V. Rijsdijk
Affiliation:
Social, Genetic and Developmental Psychiatry, Institute of Psychiatry, King's College London, UK
D. Stahl
Affiliation:
Department of Biostatistics, Institute of Psychiatry, King's College London, UK
E. Vassos
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, King's Health Partners, UK
A. K. Rodger
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, King's Health Partners, UK
D. A. Collier
Affiliation:
Social, Genetic and Developmental Psychiatry, Institute of Psychiatry, King's College London, UK
R. M. Murray
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, King's Health Partners, UK
T. Toulopoulou
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, King's College London, King's Health Partners, UK
*
*Address for correspondence: Ms. S. F. Owens, Department of Psychosis Studies, Institute of Psychiatry, King's College London, King's Health Partners, De Crespigny Park, LondonSE5 8AF, UK. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Visual and verbal episodic memory deficits are putative endophenotypes for schizophrenia; however, the extent of any genetic overlap of these with schizophrenia is unclear. In this study, we set out to quantify the genetic and environmental contributions to variance in visual and verbal memory performance, and to quantify their genetic relationship with schizophrenia.

Method

We applied bivariate genetic modelling to 280 twins in a classic twin study design, including monozygotic (MZ) and dizygotic (DZ) pairs concordant and discordant for schizophrenia, and healthy control twins. We assessed episodic memory using subtests of the Wechsler Memory Scale – Revised (WMS-R).

Results

Genetic influences (i.e. heritability) contributed significantly to variance in immediate recall of both verbal memory and visual learning, and the delayed recall of verbal and visual memory. Liability to schizophrenia was associated with memory impairment, with evidence of significant phenotypic correlations between all episodic memory measures and schizophrenia. Genetic factors were the main source of the phenotypic correlations for immediate recall of visual learning material; both immediate and delayed recall of verbal memory; and delayed recall of visual memory that, for example, shared genetic variance with schizophrenia, which accounted for 88% of the phenotypic correlation (rph=0.41) between the two.

Conclusions

Verbal memory and visual learning and memory are moderately heritable, share a genetic overlap with schizophrenia and are valid endophenotypes for the condition. The inclusion of these endophenotypes in genetic association studies may improve the power to detect susceptibility genes for schizophrenia.

Keywords

Endophenotypememoryneurocognitionschizophreniatwins
Type
Original Articles
Information
Psychological Medicine , Volume 41 , Issue 3 , March 2011 , pp. 521 - 532
Copyright
Copyright © Cambridge University Press 2010

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

Aleman, A, Hijman, R, De Haan, EHF, Kahn, RS (1999). Memory impairment in schizophrenia: a meta-analysis. American Journal of Psychiatry 156, 1358–1366.CrossRefGoogle ScholarPubMed
Andreasen, NC (1984 a). Scale for the Assessment of Negative Symptoms. University of Iowa Press: Iowa City.Google Scholar
Andreasen, NC (1984 b). Scale for the Assessment of Positive Symptoms. University of Iowa Press: Iowa City.Google Scholar
Blyler, CR, Gold, JM (2000). Cognitive effects of typical antipsychotic treatment: another look. In Cognition in Schizophrenia: Impairments, Importance and Treatment Strategies (ed. Sharma, T. and Harvey, P. D.), pp. 241–265. Oxford University Press: New York.CrossRefGoogle Scholar
Cannon, M, Caspi, A, Moffitt, TE, Harrington, H, Taylor, A, Murray, RM, Poulton, R (2002). Evidence for early-childhood, pan-developmental impairment specific to schizophreniform disorder: results from a longitudinal birth cohort. Archives of General Psychiatry 59, 449–456.CrossRefGoogle ScholarPubMed
Cannon, TD (2005). The inheritance of intermediate phenotypes for schizophrenia. Current Opinion in Psychiatry 18, 135–140.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, 369–382.CrossRefGoogle ScholarPubMed
Cannon, TD, Keller, MC (2006). Endophenotypes in the genetic analyses of mental disorders. Annual Review of Clinical Psychology 2, 267–290.CrossRefGoogle ScholarPubMed
Cannon, TD, Hennah, W, van Erp, TG, Thompson, PM, Lonnqvist, J, Huttunen, M, Gasperoni, T, Tuulio-Henriksson, A, Pirkola, T, Toga, AW, Kaprio, J, Mazziotta, J, Peltonen, L (2005). Association of DISC1/TRAX haplotypes with schizophrenia, reduced prefrontal gray matter, and impaired short- and long-term memory. Archives of General Psychiatry 62, 1205–1213.CrossRefGoogle ScholarPubMed
Chen, L-S, Rice, TK, Thompson, PA, Barch, DM, Csernansky, JG (2009). Familial aggregation of clinical and neurocognitive features in sibling pairs with and without schizophrenia. Schizophrenia Research 111, 159–166.CrossRefGoogle ScholarPubMed
Cirillo, MA, Seidman, LJ (2003). Verbal declarative memory dysfunction in schizophrenia: from clinical assessment to genetics and brain mechanisms. Neuropsychology Review 13, 43–77.CrossRefGoogle ScholarPubMed
Cohen, DJ, Dibble, E, Grawe, JM, Pollin, W (1975). Reliably separating identical from fraternal twins. Archives of General Psychiatry 32, 1371–1375.CrossRefGoogle ScholarPubMed
Dempster, EL, Toulopoulou, T, McDonald, C, Bramon, E, Walshe, M, Wickham, H, Sham, PC, Murray, RM, Collier, DA (2006). Episodic memory performance predicted by the 2bp deletion in exon 6 of the ‘alpha 7-like’ nicotinic receptor subunit gene. American Journal of Psychiatry 163, 1832–1834.CrossRefGoogle ScholarPubMed
Dickinson, D, Ramsey, ME, Gold, JM (2007). Overlooking the obvious: a meta-analytic comparison of digit symbol coding tasks and other cognitive measures in schizophrenia. Archives of General Psychiatry 64, 532–542.CrossRefGoogle ScholarPubMed
Elvevag, B, Goldberg, TE (2000). Cognitive impairment in schizophrenia is the core of the disorder. Critical Reviews in Neurobiology 14, 1–21.CrossRefGoogle ScholarPubMed
Fioravanti, M, Carlone, O, Vitale, B, Cinti, ME, Clare, L (2005). A meta-analysis of cognitive deficits in adults with a diagnosis of schizophrenia. Neuropsychology Review 15, 73–95.CrossRefGoogle ScholarPubMed
First, MB, Spitzer, RL, Gibbon, M, Williams, JBM (1997). Structured Clinical Interview for DSM-IV Axis I Disorders (SCID). New York State Psychiatric Institute: New York.Google Scholar
Glahn, DC, Almasy, L, Blangero, J, Burk, GM, Estrada, J, Peralta, JM, Meyenberg, N, Castro, MP, Barrett, J, Nicolini, H, Raventós, H, Escamilla, MA (2007). Adjudicating neurocognitive endophenotypes for schizophrenia. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 144B, 242–249.CrossRefGoogle ScholarPubMed
Goldberg, TE, Egan, MF, Gscheidle, T, Coppola, R, Weickert, T, Kolachana, BS, Goldman, D, Weinberger, DR (2003). Executive subprocesses in working memory: relationship to catechol-O-methyltransferase Val158Met genotype and schizophrenia. Archives of General Psychiatry 60, 889–896.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, 1066–1072.CrossRefGoogle ScholarPubMed
Goldberg, TE, Torrey, EF, Gold, JM, Ragland, JD, Bigelow, LB, Weinberger, DR (1993). Learning and memory in monozygotic twins discordant for schizophrenia. Psychological Medicine 23, 71–85.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
Greenwood, TA, Braff, DL, Light, GA, Cadenhead, KS, Calkins, ME, Dobie, DJ, Freedman, R, Green, MF, Gur, RE, Gur, RC, Mintz, J, Nuechterlein, KH, Olincy, A, Radant, AD, Seidman, LJ, Siever, LJ, Silverman, JM, Stone, WS, Swerdlow, NR, Tsuang, DW, Tsuang, MT, Turetsky, BI, Schork, NJ (2007). Initial heritability analyses of endophenotypic measures for schizophrenia: the consortium on the genetics of schizophrenia. Archives of General Psychiatry 64, 1242–1250.CrossRefGoogle Scholar
Gur, RE, Nimgaonkar, VL, Almasy, L, Calkins, ME, Ragland, JD, Pogue-Geile, MF, Kanes, S, Blangero, J, Gur, RC (2007). Neurocognitive endophenotypes in a multiplex multigenerational family study of schizophrenia. American Journal of Psychiatry 164, 813–819.CrossRefGoogle Scholar
Hall, M-H, Rijsdijk, F, Picchioni, M, Schulze, K, Ettinger, U, Toulopoulou, T, Bramon, E, Murray, RM, Sham, P (2007). Substantial shared genetic influences on schizophrenia and event-related potentials. American Journal of Psychiatry 164, 804–812.CrossRefGoogle ScholarPubMed
Hardin, JW, Hilbe, JM (2003). Generalized Estimating Equations. Chapman & Hall/CRC: Boca Raton, FL.Google Scholar
Heaton, RK, Gladsjo, JA, Palmer, BW, Kuck, J, Marcotte, TD, Jeste, DV (2001). Stability and course of neuropsychological deficits in schizophrenia. Archives of General Psychiatry 58, 24–32.CrossRefGoogle ScholarPubMed
Heinrichs, RW, Zakzanis, KK (1998). Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. Neuropsychology 12, 426–445.CrossRefGoogle ScholarPubMed
Husted, JA, Lim, S, Chow, EWC, Greenwood, C, Bassett, AS (2009). Heritability of neurocognitive traits in familial schizophrenia. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 150B, 845–853.CrossRefGoogle ScholarPubMed
Jones, P, Rodgers, B, Murray, R, Marmot, M (1994). Child development risk factors for adult schizophrenia in the British 1946 birth cohort. Lancet 344, 1398–1402.CrossRefGoogle ScholarPubMed
Keller, MC, Coventry, WL (2005). Quantifying and addressing parameter indeterminacy in the classical twin design. Twin Research and Human Genetics 8, 201–213.CrossRefGoogle ScholarPubMed
Lichtenstein, P, Yip, BH, Björk, C, Pawitan, Y, Cannon, TD, Sullivan, PF, Hultman, CM (2009). Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet 373, 234–239.CrossRefGoogle ScholarPubMed
Martin, N, Boomsma, D, Machin, G (1997). A twin-pronged attack on complex traits. Nature Genetics 17, 387–392.CrossRefGoogle ScholarPubMed
Neale, MC (1999). Mx: Statistical Modelling. Department of Psychiatry, Medical College of Virginia: Richmond, VA.Google Scholar
O'Donovan, MC, Craddock, N, Norton, N, Williams, H, Peirce, T, Moskvina, V, Nikolov, I, Hamshere, M, Carroll, L, Georgieva, L, Dwyer, S, Holmans, P, Marchini, JL, Spencer, CCA, Howie, B, Leung, H-T, Hartmann, AM, Moller, H-J, Morris, DW, Shi, Y, Feng, G, Hoffmann, P, Propping, P, Vasilescu, C, Maier, W, Rietschel, M, Zammit, S, Schumacher, J, Quinn, EM, Schulze, TG, Williams, NM, Giegling, I, Iwata, N, Ikeda, M, Darvasi, A, Shifman, S, He, L, Duan, J, Sanders, AR, Levinson, DF, Gejman, PV, Cichon, S, Nothen, MM, Gill, M, Corvin, A, Rujescu, D, Kirov, G, Owen, MJ (2008). Identification of loci associated with schizophrenia by genome-wide association and follow-up. Nature Genetics 40, 1053–1055.CrossRefGoogle ScholarPubMed
Prasad, KM, Chowdari, KV, Nimgaonkar, VL, Talkowski, ME, Lewis, DA, Keshavan, MS (2005). Genetic polymorphisms of the RGS4 and dorsolateral prefrontal cortex morphometry among first episode schizophrenia patients. Molecular Psychiatry 10, 213–219.CrossRefGoogle ScholarPubMed
Rabe-Hesketh, S, Skrondal, A (2005). Multilevel and Longitudinal Modeling using Stata. Stata Press: College Station, TX.Google Scholar
Reichenberg, A, Harvey, PD (2007). Neuropsychological impairments in schizophrenia: integration of performance-based and brain imaging findings. Psychological Bulletin 133, 833–858.CrossRefGoogle ScholarPubMed
Rijsdijk, FV, Sham, PC (2002). Analytic approaches to twin data using structural equation models. Briefings in Bioinformatics 3, 119–133.CrossRefGoogle ScholarPubMed
Rijsdijk, FV, van Haren, NEM, Picchioni, MM, McDonald, C, Toulopoulou, T, Hulshoff Pol, HE, Kahn, RS, Murray, R, Sham, PC (2005). Brain MRI abnormalities in schizophrenia: same genes or same environment? Psychological Medicine 35, 1399–1409.CrossRefGoogle ScholarPubMed
Simes, RJ (1986). An improved Bonferroni procedure for multiple tests of significance. Biometrika 73, 751–754.CrossRefGoogle Scholar
Sitskoorn, MM, Aleman, A, Ebisch, SJH, Appels, MCM, Kahn, RS (2004). Cognitive deficits in relatives of patients with schizophrenia: a meta-analysis. Schizophrenia Research 71, 285–295.CrossRefGoogle ScholarPubMed
Spitzer, RL, Endicott, J (1978). Schedule for Affective Disorders and Schizophrenia – Lifetime Version. New York State Psychiatric Institute: New York.Google Scholar
Stefansson, H, Rujescu, D, Cichon, S, Pietilainen, OPH, Ingason, A, Steinberg, S, Fossdal, R, Sigurdsson, E, Sigmundsson, T, Buizer-Voskamp, JE, Hansen, T, Jakobsen, KD, Muglia, P, Francks, C, Matthews, PM, Gylfason, A, Halldorsson, BV, Gudbjartsson, D, Thorgeirsson, TE, Sigurdsson, A, Jonasdottir, A, Jonasdottir, A, Bjornsson, A, Mattiasdottir, S, Blondal, T, Haraldsson, M, Magnusdottir, BB, Giegling, I, Moller, H-J, Hartmann, A, Shianna, KV, Ge, D, Need, AC, Crombie, C, Fraser, G, Walker, N, Lonnqvist, J, Suvisaari, J, Tuulio-Henriksson, A, Paunio, T, Toulopoulou, T, Bramon, E, Di Forti, M, Murray, R, Ruggeri, M, Vassos, E, Tosato, S, Walshe, M, Li, T, Vasilescu, C, Muhleisen, TW, Wang, AG, Ullum, H, Djurovic, S, Melle, I, Olesen, J, Kiemeney, LA, Franke, B, Sabatti, C, Freimer, NB, Gulcher, JR, Thorsteinsdottir, U, Kong, A, Andreassen, OA, Ophoff, RA, Georgi, A, Rietschel, M, Werge, T, Petursson, H, Goldstein, DB, Nothen, MM, Peltonen, L, Collier, DA, St Clair, D, Stefansson, K (2008). Large recurrent microdeletions associated with schizophrenia. Nature 455, 232–236.CrossRefGoogle ScholarPubMed
Sullivan, PF, Kendler, KS, Neale, MC (2003). Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Archives of General Psychiatry 60, 1187–1192.CrossRefGoogle ScholarPubMed
Tan, HY, Callicott, JH, Weinberger, DR (2008). Intermediate phenotypes in schizophrenia genetics redux: is it a no brainer? Molecular Psychiatry 13, 233–238.CrossRefGoogle ScholarPubMed
Toulopoulou, T, Picchioni, M, Rijsdijk, F, Hua-Hall, M, Ettinger, U, Sham, P, Murray, R (2007). Substantial genetic overlap between neurocognition and schizophrenia: genetic modeling in twin samples. Archives of General Psychiatry 64, 1348–1355.CrossRefGoogle ScholarPubMed
Toulopoulou, T, Quraishi, S, McDonald, C, Murray, RM (2006). The Maudsley Family Study: premorbid and current general intellectual function levels in familial bipolar I disorder and schizophrenia. Journal of Clinical and Experimental Neuropsychology 28, 243–259.CrossRefGoogle Scholar
Tuulio-Henriksson, A, Haukka, J, Partonen, T, Varilo, T, Paunio, T, Ekelund, J, Cannon, TD, Meyer, JM, Jouko, L (2002). Heritability and number of quantitative trait loci of neurocognitive functions in families with schizophrenia. American Journal of Medical Genetics 114, 483–490.CrossRefGoogle ScholarPubMed
Wechsler, D (1987). Manual for the Wechsler Memory Scale – Revised. The Psychological Corporation: San Antonio, TX.Google Scholar
Wechsler, D (1997). Wechsler Adult Intelligence Scale, Third Edition: Administration and Scoring Manual. The Psychological Corporation: London, UK.Google Scholar
Williams, RL (2000). A note on robust variance estimation for cluster-correlated data. Biometrics 56, 645–646.CrossRefGoogle ScholarPubMed
Supplementary material: File

Owens Supplementary Material

Table.doc

Download Owens Supplementary Material(File)
File 68.1 KB