Abstract
Episodic memory impairments in individuals with schizophrenia have been well documented in the literature. However, despite the abundance of findings, constituent cognitive, neural, behavioral, and genetic components of the deficits continue to elude full characterization. This review provides a characterization of these deficits by organizing findings within three frameworks of interest: 1) neuroanatomical; 2) genetic; and 3) behavioral. Within each approach, evidence from imaging studies as well as behavioral studies is examined. The hope is that by synthesizing the cognitive science paradigms, molecular genetic neurophysiological findings, and computational algorithms applied to medial temporal lobe subregions, we will be able to expand our understanding of the types of compromises in episodic memory systems of individuals with schizophrenia.
Similar content being viewed by others
References
Aleman, A., Hijman, R., de Haan, E. H. F., & Kahn, R. S. (1999). Memory impairment in schizophrenia: a meta-analysis. Am J Psychiatry, 156(9), 1358–66.
Achim, A. M., & Lepage, M. (2005). Episodic memory-related activation in schizophrenia: meta-analysis. Br J Psychiatry, 187, 500–509.
Andreasen, N. C. (1994). The mechanisms of schizophrenia. Curr Opin Neurobiol, 4, 245–251.
Andreasen, N. C., O'Leary, D. S., Cizadlo, T., Arndt, S., Rezai, K., Ponto, L. L., et al. (1996). Schizophrenia and cognitive dysmetria: a positron-emission tomography study of dysfunctional prefrontal-thalamic-cerebellar circuitry. Proc Natl Acad Sci U S A, 93, 9985–9990.
Arciniegas, D., Rojas, D. C., Teale, P., Sheeder, J., Sandberg, E., & Reite, M. (1999). The thalamus and the schizophrenia phenotype: failure to replicate reduced volume. Biol Psychiatry, 45, 1329–1335.
Bonner-Jackson, A., Yodkovik, N., Csernansky, J. G., & Barch, D. M. (2008). Episodic memory in schizophrenia: the influence of strategy use on behavior and brain activation. Psychiatry Res, 164, 1–15.
Brodeur, M., Pelletier, M., & Lepage, M. (2008). Seeing is remembering: do deficits in closure affect visual memory recognition in schizophrenia? Cogn Neuropsychiatry, 13, 385–405.
Buchsbaum, M. S., Someya, T., Teng, C. Y., Abel, L., Chin, S., Najafi, A., et al. (1996). PET and MRI of the thalamus in never-medicated patients with schizophrenia. Am J Psychiatry, 153, 191–199.
Callicott, J. H., Straub, R. E., Pezawas, L., Egan, M. F., Mattay, V. S., Hariri, A. R., et al. (2005). Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia. Proc Natl Acad Sci U S A, 102, 8627–8632.
Conway, M. A. (2001). Sensory-perceptual episodic memory and its context: autobiographical memory. Philos Trans R Soc Lond B Biol Sci, 356, 1375–1384.
Danion, J. M., Huron, C., Vidailhet, P., & Berna, F. (2007). Functional mechanisms of episodic memory impairment in schizophrenia. Can J Psychiatry, 52, 693–701.
DeLisi, L. E. (2009). Searching for the true genetic vulnerability for schizophrenia. Genome Medicine, 1, 14.
Di Giorgio, A., Blasi, G., Sambataro, F., Rampino, A., Papazacharias, A., Gambi, F., et al. (2008). Association of the Ser704Cys DISC1 polymorphism with human hippocampal formation gray matter and function during memory encoding. European Journal of Neuroscience, 28, 2129–2136.
Donohoe, G., Morris, D. W., Robertson, I. H., McGhee, K. A., Murphy, K., Kenny, N., et al. (2007). DAOA ARG30LYS and verbal memory function in schizophrenia. Molecular Psychiatry, 12, 795–6.
Egeland, J., Sundet, K., Rund, B. R., Asbjornsen, A., Hugdahl, K., Landro, N. I., et al. (2003). Sensitivity and specificity of memory dysfunction in schizophrenia: a comparison with major depression. J Clin Exp Neuropsychol, 25, 79–93.
Elvevag, B., Egan, M. F., & Goldberg, T. E. (2000). Paired-associate learning and memory interference in schizophrenia. Neuropsychologia, 38, 1565–1575.
Elvevag, B., Fisher, J. E., Weickert, T. W., Weinberger, D. R., & Goldberg, T. E. (2004). Lack of false recognition in schizophrenia: a consequence of poor memory? Neuropsychologia, 42, 546–554.
Exner, C., Nehrkorn, B., Martin, V., Huber, M., Shiratori, K., & Rief, W. (2008). Sex-dependent hippocampal volume reductions in schizophrenia relate to episodic memory deficits. J Neuropsychiatry Clin Neurosci, 20, 227–230.
Flor-Henry, P. (1990). Neuropsychology and psychopathology: a progress report. Neuropsychol Rev, 1(2), 103–123.
Gold, J. M., Fuller, R. L., Robinson, B. M., McMahon, R. P., Braun, E. L., & Luck, S. J. (2006). Intact attentional control of working memory encoding in schizophrenia. J Abnorm Psychol, 115(4), 658–73.
Goldberg, T. E., Weinberger, D. R. (2004). Genes and the parsing of cognitive processes. Trends Cogn Sci, 8(7), 325–335.
Goldberg, T. E., Straub, R. E., Callicott, J. H., Hariri, A., Mattay, V. S., Bigelow, L., et al. (2006). The G72/G30 gene complex and cognitive abnormalities in schizophrenia. Neuropsychopharmacology, 31, 2022–2032.
Goldberg, T. E., Iudicello, J., Russo, C., Elvevag, B., Straub, R., Egan, M. F., et al. (2008). BDNF Val66Met polymorphism significantly affects d' in verbal recognition memory at short and long delays. Biol Psychology, 77(1), 20–4.
Greene, R. (2001). Circuit analysis of NMDAR hypofunction in the hippocampus, in vitro, and psychosis of schizophrenia. Hippocampus, 11, 569–577.
Guillem, F., Mendrek, A., Lavoie, M. E., Pampoulova, T., & Stip, E. (2009). Sex differences in memory processing in schizophrenia: an event-related potential (ERP) study. Prog Neuropsychopharmacol Biol Psychiatry, 33(1), 1–10.
Gur, R. E., Kohler, C., Turetsky, B. I., Siegel, S. J., Kanes, S. J., Bilker, W. B., et al. (2004). A sexually dimorphic ratio of orbitofrontal to amygdala volume is altered in schizophrenia. Biol Psychiatry, 55(5), 512–7.
Hall, J., Whalley, H. C., Moorhead, T. W., Baig, B. J., McIntosh, A. M., Job, D. E., et al. (2008). Genetic variation in the DAOA (G72) gene modulates hippocampal function in subjects at high risk of schizophrenia. Biol Psychiatry, 64, 428–433.
Harrison, P. J. (2004). The hippocampus in schizophrenia: a review of the neuropathological evidence and its patholphysiological implications. Psychopharmacology, 174, 151–62.
Harrison, P. J., & Eastwood, S. L. (2001). Neuropathological studies of synaptic connectivity in the hippocampal formation in schizophrenia. Hippocampus, 11, 508–19.
Hazlett, E. A., Buchsbaum, M. S., Byne, W., Wei, T. C., Spiegel-Cohen, J., Geneve, C., et al. (1999). Three-dimensional analysis with MRI and PET of the size, shape, and function of the thalamus in the schizophrenia spectrum. Am J Psychiatry, 156, 1190–1199.
Heckers, S., Rauch, S. L., Goff, D., Savage, C. R., Schacter, D. L., Fischman, A. J., et al. (1998). Impaired recruitment of the hippocampus during conscious recollection in schizophrenia. Nat Neurosci, 1, 318–323.
Heckers, S., Curran, T., Goff, D., Rauch, S. L., Fischman, A. J., Alpert, N. M., et al. (2000). Abnormalities in the thalamus and prefrontal cortex during episodic object recognition in schizophrenia. Biol Psychiatry, 48, 651–657.
Heinrichs, R. W., & Zakzanis, K. K. (1998). Neurocognitive deficit in schizophrenia: A quantitative review of the evidence. Neuropsychology, 12, 426–445.
Hennah, W., Thomson, P., Peltonen, L., & Porteous, D. (2006). Genes and schizophrenia: beyond schizophrenia: the role of DISC1 in major mental illness. Schizophr Bull, 32, 409–416.
Hill, S. K., Harris, M. S., Herbener, E. S., Pavuluri, M., & Sweeney, J. A. (2008). Neurocognitive allied phenotypes for schizophrenia and bipolar disorder. Schizophr Bull, 34, 743–759.
Holt, D. J., Legron-Milad, K., Milad, M. R., Rauch, S. L., Pitman, R. K., Orr, S. P., et al. (2009). Extinction memory is impaired in schizophrenia. Biol Psychiatry, 65, 455–463.
Jazbec, S., Pantelis, C., Robbins, T., Weickert, T., Weinberger, D. R., & Goldberg, T. E. (2007). Intra-dimensional/extra-dimensional set-shifting performance in schizophrenia: impact of distractors. Schizophr Res, 89, 339–49.
Keefe, R. S., Arnold, M. C., Bayen, U. J., McEvoy, J. P., & Wilson, W. H. (2002). Source-monitoring deficits for self-generated stimuli in schizophrenia: multinomial modeling of data from three sources. Schizophr Res, 57(1), 51–67.
Kenney, J. W., & Gould, T. J. (2008). Modulation of hippocampus-dependent learning and synaptic plasticity by nicotine. Mol Neurobiol, 38, 101–121.
Kirwan, C. B., Wixted, J. T., & Squire, L. R. (2008). Activity in the medial temporal lobe predicts memory strength, whereas activity in the prefrontal cortex predicts recollection. J Neurosci, 28, 10541–10548.
Koppel J, Goldberg TE (in press): The genetics of episodic memory. Cognitive Neuropsychiatry.
Kvajo, M., McKellar, H., Arguello, P. A., Drew, L. J., Moore, H., MacDermott, A. B., et al. (2008). A mutation in mouse Disc1 that models a schizophrenia risk allele leads to specific alterations in neuronal architecture and cognition. Proceedings of the Nat Acad of Sciences, 105, 7076–81.
Lepage, M., Montoya, A., Pelletier, M., Achim, A. M., Menear, M., & Lal, S. (2006). Associative memory encoding and recognition in schizophrenia: an event-related fMRI study. Biol Psychiatry, 60, 1215–1223.
Lepage, M., Sergerie, K., Pelletier, M., & Harvey, P. O. (2007). Episodic memory bias and the symptoms of schizophrenia. Can J Psychiatry, 52, 702–709.
Lisman, J. E., Coyle, J. T., Green, R. W., Javitt, D. C., Benes, F. M., Heckers, S., et al. (2008). Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia. Trends Neurosci, 31, 234–242.
Lu B, Martinowich K (2008): Cell biology of BDNF and its relevance to schizophrenia. Novartis Found Symp 289:119–129; discussion 129–135, 193–115.
Manahan-Vaughan, D., Wildforster, V., & Thomsen, C. (2008). Rescue of hippocampal LTP and learning deficits in a rat model of psychosis by inhibition of glycine transporter-1 (GlyT1). Eur J Neurosci, 28, 1342–1350.
Matynia, A., Anagnostaras, S. B., Wiltgen, B. J., Lacuesta, M., Fanselow, M. S., & Silva, A. J. (2008). A high through-put reverse genetic screen identifies two genes involved in remote memory in mice. PLoS ONE, 3, e2121.
Mercer, T. R., Dinger, M. E., Mariani, J., Kosik, K. S., Mehler, M. F., & Mattick, J. S. (2008). Noncoding RNAs in Long-Term Memory Formation. Neuroscientist, 14, 434–445.
Meyer-Lindenberg, A., & Weinberger, D. R. (2006). Intermediate phenotypes and genetic mechanisms of psychiatric disorders. Nat Rev Neurosci, 7(10), 818–27.
Moritz, S., Ferahli, S., & Naber, D. (2004). Memory and attention performance in psychiatric patients: lack of correspondence between clinician-rated and patient-rated functioning with neuropsychological test results. J Int Neuropsychol Soc, 10, 623–633.
Moritz, S., Heeren, D., Andresen, B., & Krausz, M. (2001). An analysis of the specificity and the syndromal correlates of verbal memory impairments in schizophrenia. Psychiatry Res, 101, 23–31.
Moritz, S., Woodward, T. S., & Rodriguez-Raecke, R. (2006). Patients with schizophrenia do not produce more false memories than controls but are more confident in them. Psychol Med, 36, 659–667.
Ongur, D., Cullen, T. J., Wolf, D. H., Rohan, M., Barreira, P., Zalesak, M., et al. (2006). The neural basis of relational memory deficits in schizophrenia. Arch Gen Psychiatry, 63, 356–365.
Paul, B. M., Elvevag, B., Bokat, C. E., Weinberger, D. R., & Goldberg, T. E. (2005). Levels of processing effects on recognition memory in patients with schizophrenia. Schizophrenia Research, 74, 101–110.
Papassotiropoulos, A., Stephan, D. A., Huentelman, M. J., Hoerndli, F. J., Craig, D. W., Pearson, J. V., et al. (2006). Common Kibra alleles are associated with human memory performance. Science, 314, 475–8.
Parwani, A., Weiler, M. A., Blaxton, T. A., Warfel, D., Hardin, M., Frey, K., et al. (2005). The effects of a subanesthetic dose of ketamine on verbal memory in normal volunteers. Psychopharmacology (Berl), 183, 265–274.
Potkin, S. G., Turner, J. A., Brown, G. G., McCarthy, G., Greve, D. N., Glover, G. H., et al. (2009). Working memory and DLPFC inefficiency in schizophrenia: the FBIRN study. Schizophr Bull, 35, 19–31.
Potkin, S. G., Turner, J. A., Guffanti, G., Lakatos, A., Fallon, J. H., Nguyen, D. D., et al. (2009). A genome-wide association study of schizophrenia using brain activation as a quantitative phenotype. Schizophr Bull, 35, 96–108.
Ragland, J. D., Gur, R. C., Valdez, J., Turetsky, B. I., Elliott, M., Kohler, C., et al. (2004). Event-related fMRI of frontotemporal activity during word encoding and recognition in schizophrenia. Am J Psychiatry, 161, 1004–1015.
Ranganath, C., Minzenberg, M. J., & Ragland, J. D. (2008). The cognitive neuroscience of memory function and dysfunction in schizophrenia. Biol Psychiatry, 64, 18–25.
Roediger, H. L., 3 rd, Meade, M. L., & Bergman, E. T. (2001). Social contagion of memory. Psychon Bull Rev, 8, 365–371.
Rowland, L. M., Astur, R. S., Jung, R. E., Bustillo, J. R., Lauriello, J., & Yeo, R. A. (2005). Selective cognitive impairments associated with NMDA receptor blockade in humans. Neuropsychopharmacology, 30, 633–639.
Shi J, Badner JA, Gershon ES, Liu C (2007): Allelic association of G72/G30 with schizophrenia and bipolar disorder: a comprehensive meta-analysis. Schizophr Res 98(1–3):89–97. Epub 2007 Nov 26.
Skelley, S. L., Goldberg, T. E., Egan, M. F., Weinberger, D. R., & Gold, J. M. (2008). Verbal and visual memory: characterizing the clinical and intermediate phenotype in schizophrenia. Schizophr Res, 105, 78–85.
Smith, C. N., & Squire, L. R. (2009). Medial temporal lobe activity during retrieval of semantic memory is related to the age of the memory. J Neurosci, 29, 930–938.
Talamini, L. M., Meeter, M., Elvevag, B., Murre, J. M., & Goldberg, T. E. (2005). Reduced parahippocampal connectivity produces schizophrenia-like memory deficits in simulated neural circuits with reduced parahippocampal connectivity. Arch Gen Psychiatry, 62, 485–493.
Taylor MA, Abrams R (1984): Cognitive impairment in schizophrenia. Am J Psychiatry 141:196–2-1.
Taylor, M. A., Greenspan, B., & Abrams, R. (1979). Lateralized neuropsychological dysfunction in affective disorder and schizophrenia. Am J Psychiatry, 136, 1031–4.
Tulving E (1972): Episodic and semantic memory. Organization of Memory, ed. E. Tulving. New York: Academic Press, Inc.
Vita A, De Peri L, Silenzi C, Dieci M. (2006) Brain morphology in first-episode schizophrenia: a meta-analysis of quantitative magnetic resonsance imaging studies. Schizophr Res 82(1):75–88.
Weiss, A. P., Goff, D., Schacter, D. L., Ditman, T., Freudenreich, O., Henderson, D., et al. (2006). Fronto-hippocampal function during temporal context monitoring in schizophrenia. Biol Psychiatry, 60, 1268–1277.
Wolf, D. H., Gur, R. C., Valdez, J. N., Loughead, J., Elliott, M. A., Gur, R. E., et al. (2007). Alterations of fronto-temporal connectivity during word encoding in schizophrenia. Psychiatry Res, 154, 221–232.
Yeap, S., Kelly, S. P., Sehatpour, P., Magno, E., Javitt, D. C., Garavan, H., et al. (2006). Early visual sensory deficits as endophenotypes for schizophrenia: high-density electrical mapping in clinically unaffected first-degree relatives. Arch Gen Psychiatry, 63, 1180–1188.
Acknowledgments
Funding sources: 5 P30 MH074543-03 (Kane). Early Phase Schizophrenia: Optimizing Outcomes.
Disclosures
The authors have no conflicts of interest relevant to this work.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Leavitt, V.M., Goldberg, T.E. Episodic Memory in Schizophrenia. Neuropsychol Rev 19, 312–323 (2009). https://doi.org/10.1007/s11065-009-9107-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11065-009-9107-0