Cited by 836Schizophrenia research and treatmentMental Health and PsychiatryDementia and Cognitive Impairment Research

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Cognitive Impairment in Schizophrenia Is the Core of the Disorder

Elvevag, Brita, Goldberg, Terry E.·2000·Critical Reviews™ in Neurobiology

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Abstract

Patients with schizophrenia exhibit an exceedingly wide range of symptoms from a variety of domains. The cardinal features are abnormal ideas (such as delusions); abnormal perceptions (such as hallucinations); formal thought disorder (as evidenced by disorganized speech); motor, volitional, and behavioral disorders; and emotional disorders (such as affective flattening or inappropriateness). In addition to these diverse, and sometimes bizarre symptoms, it has become increasingly apparent that the disorder is, to variable degrees, accompanied by a broad spectrum of cognitive impairments. This review addresses the question of whether the cognitive deficits seen in schizophrenic patients are the core features of the disorder. In other words, we explore whether schizophrenia is best characterized by symptoms or cognitive deficits (we suggest the latter) and moreover, whether there is a specific cognitive deficit profile that may assist in diagnosis. First, we discuss what the cognitive deficits are. Then we address in turn the reality, frequency, predictive validity, specificity, course and susceptibility to neuroleptic effects of these cognitive impairments. In brief, we argue that various cognitive deficits are enduring features of the schizophrenia illness, that they are not state-related and are not specific to subtypes of the illness, and, more specifically, that working memory and attention are characteristically impaired in patients with schizophrenia, irrespective of their level of intelligence. Last, we conclude that problems in these cognitive domains are at the very core of the dysfunction in this disease.

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Background
Cognitive impairments in the STOP null mouse model of schizophrenia.
Powell, K. J., Hori, S. E., Leslie, R. A., Andrieux, A., Schellinck, H. M., Thorne, M., & Robertson, G. S. (2007) · Behavioral Neuroscience · doi:10.1037/0735-7044.121.5.826 · Cited by 62
“Cognitive deficits associated with schizophrenia have become increasingly recognized as central to both the diagnosis and treatment of this psychiatric disorder (Elvevag and Goldberg 2000).”
Motor coordination deficits in mice lacking RGS9.
Blundell, J. J., Hoang, C. V., Potts, B. W., Gold, S., & Powell, C. (2008) · Brain Research · doi:10.1016/j.brainres.2007.11.017 · Cited by 59
“Working memory impairments are often seen in schizophrenia (Elvevag and Goldberg, 2000; Goldman-Rakic and Selemon, 1997).”
Background
Specific executive/attentional deficits in patients with schizophrenia or bipolar disorder who have a positive family history of psychosis
Tabarés‐Seisdedos, R., Balanzá‐Martínez, V., Salazar-Fraile, J., Selva‐Vera, G., Cercós, C. L., & Gómez-Beneyto, M. (2003) · Journal of Psychiatric Research · doi:10.1016/s0022-3956(03)00071-2 · Cited by 53
Clinical Neuropsychology Within Adolescent and Young-Adult Psychiatry: Conceptualizing Theory and Practice
Allott, K., Proffitt, T., McGorry, P. D., Pantelis, C., Wood, S. J., Cumner, M., & Brewer, W. J. (2012) · Applied Neuropsychology Child · doi:10.1080/08841233.2012.670566 · Cited by 52
“However, cognitive dysfunction is now also recognized as a core or premorbid feature of several psychiatric illnesses (Elvevag & Goldberg, 2000 ; Mesholam-Gately, Giuliano, Faraone, Goff, & Seidman, 2009; Torres, Boudreau, & Yatham, 2007 ; Wood, Allen, & Pantelis, 2009 ).”
Background
Behavioral, Neurophysiological, and Synaptic Impairment in a Transgenic Neuregulin1 (NRG1-IV) Murine Schizophrenia Model
Papaleo, F., Yang, F., Paterson, C., Palumbo, S., Carr, G. V., Wang, Y., Floyd, K., Huang, W., Thomas, C. J., Chen, J., et al. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.4632-15.2016 · Cited by 55
“NRG1-IV regulates expression of ErbB4 and PI3K-AKT pathway signaling NRG1 signaling is involved in PSD95 organization, NMDA and AMPA receptor function, and downstream activation of AKT signaling (Hahn et al., 2006; Fazzari et al., 2010; Wen et al., 2010; Mei and Nave, 2014).”
BackgroundInfluential
Diurnal changes in perineuronal nets and parvalbumin neurons in the rat medial prefrontal cortex
Harkness, J. H., Gonzalez, A. E., Bushana, P. N., Jorgensen, E. T., Hegarty, D. M., Nardo, A. A. D., Prochiantz, A., Wisor, J. P., Aicher, S. A., Brown, T. E., et al. (2021) · Brain Structure and Function · doi:10.1007/s00429-021-02229-4 · Cited by 55
Systematic Review of Functional MRI Applications for Psychiatric Disease Subtyping
Miranda, L., Paul, R., Pütz, B., Koutsouleris, N., & Müller‐Myhsok, B. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.665536 · Cited by 55
“Having in mind how evident cognitive decay is in patients with the disease (86), Geisler et al.”
Background
Oxytocin and social cognition in affective and psychotic disorders
Pérez-Rodríguez, M. M., Mahon, K., Russo, M., Ungar, A. K., & Burdick, K. E. (2014) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2014.07.012 · Cited by 58
“Neurocognitive impairment characterizes individuals with schizophrenia (SZ) (Heinrichs and Zakzanis, 1998; Fioravanti et al., 2005; Elvevåg and Goldberg, 2000) and it has been considered a core feature of the disorder since it was first described (Kraepelin, 1921).”
Background
Factor analysis of neurocognitive tests in a large sample of schizophrenic probands, their siblings, and healthy controls
Genderson, M., Dickinson, D., Diaz-Asper, C. M., Egan, M. F., Weinberger, D. R., & Goldberg, T. E. (2007) · Schizophrenia Research · doi:10.1016/j.schres.2006.12.031 · Cited by 52
“Cognitive dysfunction is considered to be a cardinal feature of schizophrenia and appears robust irrespective of the subtype of the illness and symptoms in other domains (Elvevag and Goldberg, 2000; Heaton et al., 2001).”
BackgroundSelf-citation
Mapping pathologic circuitry in schizophrenia
Glausier, J. R., & Lewis, D. A. (2018) · Handbook of clinical neurology · doi:10.1016/b978-0-444-63639-3.00025-6 · Cited by 53
Association of a haplotype in the serotonin 5‐HT4 receptor gene (HTR4) with Japanese schizophrenia
Suzuki, T., Iwata, N., Kitamura, Y., Kitajima, T., Yamanouchi, Y., Ikeda, M., Nishiyama, T., Kamatani, N., & Ozaki, N. (2003) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.20060 · Cited by 52
“Cognitive dysfunction has been regarded as an fundamental problem of schizophrenia [Andreasen et al., 1996; Andreasen et al., 1999; Elvevag and Goldberg, 2000], therefore molecular mechanisms of cognitive function may have an important role in the pathophysiology of schizophrenia.”
Background
Cannabinoid CB1 receptors in rat medial prefrontal cortex are colocalized with calbindin but not parvalbumin- and calretinin-positive GABA-ergic neurons
Wędzony, K., & Chocyk, A. (2009) · Pharmacological Reports · doi:10.1016/s1734-1140(09)70161-6 · Cited by 50
“to those observed in schizophrenia [12, 26].”
Self-reported quality of life measure is reliable and valid in adult patients suffering from schizophrenia with executive impairment
Baumstarck, K., Boyer, L., Boucékine, M., Aghababian, V., Parola, N., Lançon, C., & Auquier, P. (2013) · Schizophrenia Research · doi:10.1016/j.schres.2013.03.008 · Cited by 50
“Cognitive deficits are a core aspect of schizophrenia (Elvevag and Goldberg, 2000; Green et al., 2004).”
Background
Alterations in hippocampal excitability, synaptic transmission and synaptic plasticity in a neurodevelopmental model of schizophrenia
Sanderson, T. M., Côtel, M.-C., O’Neill, M. J., Tricklebank, M. D., Collingridge, G. L., & Sher, E. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.08.005 · Cited by 51
Common and specific cognitive deficits in schizophrenia: relationships to function
Sheffield, J. M., Gold, J. M., Strauss, M. E., Carter, C. S., MacDonald, A. W., Ragland, J. D., Silverstein, S. M., & Barch, D. M. (2013) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/s13415-013-0211-5 · Cited by 53
Chronic nicotine improves cognitive performance in a test of attention but does not attenuate cognitive disruption induced by repeated phencyclidine administration
Amitai, N., & Markou, A. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1246-0 · Cited by 53
“Schizophrenia is a severe psychiatric disorder characterized by profound cognitive deficits (Elvevag and Goldberg 2000) that affect a wide range of cognitive modalities, including attention (Laurent et al. 1999), processing speed (Nelson et al. 1990), response inhibition/impulse control (Wykes et…”
Background
Improvement of cognitive function in schizophrenia withN-acetylcysteine: A theoretical review
Yolland, C. O. B., Phillipou, A., Castle, D. J., Neill, E., Hughes, M. E., Galletly, C. A., Smith, Z. M., Francis, P. S., Dean, O. M., Sarris, J. J., et al. (2018) · Nutritional Neuroscience · doi:10.1080/1028415x.2018.1478766 · Cited by 52
Schizophrenia genetic variants are not associated with intelligence
van Scheltinga, A. F. T., Bakker, S. C., van Haren, N. E. M., Derks, E. M., Buizer‐Voskamp, J. E., Cahn, W., Ripke, S., Ophoff, R. A., & Kahn, R. S. (2013) · Psychological Medicine · doi:10.1017/s0033291713000196 · Cited by 52
“…2013 ; Accepted 15 January 2013 ; First published online 15 February 2013 Key words : Cognition, deletion, duplication, endophenotype, IQ, polygenic, SNP. Introduction Schizophrenia is a severe mental disorder with cognitive deficits as a core feature (Kraepelin, 1919 ; Elvevag & Goldberg, 2000).”
Benzodiazepine long-term administration is associated with impaired attention/working memory in schizophrenia: results from the national multicentre FACE-SZ data set
Fond, G. B., Berna, F. S., Boyer, L., Godin, O., Brunel, L., Andrianarisoa, M., Aouizerate, B., Capdevielle, D., Chéreau, I., Danion, J., et al. (2017) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-017-0787-9 · Cited by 51
“Cognitive symptoms are thought to have a higher impact on the outcome of SZ than any other symptoms, and are considered as a core feature of this disorder [16].”
Background
Psychometric characteristics of the MATRICS Consensus Cognitive Battery in a large pooled cohort of stable schizophrenia patients
Georgiades, A., Davis, V. G., Atkins, A. S., Khan, A., Walker, T. W., Loebel, A. D., Haig, G. M., Hilt, D. C., Dunayevich, E., Umbricht, D., et al. (2017) · Schizophrenia Research · doi:10.1016/j.schres.2017.03.040 · Cited by 50
“Given the severity of theses deficits and the close association between neurocognitive impairment and functional outcomes (Elvevag and Goldberg, 2000; Green et al., 2000; Heaton et al., 2001; Heinrichs and Zakzanis, 1998; Reichenberg and Harvey, 2007) improvement of cognition has emerged as an…”
Background
Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings
Velthorst, E., Mollon, J., Murray, R. M., de Haan, L., Myin‐Germeys, I., Glahn, D. C., Arango, C., van der Ven, E., Forti, M. D., Bernardo, M., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-00969-z · Cited by 50
Cognitive dysfunctions in schizophrenia: potential benefits of cholinesterase inhibitor adjunctive therapy
Ferreri, F., Agbokou, C., & Gauthier, S. G. (2006) · Journal of Psychiatry and Neuroscience · doi:10.1139/jpn.0641 · Cited by 49
“The above data fit with the cholinergic hypothesis, which proposes that hypocholinergic cortical transmission is linked to the development of cognitive dysfunctions in schizophrenia.(23,24) Whereas the physiopathological mechanisms of cholinergic dysfunction in schizophrenia remain elusive, most authors agree that cho…”
Impaired recognition of happy, sad and neutral expressions in schizophrenia is emotion, but not valence, specific and context dependent
Silver, H., Bilker, W. B., & Goodman, C. (2009) · Psychiatry Research · doi:10.1016/j.psychres.2008.11.017 · Cited by 49
“The impaired performance in patients is consistent with earlier studies (Saykin et al., 1991; Elvevag and Goldberg, 2000; Silver and Shlomo, 2001; Silver et al., 2003) and the valence-related performance differences with evidence of emotion-specific evaluative systems (Silver et al.”
Result
Mifepristone (RU-486) treatment for depression and psychosis: a review of the therapeutic implications
Gallagher, P., & Young, A. H. (2006) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.a811 · Cited by 48
“In schizophrenia, the symptomatic clinical profile of the illness is complex and diverse, but neurocognitive impairment is consistently reported and some authors have argued that such impairments may be the cardinal feature of the illness (Elvevag and Goldberg 2000).”
Impaired Trail-Making Test-B performance in patients with acute schizophrenia is related to inefficient sequencing of planning and acting
Wölwer, W., & Gäebel, W. (2002) · Journal of Psychiatric Research · doi:10.1016/s0022-3956(02)00050-x · Cited by 48
Acute perinatal asphyxia impairs non-spatial memory and alters motor coordination in adult male rats
Simola, N., Bustamante, D., Pinna, A., Pontis, S., Morales, P., Morelli, M., & Herrera‐Marschitz, M. (2007) · Experimental Brain Research · doi:10.1007/s00221-007-1186-7 · Cited by 50
“Moreover, working memory deWcits are observed in both schizophrenia and attention deWcit hyperactivity disorder (Elvevag and Goldberg 2000; Schweitzer et al. 2006), and a possible relationship between perinatal asphyxia and these disorders has been suggested (McNeil et al. 2000; Boog 2004).”
Background
Neuropsychological functioning in first-episode schizophrenia
Kravariti, E., Morgan, K. D., Fearon, P., Zanelli, J., Lappin, J., Dazzan, P., Morgan, C., Doody, G. A., Harrison, G. L., Jones, P. B., et al. (2009) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.108.055590 · Cited by 48
Association of peripheral cytokine levels with cerebral structural abnormalities in schizophrenia
Wu, D., Lv, P., Li, F. Y., Zhang, W., Fu, G., Dai, J., Hu, N., Liu, J., Xiao, Y., Li, S., et al. (2019) · Brain Research · doi:10.1016/j.brainres.2019.146463 · Cited by 47
Comparing experiential acceptance and cognitive reappraisal as predictors of functional outcome in individuals with serious mental illness
Vilardaga, R., Hayes, S. C., Atkins, D. C., Bresee, C., & Kambiz, A. (2013) · Behaviour Research and Therapy · doi:10.1016/j.brat.2013.04.003 · Cited by 54
GABRB2 Association with Schizophrenia: Commonalities and Differences Between Ethnic Groups and Clinical Subtypes
Lo, W.-S., Harano, M., Gawlik, M., Yu, Z., Chen, J., Pun, F. W., Tong, K.-L., Zhao, C., Ng, S.-K., Tsang, S., et al. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.05.003 · Cited by 46
The impact of psychosis on the course of cognition: a prospective, nested case-control study in individuals at clinical high-risk for psychosis
Carrión, R. E., McLaughlin, D., Auther, A. M., Olsen, R. H., Correll, C. U., & Cornblatt, B. A. (2015) · Psychological Medicine · doi:10.1017/s0033291715001233 · Cited by 45
“Cognitive deficits have long been considered core features of schizophrenia and other psychotic disorders (Elvevag & Goldberg, 2000; Green et al. 2004; Keefe & Harvey, 2012).”
Background
Using Contemporary Technologies in the Assessment and Treatment of Serious Mental Illness
Ben‐Zeev, D., Drake, R. E., Corrigan, P. W., Rotondi, A. J., Nilsen, W., & Depp, C. A. (2012) · American Journal of Psychiatric Rehabilitation · doi:10.1080/15487768.2012.733295 · Cited by 47
“These may be especially prominent when compounded with the symptoms and cognitive impairment that are often seen in severe psychiatric illnesses such as schizophrenia (Elvevag and Goldberg, 2000; Nuechterlein et al., 2004; Sass & Parnas, 2003).”
Background
Infragranular gene expression disturbances in the prefrontal cortex in schizophrenia: Signature of altered neural development?
Arion, D., Horváth, S., Lewis, D. A., & Mirnics, K. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.12.013 · Cited by 44
“The disease is associated with anatomical, molecular and biochemical changes as well as impairment of cognitive function (Goldman-Rakic, 1994; Elvevag and Goldberg, 2000).”
Clozapine Reverses Phencyclidine-Induced Desynchronization of Prefrontal Cortex through a 5-HT1A Receptor-Dependent Mechanism
Kargieman, L., Riga, M. S., Artigas, F., & Celada, P. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.249 · Cited by 45
“…frequencies during sleep has been shown to improve memory (Marshall et al, 2006), and the disruption of cortical network synchrony may have a negative impact on working memory and in behavioral representation, two important PFC-dependent tasks altered in schizophrenia (Elvevag and Goldberg, 2000).”
Background
Assessment of cognitive flexibility in real life using virtual reality: A comparison of healthy individuals and schizophrenia patients
Han, K., Kim, I. Y., & Kim, J. (2012) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2012.06.007 · Cited by 50
“Cognitive deficits in schizophrenia generally occur in a variety of domains, such as verbal/nonverbal memory, motor performance, visual and auditory attention, spatial ability, executive functions, and language [11].”
Background

Authors: Elvevag, B., & Goldberg, T. E.
Affiliations: National Institutes of Health (US)
ORCID: Goldberg, Terry E.
Venue: Critical Reviews™ in Neurobiology
Publisher: Begell House
Published: 2000
Volume: 14
Issue: 1
Pages: 21
ISSN: 0892-0915 (ISSN-L)
DOI: 10.1615/critrevneurobiol.v14.i1.10
OpenAlex: W1993560189
Cited by: 835
References: 0
Citations by year: 2026: 14 · 2025: 13 · 2024: 19 · 2023: 14 · 2022: 26 · 2021: 38 · 2020: 25 · 2019: 40 · 2018: 34 · 2017: 39 · 2016: 38 · 2015: 52 · 2014: 44 · 2013: 68 · 2012: 51
FWCI: 5.62
Type: journal article
Language: en
Open access: closed
Locations: Critical Reviews in Neurobiology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: schizophrenia, cognitive impairment, working memory, attention deficits, core symptoms, diagnostic validity, antipsychotic effects, delusions and hallucinations, formal thought disorder
MeSH terms: Cognition Disorders, Humans, Schizophrenia

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Cognitive Impairment in Schizophrenia Is the Core of the Disorder

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