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Fortschr Neurol Psychiatr 2008; 76: S16-S23
DOI: 10.1055/s-2008-1038130
Originalarbeit
© Georg Thieme Verlag Stuttgart · New York

Arbeitsgedächtnis und Psychopathologie schizophrener Störungen

Working Memory and the Psychopathology of SchizophreniaH.  Walter1 , R.  C.  Wolf2
  • 1Klinik für Psychiatrie und Psychotherapie, Friedrich Wilhelms Universität Bonn, (Ärztlicher Direktor: Prof. Dr. med. W. Maier)
  • 2Universitätsklinik für Psychiatrie und Psychotherapie III, Universität Ulm, (Ärztlicher Direktor: Prof. Dr. med. Dr. phil. M. Spitzer)
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Publication History

Publication Date:
07 May 2008 (online)

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Zusammenfassung

Das Arbeitsgedächtnis (AG) gilt als eines der zentralen Modelle zur Erklärung von Kognitionsdefiziten und der Psychopathologie schizophrener Störungen. Verhaltensdaten und funktionell bildgebende Studien sprechen derzeit für eine multimodale AG-Dysfunktion, die eng an die funktionale Integrität des präfrontalen Kortex (PFC) geknüpft ist. In dieser Übersicht sollen zum einen das Spektrum von AG-Defiziten in der Schizophrenie sowie das Verhältnis von AG und Psychopathologie schizophrener Störungen dargestellt werden. Zum anderen werden bisherige Erkenntnisse zur AG-assoziierten zerebralen Aktivierung in der fMRT und zu psychopathologischen Symptomen diskutiert. Vor dem Hintergrund insgesamt heterogener funktionell bildgebender Befunde besteht hierbei möglicherweise ein Zusammenhang zwischen präfrontalen Arealen und Desorganisations- und Negativsymptomen. Eine Untersuchung der AG-Funktion schizophrener Subsyndrome mittels funktionell bildgebender Verfahren bleibt indessen ein klinisches und wissenschaftliches Desiderat.

Abstract

Working memory (WM) deficits are core symptoms of cognitive impairment in schizophrenia. WM-models serve as theoretical and empirical framework for the investigation of cognitive dysfunction as well as of schizophrenic phenomenology. Behavioral and functional neuroimaging data support the concept of a supramodal WM-deficit in schizophrenia, associated with the functional integrity of prefrontal regions. This review provides a short overview of WM-dysfunction in schizophrenia as well as its impact on psychopathology. Furthermore, the relationship of WM-associated cerebral activation and psychopathological symptoms is illustrated. Currently available studies on WM-function and psychopathology in schizophrenia obtained rather heterogeneous results, although disorganisation and negative symptoms may be closely linked to prefrontal regions. The investigation of WM-function in schizophrenic subsyndromes with functional neuroimaging techniques still remains a clinical and scientific desideratum.

Schlüsselwörter

Arbeitsgedächtnis - Schizophrenie - Psychopathologie - präfrontaler Kortex - fMRT - Negativsymptome

Key words

working memory - schizophrenia - psychopathology - prefrontal cortex - fmri - negative symptoms

Literatur

  • 1 Baddeley A D, Hitch G. Working memory. New York: Academic Press 1974
    Google Scholar
  • 2 Baddeley A. The fractionation of working memory.  Proc Natl Acad Sci USA. 1996;  93 13 468-13 472
    Google Scholar
  • 3 Miyake A, Shah N J. Models of working memory: Mechanisms of active maintenance and executive control. New York: Cambridge University Press 1999
    Google Scholar
  • 4 Baddeley A. Working memory: looking back and looking forward.  Nat Rev Neurosci. 2003;  4 829-839
    Google Scholar
  • 5 Baddeley A, Della Sala S. Working memory and executive control.  Philos Trans R Soc Lond B Biol Sci. 1996;  351 1397-1403; discussion 1403 - 1394
    Google Scholar
  • 6 Goldman-Rakic P S. Working memory dysfunction in schizophrenia.  J Neuropsychiatry Clin Neurosci. 1994;  6 348-357
    Google Scholar
  • 7 Lencz T, Bilder R M, Turkel E, Goldman R S, Robinson D, Kane J M, Lieberman J A. Impairments in perceptual competency and maintenance on a visual delayed match-to-sample test in first-episode schizophrenia.  Arch Gen Psychiatry. 2003;  60 238-243
    Google Scholar
  • 8 Okada A. Deficits of spatial working memory in chronic schizophrenia.  Schizophr Res. 2002;  53 75-82
    Google Scholar
  • 9 Park S, Puschel J, Sauter B H, Rentsch M, Hell D. Spatial working memory deficits and clinical symptoms in schizophrenia: a 4-month follow-up study.  Biol Psychiatry. 1999;  46 392-400
    Google Scholar
  • 10 Keefe R S, Silva S G, Perkins D O, Lieberman J A. The effects of atypical antipsychotic drugs on neurocognitive impairment in schizophrenia: a review and meta-analysis.  Schizophr Bull. 1999;  25 201-222
    Google Scholar
  • 11 Harvey P D, Green M F, McGurk S R, Meltzer H Y. Changes in cognitive functioning with risperidone and olanzapine treatment: a large-scale, double-blind, randomized study.  Psychopharmacology (Berl). 2003;  169 404-411
    Google Scholar
  • 12 Pantelis C, Harvey C A, Plant G, Fossey E, Maruff P, Stuart G W, Brewer W J, Nelson H E, Robbins T W, Barnes T R. Relationship of behavioral and symptomatic syndromes in schizophrenia to spatial working memory and attentional set-shifting ability.  Psychol Med. 2004;  34 693-703
    Google Scholar
  • 13 Schroder J, Tittel A, Stockert A, Karr M. Memory deficits in subsyndromes of chronic schizophrenia.  Schizophr Res. 1996;  21 19-26
    Google Scholar
  • 14 Greenwood K E, Landau S, Wykes T. Negative symptoms and specific cognitive impairments as combined targets for improved functional outcome within cognitive remediation therapy.  Schizophr Bull. 2005;  31 910-921
    Google Scholar
  • 15 Liddle P F. Cognitive impairment in schizophrenia: its impact on social functioning.  Acta Psychiatr Scand Suppl. 2000;  400 11-16
    Google Scholar
  • 16 Callicott J H, Egan M F, Mattay V S, Bertolino A, Bone A D, Verchinksi B, Weinberger D R. Abnormal fMRI response of the dorsolateral prefrontal cortex in cognitively intact siblings of patients with schizophrenia.  Am J Psychiatry. 2003;  160 709-719
    Google Scholar
  • 17 Thermenos H W, Seidman L J, Breiter H, Goldstein J M, Goodman J M, Poldrack R, Faraone S V, Tsuang M T. Functional magnetic resonance imaging during auditory verbal working memory in nonpsychotic relatives of persons with schizophrenia: a pilot study.  Biol Psychiatry. 2004;  55 490-500
    Google Scholar
  • 18 Myles-Worsley M, Park S. Spatial working memory deficits in schizophrenia patients and their first degree relatives from Palau, Micronesia.  Am J Med Genet. 2002;  114 609-615
    Google Scholar
  • 19 Wood S J, Pantelis C, Proffitt T, Phillips L J, Stuart G W, Buchanan J A, Mahony K, Brewer W, Smith D J, McGorry P D. Spatial working memory ability is a marker of risk-for-psychosis.  Psychol Med. 2003;  33 1239-1247
    Google Scholar
  • 20 McGrath J, Chapple B, Wright M. Working memory in schizophrenia and mania: correlation with symptoms during the acute and subacute phases.  Acta Psychiatr Scand. 2001;  103 181-188
    Google Scholar
  • 21 Walter H, Vasic N, Höse A, Spitzer M, Wolf R C. Working memory dysfunction in schizophrenia compared to healthy controls and patients with depression: evidence from event-related fMRI.  NeuroImage. 2007;  35 1551-1561
    Google Scholar
  • 22 Wolf R C, Vasic N, Walter H. Das Arbeitsgedächtniskonzept in der Schizophrenie: Überblick und Ausblick.  Fortschr Neurol Psychiatr. 2005;  73 1-20
    Google Scholar
  • 23 Wexler B E, Stevens A A, Bowers A A, Sernyak M J, Goldman-Rakic P S. Word and tone working memory deficits in schizophrenia.  Arch Gen Psychiatry. 1998;  55 1093-1096
    Google Scholar
  • 24 Glahn D C, Therman S, Manninen M, Huttunen M, Kaprio J, Lonnqvist J, Cannon T D. Spatial working memory as an endophenotype for schizophrenia.  Biol Psychiatry. 2003;  53 624-626
    Google Scholar
  • 25 Park S, Puschel J, Sauter B H, Rentsch M, Hell D. Visual object working memory function and clinical symptoms in schizophrenia.  Schizophr Res. 2003;  59 261-268
    Google Scholar
  • 26 Gooding D C, Tallent K A. Nonverbal working memory deficits in schizophrenia patients: evidence of a supramodal executive processing deficit.  Schizophr Res. 2004;  68 189-201
    Google Scholar
  • 27 Keefe R S, Roitman S E, Harvey P D, Blum C S, DuPre R L, Prieto D M, Davidson M, Davis K L. A pen-and-paper human analogue of a monkey prefrontal cortex activation task: spatial working memory in patients with schizophrenia.  Schizophr Res. 1995;  17 25-33
    Google Scholar
  • 28 Gooding D C, Tallent K A. Spatial working memory performance in patients with schizoaffective psychosis versus schizophrenia: a tale of two disorders?.  Schizophr Res. 2002;  53 209-218
    Google Scholar
  • 29 Pukrop R, Matuschek E, Ruhrmann S, Brockhaus-Dumke A, Tendolkar I, Bertsch A, Klosterkotter J. Dimensions of working memory dysfunction in schizophrenia.  Schizophr Res. 2003;  62 259-268
    Google Scholar
  • 30 Burglen F, Marczewski P, Mitchell K J, Linden M van der, Johnson M K, Danion J M, Salame P. Impaired performance in a working memory binding task in patients with schizophrenia.  Psychiatry Res. 2004;  125 247-255
    Google Scholar
  • 31 Gruber O, Gruber E, Falkai P. Articulatory rehearsal in verbal working memory. A possible neurocognitive endophenotype that differentiates between schizophrenia and schizoaffective disorder.  Neuroscience Letters. 2006;  405 24-28
    Google Scholar
  • 32 Conklin H M, Curtis C E, Calkins M E, Iacono W G. Working memory functioning in schizophrenia patients and their first-degree relatives: cognitive functioning shedding light on etiology.  Neuropsychologia. 2005;  43 930-942
    Google Scholar
  • 33 Hartman M, Steketee M C, Silva S, Lanning K, McCann H. Working memory and schizophrenia: evidence for slowed encoding.  Schizophr Res. 2003;  59 99-113
    Google Scholar
  • 34 Silver H, Feldman P, Bilker W, Gur R C. Working memory deficits as a core neuropsychological dysfunction in schizophrenia.  American Journal of Psychiatry. 2003;  160 1809-1816
    Google Scholar
  • 35 Callicott J H, Mattay V S, Verchinski B A, Marenco S, Egan M F, Weinberger D R. Complexity of prefrontal cortical dysfunction in schizophrenia: more than up or down.  Am J Psychiatry. 2003;  160 2209-2215
    Google Scholar
  • 36 Bagner D M, Melinder M R, Barch D M. Language comprehension and working memory deficits in patients with schizophrenia.  Schizophr Res. 2003;  60 299-309
    Google Scholar
  • 37 Condray R, Kammen D P van, Steinhauer S R, Kasparek A, Yao J K. Language comprehension in schizophrenia: trait or state indicator?.  Biol Psychiatry. 1995;  38 287-296
    Google Scholar
  • 38 Docherty N M, Hawkins K A, Hoffman R E, Quinlan D M, Rakfeldt J, Sledge W H. Working memory, attention, and communication disturbances in schizophrenia.  J Abnorm Psychol. 1996;  105 212-219
    Google Scholar
  • 39 Cohen J D, Barch D M, Carter C, Servan-Schreiber D. Context-processing deficits in schizophrenia: converging evidence from three theoretically motivated cognitive tasks.  J Abnorm Psychol. 1999;  108 120-133
    Google Scholar
  • 40 Spitzer M. The psychopathology, neuropsychology, and neurobiology of associative and working memory in schizophrenia.  Eur Arch Psychiatry Clin Neurosci. 1993;  243 57-70
    Google Scholar
  • 41 Daban C, Amado I, Bayle F, Gut A, Willard D, Bourdel M C, Loo H, Olie J P, Millet B, Krebs M O, Poirier M F. Disorganization syndrome is correlated to working memory deficits in unmedicated schizophrenic patients with recent onset schizophrenia.  Schizophr Res. 2003;  61 323-324
    Google Scholar
  • 42 Daban C, Amado I, Bayle F, Gut A, Willard D, Bourdel M C, Loo H, Olie J P, Millet B, Krebs M O, Poirier M F. Correlation between clinical syndromes and neuropsychological tasks in unmedicated patients with recent onset schizophrenia.  Psychiatry Res. 2002;  113 83-92
    Google Scholar
  • 43 Takahashi H, Iwase M, Nakahachi T, Sekiyama R, Tabushi K, Kajimoto O, Shimizu A, Takeda M. Spatial working memory deficit correlates with disorganization symptoms and social functioning in schizophrenia.  Psychiatry Clin Neurosci. 2005;  59 453-460
    Google Scholar
  • 44 Cameron A M, Oram J, Geffen G M, Kavanagh D J, McGrath J J, Geffen L B. Working memory correlates of three symptom clusters in schizophrenia.  Psychiatry Res. 2002;  110 49-61
    Google Scholar
  • 45 Guillem F, Bicu M, Bloom D, Wolf M A, Desautels R, Lalinec M, Kraus D, Debruille J B. Neuropsychological impairments in the syndromes of schizophrenia: a comparison between different dimensional models.  Brain Cogn. 2001;  46 153-159
    Google Scholar
  • 46 Wolf R C, Vasic N, Höse A, Spitzer M, Walter H. Arbeitsgedächtnisdefizite in der Schizophrenie: Eine Longitudinaluntersuchung mittels funktioneller Magnetresonanztomographie.  Der Nervenarzt. 2005;  76 34
    Google Scholar
  • 47 Bertolino A, Caforio G, Blasi G, de Candia M, Latorre V, Petruzzella V, Altamura M, Nappi G, Papa S, Callicott J H, Mattay V S, Bellomo A, Scarabino T, Weinberger D R, Nardini M. Interaction of COMT (Val(108/158)Met) genotype and olanzapine treatment on prefrontal cortical function in patients with schizophrenia.  Am J Psychiatry. 2004;  161 1798-1805
    Google Scholar
  • 48 Andreasen N C, Roy M A, Flaum M. Positive and negative symptoms. Oxford: Blackwell Science 1995: pp Pages
    Google Scholar
  • 49 Keefe R S. The neurobiology of disturbances of the self: autonoetic agnosia in schizophrenia. In Amador XF, David A (eds). Insight and psychosis. New York: Oxford University Press 1998: 142-173
    Google Scholar
  • 50 Carter C, Robertson L, Nordahl T, Chaderjian M, Kraft L, O'Shora-Celaya L. Spatial working memory deficits and their relationship to negative symptoms in unmedicated schizophrenia patients.  Biol Psychiatry. 1996;  40 930-932
    Google Scholar
  • 51 Harrow M, Jobe T H, Herbener E S, Goldberg J F, Kaplan K J. Thought disorder in schizophrenia: working memory and impaired context.  J Nerv Ment Dis. 2004;  192 3-11
    Google Scholar
  • 52 Gold J M, Harvey P. Cognitive deficits in schizophrenia.  Psychiatr Clin North Am. 1993;  16 295-312
    Google Scholar
  • 53 Gur R C, Gur R E. Hypofrontality in schizophrenia: RIP.  Lancet. 1995;  345 1383-1384
    Google Scholar
  • 54 Milner B. Effects of different brain lesions on card sorting.  Archives of Neurology. 1963;  9 90
    Google Scholar
  • 55 Stuss D T, Levine B. Adult clinical neuropsychology: lessons from studies of the frontal lobes.  Annu Rev Psychol. 2002;  53 401-433
    Google Scholar
  • 56 Miller E K, Cohen J D. An integrative theory of prefrontal cortex function.  Annu Rev Neurosci. 2001;  24 167-202
    Google Scholar
  • 57 Schlosser R, Gesierich T, Kaufmann B, Vucurevic G, Hunsche S, Gawehn J, Stoeter P. Altered effective connectivity during working memory performance in schizophrenia: a study with fMRI and structural equation modeling.  Neuroimage. 2003;  19 751-763
    Google Scholar
  • 58 Goldman-Rakic P S. The physiological approach: functional architecture of working memory and disordered cognition in schizophrenia.  Biol Psychiatry. 1999;  46 650-661
    Google Scholar
  • 59 Walter H, Wolf R C. Von der Hypofrontalität zur dynamischen Dysfunktion. fMRT Studien bei Patienten mit Schizophrenie.  Nervenheilkunde. 2002;  21 392-399
    Google Scholar
  • 60 Mendrek A, Laurens K R, Kiehl K A, Ngan E T, Stip E, Liddle P F. Changes in distributed neural circuitry function in patients with first-episode schizophrenia.  Br J Psychiatry. 2004;  185 205-214
    Google Scholar
  • 61 Wolf R C, Vasic N, Höse A, Spitzer M, Walter H. Changes over time in frontotemporal function in patients with schizophrenia during working memory performance.  Schizophr Res . 91 141-150
    Google Scholar
  • 62 Manoach D S. Prefrontal cortex dysfunction during working memory performance in schizophrenia: reconciling discrepant findings.  Schizophr Res. 2003;  60 285-298
    Google Scholar
  • 63 Jansma J M, Ramsey N F, Wee N J van der, Kahn R S. Working memory capacity in schizophrenia: a parametric fMRI study.  Schizophr Res. 2004;  68 159-171
    Google Scholar
  • 64 Bentall R P. Deconstructing the concept of schizophrenia.  Journal of Mental Health. 1993;  2 223-238
    Google Scholar
  • 65 Ingvar D H, Franzen G. Abnormalities of cerebral blood flow distribution in patients with chronic schizophrenia.  Acta Psychiatrica Scandinavica. 1974;  50 425-464
    Google Scholar
  • 66 Liddle P. The symptoms of chronic schizophrenia. A re-examination of the positive-negative dichotomy.  British Journal of Psychiatry. 1997;  151 145-151
    Google Scholar
  • 67 Liddle P. Inner connections within domain of dementia praecox: role of supervisory mental processes in schizophrenia.  Eur Arch Psychiatry Clin Neurosci. 1995;  245 210-215
    Google Scholar
  • 68 Perlstein W M, Carter C S, Noll D C, Cohen J D. Relation of prefrontal cortex dysfunction to working memory and symptoms in schizophrenia.  Am J Psychiatry. 2001;  158 1105-1113
    Google Scholar
  • 69 Menon V, Anagnoson R T, Mathalon D H, Glover G H, Pfefferbaum A. Functional neuroanatomy of auditory working memory in schizophrenia: relation to positive and negative symptoms.  Neuroimage. 2001;  13 433-446
    Google Scholar
  • 70 Snitz B E, MacDonald 3rd A W, Cohen J D, Cho R Y, Becker T, Carter C S. Lateral and medial hypofrontality in first-episode schizophrenia: Functional activity in a medication-naive state and effects of short-term atypical antipsychotic treatment.  American Journal of Psychiatry. 2005;  162 2322-2329
    Google Scholar
  • 71 Honey G D, Sharma T, Suckling J, Giampietro V, Soni W, Williams S C, Bullmore E T. The functional neuroanatomy of schizophrenic subsyndromes.  Psychol Med. 2003;  33 1007-1018
    Google Scholar
  • 72 Klein M, Habel U. Evaluation therapeutischer Effekte mittels fMRT bei ersterkrankten schizophrenen Patienten.  Nervenheilkunde. 2006;  25 59-64
    Google Scholar
  • 73 Wolf R C, Walter H. Evaluation of a novel event-related parametric fMRI paradigm investigating prefrontal function.  Psychiatry Res Neuroimaging. 2005;  140 73-83
    Google Scholar
  • 74 Wolf R C, Walter H. Differential verbal working memory dysfunction in deficit and non-deficit schizophrenia.  NeuroImage. 2004;  22 56
    Google Scholar
  • 75 Carpenter W Tj, Heinrichs D W, Wagman A M. Deficit and non-deficit forms of schizophrenia: the concept.  American Journal of Psychiatry. 1988;  145 578-583
    Google Scholar
  • 76 Carpenter Jr W T, Buchanan R W, Kirkpatrick B, Tamminga C, Wood F. Strong inference, theory testing, and the neuroanatomy of schizophrenia.  Arch Gen Psychiatry. 1993;  50 825-831
    Google Scholar
  • 77 Heckers S, Goff D, Schacter D L, Savage C R, Fischman A J, Alpert N M, Rauch S L. Functional imaging of memory retrieval in deficit vs nondeficit schizophrenia.  Arch Gen Psychiatry. 1999;  56 1117-1123
    Google Scholar
  • 78 Wolf R C, Vasic N, Walter H. Differential activation of ventrolateral prefrontal cortex during working memory retrieval.  Neuropsychologia. 2006;  44 2558-2563
    Google Scholar

Prof. Dr. med. Dr. phil. Henrik Walter

Abteilung für Medizinische Psychologie, Klinik und Poliklinik für Psychiatrie und Psychotherapie, Friedrich Wilhelms Universität Bonn

Sigmund-Freud-Str. 25

53105 Bonn

Email: henrik.walter@ukb.uni-bonn.de

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