Kognitive Störungen bei schizophrenen Patienten - Ihre Relevanz in Wissenschaft und klinischer Praxis

Kognitive Störungen stellen neben Positiv- und Negativsymptomatik ein Hauptsymptom schizophrener Erkrankungen dar, wie es schon der von Kraepelin geprägte Begriff der 'Dementia praecox' nahelegt. Die große Bedeutung dieser Störungen kommt auch in Vorschlägen zum Ausdruck, kognitive Defizite als diagnostisches Kriterium in zukünftigen Klassifikationssystemen zu berücksichtigen. In der Gesamtgruppe schizophrener Patienten finden sich entsprechende Störungen für viele verschiedene kognitive Funktionen mit einem allerdings hohen Maß an interindividueller Heterogenität, was die vermutete Heterogenität in der Pathogenese und Pathophysiologie widerspiegelt. Klinische Relevanz kommt den kognitiven Beeinträchtigungen insofern zu, als sie den Verlauf der Erkrankung gerade im Hinblick auf das soziale Funktionsniveau und die Lebensqualität deutlich beeinflussen, einen Prädiktor des Outcomes darstellen und auch als Zielsymptom pharmakologischer und nichtpharmakologischer Therapien von Interesse sind. Die Erforschung verschiedener kognitiver Endophänotypen bietet darüber hinaus die Möglichkeit einer exakteren Charakterisierung von Patientensubgruppen mit dem Ziel einer spezifischeren und erfolgreicheren Behandlung.

Cognitive dysfunction - alongside positive and negative symptoms - is a core feature of schizophrenic disorders as already suggested by Kraepelin's concept of 'dementia praecox'. The significance of cognitive deficits is also evident from suggestions to include them as diagnostic criteria in future classification systems. Within the total group of schizophrenic patients, many different cognitive functions are disturbed. However, there is also a considerable degree of interindividual variability, which might reflect the assumed heterogeneity of the pathogenesis and pathophysiology of schizophrenia. Cognitive impairments are clinically relevant as they have a negative influence on patients' social functioning and quality of life, predict functional outcome, and represent targets for pharmacological as well as non-pharmacological therapies. Moreover, the investigation of different cognitive endophenotypes provides an opportunity to more accurately characterize subgroups of patients and, in this way, to enable a more specific and successful treatment.

Key words

Schizophrenia - cognition - cognitive dysfunction - endophenotype-therapy

Literatur

• 1 Abi-Dargham A, Mawlawi O, Lombardo I. et al. . Prefrontal dopamine D1 receptors and working memory in schizophrenia.  J Neurosci. 2002;  22 3708-3719
• 2 Baddeley AD.. Is working memory still working?.  Eur Psychol. 2002;  7 85-97
• 3 Baddeley A.. Working memory: looking back and looking forward.  Nat Rev Neurosci. 2003;  10 829-839
• 4 Brewer WJ, Wood SJ, Phillips LJ. et al. . Generalized and specific cognitive performance in clinical high-risk cohorts: a review highlighting potential vulnerability markers for psychosis.  Schizophr Bull. 2006;  32 538-555
• 5 Cannon TD, Huttunen MO, Lonnqvist J. et al. . The inheritance of neuropsychological dysfunction in twins discordant for schizophrenia.  Am J Hum Genet. 2000;  67 369-382
• 6 Carter C, Robertson L, Nordahl T. et al. . Spatial working memory deficits and their relationship to negative symptoms in unmedicated schizophrenia patients.  Biol Psychiatry. 1996;  40 930-932
• 7 Castner SA, Williams GV, Goldman-Rakic PS.. Reversal of antipsychotic-induced working memory deficits by short-term dopamine D1 receptor stimulation.  Science. 2000;  287 2020-2022
• 8 Conklin HM, Curtis CE, Calkins ME, Iacono WG.. Working memory functioning in schizophrenia patients and their first-degree relatives: cognitive functioning shedding light on etiology.  Neuropsychologia. 2005;  43 930-942
• 9 Daban C, Amado I, Bourdel MC. et al. . Cognitive dysfunctions in medicated and unmedicated patients with recent-onset schizophrenia.  J Psychiatr Res. 2005;  39 391-398
• 10 Davis K, Kahn RS, Ko G, Davidson M.. Dopamine in schizophrenia: a review and reconceptualization.  Am J Psychiatry. 1991;  148 1474-1486
• 11 Ehrenreich H, Hinze-Selch D, Stawicki S. et al. . Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin.  Mol Psychiatry. 2007;  12 206-220
• 12 Fleming K, Goldberg TE, Gold JM, Weinberger DR.. Verbal working memory dysfunction in schizophrenia: use of a Brown-Peterson paradigm.  Psychiatry Res. 1995;  56 155-161
• 13 Fleming K, Goldberg TE, Binks S. et al. . Visuospatial working memory in patients with schizophrenia.  Biol Psychiatry. 1997;  41 43-49
• 14 George MS, Molnar CE, Grenesko EL. et al. . A single 20 mg dose of dihydrexidine (DAR-0100), a full dopamine D1 agonist, is safe and tolerated in patients with schizophrenia.  Schizophr Res. 2007;  93 42-50
• 15 Goff DC, Coyle JT.. The Emerging Role of Glutamate in the Pathophysiology and Treatment of Schizophrenia.  Am J Psychiatry. 2001;  158 1367-1377
• 16 Gottesman II, Gould TD.. The endophenotype concept in psychiatry: etymology and strategic intentions.  Am J Psychiatry. 2003;  160 636-645
• 17 Green MF.. What are the functional consequences of neurocognitive deficits in schizophrenia?.  Am J Psychiatry. 1996;  153 321-330
• 18 Green MF, Kern RS, Braff DL, Mintz J.. Neurocognitive deficits and functional outcome in schizophrenia: are we measuring the right stuff?.  Schizophr Bull. 2000;  26 119-136
• 19 Green MF, Kern RS, Heaton RK.. Longitudinal studies of cognition and functional outcome in schizophrenia: implications for MATRICS.  Schizophr Res. 2004;  72 41-51
• 20 Gruber O.. Effects of domain-specific interference on brain activation associated with verbal working memory task performance.  Cereb Cortex. 2001;  11 1047-1055
• 21 Gruber O, von Cramon DY.. The functional neuroanatomy of human working memory revisited. Evidence from 3-T fMRI studies using classical domain-specific interference tasks.  Neuroimage. 2003;  19 797-809
• 22 Gruber O, Gruber E, Falkai P.. Neuronale Korrelate gestörter Arbeitsgedächtnisfunktionen bei schizophrenen Patienten.  Radiologe. 2005;  45 153-160
• 23 Gruber O, Gruber E, Falkai P.. Articulatory rehearsal in verbal working memory: a possible neurocognitive endophenotype that differentiates between schizophrenia and schizoaffective disorder.  Neurosci Lett. 2006;  405 24-28
• 24 Heinrichs RW, Zakzanis KK.. Neurocognitive deficit in schizophrenia: a quantitative review of the evidence.  Neuropsychology. 1998;  12 426-445
• 25 Henik A, Salo R.. Schizophrenia and the stroop effect.  Behav Cogn Neurosci Rev.. 2004;  3 42-59
• 26 Hepp HH, Maier S, Hermle L, Spitzer M.. The Stroop effect in schizophrenic patients.  Schizophr Res. 1996;  22 187-195
• 27 Heresco-Levy U, Javitt D, Ermilov M. et al. . Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia.  Arch Gen Psychiatry. 1999;  56 29-36
• 28 Joyce EM, Hutton SB, Mutsatsa SH, Barnes TR.. Cognitive heterogeneity in first-episode schizophrenia.  Br J Psychiatry. 2005;  187 516-522
• 29 Keefe RS, Malhotra AK, Meltzer HY. et al. . Efficacy and safety of donepezil in patients with schizophrenia or schizoaffective disorder: significant placebo/practice effects in a 12-week, randomized, double-blind, placebo-controlled trial.  Neuropsychopharmacology. 2007;  11
• 30 Kurtz MM.. Neurocognitive impairment across the lifespan in schizophrenia: an update.  Schizophr Res. 2005;  74 15-26
• 31 Laws KR.. A meta-analytic review of Wisconsin Card Sort studies in schizophrenia: general intellectual deficit in disguise?.  Cognit Neuropsychiatry. 1999;  4 1-30
• 32 McGurk SR, Twamley EW, Sitzer DI. et al. . A meta-analysis of cognitive remediation in schizophrenia.  Am J Psychiatry. 2007;  164 1791-1802
• 33 Mohamed S, Paulsen JS, O'Leary D. et al. . Generalized cognitive deficits in schizophrenia: a study of first-episode patients.  Arch Gen Psychiatry. 1999;  56 749-754
• 34 Nuechterlein KH, Barch DM, Gold JM. et al. . Identification of separable cognitive factors in schizophrenia.  Schizophr Res. 2004;  72 29-39
• 35 Olincy A, Harris JG, Johnson LL. et al. . Proof-of-concept trial of an alpha7 nicotinic agonist in schizophrenia.  Arch Gen Psychiatry. 2006;  63 630-638
• 36 Ritsner MS.. Predicting quality of life impairment in chronic schizophrenia from cognitive variables.  Qual Life Res. 2007;  16 929-937
• 37 Saykin AJ, Shtasel DL, Gur RE. et al. . Neuropsychological deficits in neuroleptic naive patients with first-episode Schizophrenia.  Arch Gen Psychiatry. 1994;  51 123-31
• 38 Sitskoorn MM, Aleman A, Ebisch SJ. et al. . Cognitive deficits in relatives of patients with schizophrenia: a meta-analysis.  Schizophr Res.. 2004;  71 285-295
• 39 Smith EE, Jonides J.. Storage and executive processes in the frontal lobes.  Science. 1999;  283 1657-1661
• 40 Snitz BE, Macdonald 3rd AW, Carter CS.. Cognitive deficits in unaffected first-degree relatives of schizophrenia patients: a meta-analytic review of putative endophenotypes.  Schizophr Bull. 2006;  32 179-194
• 41 Wexler BE, Stevens AA, Bowers AA. et al. . Word and tone working memory deficits in schizophrenia.  Arch Gen Psychiatry. 1998;  55 1093-1096
• 42 Wood SJ, Pantelis C, Proffitt T.. Spatial working memory ability is a marker of risk-for-psychosis.  Psychol Med. 2003;  33 1239-1247
• 43 Zilles D, Gruber O, Burke S, Falkai P.. The influence of genetic loading on working memory performance in schizophrenia.  Pharmacopsychiatry. 2007;  40 229-230

Korrespondenz