Download PDF
Nervenheilkunde 2005; 24(07): 573-583
DOI: 10.1055/s-0038-1629998
Original Article
Schattauer GmbH

Kognitive Defizite in der Schizophrenie

Präfrontale Dysfunktion und funktionelle EntkopplungCognitive deficits in schizophreniaPrefrontal dysfunction and functional decoupling
R. C. Wolf
1   Abteilung für Psychiatrie III der Universität Ulm (Ärztlicher Direktor: Prof. Dr. Dr. M. Spitzer)
,
N. Vasic
1   Abteilung für Psychiatrie III der Universität Ulm (Ärztlicher Direktor: Prof. Dr. Dr. M. Spitzer)
,
H. Walter
1   Abteilung für Psychiatrie III der Universität Ulm (Ärztlicher Direktor: Prof. Dr. Dr. M. Spitzer)
› Author Affiliations
Further Information

Publication History

Publication Date:
25 January 2018 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Erkrankungen aus dem schizophrenen Formenkreis und insbesondere die Schizophrenie sind oft mit Einbußen kognitiver Leistungen assoziiert. Aufmerksamkeit und Vigilanz sowie ‚höhere‘ geistige Funktionen wie etwa das Arbeitsgedächtnis, exekutive Funktionen, episodisches und semantisches Gedächtnis und Sprachleistungen sind bei schizophrenen Patienten gestört und gelten zum Teil als reliable Verlaufsprädiktoren. Defizite im Arbeitsgedächtnis sowie im Bereich exekutiver Leistungen werden seit nunmehr dreißig Jahren mit einem empirisch nachweisbaren funktionellen Korrelat im präfrontalen Kortex in Verbindung gebracht. Mit zunehmendem Einsatz funktionell bildgebender Verfahren traten in den letzten Jahren auch gehäuft Zweifel am früher postulierten ‚Hypofrontalitätskonzept‘ auf. Neuere Untersuchungen weisen derzeit darauf hin, dass kognitive Defizite in der Schizophrenie weniger eine Folge einer isolierten, funktionell lokalisierbaren präfrontalen Dysfunktion sind sondern vielmehr als funktionelle Entkopplung eines frontotemporalen Netzwerks zu verstehen sind. Dieser Befund ist möglicherweise spezifisch für schizophrene Störungen und könnte sich in Zukunft als wertvoll für eine weiterführende Zusatzdiagnostik erweisen.

Summary

Disorders from the schizophrenia spectrum – particularly schizophrenia – are often associated with cognitive deficits. Attention, vigilance and higher cognitive functions such as working memory, executive functions, episodic and semantic memory as well as language are impaired in patients with schizophrenia. Moreover, these impaired domains are thought to be reliable predictors throughout the course of the disease. For three decades, impaired working memory and executive functions have been empirically associated with abnormalities of the prefrontal cortex. However, the advent of functional imaging techniques using cognitive activation paradigms has challenged the concept of ‘hypofrontality’ in schizophrenia. Recent work suggests that the cognitive deficits seen in schizophrenic patients maybe not the result of an isolated dysfunction of the prefrontal cortex, but rather a consequence from a functionally decoupled frontotemporal network. This finding maybe specific for schizophrenia and may prove to be useful for additional diagnostic application.

Schlüsselwörter

Schizophrenie - fMRT - frontaler Kortex - Dyskonnektivität

Key words

Schizophrenia - fMRI - frontal cortex - dysconnectivity
 

  • Literatur

  • 1 Andreasen NC. et al. Schizophrenia and cognitive dysmetria: A positron-emission tomography study of dysfunctional prefrontal-thalamic-cerebellar circuitry. Proc Natl Acad Sci USA 1996; 93: 9985-90.
    CrossrefPubMedGoogle Scholar
  • 2 Baddeley AD. Working memory: looking back and looking forward. Nat Neurosci 2003; 4: 829-39.
    CrossrefPubMedGoogle Scholar
  • 3 Barch DM. et al. Working memory and prefrontal cortex dysfunction: specificity to schizophrenia compared with major depression. Biol Psychiatry 2003; 53: 376-84.
    CrossrefPubMedGoogle Scholar
  • 4 Berman KF, Weinberger DR. Functional localization in the brain in schizophrenia. In: Tasman A, Goldfinger SM. (Hrsg): American Psychiatric Press Review of Psychiatry, Bd 10. Washington: American Psychiatric Press; 1991: 24-59.
    Google Scholar
  • 5 Braver TS, Barch DM, Cohen JD. Cognition and control in schizophrenia: a computational model of dopamine and prefrontal function. Biol Psychiatry 1999; 46: 312-28.
    CrossrefPubMedGoogle Scholar
  • 6 Burns J. et al. Structural disconnectivity in schizophrenia: a diffusion tensor magnetic resonance imaging study. Br J Psychiatry 2003; 182: 439-43.
    CrossrefPubMedGoogle Scholar
  • 7 Cabeza R, Nyberg L. Imaging cognition II: An empirical review of 275 PET and fMRI studies. J Cogn Neurosci 2000; 12: 1-47.
    PubMedGoogle Scholar
  • 8 Callicott JH. et al. Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited. Cereb Cortex 2000; 10: 1078-92.
    CrossrefPubMedGoogle Scholar
  • 9 Callicott JH. et al. Complexity of prefrontal cortical dysfunction in schizophrenia: More than up or down. Am J Psychiatry 2003; 160: 2209-15.
    CrossrefPubMedGoogle Scholar
  • 10 Curtis VA. et al. Attenuated frontal activation in schizophrenia may be task dependent. Schizophr Res 1999; 37: 35-44.
    CrossrefPubMedGoogle Scholar
  • 11 De Lacoste MC, White CL. The role of cortical connectivity in Alzheimer’s disease pathogenesis: a review and model system. Neurobiol Aging 1993; 14: 1-16.
    CrossrefPubMedGoogle Scholar
  • 12 Dickey CC. et al. Schizotypal personality disorder and MRI abnormalities of temporal lobe gray matter. Biol Psychiatry 1999; 45: 1393-1402.
    CrossrefPubMedGoogle Scholar
  • 13 Dolan RJ. et al. Abnormal integration related to cognition in schizophrenia. Acta Psychiatr Scand Suppl 1999; 395: 58-67.
    Google Scholar
  • 14 Dye SM. et al. No evidence for left superior temporal dysfunction in asymptomatic schizophrenia and bipolar disorder. PET study of verbal fluency. Br J Psychiatry 1999; 175: 367-74.
    CrossrefPubMedGoogle Scholar
  • 15 Elliott R, Sahakian BJ. The neuropsychology of schizophrenia: Relations with clinical and neurobiological dimensions. Psychol Med 1995; 25: 581-94.
    CrossrefPubMedGoogle Scholar
  • 16 Fletcher PC. et al. Local and distributed effects of apomorphine upon fronto-temporal function in acute unmedicated schizophrenia. J Neurosci 1996; 16: 7055-62.
    CrossrefPubMedGoogle Scholar
  • 17 Fletcher PC. et al. Brain activation in schizophrenia during a graded memory task studied with functional neuroimaging. Arch Gen Psychiatry 1998; 55: 1001-08.
    CrossrefPubMedGoogle Scholar
  • 18 Friston KJ, Frith CD. Schizophrenia: a disconnection syndrome?. Clin Neurosci 1995; 3: 89-97.
    Google Scholar
  • 19 Friston KJ. Schizophrenia and the disconnection hypothesis. Acta Psychiatr Scand 1999; 395: 68-79.
    Google Scholar
  • 20 Frith CD. et al. Regional brain activity in chronic schizophrenic patients during the performance of a verbal fluency task: Evidence for a failure of inhibition in left superior temporal cortex. Br J Psychiatry 1995; 167: 343-9.
    CrossrefPubMedGoogle Scholar
  • 21 Garey LJ. et al. Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia. J Neurol Neurosurg Psychiatry 1998; 65: 446-53.
    CrossrefPubMedGoogle Scholar
  • 22 Gaser C. et al. Neuroanatomy of „hearing voices“: a frontotemporal brain structural abnormality associated with auditory hallucinations in schizophrenia. Cereb Cortex 2004; 14: 91-6.
    CrossrefPubMedGoogle Scholar
  • 23 Goldberg TE. et al. Course of schizophrenia: Neuropsychological evidence for a static encephalopathy. Schizophr Bull 1993; 19: 797-804.
    CrossrefPubMedGoogle Scholar
  • 24 Goldman-Rakic PS. Working memory dysfunction in schizophrenia. J Neuropsychiatry 1994; 6: 348-57.
    CrossrefPubMedGoogle Scholar
  • 25 Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia?. Am J Psychiatry 1996; 151: 357-62.
    Google Scholar
  • 26 Gur RC, Gur RE. Hypofrontality in schizophrenia: RIP. Lancet 1995; 345: 1383-4.
    CrossrefPubMedGoogle Scholar
  • 27 Harrison PJ. The neuropathology of schizophrenia. A critical review of the data and their interpretation. Brain 1999; 122: 593-624.
    CrossrefPubMedGoogle Scholar
  • 28 Hirayasu Y. et al. Lower left temporal lobe MRI volumes in patients with first episode schizophrenia compared with psychotic patients with first episode affective disorder and normal subjects. Am J Psychiatry 1998; 155: 1384-91.
    CrossrefPubMedGoogle Scholar
  • 29 Honey RAE, Friston KJ, Fletcher PC. Imaging brain structure and function in schizophrenia: new techniques encounter old problems. In: Fu CHY, Senior C, Russell TA, Weinberger D, Murray R. (Hrsg): Neuroimaging in Psychiatry. New York: Martin Dunitz; 2003: 225-55.
    Google Scholar
  • 30 Hugdahl K. et al. Brain activation measured with FMRI during a mental arithmetic task in schizophrenia and major depression. Am J Psychiatry 2004; 161: 286-93.
    CrossrefPubMedGoogle Scholar
  • 31 Ingvar DH, Franzén G. Abnormalities of cerebral blood flow distribution in patients with chronic schizophrenia. Acta Psychiatr Scand 1974; 425-62.
    PubMedGoogle Scholar
  • 32 Kircher TT. et al. Differential activation of temporal cortex during sentence completion in schizophrenic patients with and without formal thought disorder. Schizophr Res 2001; 50: 27-40.
    CrossrefPubMedGoogle Scholar
  • 33 Kircher TT. et al. Neural correlates of formal thought disorder in schizophrenia: preliminary findings from a functional magnetic resonance imaging study. Arch Gen Psychiatry 2002; 58: 769-74 2002;
    Google Scholar
  • 34 Kraepelin E. Psychiatrie. 8. Aufl.. Leipzig: Johann Ambrosius Barth; 1913
    Google Scholar
  • 35 Lawrie SM. et al. Reduced frontotemporal functional connectivity in schizophrenia associated with auditory hallucinations. Biol Psychiatry 2002; 51: 1008-11.
    CrossrefPubMedGoogle Scholar
  • 36 Lewis R. Should cognitive deficits be a diagnostic criterion for schizophrenia?. Rev Psychiatr Neurosci 2004; 29: 102-13.
    Google Scholar
  • 37 Manoach DS. et al. Schizophrenic subjects activate dorsolateral prefrontal cortex during a working memory task, as measured by fMRI. Biol Psychiatry 1999; 45: 1128-37.
    CrossrefPubMedGoogle Scholar
  • 38 Manoach DS. Prefrontal cortex dysfunction during working memory performance in schizophrenia: reconciling discrepant findings. Schizophr Res 2003; 60: 285-8.
    PubMedGoogle Scholar
  • 39 Meyer-Lindenberg A. et al. Evidence for abnormal cortical functional connectivity during working memory in schizophrenia. Am J Psychiatry 2001; 158: 1809-17.
    CrossrefPubMedGoogle Scholar
  • 40 Milner B. Effects of different brain lesions on card sorting. Arch Neurol 1963; 9: 90-100.
    CrossrefGoogle Scholar
  • 41 Ogawa S. et al. Oxygenation-sensitive contrast in magnetic resonance image of rodent brain at high magnetic fields. Mag Reson Med 1990; 14: 68-78.
    CrossrefPubMedGoogle Scholar
  • 42 Petrides M, Pandya DN. Association fiber pathways to the frontal cortex from the superior temporal region in the rhesus monkey. J Comp Neurology 1988; 273: 52-66.
    CrossrefPubMedGoogle Scholar
  • 43 Quintana J. et al. Prefrontal-posterior parietal networks in schizophrenia: primary dysfunctions and secondary compensations. Biol Psychiatry 2003; 53: 12-24.
    CrossrefPubMedGoogle Scholar
  • 44 Ragland JD. Profiles of neuropsychologic function in schizophrenia. Curr Psychiatry Rep 2003; 5: 299-302.
    CrossrefPubMedGoogle Scholar
  • 45 Rajkowska G, Selemon LD, Goldman-Rakic PS. Neuronal and glial somal size in the prefrontal cortex: a postmortem morphometric study of schizophrenia and Huntington’s disease. Arch Gen Psychiatry 1998; 55: 215-24.
    CrossrefPubMedGoogle Scholar
  • 46 Schlösser R. et al. Funktionelle und effektive Konnektivität: neue Analyseansätze für funktionelle bildgebende Verfahren. Nervenheilkunde 2002; 7: 351-5.
    Google Scholar
  • 47 Schlösser R. et al. Altered effective connectivity during working memory performance in schizophrenia: a study with fMRI and structural equation modeling. Neuroimage 2003; 19: 751-63.
    CrossrefPubMedGoogle Scholar
  • 48 Schlösser R. et al. Altered effective connectivity in drug free schizophrenic patients. Neuroreport 2003; 14: 2233-7.
    CrossrefPubMedGoogle Scholar
  • 49 Sharma T, Antonova L. Cognitive function in schizophrenia. Deficits, functional consequences, and future treatment. Psychiatr Clin North Am 2003; 26: 25-40.
    CrossrefPubMedGoogle Scholar
  • 50 Shenton ME. et al. A review of MRI findings in schizophrenia. Schizophr Res 2001; 49: 1-52.
    PubMedGoogle Scholar
  • 51 Shergill SS. et al. Mapping auditory hallucinations in schizophrenia using functional magnetic resonance imaging. Arch Gen Psychiatry 2000; 57: 1033-8.
    CrossrefPubMedGoogle Scholar
  • 52 Shergill SS. et al. Engagement of brain areas implicated in processing inner speech in people with auditory hallucinations. Br J Psychiatry 2003; 182: 525-31.
    CrossrefPubMedGoogle Scholar
  • 53 Spence SA. et al. Functional anatomy of verbal fluency in people with schizophrenia and those at genetic risk. Focal dysfunction and distributed disconnectivity reappraised. Br J Psychiatry 2000; 176: 52-60.
    PubMedGoogle Scholar
  • 54 Sternberg S. High-speed scanning in human memory. Science 1966; 153: 652-4
    CrossrefPubMedGoogle Scholar
  • 55 Stevens AA. et al. Cortical Dysfunction in schizophrenia during auditory and tone working memory demonstrated by functional magnetic resonance imaging. Arch Gen Psychiatry 1998; 55: 1097-103.
    CrossrefPubMedGoogle Scholar
  • 56 Stuss DT, Levine B. Adult clinical Neuropsychology: Lessons from Studies of the Frontal Lobes. Annu Rev Psychol 2002; 53: 401-33.
    CrossrefPubMedGoogle Scholar
  • 57 Tononi G, Sporns O, Edelman GM. Reentry and the problem of integrating multiple cortical areas: simulation of dynamic integration in the visual system. Cereb Cortex 1992; 2: 310-35.
    CrossrefPubMedGoogle Scholar
  • 58 Uttal WR. The New Phrenology: The Limits of Localizing Cognitive Processes in the Brain (Life and Mind: Philosophical Issues in Biology and Psychology). Cambridge: MIT Press; 2001
    Google Scholar
  • 59 Walter H, Riepe MW, Grön G. Funktionelle Bildgebung als klinisches Instrument in der Psychiatrie. Nervenheilkunde 1999; 18: 322-31.
    Google Scholar
  • 60 Walter H, Wolf RC. Von der Hypofrontalität zur dynamischen frontalen Dysfunktion. Nervenheilkunde 2002; 21: 392-9.
    Google Scholar
  • 61 Walter H. et al. A rapid event related, parametric fMRI-paradigm to test prefrontal function in patients with schizophrenia. Neuroimage Suppl 2002; 996.
    Google Scholar
  • 62 Walter H. et al. No hypofrontality, but absence of prefrontal lateralization comparing verbal and spatial working memory in schizophrenia. Schizophr Res 2003; 61: 175-84.
    CrossrefPubMedGoogle Scholar
  • 63 Walter H, Braus D. Schizophrenie. In Walter H. (Hrsg) Funktionelle Bildgebung in Psychiatrie und Psychotherapie. Methodische Grundlagen und klinische Anwendungen. Stuttgart: Schattauer Verlag; 2004
    Google Scholar
  • 64 Walter H. et al. Differential brain activation in an event related working memory task for schizophrenia as compared to depression. Paper in review 2004
    PubMedGoogle Scholar
  • 65 Weinberger DR, Berman KF. Prefrontal function in schizophrenia: confounds and controversies. Philos Trans R Soc London 1996; 351: 1495-503.
    CrossrefPubMedGoogle Scholar
  • 66 Weinberger DR. et al. Prefrontal neurons and the genetics of schizophrenia. Biol Psychiatry 2001; 50: 825-44.
    CrossrefPubMedGoogle Scholar
  • 67 Wernicke C. Grundrisse der Psychiatrie. Thieme, Leipzig; 1906
    Google Scholar
  • 68 Winterer G. et al. Functional and effective frontotemporal connectivity and genetic risk for schizophrenia. Biol Psychiatry 2003; 54: 1181-92.
    CrossrefPubMedGoogle Scholar
  • 69 Wolf RC. et al. Manipulating the contents of working memory: An event-related fMRI study. J Cog Neurosci Suppl 2002; 22: 140.
    Google Scholar
  • 70 Woo TU. et al. A subclass of prefrontal gammaaminobutyric acid axon terminals are selectively altered in schizophrenia. Proc Natl Acad Sci USA 1998; 95: 5341-6.
    CrossrefPubMedGoogle Scholar