Neurobiologische Fundierung von Sprach- und Denkstörungen bei Patienten mit Schizophrenie

 

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Zusammenfassung

Störungen der Sprache und des Denkens sind Kernsymptome der Schizophrenie. Untersuchungen mit strukturellen und funktionellen bildgebenden Methoden (fMRT) sowie Magnetenzephalographie (MEG) zu Sprachprozessen bei Patienten mit Schizophrenie geben Hinweise auf deren Pathogenese. In einem Erklärungsmodell für sprachvermittelte kognitive Defizite und psychopathologische Symptome werden verschiedene Beschreibungs- und Befundebenen integriert. Positive Formale Denkstörungen gehen mit einer „funktionellen” Läsion im linken G. temp. sup., einem Teil der Wernicke-Area, einher. Dem zugrunde liegen eine interne Störung des semantischen Netzes, das durch ein Sprachlateralisationsdefizit im lateralen Temporallappen bei Patienten verursacht wird. Weiterhin liegen den formalen Denkstörungen ein gestörtes verbales Selbst-Monitoring zugrunde. Normalerweise werden Sprachfehler präartikulatorisch korrigiert und das Verbesserte artikuliert. Dieser Fehlerdetektions- und Korrektionsmechanismus, der vor allem im linken sulcus temp. sup. in Verbindung gebracht wurde, ist bei Patienten gestört. Formalen Denkstörungen liegen komplexe kognitive und zerebrale Prozesse zugrunde, die wir gerade erst zu verstehen beginnen.

Abstract

Alterations in thought and language are core symptoms of schizophrenia. Studies with structural and functional imaging (fMRI) as well as magneto/electroencephalography (EEG, MEG) on language in schizophrenia are reviewed which will help to reveal the correlates of formal thought disorder (FTD) and concretism. A model will be presented, where brain structure, function, receptorchemistry, cognitive deficits and psychopathology of language related phenomena are integrated. Positive formal thought disorder is correlated with a “functional” lesion in the superior temporal gyrus, part of Wernickes area. There is secondly a dysfunction of the semantic network, which is due to a language lateralisation deficit in the lateral temporal lobe in FTD. Further, a dysfunctional verbal self monitoring and error correction process in part responsible for FTD. Taken together, there is much evidence that the lateral temporal lobes bilaterally are predominantly involved in the generation of positive formal thought disorder in schizophrenia.

Literatur

• 1 Kircher T. Psychopathologie und Hirnfunktion.  Nervenheilkunde. 2002;  21 336-343
  Google Scholar
• 2 Kircher T. Neuronale Korrelate psychopathologischer Symptome. Denk- und Sprachprozesse bei Gesunden und Patienten mit Schizophrenie. Darmstadt: Steinkopff 2003
  Google Scholar
• 3 Kircher T TJ, Bullmore E T, Brammer M J, Williams S CR, Broome M R, Murray R M, McGuire P K. Differential activation of temporal cortex during sentence completion in schizophrenic patients with and without formal thought disorder.  Schizophr Res. 2001;  50 27-40
  Google Scholar
• 4 Tononi G, Sporns O, Edelman G M. A measure for brain complexity: relating functional segregation and integration in the nervous system.  Proc Natl Acad Sci U S A. 1994;  91 5033-5037
  Google Scholar
• 5 Pauen M. Grundprobleme der Philosophie des Geistes. Eine Einführung. Frankfurt: Fischer Taschenbuchverlag 2001
  Google Scholar
• 6 Kircher T TJ, David A S. The Self in Neuroscience and Psychiatry. Cambridge, UK: Cambridge University Press 2003
  Google Scholar
• 7 Roth G. Das Gehirn und seine Wirklichkeit. Frankfurt: Suhrkamp 1997
  Google Scholar
• 8 Habel U, Posse S, Schneider F. Funktionelle Kernspintomographie in der klinischen Psychologie und Psychiatrie.  Fortschr Neurol Psychiatr. 2002;  70 61-70
  Google Scholar
• 9 Logothetis N K, Pauls J, Augath M, Trinath T, Oeltermann A. Neurophysiological investigation of the basis of the fMRI signal.  Nature. 2001;  412 150-157
  Google Scholar
• 10 Faber R, Abrams R, Taylor M A, Kasprison A, Morris C, Weisz R. Comparison of schizophrenic patients with formal thought disorder and neurologically impaired patients with aphasia.  Am J Psychiatry. 1983;  140 1348-1351
  Google Scholar
• 11 Liddle P F, Ngan E, Caissie S, Anderson C, Bates A, Quested D, White R, Weg R. Thought and Language Index: an instrument for assessing thought and language in schizophrenia.  Br J Psychiatry. 2002;  181 326-330
  Google Scholar
• 12 Kircher T TJ, Liddle P F, Brammer M J, Williams S CR, Murray R M, McGuire P K. Neural correlates of formal thought disorder in schizophrenia.  Arch Gen Psychiatry. 2001;  58 769-774
  Google Scholar
• 13 McGuire P K, Quested D J, Spence S A, Murray R M, Frith C D, Liddle P F. Pathophysiology of "positive" thought disorder in schizophrenia.  Br J Psychiatry. 1998;  173 231-235
  Google Scholar
• 14 Kircher T, Liddle P, Brammer M, Murray R, McGuire P. Neuronale Korrelate „negativer” formaler Denkstörungen.  Nervenarzt. 2003;  74 748-754
  Google Scholar
• 15 Kircher T, Schneider F, Sauer H, Buchkremer G. Funktionelle Bildgebung in der Psychiatrie. Deutsches Ärzteblatt 2004; im Druck
  Google Scholar
• 16 Shenton M E, Dickey C C, Frumin M, McCarley R W. A review of MRI findings in schizophrenia.  Schizophr Res. 2001;  49 1-52
  Google Scholar
• 17 Gaser C, Nenadic I, Volz H P, Büchel C, Sauer H. Neuroanatomy of „Hearing Voices”: A Frontotemporal Brain Structural Abnormality Associated with Auditory Hallucinations in Schizophrenia. Cereb Cortex 2004; in press
  Google Scholar
• 18 Falkai P, Bogerts B, Schneider T, Greve B, Pfeiffer U, Pilz K, Gonsiorzcyk C, Majtenyi C, Ovary I. Disturbed planum temporale asymmetry in schizophrenia. A quantitative post-mortem study.  Schizophr Res. 1995;  14 161-176
  Google Scholar
• 19 Manschreck T C, Maher B A, Milavetz J J, Ames D, Weisstein C C, Schneyer M L. Semantic priming in thought disordered schizophrenic patients.  Schizophr Res. 1988;  1 61-66
  Google Scholar
• 20 Spitzer M, Braun U, Maier S, Hermle L, Maher B A. Indirect semantic priming in schizophrenic patients.  Schizophr Res. 1993;  11 71-80
  Google Scholar
• 21 Kircher T TJ, Liddle P F, Brammer M J, Williams S CR, Murray R M, McGuire P K. Reversed lateralisation of temporal activation during speech production in thought disordered patients with schizophrenia.  Psychol Med. 2002;  32 439-449
  Google Scholar
• 22 Kircher T TJ, Brammer M J, Williams S CR, McGuire P K. Lexical retrieval during fluent speech production: an fmri study.  Neuroreport. 2000;  11 4093-4096
  Google Scholar
• 23 St George M, Kutas M, Martinez A, Sereno M I. Semantic integration in reading: engagement on the right hemisphere during discourse processing.  Brain. 1999;  122 1317-1325
  Google Scholar
• 24 Faust M, Chiarello C. Sentence context and lexical ambiguity resolution by the two hemispheres.  Neuropsychologia. 1998;  36 827-835
  Google Scholar
• 25 Beeman M. Semantic processing in the right hemisphere may contribute to drawing inferences from discourse.  Brain Lang. 1993;  44 80-120
  Google Scholar
• 26 Spitzer M, Braun U, Hermle L, Maier S. Associative semantic network dysfunction in thought-disordered schizophrenic patients: direct evidence from indirect semantic priming.  Biol Psychiatry. 1993;  34 864-877
  Google Scholar
• 27 Weisbrod M, Maier S, Harig S, Himmelsbach U, Spitzer M. Lateralised semantic and indirect semantic priming effects in people with schizophrenia.  Br J Psychiatry. 1998;  172 142-146
  Google Scholar
• 28 Blakemore S J, Frith C D. Disorders of Self-Monitoring and the Symptoms of Schizophrenia. In: Kircher T, David A (eds). The Self in Neuroscience and Psychiatry. Cambridge, UK: Cambridge University Press 2003
  Google Scholar
• 29 Jeannerod M, Farrer M, Franck N, Fourneret P, Posada A, Daprati E, Georgieff N. Action recognition in normal and schizophrenic subjects. In: Kircher T, David A (eds). The Self in Neuroscience and Psychiatry. Cambridge, UK: Cambridge University Press 2003
  Google Scholar
• 30 Levelt W JM. Speaking. From Intention to Articulation. 1 ed. Cambridge, MA; London, England: MIT Press 1989
  Google Scholar
• 31 Knoblich G, Stottmeister F, Kircher T TJ. Self-monitoring in Schizophrenia. Psychol Med 2004; in press
  Google Scholar
• 32 Knoblich G, Kircher T. Deceiving oneself about control: Sensitivity for mapping changes between movements and their consequences. J Exp Psychol Hum Percept Perform 2004; in press
  Google Scholar
• 33 Leube D T, Knoblich G, Erb M, Grodd W, Bartels M, Kircher T TJ. The neural correlates for Identifying One's Own Movements.  Neuroimage. 2003;  20 2084-2090
  Google Scholar
• 34 Kircher T TJ, Brammer M J, Levelt W J, Bartels M, McGuire P K. Pausing for thought: activation of left temporal cortex during pauses in speech.  Neuroimage. 2004;  21 84-90
  Google Scholar
• 35 Rapp A, Leube D T, Erb M, Grodd W, Kircher T TJ. Neural correlates of metaphor processing. Cognit Brain Res 2004; in press
  Google Scholar
• 36 Kircher T TJ, Leube D, Erb M, Ackermann H, Grodd W, Rapp A. Processing of metaphors in schizophrenia. in Vorbereitung
  Google Scholar
• 37 Kircher T T, Bullmore E T, Brammer M J, Williams S C, Broome M R, Murray R M, McGuire P K. Differential activation of temporal cortex during sentence completion in schizophrenic patients with and without formal thought disorder.  Schizophr Res. 2001;  50 27-40
  Google Scholar
• 38 Strik W. Psychiatrische Neurophysiologie. In: Helmchen H, Henn F, Lauter H, Sartorius N (eds). Psychiatrie der Gegenwart, Bd. 1, Grundlagen der Psychiatrie. Berlin, Heidelberg, New York: Springer 1999: 251-275
  Google Scholar
• 39 Umbricht D, Koller R, Schmid L, Skrabo A, Grubel C, Huber T, Stassen H. How specific are deficits in mismatch negativity generation to schizophrenia?.  Biol Psychiatry. 2003;  53 1120-1131
  Google Scholar
• 40 Hirayasu Y, Potts G F, O'Donnell B F, Kwon J S, Arakaki H, Akdag S J, Levitt J J, Shenton M E, McCarley R W. Auditory mismatch negativity in schizophrenia: topographic evaluation with a high-density recording montage.  Am J Psychiatry. 1998;  155 1281-1284
  Google Scholar
• 41 Youn T, Park H J, Kim J J, Kim M S, Kwon J S. Altered hemispheric asymmetry and positive symptoms in schizophrenia: equivalent current dipole of auditory mismatch negativity.  Schizophr Res. 2003;  59 253-260
  Google Scholar
• 42 Park H J, Kwon J S, Youn T, Pae J S, Kim J J, Kim M S, Ha K S. Statistical parametric mapping of LORETA using high density EEG and individual MRI: application to mismatch negativities in Schizophrenia.  Hum Brain Mapp. 2002;  17 168-178
  Google Scholar
• 43 Sauer H, Rosburg T, Kreitschmann Andermahr I, Volz H P, Huonker R, Nowak H, Hajek M. Geschlechtsspezifische Unterschiede der Hemisphärenlateralisation bei Schizophrenien? Eine MEG-MRT-Studie.  Nervenarzt. 1998;  69 249-256
  Google Scholar
• 44 Hall D A, Haggard M P, Akeroyd M A, Palmer A R, Summerfield A Q, Elliott M R, Gurney E M, Bowtell R W. “Sparse” temporal sampling in auditory fMRI.  Hum Brain Mapp. 1999;  7 213-223
  Google Scholar
• 45 Le T H, Patel S, Roberts T P. Functional MRI of human auditory cortex using block and event-related designs.  Magn Reson Med. 2001;  45 254-260
  Google Scholar
• 46 Kircher T TJ, Rapp A, Grodd W, Buchkremer G, Weiskopf N, Lutzenberger W, Ackermann H, Mathiak K. Mismatch responses in schizophrenia: a combined fMRI and whole-head MEG study.  Am J Psychiatry. 2004;  161 294-304
  Google Scholar
• 47 Mathiak K, Rapp A, Kircher T TJ, Grodd W, Hertrich I, Weiskopf N, Lutzenberger W, Ackermann H. Mismatch response to randomized gradient switching noise as reflected by fMRI and whole-head magnetoencephalography.  Hum Brain Mapp. 2002;  16 190-195
  Google Scholar
• 48 Umbricht D, Schmid L, Koller R, Vollenweider F X, Hell D, Javitt D C. Ketamine-induced deficits in auditory and visual context-dependent processing in healthy volunteers: implications for models of cognitive deficits in schizophrenia.  Arch Gen Psychiatry. 2000;  57 1139-1147
  Google Scholar
• 49 Olney J W, Farber N B. Glutamate receptor dysfunction and schizophrenia.  Arch Gen Psychiatry. 1995;  52 998-1007
  Google Scholar
• 50 Sherman A D, Hegwood T S, Baruah S, Waziri R. Deficient NMDA-mediated glutamate release from synaptosomes of schizophrenics.  Biol Psychiatry. 1991;  30 1191-1198
  Google Scholar
• 51 Akbarian S, Sucher N J, Bradley D, Tafazzoli A, Trinh D, Hetrick W P, Potkin S G, Sandman C A, Bunney W-E J, Jones E G. Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics.  J Neurosci. 1996;  16 19-30
  Google Scholar
• 52 Humphries C, Mortimer A, Hirsch S, de Belleroche J. NMDA receptor mRNA correlation with antemortem cognitive impairment in schizophrenia.  Neuroreport. 1996;  7 2051-2055
  Google Scholar
• 53 Naatanen R. The perception of speech sounds by the human brain as reflected by the mismatch negativity (MMN) and its magnetic equivalent (MMNm).  Psychophysiology. 2001;  38 1-21
  Google Scholar
• 54 Michie P T. What has MMN revealed about the auditory system in schizophrenia?.  Int J Psychophysiol. 2001;  42 177-194
  Google Scholar
• 55 Kircher T. Sprache, Gehirn und Schizophrenie.  Nervenheilkunde. 2003;  5 245-252
  Google Scholar
• 56 Jakob H, Beckmann H. Prenatal developmental disturbances in the limbic allocortex in schizophrenics.  J Neural Transm. 1986;  65 303-326
  Google Scholar
• 57 Perrone-Bizzozero N I, Sower A C, Bird E D, Benowitz L I, Ivins K J, Neve R L. Levels of the growth-associated protein GAP-43 are selectively increased in association cortices in schizophrenia.  Proc Natl Acad Sci USA. 1996;  93 14 182-14 187
  Google Scholar
• 58 Fatemi S H. Reelin mutations in mouse and man: from reeler mouse to schizophrenia, mood disorders, autism and lissencephaly.  Mol Psychiatry. 2001;  6 129-133
  Google Scholar
• 59 Impagnatiello F, Guidotti A R, Pesold C, Dwivedi Y, Caruncho H, Pisu M G, Uzunov D P, Smalheiser N R, Davis J M, Pandey G N, Pappas G D, Tueting P, Sharma R P, Costa E. A decrease of reelin expression as a putative vulnerability factor in schizophrenia.  Proc Natl Acad Sci U S A. 1998;  95 15 718-15 723
  Google Scholar
• 60 Jones P, Rodgers B, Murray R, Marmot M. Child development risk factors for adult schizophrenia in the British 1946 birth cohort.  Lancet. 1994;  344 1398-1402
  Google Scholar
• 61 Orr K G, Cannon M, Gilvarry C M, Jones P B, Murray R M. Schizophrenic patients and their first-degree relatives show an excess of mixed-handedness.  Schizophr Res. 1999;  39 167-176
  Google Scholar
• 62 Taylor P, Dalton R, Fleminger J J. Handedness and schizophrenic symptoms.  Br J Med Psychol. 1982;  55 287-291
  Google Scholar
• 63 Manoach D S, Maher B A, Manschreck T C. Left-handedness and though disorder in the schizophrenias.  J Abnorm Psychol. 1988;  97 97-99
  Google Scholar
• 64 Cardno A G, Sham P C, Murray R M, McGuffin P. Twin study of symptom dimensions in psychoses.  Br J Psychiatry. 2001;  179 39-45
  Google Scholar
• 65 Shergill S S, Brammer M J, Williams S CR, Murray R M, McGuire P K. Mapping auditory hallucinations in schizophrenia using functional magnetic resonance imaging.  Arch Gen Psychiatry. 2000;  57 1033-1038
  Google Scholar
• 66 Dierks T, Linden D E, Jandl M, Formisano E, Goebel R, Lanfermann H, Singer W. Activation of Heschl's gyrus during auditory hallucinations.  Neuron. 1999;  22 615-621
  Google Scholar
• 67 Silbersweig D A, Stern E, Frith C, Cahill C, Holmes A, Grootoonk S, Seaward J, McKenna P, Chua S E, Schnorr L. et al . A functional neuroanatomy of hallucinations in schizophrenia.  Nature. 1995;  378 176-179
  Google Scholar
• 68 McGuire P K, Shah G M, Murray R M. Increased blood flow in Broca's area during auditory hallucinations in schizophrenia.  Lancet. 1993;  342 703-706
  Google Scholar
• 69 Suzuki M, Yuasa S, Minabe Y, Murata M, Kurachi M. Left superior temporal blood flow increases in schizophrenic and schizophreniform patients with auditory hallucination: a longitudinal case study using 123I-IMP SPECT.  Eur Arch Psychiatry Clin Neurosci. 1993;  242 257-261
  Google Scholar
• 70 Kircher T, Gauggel S. Neuropsychologie der Schizophrenie. Symptome, Kognition, Gehirn. Berlin, Heidelberg: Springer Verlag 2007
  Google Scholar

Univ.-Prof. Dr. med. Tilo Kircher

Universitätsklinik für Psychiatrie und Psychotherapie Klinikum der RWTH Aachen

Pauwelsstr. 30

52074 Aachen

Email: tkircher@ukaachen.de