Aktueller Überblick über strukturelle Magnet-resonanztomographie bei Schizophrenie

Zusammenfassung:

Die nichtinvasive morphologische Bildgebung (Computertomographie, Kernspintomographie, MRT) hat wesentlich zu der Erkenntnis beigetragen, dass die Schizophrenien Erkrankungen des Gehirns sind. Eine verbesserte MRT-Technik erlaubt zwischenzeitlich die Analyse anatomischer Substrukturen. In diesem aktuellen Überblick wurden peer-reviewed MRT-Studien von 1994 bis Juli 2000 ausgewertet und mit eigenen Befunden verglichen.

Bei chronisch schizophrenen Patienten zeigen sich als häufigste Befunde vergrößerte Liquorräume und ein vermindertes Volumen der grauen Substanz. Eine detaillierte Aufteilung in kortikale und subkortikale Regionen zeigt, dass die Volumenreduktion nicht einheitlich über das Gehirn verteilt ist sondern auf distinkte Areale beschränkt bleibt.

Im Temporallappen sind der Hippokampus und der Gyrus temporalis superior am häufigsten betroffen. Die Veränderungen korrelieren mit klinischen Symptomen wie Halluzinationen und Denkstörungen. Im frontalen Kortex zeigen 70 % aller Untersuchungen eine Volumenabnahme, im Thalamus finden 63 % und im Zerebellum 60 % aller Studien eine Größenminderung. Diese Strukturen haben aus morphologischer Sicht damit die größte Bedeutung für die Pathophysiologie der Schizophrenie und für das Auftreten klinischer Symptome.

Subgruppen von Patienten zeigen eine über die normale Alterung hinausgehende Progredienz in der Volumenminderung, die auf einen neurodegenerativen Prozess hinweist. Zusätzlich finden sich differenzielle Antipsychotikaeffekte nach Langzeitbehandlung mit typischen Neuroleptika im Vergleich zu atypischen Antipsychotika. Aufgrund dieser aktuellen Daten sollten zukünftige Longitudinalstudien mit automatischen Auswertestrategien prüfen, inwieweit eine progrediente Volumenabnahme durch moderne Antipsychotika beeinflussbar ist.

Structural Magnetic Resonance Imaging in Schizophrenia: An Overview:

Non-invasive morphologic imaging (computer tomography, magnetic resonance imaging, MRT) has contributed significantly to our understanding of schizophrenic disorders as diseases of the brain. Improved MRT techniques enable us to analyse anatomical substructures. The present overview evaluates peer-reviewed MRT studies published between 1994 and July 2000 and provides a comparison with our own results.

Chronic schizophrenic patients most frequently show an enlargement in the ventricular system along with a reduction in grey matter. A more detailed subdivision into cortical and subcortical regions additionally shows the noted volume reduction to be limited to specific areas within the brain rather than being distributed equally throughout the brain.

Within the area of the temporal lobes the two most frequently affected areas are the hippocampus and the gyrus temporalis superior. Alterations within these areas correlate with clinical symptoms such as hallucinations or thought disorders. Within the frontal cortex nearly 70 % of all studies show a decrease in overall volume, while 63 % note a reduction in size within the thalamus and 60 % in the cerebellum. Morphologically speaking these structures therefore play the greatest role in the pathophysiology of schizophrenia and the onset of clinical symptoms.

More recent studies also showed a specific progression in subgroups of patients pointing toward a neurodegenerative process. Additionally there are a number of differential antipsychotic effects following longterm treatment with typical neuroleptics as compared to atypical antipsychotics. Based on these findings future longitudinal studies should examine to what extent such a progressive decrease in volume might be influenced by treatment with modern antipsychotics.

Literatur

• 1 Johnstone E C, Crow T J, Frith C D, Husband J, Kreel L. Cerebral ventricular size and cognitive impairment in chronic schizophrenia.  Lancet. 1976;  2 924-926
• 2 Kovelman J A, Scheibel A B. A neurohistological correlate of schizophrenia.  Biol Psychiatry. 1984;  19 1601-1621
• 3 Henn F A, Nasrallah H A. (Hrsg) .Schizophrenia as a brain disease. New York, Oxford: Oxford University Press 1982
• 4 Ashburner J, Friston K J. Nonlinear spatial normalization using basis functions.  Hum Brain Mapp. 1999;  7 254-266
• 5 Gur R E, Turetsky B I, Bilker W B, Gur R C. Reduced gray matter volume in schizophrenia.  Arch Gen Psychiatry. 1999;  56 905-911
• 6 Zipursky R B, Zhang-Wong J, Lambe E K, Bean G, Beiser M. MRI correlates of treatment response in first episode psychosis.  Schizophr Res. 1998;  30 81-90
• 7 Sanfilipo M, Lafargue T, Rusinek H, Arena L, Loneragan C, Lautin A, Feiner D, Rotrosen J, Wolkin A. Volumetric measure of the frontal and temporal lobe regions in schizophrenia: relationship to negative symptoms.  Arch Gen Psychiatry. 2000;  57 471-480
• 8 Lim K O, Harris D, Beal M, Hoff A L, Minn K, Csernansky J G, Faustman W O, Marsh L, Sullivan E V, Pfefferbaum A. Gray matter deficits in young onset schizophrenia are independent of age of onset.  Biol Psychiatry. 1996;  40 4-13
• 9 Crow T J, Ball J, Bloom S R, Brown R, Bruton C J, Colter N, Frith C D, Johnstone E C, Owens D G, Roberts G W. Schizophrenia as an anomaly of development of cerebral asymmetry. A postmortem study and a proposal concerning the genetic basis of the disease.  Arch Gen Psychiatry. 1989;  46 1145-1150
• 10 Harrison P J. The neuropathology of schizophrenia. A critical review of the data and their interpretation.  Brain. 1999;  122 593-624
• 11 Bogerts B. The temporolimbic system theory of positive schizophrenic symptoms.  Schizophr Bull. 1997;  23 423-435
• 12 Symonds L L, Archibald S L, Grant I, Zisook S, Jernigan T L. Does an increase in sulcal or ventricular fluid predict where brain tissue is lost?.  J Neuroimaging. 1999;  9 201-209
• 13 Turetsky B, Cowell P E, Gur R C, Grossman R I, Shtasel D L, Gur R E. Frontal and temporal lobe brain volumes in schizophrenia. Relationship to symptoms and clinical subtype.  Arch Gen Psychiatry. 1995;  52 1061-1070
• 14 Marsh L, Harris D, Lim K O, Beal M, Hoff A L, Minn K, Csernansky J G, DeMent S, Faustman W O, Sullivan E V, Pfefferbaum A. Structural magnetic resonance imaging abnormalities in men with severe chronic schizophrenia and an early age at clinical onset.  Arch Gen Psychiatry. 1997;  54 1104-1112
• 15 Lieberman J A, Alvir J M, Woerner M, Degreef G, Bilder R M, Ashtari M, Bogerts B, Mayerhoff D I, Geisler S H, Loebel A. et al . Prospective study of psychobiology in first-episode schizophrenia at Hillside Hospital.  Schizophr Bull. 1992;  18 351-371
• 16 Ashburner J, Hutton C, Frackowiak R, Johnsrude I, Price C, Friston K. Identifying global anatomical differences: deformation-based morphometry.  Hum Brain Mapp. 1998;  6 348-357
• 17 Murray R M, O'Callaghan E, Castle D J, Lewis S W. A neurodevelopmental approach to the classification of schizophrenia.  Schizophr Bull. 1992;  18 319-332
• 18 Bryant N L, Buchanan R W, Vladar K, Breier A, Rothman M. Gender differences in temporal lobe structures of patients with schizophrenia: a volumetric MRI study.  Am J Psychiatry. 1999;  156 603-609
• 19 McCarley R W, Wible C G, Frumin M, Hirayasu Y, Levitt J J, Fischer I A, Shenton M E. MRI anatomy of schizophrenia.  Biol Psychiatry. 1999;  45 1099-1119
• 20 Wright I C, Rabe-Hesketh S, Woodruff P W, David A S, Murray R M, Bullmore E T. Metaanalysis of regional brain volumes in schizophrenia.  Am J Psychiatry. 2000;  157 16-25
• 21 McCarley R W, Niznikiewicz M A, Salisbury D F, Nestor P G, O'Donnell B F, Hirayasu Y, Grunze H, Greene R W, Shenton M E. Cognitive dysfunction in schizophrenia: unifying basic research and clinical aspects.  Eur Arch Psychiatry Clin Neurosci. 1999;  249 69-82
• 22 Levitan C, Ward P B, Catts S V. Superior temporal gyral volumes and laterality correlates of auditory hallucinations in schizophrenia.  Biol Psychiatry. 1999;  46 955-962
• 23 Rajarethinam R P, DeQuardo J R, Nalepa R, Tandon R. Superior temporal gyrus in schizophrenia: a volumetric magnetic resonance imaging study.  Schizophr Res. 2000;  41 303-312
• 24 Menon R R, Barta P E, Aylward E H, Richards S S, Vaughn D D, Tien A Y, Harris G J, Pearlson G D. Posterior superior temporal gyrus in schizophrenia: grey matter changes and clinical correlates.  Schizophr Res. 1995;  16 127-135
• 25 Rossi A, Serio A, Stratta P, Petruzzi C, Schiazza G, Mancini F, Casacchia M. Planum temporale asymmetry and thought disorder in schizophrenia.  Schizophr Res. 1994;  12 1-7
• 26 Petty R G, Barta P E, Pearlson G D, McGilchrist I K, Lewis R W, Tien A Y, Pulver A, Vaughn D D, Casanova M F, Powers R E. Reversal of asymmetry of the planum temporale in schizophrenia.  Am J Psychiatry. 1995;  152 715-721
• 27 Nestor P G, Shenton M E, McCarley R W, Haimson J, Smith R S, O'Donnell B, Kimble M, Kikinis R, Jolesz F A. Neuropsychological correlates of MRI temporal lobe abnormalities in schizophrenia.  Am J Psychiatry. 1993;  150 1849-1855
• 28 Jacobsen L K, Giedd J N, Castellanos F X, Vaituzis A C, Hamburger S D, Kumra S, Lenane M C, Rapoport J L. Progressive reduction of temporal lobe structures in childhood-onset schizophrenia.  Am J Psychiatry. 1998;  155 678-685
• 29 Falkai P, Bogerts B, Greve B, Pfeiffer U, Machus B, Folsch-Reetz B, Majtenyi C, Ovary I. Loss of sylvian fissure asymmetry in schizophrenia. A quantitative post mortem study.  Schizophr Res. 1992;  7 23-32
• 30 Jakob H, Beckmann H. Prenatal developmental disturbances in the limbic allocortex in schizophrenics.  J Neural Transm. 1986;  65 303-326
• 31 Arnold S E, Franz B R, Gur R C, Gur R E, Shapiro R M, Moberg P J, Trojanowski J Q. Smaller neuron size in schizophrenia in hippocampal subfields that mediate cortical-hippocampal interactions.  Am J Psychiatry. 1995;  152 738-748
• 32 Weinberger D R. Cell biology of the hippocampal formation in schizophrenia.  Biol Psychiatry. 1999;  45 395-402
• 33 Zaidel D W, Esiri M M, Harrison P J. Size, shape, and orientation of neurons in the left and right hippocampus: investigation of normal asymmetries and alterations in schizophrenia.  Am J Psychiatry. 1997;  154 812-818
• 34 Henke K, Weber B, Kneifel S, Wieser H G, Buck A. Human hippocampus associates information in memory.  Proc Natl Acad Sci USA. 1999;  96 5884-5889
• 35 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
• 36 Chua S E, Murray R M. The neurodevelopmental theory of schizophrenia: evidence concerning structure and neuropsychology.  Ann Med. 1996;  28 547-555
• 37 Gold J M, Harvey P D. Cognitive deficits in schizophrenia.  Psychiatr Clin North Am. 1993;  16 295-312
• 38 Goldstein P C, Rosenbaum G, Taylor M J. Assessment of differential attention mechanism in seizure disorders and schizophrenia.  Neuropsychology. 1997;  11 309-317
• 39 Kareken D A, Gur R C, Mozley P D, Mozley L H, Saykin A J, Shtasel D L, Gur R E. Cognitive functioning and neuroanatomic volume measures in schizophrenia.  Neuropsychology. 1995;  2 211-219
• 40 Kinney D K, Levy D L, Yurgelun-Todd D A, Tramer S J, Holzman P S. Inverse relationship of perinatal complications and eye tracking dysfunction in relatives of patients with schizophrenia: evidence for a two-factor model.  Am J Psychiatry. 1998;  155 976-978
• 41 Carter C S, Mintun M, Nichols T, Cohen J D. Anterior cingulate gyrus dysfunction and selective attention deficits in schizophrenia: [150]H₂O PET study during single-trial Stroop task performance.  Am J Psychiatry. 1997;  154 1670-1675
• 42 Carter C S, Perlstein W, Ganguli R, Brar J, Mintun M, Cohen J D. Functional hypofrontality and working memory dysfunction in schizophrenia.  Am J Psychiatry. 1998;  155 1285-1287
• 43 Schröder J, Buchsbaum M S, Siegel B V, Geider F J, Lohr J, Tang C, Wu J, Potkin S G. Cerebral metabolic activity correlates of subsyndromes in chronic schizophrenia.  Schizophr Res. 1996;  19 41-53
• 44 Bertolino A, Knable M B, Saunders R C, Callicott J H, Kolachana B, Mattay V S, Bachevalier J, Frank J A, Egan M, Weinberger D R. The relationship between dorsolateral prefrontal N-acetylaspartate measures and striatal dopamine activity in schizophrenia.  Biol Psychiatry. 1999;  45 660-667
• 45 Bertolino A, Esposito G, Callicott J H, Mattay V S, Van Horn J D, Frank J A, Berman K F, Weinberger D R. Specific relationship between prefrontal neuronal N-acetylaspartate and activation of the working memory cortical network in schizophrenia.  Am J Psychiatry. 2000;  157 26-33
• 46 Volz H P, Rossger G, Riehemann S, Hubner G, Maurer I, Wenda B, Rzanny R, Kaiser W A, Sauer H. Increase of phosphodiesters during neuroleptic treatment of schizophrenics: a longitudinal 31P-magnetic resonance spectroscopic study.  Biol Psychiatry. 1999;  45 1221-1225
• 47 Volz H P, Rzanny R, Rossger G, Hubner G, Kreitschmann-Andermahr I, Kaiser W A, Sauer H. 31Phosphorus magnetic resonance spectroscopy of the dorsolateral prefrontal region in schizophrenics - a study including 50 patients and 36 controls.  Biol Psychiatry. 1998;  44 399-404
• 48 Bilder R M, Wu H, Bogerts B, Degreef G, Ashtari M, Alvir J M, Snyder P J, Lieberman J A. Absence of regional hemispheric volume asymmetries in first-episode schizophrenia.  Am J Psychiatry. 1994;  151 1437-1447
• 49 Noga J T, Aylward E, Barta P E, Pearlson G D. Cingulate gyrus in schizophrenic patients and normal volunteers.  Psychiatry Res. 1995;  61 201-208
• 50 Baare W F, Pol H E, Hijman R, Mali W P, Viergever M A, Kahn R S. Volumetric analysis of frontal lobe regions in schizophrenia: relation to cognitive function and symptomatology.  Biol Psychiatry. 1999;  45 1597-1605
• 51 Seidman L J, Yurgelun-Todd D, Kremen W S, Woods B T, Goldstein J M, Faraone S V, Tsuang M T. Relationship of prefrontal and temporal lobe MRI measures of neuropsychological performance in chronic schizophrenia.  Biol Psychiatry. 1994;  35 235-246
• 52 Zakzanis K K, Heinrichs R W. Schizophrenia and the frontal brain: a quantitative review.  J Int Neuropsychol Soc. 1999;  5 556-566
• 53 Schlaepfer T E, Harris G J, Tien A Y, Peng L W, Lee S, Federman E B, Chase G A, Barta P E, Pearlson G D. Decreased regional cortical gray matter volume in schizophrenia.  Am J Psychiatry. 1994;  51 842-848
• 54 Pearlson G D, Petty R G, Ross C A, Tien A Y. Schizophrenia: a disease of heteromodal association cortex?.  Neuropsychopharmacology. 1996;  14 1-17
• 55 Andreasen N C, Flashman L, Flaum M, Arndt S, Swayze 2nd V, O'Leary D S, Ehrhardt J C, Yuh W T. Regional brain abnormalities in schizophrenia measured with magnetic resonance imaging.  Jama. 1994;  272 1763-1769
• 56 Bilder R M, Bogerts B, Ashtari M, Wu H, Alvir J M, Jody D, Reiter G, Bell L, Lieberman J A. Anterior hippocampal volume reductions predict frontal lobe dysfunction in first episode schizophrenia.  Schizophr Res. 1995;  17 47-58
• 57 Zipursky R B, Marsh L, Lim K O, DeMent S, Shear P K, Sullivan E V, Murphy G M, Csernansky J G, Pfefferbaum A. Volumetric MRI assessment of temporal lobe structures in schizophrenia.  Biol Psychiatry. 1994;  35 501-516
• 58 Frederikse M, Lu A, Aylward E, Barta P, Sharma T, Pearlson G. Sex differences in inferior parietal lobule volume in schizophrenia.  Am J Psychiatry. 2000;  157 422-427
• 59 Nopoulos P, Torres I, Flaum M, Andreasen N C, Ehrhardt J C, Yuh W T. Brain morphology in first-episode schizophrenia.  Am J Psychiatry. 1995;  152 1721-1723
• 60 Sullivan E V, Lim K O, Mathalon D, Marsh L, Beal D M, Harris D, Hoff A L, Faustman W O, Pfefferbaum A. A profile of cortical gray matter volume deficits characteristic of schizophrenia.  Cereb Cortex. 1998;  8 117-124
• 61 Liddle P F, Friston K J, Frith C D, Hirsch S R, Jones T, Frackowiak R S. Patterns of cerebral blood flow in schizophrenia.  Br J Psychiatry. 1992;  160 179-186
• 62 Ross C A, Pearlson G D. Schizophrenia, the heteromodal association neocortex and development: potential for a neurogenetic approach.  Trends Neurosci. 1996;  19 171-176
• 63 Henn F A. Neurobiologie der Schizophrenie.  Schweiz Arch Neurol Psychiatr. 1995;  146 224-229
• 64 Stefan M D, Murray R M. Schizophrenia: developmental disturbance of brain and mind.  Acta Paediatr Suppl. 1997;  442 112-116
• 65 Carlsson A, Hansson L O, Waters N, Carlsson M L. Neurotransmitter aberrations in schizophrenia: new perspectives and therapeutic implications.  Life Sci. 1997;  61 75-94
• 66 Heckers S. Neuropathology of schizophrenia: cortex, thalamus, basal ganglia, and neurotransmitter-specific projection systems.  Schizophr Bull. 1997;  23 403-421
• 67 Elkashef A M, Buchanan R W, Gellad F, Munson R C, Breier A. Basal ganglia pathology in schizophrenia and tardive dyskinesia: an MRI quantitative study.  Am J Psychiatry. 1994;  151 752-755
• 68 Chakos M H, Lieberman J A, Alvir J, Bilder R, Ashtari M. Caudate nuclei volumes in schizophrenic patients treated with typical antipsychotics or clozapine.  Lancet. 1995;  345 456-457
• 69 Lee H, Tarazi F I, Chakos M, Wu H, Redmond M, Alvir J M, Kinon B J, Bilder R, Creese I, Lieberman J A. Effects of chronic treatment with typical and atypical antipsychotic drugs on the rat striatum.  Life Sci. 1999;  64 1595-1602
• 70 Cohen B W, Wan W. The thalamus as a site of action of antipsychotic drugs.  Am J Psychiatry. 1996;  153 104-106
• 71 Gaser C, Volz H P, Kiebel S, Riehemann S, Sauer H. Detecting structural changes in whole brain based on nonlinear deformations-application to schizophrenia research.  Neuroimage. 1999;  10 107-113
• 72 Buchsbaum M S, Someya T, Teng C Y, Abel L, Chin S, Najafi A, Haier R J, Wu J, Bunney Jr W E. PET and MRI of the thalamus in never-medicated patients with schizophrenia.  Am J Psychiatry. 1996;  153 191-199
• 73 Pakkenberg B. Pronounced reduction of total neuron number in mediodorsal thalamic nucleus and nucleus accumbens in schizophrenics.  Arch Gen Psychiatry. 1990;  47 1023-1028
• 74 Highley J R, Esiri M M, McDonald B, Roberts H C, Walker M A, Crow T J. The size and fiber composition of the anterior commissure with respect to gender and schizophrenia.  Biol Psychiatry. 1999;  45 1120-1127
• 75 Berman K F, Ostrem J L, Randolph C, Gold J, Goldberg T E, Coppola R, Carson R E, Herscovitch P, Weinberger D R. Physiological activation of a cortical network during performance of the Wisconsin Card Sorting Test: a positron emission tomography study.  Neuropsychologia. 1995;  33 1027-1046
• 76 Schmahmann J D, Pandya D N. Prefrontal cortex projections to the basilar pons in rhesus monkey: implications for the cerebellar contribution to higher function.  Neurosci Lett. 1995;  199 175-178
• 77 Andreasen N C, Nopoulos P, O'Leary D S, Miller D D, Wassink T, Flaum M. Defining the phenotype of schizophrenia: cognitive dysmetria and its neural mechanisms.  Biol Psychiatry. 1999;  46 908-920
• 78 Nopoulos P C, Ceilley J W, Gailis E A, Andreasen N C. An MRI study of cerebellar vermis morphology in patients with schizophrenia: evidence in support of the cognitive dysmetria concept.  Biol Psychiatry. 1999;  46 703-711
• 79 Tran K D, Smutzer G S, Doty R L, Arnold S E. Reduced Purkinje cell size in the cerebellar vermis of elderly patients with schizophrenia.  Am J Psychiatry. 1998;  155 1288-1290
• 80 Sandyk R, Kay S R, Merriam A E. Atrophy of the cerebellar vermis: relevance to the symptoms of schizophrenia.  Int J Neurosci. 1991;  57 205-212
• 81 Wassink T H, Andreasen N C, Nopoulos P, Flaum M. Cerebellar morphology as a predictor of symptom and psychosocial outcome in schizophrenia.  Biol Psychiatry. 1999;  45 41-48
• 82 Levitt J J, McCarley R W, Nestor P G, Petrescu C, Donnino R, Hirayasu Y, Kikinis R, Jolesz F A, Shenton M E. Quantitative volumetric MRI study of the cerebellum and vermis in schizophrenia: clinical and cognitive correlates.  Am J Psychiatry. 1999;  156 1105-1107
• 83 Colombo C, Abbruzzese M, Livian S, Scotti G, Locatelli M, Bonfanti A, Scarone S. Memory functions and temporal-limbic morphology in schizophrenia.  Psychiatry Res. 1993;  50 45-56
• 84 DeLisi L E, Hoff A L, Schwartz J E, Shields G W, Halthore S N, Gupta S M, Henn F A, Anand A K. Brain morphology in first-episode schizophrenic-like psychotic patients: a quantitative magnetic resonance imaging study.  Biol Psychiatry. 1991;  29 159-175
• 85 DeLisi L E, Sakuma M, Tew W, Kushner M, Hoff A L, Grimson R. Schizophrenia as a chronic active brain process: a study of progressive brain structural change subsequent to the onset of schizophrenia.  Psychiatry Res. 1997;  74 129-140
• 86 DeLisi L E, Tew W, Xie S, Hoff A L, Sakuma M, Kushner M, Lee G, Shedlack K, Smith A M, Grimson R. A prospective follow-up study of brain morphology and cognition in first-episode schizophrenic patients: preliminary findings.  Biol Psychiatry. 1995;  38 349-360
• 87 Nair T R, Christensen J D, Kingsbury S J, Kumar N G, Terry W M, Garver D L. Progression of cerebroventricular enlargement and the subtyping of schizophrenia.  Psychiatry Res. 1997;  74 141-150
• 88 Gur R E, Cowell P, Turetsky B I, Gallacher F, Cannon T, Bilker W, Gur R C. A follow-up magnetic resonance imaging study of schizophrenia. Relationship of neuroanatomical changes to clinical and neurobehavioral measures.  Arch Gen Psychiatry. 1998;  55 145-152
• 89 Woods B T. Is schizophrenia a progressive neurodevelopmental disorder? Toward a unitary pathogenetic mechanism.  Am J Psychiatry. 1998;  155 1661-1670
• 90 Spitzer M, Kammer T, Bellemann M E, Brix G, Layer B, Maier S, Kischka U, Gückel F. Funktionelle Magnetresonanztomographie in der psychopathologischen Forschung.  Fortschr Neurol Psychiat. 1998;  66 241-258
• 91 Jentsch J D, Redmond Jr D E, Elsworth J D, Taylor J R, Youngren K D, Roth R H. Enduring cognitive deficits and cortical dopamine dysfunction in monkeys after long-term administration of phencyclidine.  Science. 1997;  277 953-955
• 92 Honey G D, Bullmore E T, Soni W, Varatheesan M, Williams S C, Sharma T. Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia.  Proc Natl Acad Sci USA. 1999;  96 13432-13437
• 93 Braus D F, Ende G, Sartorius A, Krier A, Stuck S, Henn F A. Atypical vs. typical neuroleptics: a combined fMRI and MRSI study in schizophrenic patients.  Eur Arch of Psychiatry Clin Neurosci. 1998;  238 138
• 94 Braus D F, Ende G, Tost H, Weber-Fahr W, Jatzko A, Schmitt A, Demirakca T, Ruf M. Funktionelle Kernspintomographie und Schizophrenie: Medikamenteneffekte, methodische Grenzen und Perspektiven.  Naturheilkunde. 2000;  3 121-128
• 95 Braus D F, Ende G, Weber-Fahr W, Sartorius A, Krier A, Hubrich-Ungureanu P, Ruf M, Stuck S, Henn F A. Antipsychotic drug effects on motor activation measured by functional magnetic resonance imaging in schizophrenic patients.  Schizophr Res. 1999;  39 19-29
• 96 Wolkin A, Rusinek H, Vaid G, Arena L, Lafargue T, Sanfilipo M, Loneragan C, Lautin A, Rotrosen J. Structural magnetic resonance image averaging in schizophrenia.  Am J Psychiatry. 1998;  155 1064-1073
• 97 Frazier J A, Giedd J N, Hamburger S D, Albus K E, Kaysen D, Vaituzis A C, Rajapakse J C, Lenane M C, McKenna K, Jacobsen L K, Gordon C T, Breier A, Rapoport J L. Brain anatomic magnetic resonance imaging in childhood-onset schizophrenia.  Arch Gen Psychiatry. 1996;  53 617-624
• 98 Harvey I, Persaud R, Ron M A, Baker G, Murray R M. Volumetric MRI measurements in bipolars compared with schizophrenics and healthy controls.  Psychol Med. 1924;  24 689-699
• 99 Jacobsen L K, Giedd J N, Vaituzis A C, Hamburger S D, Rajapakse J C, Frazier J A, Kaysen D, Lenane M C, McKenna K, Gordon C T, Rapoport J L. Temporal lobe morphology in childhood-onset schizophrenia.  Am J Psychiatry. 1996;  153 355-361
• 100 Whitworth A B, Honeder M, Kremser C, Kemmler G, Felber S, Hausmann A, Wanko C, Wechdorn H, Aichner F, Stuppaeck C H. Fleischhacker WW. Hippocampal volume reduction in male schizophrenic patients.  Schizophr Res. 1998;  31 73-81
• 101 Staal W G, Hulshoff Pol H E, Schnack H G, Hoogendoorn M L, Jellema K, Kahn R S. Structural brain abnormalities in patients with schizophrenia and their healthy siblings.  Am J Psychiatry. 2000;  157 416-421
• 102 Friedman L, Findling R L, Kenny J T, Swales T P, Stuve T A, Jesberger J A, Lewin J S, Schulz S C. An MRI study of adolescent patients with either schizophrenia or bipolar disorder as compared to healthy control subjects.  Biol Psychiatry. 1999;  46 78-88
• 103 Rossi A, Stratta P, Mancini F, Gallucci M, Mattei P, Core L, Di Michele V, Casacchia M. Magnetic resonance imaging findings of amygdala-anterior hippocampus shrinkage in male patients with schizophrenia.  Psychiatry Res. 1994;  52 43-53
• 104 Marsh L, Suddath R L, Higgins N, Weinberger D R. Medial temporal lobe structures in schizophrenia: relationship of size to duration of illness.  Schizophr Res. 1994;  11 225-238
• 105 Meisenzahl E M, Frodl T, Greiner J, Leinsinger G, Maag K P, Heiss D, Hahn K, Hegerl U, Moller H J. Corpus callosum size in schizophrenia - a magnetic resonance imaging analysis.  Eur Arch Psychiatry Clin Neurosci. 1999;  249 305-312
• 106 Flaum M, Swayze 2nd V W, O'Leary D S, Yuh W T, Ehrhardt J C, Arndt S V, Andreasen N C. Effects of diagnosis, laterality, and gender on brain morphology in schizophrenia.  Am J Psychiatry. 1995;  152 704-714
• 107 Vita A, Dieci M, Giobbio G M, Caputo A, Ghiringhelli L, Comazzi M, Garbarini M, Mendini A P, Morganti C, Tenconi F. et al . Language and thought disorder in schizophrenia: brain morphological correlates.  Schizophr Res. 1995;  15 243-251
• 108 Barta P E, Pearlson G D, Brill 2nd L B, Royall R, McGilchrist I K, Pulver A E, Powers R E, Casanova M F, Tien A Y, Frangou S, Petty R G. Planum temporale asymmetry reversal in schizophrenia: replication and relationship to gray matter abnormalities.  Am J Psychiatry. 1997;  154 661-667
• 109 Reite M, Sheeder J, Teale P, Adams M, Richardson D, Simon J, Jones R H, Rojas D C. Magnetic source imaging evidence of sex differences in cerebral lateralization in schizophrenia.  Arch Gen Psychiatry. 1997;  54 433-440
• 110 Yeo R A, Hodde-Vargas J, Hendren R L, Vargas L A, Brooks W M, Ford C C, Gangestad S W, Hart B L. Brain abnormalities in schizophrenia-spectrum children: implications for a neurodevelopmental perspective.  Psychiatry Res. 1997;  76 1-13
• 111 Zipursky R B, Seeman M V, Bury A, Langevin R, Wortzman G, Katz R. Deficits in gray matter volume are present in schizophrenia but not bipolar disorder.  Schizophr Res. 1997;  26 85-92
• 112 Hirayasu Y, Shenton M E, Salisbury D F, Dickey C C, Fischer I A, Mazzoni P, Kisler T, Arakaki H, Kwon J S, Anderson J E, Yurgelun-Todd D, Tohen M, McCarley R W. 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 1384-1391
• 113 Zipursky R B, Lambe E K, Kapur S, Mikulis D J. Cerebral gray matter volume deficits in first episode psychosis.  Arch Gen Psychiatry. 1998;  55 540-546
• 114 Lauriello J, Hoff A, Wieneke M H, Blankfeld H, Faustman W O, Rosenbloom M, DeMent S, Sullivan E V, Lim K O, Pfefferbaum A. Similar extent of brain dysmorphology in severely ill women and men with schizophrenia.  Am J Psychiatry. 1997;  154 819-825
• 115 Lim K O, Tew W, Kushner M, Chow K, Matsumoto B, DeLisi L E. Cortical gray matter volume deficit in patients with first-episode schizophrenia.  Am J Psychiatry. 1996;  153 1548-1553
• 116 Sullivan E V, Shear P K, Lim K O, Zipursky R B, Pfefferbaum A. Cognitive and motor impairments are related to gray matter volume deficits in schizophrenia.  Biol Psychiatry. 1996;  39 234-240
• 117 Cannon T D, van Erp T G, Huttunen M, Lonnqvist J, Salonen O, Valanne L, Poutanen V P, Standertskjold-Nordenstam C G, Gur R E, Yan M. Regional gray matter, white matter, and cerebrospinal fluid distributions in schizophrenic patients, their siblings, and controls.  Arch Gen Psychiatry. 1998;  55 1084-1091
• 118 Lim K O, Hedehus M, Moseley M, de Crespigny A, Sullivan E V, Pfefferbaum A. Compromised white matter tract integrity in schizophrenia inferred from diffusion tensor imaging.  Arch Gen Psychiatry. 1999;  56 367-374
• 119 Barr W B, Ashtari M, Bilder R M, Degreef G, Lieberman J A. Brain morphometric comparison of first-episode schizophrenia and temporal lobe epilepsy.  Br J Psychiatry. 1997;  170 515-519
• 120 Woodruff P W, Wright I C, Shuriquie N, Russouw H, Rushe T, Howard R J, Graves M, Bullmore E T, Murray R M. Structural brain abnormalities in male schizophrenics reflect frontotemporal dissociation.  Psychol Med. 1997;  27 1257-1266
• 121 Roy P D, Zipursky R B, Saint-Cyr J A, Bury A, Langevin R, Seeman M V. Temporal horn enlargement in present in schizophrenia and bipolar disorder.  Biol Psychiatry. 1998;  44 418-422
• 122 Davis K L, Buchsbaum M S, Shihabuddin L, Spiegel-Cohen J, Metzger M, Frecska E, Keefe R S, Powchik P. Ventricular enlargement in poor-outcome schizophrenia.  Biol Psychiatry. 1998;  43 783-793
• 123 Seidman L J, Faraone S V, Goldstein J M, Goodman J M, Kremen W S, Toomey R, Tourville J, Kennedy D, Makris N, Caviness V S, Tsuang M T. Thalamic and amygdala-hippocampal volume reductions in first-degree relatives of patients with schizophrenia: an MRI-based morphometric analysis.  Biol Psychiatry. 1999;  46 941-954
• 124 Rossi A, Bustini M, Prosperini P, Marinangeli M G, Splendiani A, Daneluzzo E, Stratta P. Neuromorphological abnormalities in schizophrenic patients with good and poor outcome.  Acta Psychiatr Scand. 2000;  101 161-166
• 125 Sanfilipo M, Lafargue T, Arena L, Rusinek H, Kushner K, Lautin A, Loneragan C, Vaid G, Rotrosen J, Wolkin A. Fine volumetric analysis of the cerebral ventricular system in schizophrenia: further evidence for multifocal mild to moderate enlargement.  Schizophr Bull. 2000;  26 201-216
• 126 Corey-Bloom J, Jernigan T, Archibald S, Harris M J, Jeste D V. Quantitative magnetic resonance imaging of the brain in late-life schizophrenia.  Am J Psychiatry. 1995;  152 447-449
• 127 Buchsbaum M S, Yang S, Hazlett E, Siegel Jr B V, Germans M, Haznedar M, O'Flaithbheartaigh S, Wei T, Silverman J, Siever L J. Ventricular volume and asymmetry in schizotypal personality disorder and schizophrenia assessed with magnetic resonance imaging.  Schizophr Res. 1997;  27 45-53
• 128 James A C, Crow T J, Renowden S, Wardell A M, Smith D M, Anslow P. Is the course of brain development in schizophrenia delayed? Evidence from onsets in adolescence.  Schizophr Res. 1999;  40 1-10
• 129 Leonard C M, Kuldau J M, Breier J I, Zuffante P A, Gautier E R, Heron D C, Lavery E M, Packing J, Williams S A, DeBose C A. Cumulative effect of anatomical risk factors for schizophrenia: an MRI study.  Biol Psychiatry. 1999;  46 374-382
• 130 Becker T, Elmer K, Schneider F, Schneider M, Grodd W, Bartels M, Heckers S, Beckmann H. Confirmation of reduced temporal limbic structure volume on magnetic resonance imaging in male patients with schizophrenia.  Psychiatry Res. 1996;  67 135-143
• 131 Egan M F, Duncan C C, Suddath R L, Kirch D G, Mirsky A F, Wyatt R J. Event-related potential abnormalities correlate with structural brain alterations and clinical features in patients with chronic schizophrenia.  Schizophr Res. 1994;  11 259-271
• 132 Woods B T, Yurgelun-Todd D, Goldstein J M, Seidman L J, Tsuang M T. MRI brain abnormalities in chronic schizophrenia: one process or more?.  Biol Psychiatry. 1996;  40 585-596
• 133 Nopoulos P, Swayze V, Andreasen N C. Pattern of brain morphology in patients with schizophrenia and large cavum septi pellucidi.  J Neuropsychiatry Clin Neurosci. 1996;  8 147-152
• 134 Fukuzako H, Fukazako T, Hashiguchi T, Hokazono Y, Takeuchi K, Hirakawa K, Ueyama K, Takigawa M, Kajiya Y, Nakajo M, Fujimoto T. Reduction in hippocampal formation volume is caused mainly by its shortening in chronic schizophrenia: assessment by MRI.  Biol Psychiatry. 1996;  39 938-945
• 135 Ohnuma T, Kimura M, Takahashi T, Iwamoto N, Arai H. A magnetic resonance imaging study in first-episode disorganized-type patients with schizophrenia.  Psychiatry Clin Neurosci. 1997;  51 9-15
• 136 Nelson M D, Saykin A J, Flashman L A, Riordan H J. Hippocampal volume reduction in schizophrenia as assessed by magnetic resonance imaging: a meta-analytic study.  Arch Gen Psychiatry. 1998;  55 433-440
• 137 Razi K, Greene K P, Sakuma M, Ge S, Kushner M, DeLisi L E. Reduction of the parahippocampal gyrus and the hippocampus in patients with chronic schizophrenia.  Br J Psychiatry. 1999;  174 512-519
• 138 Stefanis N, Frangou S, Yakeley J, Sharma T, O'Connell P, Morgan K, Sigmudsson T, Taylor M, Murray R. Hippocampal volume reduction in schizophrenia: effects of genetic risk and pregnancy and birth complications.  Biol Psychiatry. 1999;  46 697-702
• 139 Velakoulis D, Pantelis C, McGorry P D, Dudgeon P, Brewer W, Cook M, Desmond P, Bridle N, Tierney P, Murrie V, Singh B, Copolov D. Hippocampal volume in first-episode psychoses and chronic schizophrenia: a high-resolution magnetic resonance imaging study.  Arch Gen Psychiatry. 1999;  56 133-141
• 140 Kegeles L S, Shungu D C, Anjilvel S, Chan S, Ellis S P, Xanthopoulos E, Malaspina D, Gorman J M, Mann J J, Laruelle M, Kaufmann C A. Hippocampal pathology in schizophrenia: magnetic resonance imaging and spectroscopy studies.  Psychiatry Res. 2000;  98 163-175
• 141 Hajek M, Huonker R, Boehle C, Volz H P, Nowak H, Sauer H. Abnormalities of auditory evoked magnetic fields and structural changes in the left hemisphere of male schizophrenics - a magnetoencephalographic-magnetic resonance imaging study.  Biol Psychiatry. 1997;  42 609-616
• 142 Keshavan M S, Haas G L, Kahn C E, Aguilar E, Dick E L, Schooler N R, Sweeney J A, Pettegrew J W. Superior temporal gyrus and the course of early schizophrenia: progressive, static, or reversible?.  J Psychiatr Res. 1998;  32 161-167
• 143 Holinger D P, Shenton M E, Wible C G, Donnino R, Kikinis R, Jolesz F A, McCarley R W. Superior temporal gyrus volume abnormalities and thought disorder in left-handed schizophrenic men.  Am J Psychiatry. 1999;  156 1730-1735
• 144 Tune L, Barta P, Wong D, Powers R E, Pearlson G, Tien A Y, Wagner H N. Striatal dopamine D2 receptor quantification and superior temporal gyrus: volume determination in 14 chronic schizophrenic subjects.  Psychiatry Res. 1996;  67 155-158
• 145 DeLisi L E, Hoff A L, Neale C, Kushner M. Asymmetries in the superior temporal lobe in male and female first-episode schizophrenic patients: measures of the planum temporale and superior temporal gyrus by MRI.  Schizophr Res. 1994;  12 19-28
• 146 Kwon J S, McCarley R W, Hirayasu Y, Anderson J E, Fischer I A, Kikinis R, Jolesz F A, Shenton M E. Left planum temporale volume reduction in schizophrenia.  Arch Gen Psychiatry. 1999;  56 142-148
• 147 Kulynych J J, Vladar K, Jones D W, Weinberger D R. Superior temporal gyrus volume in schizophrenia: a study using MRI morphometry assisted by surface rendering.  Am J Psychiatry. 1996;  153 50-56
• 148 Hirayasu Y, McCarley R W, Salisbury D F, Tanaka S, Kwon J S, Frumin M, Snyderman D, Yurgelun-Todd D, Kikinis R, Jolesz F A, Shenton M E. Planum temporale and Heschl gyrus volume reduction in schizophrenia: a magnetic resonance imaging study of first-episode patients.  Arch Gen Psychiatry. 2000;  57 692-699
• 149 Kleinschmidt A, Falkai P, Huang Y, Schneider T, Furst G, Steinmetz H. In vivo morphometry of planum temporale asymmetry in first-episode schizophrenia.  Schizophr Res. 1994;  12 9-18
• 150 Buchanan R W, Vladar K, Barta P E, Pearlson G D. Structural evaluation of the prefrontal cortex in schizophrenia.  Am J Psychiatry. 1998;  155 1049-1055
• 151 Goldstein J M, Goodman J M, Seidman L J, Kennedy D N, Makris N, Lee H, Tourville J, Caviness Jr V S, Faraone S V, Tsuang M T. Cortical abnormalities in schizophrenia identified by structural magnetic resonance imaging.  Arch Gen Psychiatry. 1999;  56 537-547
• 152 Kikinis R, Shenton M E, Gerig G, Hokama H, Haimson J, O'Donnell B F, Wible C G, McCarley R W, Jolesz F A. Temporal lobe sulco-gyral pattern anomalies in schizophrenia: an in vivo MR three-dimensional surface rendering study.  Neurosci Lett. 1994;  182 7-12
• 153 Wible C G, Shenton M E, Hokama H, Kikinis R, Jolesz F A, Metcalf D, McCarley R W. Prefrontal cortex and schizophrenia. A quantitative magnetic resonance imaging study.  Arch Gen Psychiatry. 1995;  52 279-288
• 154 Hirayasu Y, Shenton M E, Salisbury D F, Kwon J S, Wible C G, Fischer I A, Yurgelun-Todd D, Zarate C, Kikinis R, Jolesz F A, McCarley R W. Subgenual cingulate cortex volume in first-episode psychosis.  Am J Psychiatry. 1999;  156 1091-1093
• 155 Andreasen N C, Arndt S, Swayze 2nd V, Cizadlo T, Flaum M, O'Leary D, Ehrhardt J C, Yuh W T. Thalami abnormalities in schizophrenia visualized through magnetic resonance image averaging.  Science. 1994;  266 294-298
• 156 Hazlett E A, Buchsbaum M S, Byne W, Wei T C, Spiegel-Cohen J, Geneve C, Kinderlehrer R, Haznedar M M, Shihabuddin L, Siever L J. Three-dimensional analysis with MRI and PET of the size, shape, and function of the thalamus in the schizophrenia spectrum.  Am J Psychiatry. 1999;  156 1190-1199
• 157 Dasari M, Friedman L, Jesberger J, Stuve T A, Findling R L, Swales T P, Schulz S C. A magnetic resonance imaging study of thalamic area in adolescent patients with either schizophrenia or bipolar disorder as compared to healthy controls.  Psychiatry Res. 1999;  91 155-162
• 158 Portas C M, Goldstein J M, Shenton M E, Hokama H H, Wible C G, Fischer I, Kikinis R, Donnino R, Jolesz F A, McCarley R W. Volumetric evaluation of the thalamus in schizophrenic male patients using magnetic resonance imaging.  Biol Psychiatry. 1998;  43 649-659
• 159 Arciniegas D, Rojas D C, Teale P, Sheeder J, Sandberg E, Reite M. The thalamus and the schizophrenia phenotype: failure to replicate reduced volume.  Biol Psychiatry. 1999;  45 1329-1335
• 160 Chakos M H, Lieberman J A, Bilder R M, Borenstein M, Lerner G, Bogerts B, Wu H, Kinon B, Ashtari M. Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs.  Am J Psychiatry. 1994;  151 1430-1436
• 161 Hokama H, Shenton M E, Nestor P G, Kikinis R, Levitt J J, Metcalf D, Wible C G, O'Donnell B F, Jolesz F A, McCarley R W. Caudate, putamen, and globus pallidus volume in schizophrenia: a quantitative MRI study.  Psychiatry Res. 1995;  61 209-229
• 162 Keshavan M S, Rosenberg D, Sweeney J A, Pettegrew J W. Decreased caudate volume in neuroleptic-naive psychotic patients.  Am J Psychiatry. 1998;  155 774-778
• 163 Gur R E, Maany V, Mozley P D, Swanson C, Bilker W, Gur R C. Subcortical MRI volumes in neuroleptic-naive and treated patients with schizophrenia.  Am J Psychiatry. 1998;  155 1711-1717
• 164 Corson P W, Nopoulos P, Miller D D, Arndt S, Andreasen N C. Change in basal ganglia volume over 2 years in patients with schizophrenia: typical versus atypical neuroleptics.  Am J Psychiatry. 1999;  156 1200-1204
• 165 Corson P W, Nopoulos P, Andreasen N C, Heckel D, Arndt S. Caudate size in first-episode neuroleptic-naive schizophrenic patients measured using an artificial neural network.  Biol Psychiatry. 1999;  46 712-720
• 166 Hoff A L, Neal C, Kushner M, DeLisi L E. Gender differences in corpus callosum size in first-episode schizophrenics.  Biol Psychiatry. 1994;  35 913-919
• 167 DeQuardo J R. Landmark analysis of corpus callosum shape in schizophrenia.  Biol Psychiatry. 1999;  46 1712-1714
• 168 Tibbo P, Nopoulos P, Arndt S, Andreasen N C. Corpus callosum shape and size in male patients with schizophrenia.  Biol Psychiatry. 1998;  44 405-412
• 169 Colombo C, Bonfanti A, Scarone S. Anatomical characteristics of the corpus callosum and clinical correlates in schizophrenia.  Eur Arch Psychiatry Clin Neurosci. 1994;  243 244-248
• 170 Woodruff P W, Phillips M L, Rushe T, Wright I C, Murray R M, David A S. Corpus callosum size and inter-hemispheric function in schizophrenia.  Schizophr Res. 1997;  23 189-196