Recent advances in the neuropathology of schizophrenia.

This article reviews some 50 neuroanatomical postmortem studies published in the last 20 years. The majority of these studies demonstrated various types of subtle anomalies in limbic structures, that is, the hippocampus, parahippocampal gyrus, entorhinal cortex, amygdala, cingulate gyrus, and septum of schizophrenia patients. A number of schizophrenic symptoms might be related to structural and functional disturbances of these brain regions. But these studies also reported subtle changes in parts of the basal ganglia, thalamus, cortex, corpus callosum, and brainstem neurotransmitter systems. Many of the studies, however, are based on small sample sizes and, therefore, must be regarded as preliminary. Cytoarchitectonic abnormalities and lack of gliosis in limbic structures as well as the absence of normal structural cerebral asymmetry in a substantial proportion of patients indicate that these structural anomalies may reflect a disorder of prenatal brain development and argue against the notion that schizophrenia is a progressive degenerative brain disorder.

[1]  B. Bogerts,et al.  A morphometric study of the dopamine-containing cell groups in the mesencephalon of normals, Parkinson patients, and schizophrenics. , 1983, Biological psychiatry.

[2]  M. Raichle,et al.  Left globus pallidus abnormality in never-medicated patients with schizophrenia. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Lutz Jäncke,et al.  Anatomical left‐right asymmetry of language‐related temporal cortex is different in left‐ and right‐handers , 1991, Annals of neurology.

[4]  D. Jeste,et al.  Hippocampal pathologic findings in schizophrenia. A morphometric study. , 1989, Archives of general psychiatry.

[5]  A. Scheibel,et al.  A neurohistological correlate of schizophrenia. , 1984, Biological psychiatry.

[6]  A. Scheibel,et al.  Hippocampal pyramidal cell disarray in schizophrenia as a bilateral phenomenon. , 1991, Archives of general psychiatry.

[7]  T. Powell,et al.  An anatomical study of converging sensory pathways within the cerebral cortex of the monkey. , 1970, Brain : a journal of neurology.

[8]  F. Benes,et al.  Deficits in small interneurons in prefrontal and cingulate cortices of schizophrenic and schizoaffective patients. , 1991, Archives of general psychiatry.

[9]  W. Seifert Neurobiology of the hippocampus , 1983 .

[10]  R. Mathew,et al.  Midsagittal sections of the cerebellar vermis and fourth ventricle obtained with magnetic resonance imaging of schizophrenic patients. , 1985, The American journal of psychiatry.

[11]  Nancy C. Andreasen,et al.  Negative Versus Positive Schizophrenia , 1991, Springer Berlin Heidelberg.

[12]  P. Flor-Henry,et al.  Psychosis and Temporal Lobe Epilepsy; A Controlled Investigation , 1969, Epilepsia.

[13]  F. Benes,et al.  Reduced neuronal size in posterior hippocampus of schizophrenic patients. , 1991, Schizophrenia bulletin.

[14]  L. Bigelow,et al.  Quantitative Brain Measurements in Chronic Schizophrenia , 1972, British Journal of Psychiatry.

[15]  J. Shields The major psychoses. , 1977, Journal of medical genetics.

[16]  M. Cooper,et al.  Basal ganglia regional glucose metabolism asymmetry during a catatonic episode , 1989, Biological Psychiatry.

[17]  Henry A. Nasrallah,et al.  A controlled magnetic resonance imaging study of corpus callosum thickness in schizophrenia , 1986, Biological Psychiatry.

[18]  H. Nasrallah,et al.  Corpus Callosum Thickness in Chronic Schizophrenia , 1983, British Journal of Psychiatry.

[19]  Eve C. Johnstone,et al.  Is there gliosis in schizophrenia? Investigation of the temporal lobe , 1987, Biological Psychiatry.

[20]  W. Grodd,et al.  MRI findings in medial temporal lobe structures in schizophrenia , 1990, European Neuropsychopharmacology.

[21]  F. Smith,et al.  Nuclear Magnetic Resonance Brain Imaging in Chronic Schizophrenia , 1987, British Journal of Psychiatry.

[22]  Peter Falkai,et al.  Loss of sylvian fissure asymmetry in schizophrenia A quantitative post mortem study , 1992, Schizophrenia Research.

[23]  J. Stevens An anatomy of schizophrenia? , 1973, Archives of general psychiatry.

[24]  S. Mednick Developmental Neuropathology of Schizophrenia , 1991, NATO ASI Series.

[25]  A. Bhalla,et al.  Behaviour disturbances during recovery from herpes simplex encephalitis. , 1983, Journal of neurology, neurosurgery, and psychiatry.

[26]  S. Heckers,et al.  Cortex, white matter, and basal ganglia in schizophrenia: A volumetric postmortem study , 1991, Biological Psychiatry.

[27]  D. Weinberger,et al.  Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia. I. Regional cerebral blood flow evidence. , 1986, Archives of general psychiatry.

[28]  S. Heckers,et al.  Hippocampal neuron number in schizophrenia. A stereological study. , 1991, Archives of general psychiatry.

[29]  T. Crow,et al.  Schizophrenia as an anomaly of development of cerebral asymmetry. A postmortem study and a proposal concerning the genetic basis of the disease. , 1989, Archives of general psychiatry.

[30]  N. Geschwind,et al.  Developmental dyslexia: Four consecutive patients with cortical anomalies , 1985, Annals of neurology.

[31]  R Jagoe,et al.  Postmortem evidence of structural brain changes in schizophrenia. Differences in brain weight, temporal horn area, and parahippocampal gyrus compared with affective disorder. , 1986, Archives of general psychiatry.

[32]  I. Sherwin The Effect of the Location of an Epileptogenic Lesion on the Occurrence of Psychosis in Epilepsy , 1982 .

[33]  H J Gundersen,et al.  Total number of neurons and glial cells in human brain nuclei estimated by the disector and the fractionator , 1988, Journal of microscopy.

[34]  J A Wada,et al.  Cerebral hemispheric asymmetry in humans. Cortical speech zones in 100 adults and 100 infant brains. , 1975, Archives of neurology.

[35]  E. B. Southard,et al.  ON THE TOPOGRAPHICAL DISTRIBUTION OF CORTEX LESIONS AND ANOMALIES IN DEMENTIA PRÆCOX, WITH SOME ACCOUNT OF THEIR FUNCTIONAL SIGNIFICANCE , 1914 .

[36]  M Ashtari,et al.  Volumes of ventricular system subdivisions measured from magnetic resonance images in first-episode schizophrenic patients. , 1992, Archives of general psychiatry.

[37]  A. Raine,et al.  Structural and functional characteristics of the corpus callosum in schizophrenics, psychiatric controls, and normal controls: A magnetic resonance imaging and neuropsychological evaluation. , 1990 .

[38]  A. Galaburda,et al.  Developmental dyslexia: four consecutive cases with cortical anomalies , 1995 .

[39]  P. Falkai,et al.  Morphometric evidence for developmental disturbances in brains of some schizophrenics , 1989, Schizophrenia Research.

[40]  D. Weinberger Implications of normal brain development for the pathogenesis of schizophrenia. , 1987, Archives of general psychiatry.

[41]  J. Okamoto Schizophrenia-like psychosis of epilepsy , 1952 .

[42]  N. Malamud Psychiatric disorder with intracranial tumors of limbic system. , 1967, Archives of neurology.

[43]  D. Weinberger,et al.  The Neurology of schizophrenia , 1986 .

[44]  P. Maclean Some psychiatric implications of physiological studies on frontotemporal portion of limbic system (visceral brain). , 1952, Electroencephalography and clinical neurophysiology.

[45]  T. Crow,et al.  White matter reduction in the parahippocampal gyrus of patients with schizophrenia. , 1987, Archives of general psychiatry.

[46]  A. Alzheimer Beiträge zur pathologischen Anatomie der Hirnrinde und zur anatomischen Grundlage einiger Psychosen. (Part 2 of 2) , 1897 .

[47]  D. Richter Schizophrenia : somatic aspects , 1957 .

[48]  F H Duffy,et al.  CT abnormalities in schizophrenia. A preliminary study of their correlations with P300/P200 electrophysiological features and positive/negative symptoms. , 1989, Archives of general psychiatry.

[49]  F. Benes Post-mortem structural analyses of schizophrenic brain: study designs and the interpretation of data. , 1988, Psychiatric developments.

[50]  J. Kelsoe,et al.  Temporal lobe pathology in schizophrenia: a quantitative magnetic resonance imaging study. , 1989, The American journal of psychiatry.

[51]  F. Benes,et al.  Increased vertical axon numbers in cingulate cortex of schizophrenics. , 1987, Archives of general psychiatry.

[52]  S. Heckers,et al.  Limbic structures and lateral ventricle in schizophrenia. A quantitative postmortem study. , 1990, Archives of general psychiatry.

[53]  T. Crow Temporal lobe asymmetries as the key to the etiology of schizophrenia. , 1990, Schizophrenia bulletin.

[54]  B. Bogerts Interaktion von alters- und streßabhängigen Faktoren mit limbischen Strukturdefiziten bei schizophrenen Erkrankungen , 1988 .

[55]  B. Pakkenberg,et al.  Post-mortem Study of Chronic Schizophrenic Brains , 1987, British Journal of Psychiatry.

[56]  F. Benes,et al.  An analysis of the arrangement of neurons in the cingulate cortex of schizophrenic patients. , 1987, Archives of general psychiatry.

[57]  D. Weinberger,et al.  Schizophrenia and cerebral asymmetry detected by computed tomography. , 1982, The American journal of psychiatry.

[58]  Sarah D. Cramer,et al.  Pathology of the Nervous System , 2019, Toxicologic Pathology for Non-Pathologists.

[59]  M. LeMay,et al.  Abnormalities of the left temporal lobe and thought disorder in schizophrenia. A quantitative magnetic resonance imaging study. , 1992, The New England journal of medicine.

[60]  T. Crow,et al.  Gliosis in schizophrenia: A survey , 1986, Biological Psychiatry.

[61]  J. Lieberman,et al.  Increased prevalence of the cavum septum pellucidum in MRI scans and postmortem brains of schizophrenic patients , 1992, Schizophrenia Research.

[62]  E. Alvord,et al.  Cava septi pellucidi et vergae: their normal and pathogical states. , 1969, Brain : a journal of neurology.

[63]  G. Tucker,et al.  Sub-Acute Encephalitis: Behavioural and Neurological Aspects , 1970, British Journal of Psychiatry.

[64]  J A Wada,et al.  Fundamental Nature of Human Infant's Brain Asymmetry , 1977, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[65]  M. Mesulam Principles of behavioral neurology , 1985 .

[66]  J. Stevens,et al.  Abnormal reinnervation as a basis for schizophrenia: a hypothesis. , 1992, Archives of general psychiatry.

[67]  Dr. Robert Miller Cortico-Hippocampal Interplay and the Representation of Contexts in the Brain , 1991, Studies of Brain Function.

[68]  Henry A. Nasrallah,et al.  A histological study of the corpus callosum in chronic schizophrenia , 1983, Psychiatry Research.

[69]  B. McEwen,et al.  The Vulnerability of the Hippocampus to Protective and Destructive Effects of Glucocorticoids in Relation to Stress , 1992, British Journal of Psychiatry.

[70]  J. Panksepp,et al.  Anatomy of the hypothalamus , 1979 .

[71]  G. Roberts Schizophrenia: A Neuropathological Perspective , 1991, British Journal of Psychiatry.

[72]  T. Goldberg,et al.  The hippocampus and parahippocampus in schizophrenia, suicide, and control brains. , 1990, Archives of general psychiatry.

[73]  P. Riederer,et al.  Pathochemical Markers in Major Psychoses , 1985, Springer Berlin Heidelberg.

[74]  E. Torrey,et al.  Schizophrenia and the limbic system. , 1974, Lancet.

[75]  T. Crow,et al.  Temporal lobe structure as determined by nuclear magnetic resonance in schizophrenia and bipolar affective disorder. , 1989, Journal of neurology, neurosurgery, and psychiatry.

[76]  L. DeLisi,et al.  Increased temporal lobe glucose use in chronic schizophrenic patients , 1989, Biological Psychiatry.

[77]  J. Kleinman,et al.  The neuropathology of schizophrenia: A critical assessment of research methodologies , 1990, Biological Psychiatry.

[78]  J. Stevens Schizophrenia: static or progressive pathophysiology? , 1991, Schizophrenia research.

[79]  A. Scheibel,et al.  Hippocampal pyramidal cell orientation in schizophrenia. A controlled neurohistologic study of the Yakovlev collection. , 1987, Archives of general psychiatry.

[80]  S. F. Witelson,et al.  Left hemisphere specialization for language in the newborn. Neuroanatomical evidence of asymmetry. , 1973, Brain : a journal of neurology.

[81]  L. DeLisi,et al.  Anteroposterior gradients in cerebral glucose use in schizophrenia and affective disorders. , 1984, Archives of general psychiatry.

[82]  D. Jeste,et al.  Locus ceruleus morphometry in aging and schizophrenia , 1988, Acta psychiatrica Scandinavica.

[83]  T. Crow,et al.  A “Mock up” of schizophrenia: Temporal lobe epilepsy and schizophrenia-like psychosis , 1990, Biological Psychiatry.

[84]  L. DeLisi,et al.  Perinatal complications and reduced size of brain limbic structures in familial schizophrenia. , 1988, Schizophrenia bulletin.

[85]  D. Weinberger,et al.  Anatomical abnormalities in the brains of monozygotic twins discordant for schizophrenia. , 1990, The New England journal of medicine.

[86]  J. Minckler Pathology of the nervous system , 1968 .

[87]  T. Crow,et al.  Reduction in temporal lobe size in siblings with schizophrenia: A magnetic resonance imaging study , 1990, Psychiatry Research: Neuroimaging.

[88]  B. Bogerts Limbic and paralimbic pathology in schizophrenia: Interaction with age- and stress-related factors. , 1989 .

[89]  E. O'callaghan,et al.  Physical anomalies and neurodevelopmental abnormality in schizophrenia: New clinical correlates , 1990, Schizophrenia Research.

[90]  S. Hans,et al.  Infants at risk for schizophrenia: sequelae of a genetic neurointegrative defect. A review and replication analysis of pandysmaturation in the Jerusalem Infant Development Study. , 1992, Archives of general psychiatry.

[91]  P. Eames Behavior disturbances during recovery from herpes simplex encephalitis. , 1984, Journal of neurology, neurosurgery, and psychiatry.

[92]  Hisanobu Kaiya,et al.  The morphology of the corpus callosum in schizophrenia An MRI study , 1988, Schizophrenia Research.

[93]  F. Benes,et al.  Quantitative cytoarchitectural studies of the cerebral cortex of schizophrenics. , 1986, Archives of general psychiatry.

[94]  T. Crow,et al.  Loss of sylvian fissure asymmetry in schizophrenia: Findings in the runwell 2 series of brains , 1992, Schizophrenia Research.

[95]  P. Stratta,et al.  Reduced temporal lobe areas in schizophrenia: Preliminary evidences from a controlled multiplanar magnetic resonance imaging study , 1990, Biological Psychiatry.

[96]  K. Jellinger Morphological Backgrounds of Pathochemical Studies in Major Psychoses , 1985 .

[97]  G. F. Tremblay,et al.  The Prefrontal Cortex , 1989, Neurology.

[98]  J. Gray,et al.  Précis of The neuropsychology of anxiety: An enquiry into the functions of the septo-hippocampal system , 1982, Behavioral and Brain Sciences.

[99]  G. Huber,et al.  Basisstadien endogener Psychosen und das Borderline-Problem , 1985 .

[100]  B. Bogerts,et al.  Post-mortem volume measurements of limbic system and basal ganglia structures in chronic schizophrenics Initial results from a new brain collection , 1990, Schizophrenia Research.

[101]  B. Bogerts,et al.  Clinical and Neurodevelopmental Aspects of Brain Pathology in Schizophrenia , 1991 .

[102]  G. Mazars Criteria for Identifying Cingulate Epilepsies* , 1970, Epilepsia.

[103]  E. Garcia-Rill,et al.  The brain stem reticular formation in schizophrenia , 1991, Psychiatry Research: Neuroimaging.

[104]  B. Bogerts,et al.  Quantitative study of gliosis in schizophrenia and huntington's chorea , 1988, Biological Psychiatry.

[105]  P. McGuffin,et al.  Schizophrenia: The Major Issues , 1988 .

[106]  M S Buchsbaum,et al.  Cerebral glucography with positron tomography. Use in normal subjects and in patients with schizophrenia. , 1982, Archives of general psychiatry.

[107]  B T Hyman,et al.  Some cytoarchitectural abnormalities of the entorhinal cortex in schizophrenia. , 1991, Archives of general psychiatry.

[108]  E. Fünfgeld Über anatomische Untersuchungen bei Dementia praecox mit besonderer Berücksichtigung des Thalamus opticus , 1925 .

[109]  James C. Ehrhardt,et al.  Subcortical and temporal structures in affective disorder and schizophrenia: A magnetic resonance imaging study , 1992, Biological Psychiatry.

[110]  J. Kleinman,et al.  A quantitative investigation of hippocampal pyramidal cell size, shape, and variability of orientation in schizophrenia. , 1989, Archives of general psychiatry.

[111]  J. Lieberman,et al.  Reduced temporal limbic structure volumes on magnetic resonance images in first episode schizophrenia , 1990, Psychiatry Research: Neuroimaging.

[112]  J. Lieberman,et al.  A VOLUMETRIC MRI STUDY OF LIMBIC STRUCTURES IN CHRONIC SCHIZOPHRENIA ‐ RELATIONSHIP TO PSYCHOPATHOLOGY , 1992, Clinical neuropharmacology.

[113]  T. Crow,et al.  The neuropathology of schizophrenia--a progress report. , 1987, British medical bulletin.

[114]  J. Zubin,et al.  Vulnerability--a new view of schizophrenia. , 1977, Journal of abnormal psychology.

[115]  T. Crow,et al.  Schizophrenia and the brain: a prospective clinico-neuropathological study , 1990, Psychological Medicine.

[116]  N. Newman,et al.  Paraneoplastic limbic encephalitis: Neuropsychiatric presentation , 1990, Biological Psychiatry.

[117]  M. Casanova 2. Astrocytosis and schizophrenia , 1991, Schizophrenia Research.

[118]  P. Stratta,et al.  Quantification of corpus callosum and ventricles in schizophrenia with nuclear magnetic resonance imaging: a pilot study. , 1989, The American journal of psychiatry.

[119]  Karl J. Friston,et al.  Patterns of Cerebral Blood Flow in Schizophrenia , 1992, British Journal of Psychiatry.

[120]  F. Benes,et al.  Myelination of cortical-hippocampal relays during late adolescence. , 1989, Schizophrenia bulletin.

[121]  D L Braff,et al.  Magnetic resonance imaging abnormalities in lenticular nuclei and cerebral cortex in schizophrenia. , 1991, Archives of general psychiatry.

[122]  D. Ingvar,et al.  ABNORMALITIES OF CEREBRAL BLOOD FLOW DISTRIBUTION IN PATIENTS WITH CHRONIC SCHIZOPHRENIA , 1974, Acta psychiatrica Scandinavica.

[123]  E. Alvord,et al.  CAVA SEPTI PELLUCIDI ET VERG Æ: THEIR NORMAL AND PATHOLOGICAL STATES , 1969 .

[124]  Tyrone D. Cannon,et al.  Fetal Neural Development and Adult Schizophrenia , 1991 .

[125]  R. Murray,et al.  The Genetics of Schizophrenia is the Genetics of Neurodevelopment , 1991, British Journal of Psychiatry.

[126]  C. Tamminga,et al.  Schizophrenia: Scientific Progress , 1989 .

[127]  R. Monroe Temporal Lobe Epilepsy, Mania and Schizophrenia and the Limbic System , 1986 .

[128]  M. Fisman The Brain Stem in Psychosis , 1975, British Journal of Psychiatry.

[129]  Glenn D. Rosen,et al.  Planum temporale asymmetry, reappraisal since Geschwind and Levitsky , 1987, Neuropsychologia.

[130]  D. Daly,et al.  Psychiatric symptoms associated with lesions of temporal lobe. , 1952, Journal of the American Medical Association.

[131]  N. Schmajuk Animal models for schizophrenia: the hippocampally lesioned animal. , 1987, Schizophrenia bulletin.

[132]  Mathew Rj,et al.  Midsagittal sections of the cerebellar vermis and fourth ventricle obtained with magnetic resonance imaging of schizophrenic patients. , 1985, The American journal of psychiatry.

[133]  Pathological cerebral blood blow and corpus callosum abnormalities in schizophrenia: Relations to EEG mapping and PET data , 1989, Psychiatry Research.

[134]  G. V. Hoesen,et al.  The parahippocampal gyrus: New observations regarding its cortical connections in the monkey , 1982, Trends in Neurosciences.

[135]  Monatsschrift für Psychiatrie und Neurologie , 1912 .

[136]  B. Pakkenberg,et al.  Pronounced reduction of total neuron number in mediodorsal thalamic nucleus and nucleus accumbens in schizophrenics. , 1990, Archives of general psychiatry.

[137]  N C Andreasen,et al.  Ventricular enlargement in schizophrenia: relationship to positive and negative symptoms. , 1982, The American journal of psychiatry.

[138]  N. Geschwind,et al.  Human Brain: Left-Right Asymmetries in Temporal Speech Region , 1968, Science.