The neuropathology of schizophrenia. A critical review of the data and their interpretation.
TLDR
Functional imaging data indicate that the pathophysiology of schizophrenia reflects aberrant activity in, and integration of, the components of distributed circuits involving the prefrontal cortex, hippocampus and certain subcortical structures.Abstract:
Despite a hundred years' research, the neuropathology of schizophrenia remains obscure. However, neither can the null hypothesis be sustained--that it is a 'functional' psychosis, a disorder with no structural basis. A number of abnormalities have been identified and confirmed by meta-analysis, including ventricular enlargement and decreased cerebral (cortical and hippocampal) volume. These are characteristic of schizophrenia as a whole, rather than being restricted to a subtype, and are present in first-episode, unmedicated patients. There is considerable evidence for preferential involvement of the temporal lobe and moderate evidence for an alteration in normal cerebral asymmetries. There are several candidates for the histological and molecular correlates of the macroscopic features. The probable proximal explanation for decreased cortical volume is reduced neuropil and neuronal size, rather than a loss of neurons. These morphometric changes are in turn suggestive of alterations in synaptic, dendritic and axonal organization, a view supported by immunocytochemical and ultrastructural findings. Pathology in subcortical structures is not well established, apart from dorsal thalamic nuclei, which are smaller and contain fewer neurons. Other cytoarchitectural features of schizophrenia which are often discussed, notably entorhinal cortex heterotopias and hippocampal neuronal disarray, remain to be confirmed. The phenotype of the affected neuronal and synaptic populations is uncertain. A case can be made for impairment of hippocampal and corticocortical excitatory pathways, but in general the relationship between neurochemical findings (which centre upon dopamine, 5-hydroxytryptamine, glutamate and GABA systems) and the neuropathology of schizophrenia is unclear. Gliosis is not an intrinsic feature; its absence supports, but does not prove, the prevailing hypothesis that schizophrenia is a disorder of prenatal neurodevelopment. The cognitive impairment which frequently accompanies schizophrenia is not due to Alzheimer's disease or any other recognized neurodegenerative disorder. Its basis is unknown. Functional imaging data indicate that the pathophysiology of schizophrenia reflects aberrant activity in, and integration of, the components of distributed circuits involving the prefrontal cortex, hippocampus and certain subcortical structures. It is hypothesized that the neuropathological features represent the anatomical substrate of these functional abnormalities in neural connectivity. Investigation of this proposal is a goal of current neuropathological studies, which must also seek (i) to establish which of the recent histological findings are robust and cardinal, and (ii) to define the relationship of the pathological phenotype with the clinical syndrome, its neurochemistry and its pathogenesis.read more
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The Endophenotype Concept in Psychiatry: Etymology and Strategic Intentions
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A review of MRI findings in schizophrenia
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TL;DR: This review critically summarizes the neuropathology and genetics of schizophrenia, the relationship between them, and speculates on their functional convergence via an influence upon synaptic plasticity and the development and stabilization of cortical microcircuitry.
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Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia
Susan Whitfield-Gabrieli,Heidi W. Thermenos,Snezana Milanovic,Ming T. Tsuang,Stephen V. Faraone,Robert W. McCarley,Martha E. Shenton,Alan I. Green,Alfonso Nieto-Castanon,Peter S. LaViolette,Joanne Wojcik,John D. E. Gabrieli,Larry J. Seidman +12 more
TL;DR: Among patients, the magnitude of MPFC task suppression negatively correlated with default connectivity, suggesting an association between the hyperactivation and hyperconnectivity in schizophrenia.
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Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison.
Christos Pantelis,Christos Pantelis,Dennis Velakoulis,Dennis Velakoulis,Patrick D. McGorry,Stephen J. Wood,Stephen J. Wood,John Suckling,Lisa J. Phillips,Alison R. Yung,Edward T. Bullmore,Warrick J. Brewer,Warrick J. Brewer,Bridget Soulsby,Bridget Soulsby,Patricia Desmond,Philip McGuire +16 more
TL;DR: Some of the grey-matter abnormalities associated with psychotic disorders predate the onset of frank symptoms, whereas others appear in association with their first expression.
References
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Recent advances in the phencyclidine model of schizophrenia.
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