A review of MRI findings in schizophrenia

Basal ganglia and cerebellar loops: motor and cognitive circuits.

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.

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The neuropathology of schizophrenia. A critical review of the data and their interpretation.

http://psych.colorado.edu/~kimlab/middleton.strick.BrainCog.2000.pdf

Basal Ganglia Output and Cognition: Evidence from Anatomical, Behavioral, and Clinical Studies

Epidemiological and anatomical studies support the theory that disturbances of brain development may play a contributory role in the etiology of schizophrenia. Anatomical findings suggest that the normal pattern of neuronal migration during development of the cerebral cortex may be affected in the brains of schizophrenics, with the implication that cortical connectivity and associative function will be disrupted. In the present investigation in matched schizophrenic and control brains, we examined a particular population of neurons found in the prefrontal cortex and underlying white matter and characterized by histochemical staining for the enzyme nicotinamide-adenine dinucleotide phosphate-diaphorase. In normal brains, these neurons are found in highest numbers in the white matter immediately deep to layer VI of the cortex where they remain from the subplate, an early formed, but transitory structure that plays a key role in cortical development and connection formation. The dorsolateral prefrontal area of schizophrenics showed a significant decline in nicotinamide-adenine dinucleotide phosphate-diaphorase neurons in the superficial white matter and in the overlying cortex but a significant increase in these neurons in white matter deeper than 3 mm from the cortex. These findings are consistent with a disturbance of the subplate during development in which the normal pattern of programmed cell death is compromised and accompanied by a defect in the normal orderly migration of neurons toward the cortical plate. These are likely to have serious consequences for the establishment of a normal pattern of cortical connections leading to a potential breakdown of frontal lobe function in schizophrenics.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/496093/archpsyc_50_3_001.pdf

Altered Distribution of Nicotinamide-Adenine Dinucleotide Phosphate—Diaphorase Cells in Frontal Lobe of Schizophrenics Implies Disturbances of Cortical Development

Cortex, white matter, and basal ganglia in schizophrenia: A volumetric postmortem study

Volumetry of the parahippocampal gyrus was performed applying stereological methods. No difference was found comparing 18 schizophrenic brains with 18 sex- and age-matched controls. Variable sulcal pattern may contribute to inconsistency with previous findings.

Morphometry of the parahippocampal gyrus in schizophrenics and controls. Some anatomical considerations

In a quantitative study on thick frozen sections stained by the Gallyas’ silver impregnation method neurofibrillary tangles (NFT), neuritic plaques (NP) and neuropil threads (NT) in the entorhinal as well as transentorhinal area (Braak and Braak, 1985) have been evaluated. The amount of NT exceeded by far that of NFT and NP.

Y. L. Heinsen

Papers

Cortex, white matter, and basal ganglia in schizophrenia: A volumetric postmortem study

Morphometry of the parahippocampal gyrus in schizophrenics and controls. Some anatomical considerations

Quantitative investigations of presenile and senile changes of the human entorhinal region

Quantitative investigations in thick frozen sections stained with Gallyas' silver impregnation for the demonstration of Alzheimer changes