Cerebellar morphology in chronic schizophrenic patients: A controlled computed tomography study

Dewan, Mantosh; Pandurangi, Anand K.; Lee, Seungho Howard; Ramachandran, Tarakad S.; Levy, Benjamin F.; Boucher, M F; Yozawitz, Allan; Major, Leslie F.

doi:10.1016/0165-1781(83)90108-7

Cited by 56 publications

(22 citation statements)

References 23 publications

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“…In their early studies, Weinberger and colleagues (1980) reported anterior vermal atrophy accompanied by Purkinje and granule cell loss, thus resulting in thinning of the granular and molecular layers (Martin and Albers, 1995, for review). These early post mortem findings are consistent with reports derived from in vivo brain imaging research confirming vermal atrophy by computerised tomography (e.g., Weinberger et al, 1979;Heath et al, 1979;Lippmann et al, 1982;Dewan et al, 1983) and magnetic resonance imaging (MRI; e.g., Rossi et al, 1993;Nopoulos et al, 1999;Volz et al, 2000;Ichimiya et al, 2001;Loeber et al, 2001;Joyal et al, 2004;Okugawa et al, 2002Okugawa et al, , 2003Okugawa et al, , 2007. More recent reports also suggest an altered proportional relationship of vermal grey to white matter in schizophrenia (e.g., Lawyer et al, 2009).…”

Section: Introductionsupporting

confidence: 79%

Cerebellar grey matter deficits in first-episode schizophrenia mapped using cortical pattern matching

et al. 2010

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Section: Introductionsupporting

confidence: 79%

Cerebellar grey matter deficits in first-episode schizophrenia mapped using cortical pattern matching

et al. 2010

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“…Another study (25) reported decreased cerebellar Purkinje neuron size in the superior vermis of elderly SZ patients. Atrophy of the anterior cerebellar vermis was initially reported by Weinberger et al (26) and subsequently confirmed by others (27)(28)(29).…”

Section: Discussionmentioning

confidence: 56%

Lower number of cerebellar Purkinje neurons in psychosis is associated with reduced reelin expression

Maloku

Covelo

Hanbauer

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Reelin is an extracellular matrix protein synthesized in cerebellar granule cells that plays an important role in Purkinje cell positioning during cerebellar development and in modulating adult synaptic function. In the cerebellum of schizophrenia (SZ) and bipolar (BP) disorder patients, there is a marked decrease (≈50%) of reelin expression. In this study we measured Purkinje neuron density in the Purkinje cell layer of cerebella of 13 SZ and 17 BP disorder patients from the McLean 66 Cohort Collection, Harvard Brain Tissue Resource Center. The mean number of Purkinje neurons (linear density, neurons per millimeter) was 20% lower in SZ and BP disorder patients compared with nonpsychiatric subjects (NPS; n = 24). This decrease of Purkinje neuron linear density was unrelated to postmortem interval, pH, drugs of abuse, or to the presence, dose, or duration of antipsychotic medications. A comparative study in the cerebella of heterozygous reeler mice (HRM), in which reelin expression is downregulated by ≈50%, showed a significant loss in the number of Purkinje cells in HRM (10-15%) compared with age-matched (3-9 months) wild-type mice. This finding suggests that lack of reelin impairs GABAergic Purkinje neuron expression and/or positioning during cerebellar development.A number of behavioral, neuropathologic, neuroimaging, and neurochemical studies suggest that the cerebellum may be defective in schizophrenia (SZ) (for a review see ref. 1). We (2, 3) and others (4) have reported that cerebella from SZ and bipolar (BP) disorder patients exhibit a 50% decrease in the expression of glutamic acid decarboxylase 67 (GAD67), which is a major GABA synthesizing enzyme present in cerebellar Purkinje neurons. This decrease suggests that these GABAergic principal neurons may be damaged. We also reported that in the cerebellar glutamatergic granule cells of SZ and BP disorder patients, there is a marked decrease of reelin mRNA levels (2, 3).A decrease of reelin levels in the cerebellum of SZ patients has been confirmed in other studies (4). In addition, the reduction of reelin mRNA is negatively correlated with the expression of the transcription factor semaphorin 3A in the cerebella of subjects with SZ (5).Reelin is a large (≈400 kDa) extracellular matrix protein synthesized by GABAergic interneurons in the telencephalon and by glutamatergic granule cells in the cerebellum (6-9). It is secreted extracellularly by constitutive mechanisms (10) and is believed to play a significant role in glutamate receptor homeostasis and spine formation in the adult brain (11)(12)(13)(14).The heterozygous reeler mouse (HRM), which expresses ≈50% of the amount of reelin present in brains of wild-type mice (WTM), displays certain behavioral and anatomic abnormalities reminiscent of those found in SZ patients. These include (i) prepulse inhibition deficits, which are a measure of sensory motor gating of the CNS (15), (ii) contextual fear conditioning deficits, which are a measure of a hippocampal/amygdaladependent function (16), and (iii) long-te...

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“…A common finding in the brain of schizophrenic patients is a reduced volume of limbic areas (Dewan et al, 1983;Lesch and Bogerts, 1984;Bogerts et al, 1985;Brown et al, 1986;Suddath et al, 1989;Falkai et al, 1988). Recently, Nelson et al (1998) conducted a meta-analysis of 18 magnetic resonance imaging (MRI) studies and concluded that schizophrenia is associated with a bilateral volumetric reduction of the hippocampus.…”

Section: Morphological Changes In Hippocampus and Related Areas Are Pmentioning

confidence: 94%

Hippocampal dysfunction in schizophrenia

Schmajuk

2001

Hippocampus

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Although not necessarily primary to the disease, hippocampal dysfunction in schizophrenia is suggested by morphological changes in the hippocampal formation reported in schizophrenic patients. This notion receives additional support from studies showing that 1) similar behavioral deficits are exhibited by both schizophrenics and animals with hippocampal lesions, and 2) some of these behavioral deficits are reversed by neuroleptics in both schizophrenics and lesioned animals. A brain-mapped neural network model is used to explain how some impairments in attention can be caused by hippocampal dysfunction and ameliorated by dopaminergic blockers.

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Cerebellar morphology in chronic schizophrenic patients: A controlled computed tomography study

Cited by 56 publications

References 23 publications

Cerebellar grey matter deficits in first-episode schizophrenia mapped using cortical pattern matching

Cerebellar grey matter deficits in first-episode schizophrenia mapped using cortical pattern matching

Lower number of cerebellar Purkinje neurons in psychosis is associated with reduced reelin expression

Hippocampal dysfunction in schizophrenia

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