Quantitative Cytoarchitectural Studies of the Cerebral Cortex of Schizophrenics

Beneš, Francine M.; Davidson, Jessica; Bird, Edward D.

doi:10.1001/archpsyc.1986.01800010033004

Cited by 489 publications

(207 citation statements)

References 22 publications

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“…(iii) The abnormality shows a degree of anatomical and neurochemical specificity; the medial temporal lobe (amygdala hippocampus, parahippocampal gyrus and related cortex) and the prefrontal cortex are directly implicated by virtue of their role in learning and memory and their high plastic potential (Haracz, 1985). The fact that these structures have been repeatedly implicated in schizophrenia by functional and structural imaging, cytoarchitectonic and histochemical studies (e.g., Benes et al, 1986;Deakin et al, 1989;Bogerts et al, 1991) is entirely consistent with the current formulation. (iv) It directly posits a mechanistic role for the ascending modulatory neurotransmitter systems that have been implicated in schizophrenia from both a pharmacological perspective (e.g., Dolan et al, 1995) and in terms of animal models (e.g., Sawaguchi and Goldman-Rakic, 1991).…”

Section: Explanatory Powersupporting

confidence: 77%

The disconnection hypothesis

Friston

1998

Schizophrenia Research

790

469

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This article reviews the disconnection hypothesis of schizophrenia and presents a mechanistic account of how dysfunctional integration among neuronal systems might arise. This neurobiological account is based on the central role played by neuronal plasticity in shaping the connections and the ensuing dynamics that underlie brain function. The particular hypothesis put forward here is that the pathophysiology of schizophrenia is expressed at the level of modulation of associative changes in synaptic efficacy; specifically the modulation of plasticity in those brain systems responsible for emotional learning and memory, in the post-natal period. This modulation is mediated by ascending neurotransmitter systems that: (i) have been implicated in schizophrenia; and (ii) are known to be involved in consolidating synaptic connections during learning. The proposed pathophysiology would translate, in functional terms, into a disruption of the reinforcement of adaptive behaviour that is consistent with the disintegrative aspects of schizophrenic neuropsychology.

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Section: Explanatory Powersupporting

confidence: 77%

The disconnection hypothesis

Friston

1998

Schizophrenia Research

790

469

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“…These are the same brain regions where neuropathological and neuroimaging abnormalities have been reported for disorders such as schizophrenia (29)(30)(31). While specific disease-related hypotheses will require more detailed anatomical studies, our results also imply that developmental stimulation or inhibition of dopamine receptor subtypes by drugs, both therapeutically and abusively, may result in profound pre-and postnatal changes in neuronal morphology and function.…”

supporting

confidence: 52%

Morphogenic potentials of D2, D3, and D4 dopamine receptors revealed in transfected neuronal cell lines.

Swarzenski

Tang

et al. 1994

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

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Molecular cloning studies have defined a family of dopamine D2-like receptors (D2, D3, and D4), which are the products of separate genes. Our previous work has shown that stimulation of dopamine D2-like receptors in cultures of fetal cortical neurons increases the extension and branching of neurites. To determine which D2-like receptors possess morphogenic potentials, a clonal mesencephalic cell line (MN9D) was transfected with D2, D3, or D4 receptor subtypes and treated with quinpirole, an agonist of D2-like receptors, and changes in morphological characteristics were quantitated. Stimulation of D2 receptors increased the number and branching of neurites with little effect on neurite extension; stimulation of D3 and D4 receptors increased the branching and extension of neurites. Similar results were found for primary mesencephalic cultures stimulated with quinpirole. These results suggest that the known D2-like receptors have specific developmental roles in regulating neuronal morphogenesis of dopaminergic pathways.The expression of neurotransmitters prior to the establishment of synaptic circuitry suggests they play a nonsynaptic role in development (1). Recent studies demonstrate that neurotransmitters expressed early are involved in regulating neuronal outgrowth and survival and thus have the potential to control the development of their own synaptogenesis and subsequent adult form. Such neurotrophic roles have been best documented for excitatory amino acids in the developing cortex (2, 3) or hippocampus (4, 5). However, acetylcholine (6), t-aminobutyric acid (7), serotonin (8, 9), and opioids (10) Living cells were photographed after 90-115 hr in culture by using phase-contrast microscopy (Nikon Diaphot) or a digital image-processing system (Image-1; Universal Imaging, Media, PA). Morphological characteristics of individual cells were quantitated at x 1600 by using a computerinterfaced drawing system with a digitizing light pad (Bioquant) as previously described (11,23). Without knowledge of the treatment condition, cells were measured consecutively over two to three dishes. A neurite was defined as a cell process arising from the soma; a neurite branch was defined as a bifurcation of a neurite; neurite length was defined as the distance from the soma to the tip of the longest branch; total neurite extent represented the combined lengths of all neurites and neurite branches per cell (23). Processes shorter than 5 ,um could not be reliably remeasured (23) and were excluded from morphometric analysis. All statistical analy§To whom reprint requests should be addressed. 649

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“…Abnormalities in cellular orientation, connectivity, receptor distribution and sensitivity, and neurotransmitter distribution, among other factors, are not detectable by MRI and have been previously reported (Benes et al, 1986(Benes et al, , 1991. However, a histological study reporting abnormalities in prefrontal areas did not find a significant difference between schizophrenic and control subjects in the cortical thickness of area 9 of the prefrontal cortex because the differences were not large enough to reach significance (Selemon et al, 1995).…”

Section: Discussionmentioning

confidence: 93%

Prefrontal cortex, negative symptoms, and schizophrenia: an MRI study

Wible

Anderson

Shenton

et al. 2001

Psychiatry Research: Neuroimaging

185

100

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The present study measured prefrontal cortical gray and white matter volume in chronic, male schizophrenic subjects who were characterized by a higher proportion of mixed or negative symptoms than previous patients that we have evaluated. Seventeen chronic male schizophrenic subjects and 17 male control subjects were matched on age and handedness. Regions of interest (ROI) were measured using high-resolution magnetic resonance (MR) acquisitions consisting of contiguous 1.5-mm slices of the entire brain. No significant differences were found between schizophrenic and control subjects in mean values for prefrontal gray matter volume in either hemisphere. However, right prefrontal white matter was significantly reduced in the schizophrenic group. In addition, right prefrontal gray matter volume was significantly correlated with right hippocampal volume in the schizophrenic, but not in the control group. Furthermore, an analysis in which the current data were combined with those from a previous study showed that schizophrenic subjects with high negative symptom scores had significantly smaller bilateral white matter volumes than those with low negative symptom scores. White matter was significantly reduced in the right hemisphere in this group of schizophrenic subjects. Prefrontal volumes were also associated with negative symptom severity and with volumes of medial-temporal lobe regions -two results that were also found previously in schizophrenic subjects with mostly positive symptoms. These results underscore the importance of temporal-prefrontal pathways in the symptomatology of schizophrenia, and they suggest an association between prefrontal abnormalities and negative symptoms.

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Quantitative Cytoarchitectural Studies of the Cerebral Cortex of Schizophrenics

Cited by 489 publications

References 22 publications

The disconnection hypothesis

The disconnection hypothesis

Morphogenic potentials of D2, D3, and D4 dopamine receptors revealed in transfected neuronal cell lines.

Prefrontal cortex, negative symptoms, and schizophrenia: an MRI study

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