On Localizing Schizophrenic Neuropathology

Weinberger, Daniel R.

doi:10.1093/schbul/23.3.537

Cited by 32 publications

(12 citation statements)

References 21 publications

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“…In Brodmann's area 46, these findings are predominantly the result of a reduction in the interneuronal neuropil in layer II. In agreement with this observation, a cerebral ventricle dilation is present in a significant proportion of patients when schizophrenia is first diagnosed (8).…”

supporting

confidence: 81%

A decrease of reelin expression as a putative vulnerability factor in schizophrenia

Impagnatiello

Guidotti

Pesold

et al. 1998

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

696

500

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Postmortem prefrontal cortices (PFC) (Brodmann's areas 10 and 46), temporal cortices (Brodmann's area 22), hippocampi, caudate nuclei, and cerebella of schizophrenia patients and their matched nonpsychiatric subjects were compared for reelin (RELN) mRNA and reelin (RELN) protein content. In all of the brain areas studied, RELN and its mRNA were significantly reduced (Ϸ50%) in patients with schizophrenia; this decrease was similar in patients affected by undifferentiated or paranoid schizophrenia. To exclude possible artifacts caused by postmortem mRNA degradation, we measured the mRNAs in the same PFC extracts from ␥-aminobutyric acid (GABA) A receptors ␣ 1 and ␣ 5 and nicotinic acetylcholine receptor ␣ 7 subunits. Whereas the expression of the ␣ 7 nicotinic acetylcholine receptor subunit was normal, that of the ␣ 1 and ␣ 5 receptor subunits of GABA A was increased when schizophrenia was present. RELN mRNA was preferentially expressed in GABAergic interneurons of PFC, temporal cortex, hippocampus, and glutamatergic granule cells of cerebellum. A protein putatively functioning as an intracellular target for the signaltransduction cascade triggered by RELN protein released into the extracellular matrix is termed mouse disabled-1 (DAB1) and is expressed at comparable levels in the neuroplasm of the PFC and hippocampal pyramidal neurons, cerebellar Purkinje neurons of schizophrenia patients, and nonpsychiatric subjects; these three types of neurons do not express RELN protein. In the same samples of temporal cortex, we found a decrease in RELN protein of Ϸ50% but no changes in DAB1 protein expression. We also observed a large (up to 70%) decrease of GAD67 but only a small decrease of GAD65 protein content. These findings are interpreted within a neurodevelopmental͞vulnerability ''twohit'' model for the etiology of schizophrenia.

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supporting

confidence: 81%

A decrease of reelin expression as a putative vulnerability factor in schizophrenia

Impagnatiello

Guidotti

Pesold

et al. 1998

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

696

500

View full text Add to dashboard Cite

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“…Consistently, impaired facial expression recognition in schizophrenia patients relates to hypoactivation of distributed brain regions, including the inferior prefrontal cortex (27). Interestingly, following histological, anatomical, and functional arguments, authors have reported insular and amygdalar involvement in schizophrenia pathophysiology (43). Consistent with this, patients with schizophrenia are impaired in processing negative emotions from several sensorial modalities: facial expressions, prosody (20), and olfactory stimuli (44).…”

Section: Schizophrenia Patients Are Impaired In the Recognition Of Spmentioning

confidence: 84%

Facial Expression and Sex Recognition in Schizophrenia and Depression

et al. 2005

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Background: Impaired facial expression recognition in schizophrenia patients contributes to abnormal social functioning and may predict functional outcome in these patients. Facial expression processing involves individual neural networks that have been shown to malfunction in schizophrenia. Whether these patients have a selective deficit in facial expression recognition or a more global impairment in face processing remains controversial. Objective: To investigate whether patients with schizophrenia exhibit a selective impairment in facial emotional expression recognition, compared with patients with major depression and healthy control subjects. Methods: We studied performance in facial expression recognition and facial sex recognition paradigms, using original morphed faces, in a population with schizophrenia ( n = 29) and compared their scores with those of depression patients ( n = 20) and control subjects ( n = 20). Results: Schizophrenia patients achieved lower scores than both other groups in the expression recognition task, particularly in fear and disgust recognition. Sex recognition was unimpaired. Conclusion: Facial expression recognition is impaired in schizophrenia, whereas sex recognition is preserved, which highly suggests an abnormal processing of changeable facial features in this disease. A dysfunction of the top-down retrograde modulation coming from limbic and paralimbic structures on visual areas is hypothesized.

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“…3, 4, 5, 6, 7 Owing to the heterogeneous nature of the clinical symptoms, attempts to define a single underlying pathogenomic lesion have been unsuccessful. Various cortical and subcortical abnormalities have been associated with SZ, 8, 9, 10, 11, 12, 13, 14, 15 as well as alterations at the level of morphology, 16, 17 neurotransmitter systems 18, 19 and neurophysiology. 20, 21, 22, 23 Additionally, polymorphisms in multiple genes have been identified as risk factors for disease development through genome-wide association studies.…”

Section: Introductionmentioning

confidence: 99%

Altered gene expression in the dorsolateral prefrontal cortex of individuals with schizophrenia

et al. 2013

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The underlying pathology of schizophrenia (SZ) is likely as heterogeneous as its symptomatology. A variety of cortical and subcortical regions, including the prefrontal cortex, have been implicated in its pathology, and a number of genes have been identified as risk factors for disease development. We used in situ hybridization (ISH) to examine the expression of 58 genes in the dorsolateral prefrontal cortex (DLPFC, comprised of Brodmann areas 9 and 46) from 19 individuals with a premorbid diagnosis of SZ and 33 control individuals. Genes were selected based on: (1) previous identification as risk factors for SZ; (2) cell type markers or (3) laminar markers. Cell density and staining intensity were compared in the DLPFC, as well as separately in Brodmann areas 9 and 46. The expression patterns of a variety of genes, many of which are associated with the GABAergic system, were altered in SZ when compared with controls. Additional genes, including C8orf79 and NR4A2, showed alterations in cell density or staining intensity between the groups, highlighting the need for additional studies. Alterations were, with only a few exceptions, limited to Brodmann area 9, suggesting regional specificity of pathology in the DLPFC. Our results agree with previous studies on the GABAergic involvement in SZ, and suggest that areas 9 and 46 may be differentially affected in the disease. This study also highlights additional genes that may be altered in SZ, and indicates that these potentially interesting genes can be identified by ISH and high-throughput image analysis techniques.

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On Localizing Schizophrenic Neuropathology

Cited by 32 publications

References 21 publications

A decrease of reelin expression as a putative vulnerability factor in schizophrenia

A decrease of reelin expression as a putative vulnerability factor in schizophrenia

Facial Expression and Sex Recognition in Schizophrenia and Depression

Altered gene expression in the dorsolateral prefrontal cortex of individuals with schizophrenia

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