Regional Specificity in the Neuropathologic Substrates of Schizophrenia

Selemon, Lynn D.; Mrzljak, Jasna; Kleinman, Joel E.; Herman, Mary M.; Goldman‐Rakic, Patricia S.

doi:10.1001/archpsyc.60.1.69

Cited by 132 publications

(94 citation statements)

References 48 publications

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“…Indeed, the area where loss of gray matter density was most pronounced in our study (Brodmann area 9) is the same as was reported to be affected in earlier post-mortem studies (Selemon et al, 1995(Selemon et al, , 2003. Interestingly, in post-mortem studies it was suggested that there was tissue loss in Brodmann area 9 secondary to loss of neuropil, not to a diminished number of neuronal cells (Selemon et al, 1995(Selemon et al, , 2003. Possibly, this gray matter tissue loss in the frontal cortex is of a progressive, not a static nature.…”

Section: Discussionsupporting

confidence: 87%

“…The loss of brain tissue over time was localized in those brain areas that have been found to be affected in schizophrenia in cross-sectional neuroimaging Kubicki et al, 2002;Wright et al, 1999) as well as in post-mortem studies (Harrison, 1999). Indeed, the area where loss of gray matter density was most pronounced in our study (Brodmann area 9) is the same as was reported to be affected in earlier post-mortem studies (Selemon et al, 1995(Selemon et al, , 2003. Interestingly, in post-mortem studies it was suggested that there was tissue loss in Brodmann area 9 secondary to loss of neuropil, not to a diminished number of neuronal cells (Selemon et al, 1995(Selemon et al, , 2003.…”

Section: Discussionsupporting

confidence: 87%

“…Brain abnormalities have been hypothesized to be present in schizophrenia from the first delineation of the illness by Kraepelin, who postulated frontal-and temporal-lobe abnormalities to be central to the pathology of the disease (Kraepelin, 1919). Indeed, recent post-mortem (Selemon et al, 2003) as well as crosssectional region of interest and statistical parametric mapping studies Kubicki et al, 2002;Wright et al, 1999) have provided a considerable amount of evidence for brain volume abnormalities in frontal and temporal regions of the brain in schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Focal Gray Matter Changes in Schizophrenia across the Course of the Illness: A 5-Year Follow-Up Study

Haren

Pol

Schnack

et al. 2007

Neuropsychopharmacol

280

192

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Recent volumetric magnetic resonance imaging (MRI) studies have suggested brain volume changes in schizophrenia to be progressive in nature. Whether this is a global process or some brain areas are more affected than others is not known. In a 5-year longitudinal study, MRI whole brain scans were obtained from 96 patients with schizophrenia and 113 matched healthy comparison subjects. Changes over time in focal gray and white matter were measured with voxel-based morphometry throughout the brain. Over the 5-year interval, excessive decreases in gray matter density were found in patients in the left superior frontal area (Brodmann areas 9/10), left superior temporal gyrus (Brodmann area 42), right caudate nucleus, and right thalamus as compared to healthy individuals. Excessive gray matter density decrease in the superior frontal gray matter was related to increased number of hospitalizations, whereas a higher cumulative dose of clozapine and olanzapine during the scan interval was related to lesser decreases in this area. In conclusion, gray matter density loss occurs across the course of the illness in schizophrenia, predominantly in left frontal and temporal cortices. Moreover, the progression in left frontal density loss appears to be related to an increased number of psychotic episodes, with atypical antipsychotic medication attenuating these changes.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Focal Gray Matter Changes in Schizophrenia across the Course of the Illness: A 5-Year Follow-Up Study

Haren

Pol

Schnack

et al. 2007

Neuropsychopharmacol

280

192

View full text Add to dashboard Cite

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“…Several mechanisms of action have been proposed to explain the actions of MAM-E17 treatment, including a decrease in the levels of reelin and the 67 kDa form of glutamic acid decarboxylase (GAD67), as reported in schizophrenic patients, or by methylation of genes critical for neuronal development and plasticity [158][159][160] . Neuroanatomical findings reported in parallel for the MAM-E17 model and schizophrenic patients include morphological changes in the prefrontal cortex, parahippocampal cortex and hippocampus, reduced size of the medial dorsal thalamus and increased neuron packaging in the frontal lobe 114,[161][162][163][164][165] . A decrease in whole brain volume of MAM-E17 rats was mainly focussed on the prefrontal cortex, hippocampus and nucleus accumbens 120 .…”

Section: Interruption Of Neurogenesismentioning

confidence: 99%

Estudos traducionais de neuropsiquiatria e esquizofrenia: modelos animais genéticos e de neurodesenvolvimento

Gottschalk

Sarnyai

Guest

et al. 2012

Arch. Clin. Psychiatry (São Paulo)

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Psychiatric symptoms are subjective by nature and tend to overlap between different disorders. The modelling of a neuropsychiatric disorder therefore faces challenges because of missing knowledge of the fundamental pathophysiology and a lack of accurate diagnostics. Animal models are used to test hypotheses of aetiology and to represent the human condition as close as possible to increase our understanding of the disease and to evaluate new targets for drug discovery. In this review, genetic and neurodevelopmental animal models of schizophrenia are discussed with respect to behavioural and neurophysiological findings and their association with the clinical condition. Only specific animal models of schizophrenia may ultimately lead to novel diagnostic approaches and drug discovery. We argue that molecular biomarkers are important to improve animal to human translation since behavioural readouts lack the necessary specificity and reliability to assess human psychiatric symptoms.Gottschalk MG, et al. / Rev Psiq Clín. 2013;40(1):41-50 Keywords: Translational research, neuropsychiatry, genetic, neurodevelopment, animal model, schizophrenia. ResumoSintomas psiquiátricos são subjetivos por natureza e tendem a se sobrepor entre diferentes desordens. Sendo assim, a criação de modelos de uma desordem neuropsiquiátrica encontra desafios pela falta de conhecimento dos fundamentos da fisiopatologia e diagnósticos precisos. Modelos animais são usados para testar hipóteses de etiologia e para representar a condição humana tão próximo quanto possível para aumentar nosso entendimento da doença e avaliar novos alvos para a descoberta de drogas. Nesta revisão, modelos animais genéticos e de neurodesenvolvimento de esquizofrenia são discutidos com respeito a achados comportamentais e neurofisiológicos e sua associação com a condição clínica. Somente modelos animais específicos de esquizofrenia podem, em último caso, levar a novas abordagens diagnósticas e descoberta de drogas. Argumentamos que biomarcadores moleculares são importantes para aumentar a tradução de animais a humanos, já que faltam a especificidade e a fidelidade necessárias às leituras comportamentais para avaliar sintomas psiquiátricos humanos.Gottschalk MG, et al. / Rev Psiq Clín. 2013;40(1):41-50

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“…Although neuron loss is reported in the thalamus (Thune and Pakkenberg 2000), there appears to be no net loss of neurons in the cerebral cortex; thus, decreased cortical thickness in schizophrenia is concomitant with increased neuronal density (Selemon et al 1995;Thune and Pakkenberg 2000). Moreover this increased neuronal density, interpreted as a decrease in neuropil, is observed in prefrontal and occipital regions but not in the ventral lateral frontal cortex (Selemon et al 2003).…”

Section: Introductionmentioning

confidence: 99%

A Neurobehavioral Systems Analysis of Adult Rats Exposed to Methylazoxymethanol Acetate on E17: Implications for the Neuropathology of Schizophrenia

Moore

Jentsch

Ghajarnia

et al. 2006

Biological Psychiatry

320

405

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Background-As a test of plausibility for the hypothesis that schizophrenia can result from abnormal brain, especially cerebral cortical, development, these studies examined whether, in the rat, disruption of brain development initiated on embryonic day (E) 17, using the methylating agent methylazoxymethanol acetate (MAM), leads to a schizophrenia-relevant pattern of neural and behavioral pathology. Specifically, we tested whether this manipulation leads to disruptions of frontal and limbic corticostriatal circuit function, while producing schizophrenia-like, regiondependent reductions in gray matter in cortex and thalamus.

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Regional Specificity in the Neuropathologic Substrates of Schizophrenia

Cited by 132 publications

References 48 publications

Focal Gray Matter Changes in Schizophrenia across the Course of the Illness: A 5-Year Follow-Up Study

Focal Gray Matter Changes in Schizophrenia across the Course of the Illness: A 5-Year Follow-Up Study

Estudos traducionais de neuropsiquiatria e esquizofrenia: modelos animais genéticos e de neurodesenvolvimento

A Neurobehavioral Systems Analysis of Adult Rats Exposed to Methylazoxymethanol Acetate on E17: Implications for the Neuropathology of Schizophrenia

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