Fornix Integrity and Hippocampal Volume in Male Schizophrenic Patients

Kuroki, Noriomi; Kubicki, Marek; Nestor, Paul G.; Salisbury, Dean F.; Park, Hae Jeong; Levitt, James J.; Woolston, Sophie; Frumin, Melissa; Niznikiewicz, Margaret; Westin, Carl‐Fredrik; Maier, Stephan E.; McCarley, Robert W.; Shenton, Martha E.

doi:10.1016/j.biopsych.2005.09.021

Cited by 138 publications

(101 citation statements)

References 62 publications

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“…These microarray data and our light microscopic Wndings in the posterior part of the hippocampus are supported by in vivo diVusion tensor imaging (DTI) studies of white matter tracts of the fornix body and posterior part of the hippocampus in schizophrenia, showing decreased fractional anisotropy and supporting the hypothesis of functional dysconnectivity in schizophrenia [41,47,78,85]. Moreover, cognitive function such as verbal declarative memory is correlated with the fractional anisotropy of the hippocampus in schizophrenia [48].…”

Section: Discussionsupporting

confidence: 79%

“…Moreover, cognitive function such as verbal declarative memory is correlated with the fractional anisotropy of the hippocampus in schizophrenia [48]. This disruption of connectivity in this region could result in cognitive as well as clinical negative symptoms [28,47,56]. This is due to the fact that neuronal Wbers traversing the limbic pathways from the posterior part of the hippocampus are connected to prefrontal regions and pathways involved in higher cognition [25].…”

Section: Discussionmentioning

confidence: 99%

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Stereologic investigation of the posterior part of the hippocampus in schizophrenia

et al. 2008

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Structural magnetic resonance imaging and postmortem studies showed volume loss in the hippocampus in schizophrenia. The noted tissue reduction in the posterior section suggests that some cellular subfractions within this structure might be reduced in schizophrenia. To address this, we investigated numbers and densities of neurons, oligodendrocytes and astrocytes in the posterior hippocampal subregions in postmortem brains from ten patients with schizophrenia and ten matched controls using design-based stereology performed on Nissl-stained sections. Compared to the controls, the patients with schizophrenia showed a signiWcant decrease in the mean number of oligodendrocytes in the left and right CA4. This is the Wrst Wnding of reduced numbers of oligodendrocytes in CA4 of the posterior part of the hippocampus in schizophrenia. Our results are in line with earlier Wndings in the literature concerning decreased numbers of oligodendrocytes in the prefrontal cortex in schizophrenia. Our results may indicate disturbed connectivity of the CA4 of the posterior part of the hippocampus in schizophrenia and, thus, contribute to the growing number of studies showing the involvement of posterior hippocampal pathology in the pathophysiology of schizophrenia.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Stereologic investigation of the posterior part of the hippocampus in schizophrenia

et al. 2008

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“…Newer developments in neuroimaging techniques like diffusion tensor imaging (DTI) afforded the investigation of disturbances in connectivity and neuronal networks. DTI studies of white matter tracts of the fornix body and hippocampus in schizophrenia show decreased fractional anisotropy and support the hypothesis of structural and functional dysconnectivity [13][14][15][16] which is correlated with deficits in cognitive function, e.g. verbal declarative memory 17 .…”

Section: Neuronal Circuits Involved In Schizophreniasupporting

confidence: 66%

Estudos transcriptômicos no contexto da conectividade perturbada em esquizofrenia

Schmitt

Reich‐Erkelenz²,

Gebicke‐Härter

et al. 2012

Arch. Clin. Psychiatry (São Paulo)

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Schizophrenia is a severe neurobiological disease with genetic and environmental factors playing a role in the pathophysiology. Several brain regions have been implicated in the disease process and are connected in complex neuronal circuits. On the cellular and molecular level, affected connectivity between these regions, involving dysfunctional myelination of neuronal axons, as well as alterations on the synaptic level and energy metabolism of neurons leading to disturbances in synaptic plasticity are major findings in post-mortem studies. Microarray studies investigating genome-wide gene expression have contributed to the findings of alterations in complex pathways in relevant brain regions in schizophrenia. Moreover, first laser-capture microdissection studies allowed the investigation of gene expression in specific groups of neurons. However, it must be kept in mind that in post-mortem studies confounding effects of medication, mRNA quality as well as the capability of the brain for neuroplastic regenerative mechanisms in individuals with a lifetime history of schizophrenia may influence the complex pattern of alterations on the molecular level. Despite these limitations, hypothesis-free transcriptome studies in brain tissue from schizophrenia patients offer a unique possibility to learn more about underlying mechanisms, leading to new insights in the pathophysiology of the disease. A, et al. / Rev Psiq Clín. 2013;40(1):10-5 Keywords: Schizophrenia, gene expression, microarray, RT-PCR, in situ hybridization, brain regions. Schmitt ResumoEsquizofrenia é uma severa doença neurobiológica com fatores genéticos e ambientais desempenhando um papel na fisiopatologia. Diversas regiões cerebrais têm sido implicadas no processo da doença e estão conectadas em complexos circuitos neuronais. Nos níveis molecular e celular, a conectividade afetada entre essas regiões, envolvendo mielinização disfuncional dos axônios neuronais, bem como as alterações no nível sináptico e metabolismo energético levando a distúrbios na plasticidade sináptica, são os maiores achados em estudos post-mortem. Estudos de microarranjos investigando a expressão gênica contribuíram para os achados de alterações em vias complexas em regiões cerebrais relevantes na esquizofrenia. Além disso, estudos utilizando microdissecção e captura a laser permitiram a investigação da expressão gênica em grupos específicos de neurônios. Entretanto, deve ser mantido em mente que em estudos post-mortem, confusos efeitos de medicação, qualidade de RNAm, bem como capacidade de mecanismos regenerativos neuroplásticos do cérebro em indivíduos com história de vida de esquizofrenia, podem influenciar o complexo padrão de alterações no nível molecular. Apesar dessas limitações, estudos transcriptômicos livres de hipóteses em tecido cerebral de pacientes esquizofrênicos oferecem uma possibilidade única para aprender mais sobre os mecanismos subjacentes, levando a novas ópticas da fisiopatologia da doença. A, et al. / Rev Psiq Clín. 2013;40(1):10-5 Palavras-cha...

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“…Several additional regions beyond the callosal body have been implicated in chronic schizophrenia including SLF (Rotarska-Jagiela et al, 2009;Rowland et al, 2009;Seok et al, 2007;Shergill et al, 2007;Szeszko et al, 2008) DMRI study in severe chronic schizophrenia L Holleran et al Jagiela et al, 2009;Seal et al, 2008), UF (Burns et al, 2003;McIntosh et al, 2008;Miyata et al, 2010;Mori et al, 2007b;Seal et al, 2008), internal capsule (Buchsbaum et al, 1998;Lim et al, 1999), external capsule (Rotarska-Jagiela et al, 2009;Seal et al, 2008), cingulum (Kubicki et al, 2003;Mori et al, 2007b;Seok et al, 2007;Sun et al, 2003;Wang et al, 2004), fornix (Fitzsimmons et al, 2009;Kuroki et al, 2006), anterior commissure (Choi et al, 2011), arcuate fasciculus (Burns et al, 2003;Phillips et al, 2009), and cerebellar peduncles (Okugawa et al, 2006;Seok et al, 2007). Differences in RD are less examined, yet to date increases have been detected in the external capsule (Seal et al, 2008), in the left inferior temporal and left occipital lobe (Ashtari et al, 2007), in temporal WM (Koch et al, 2011), and in the middle cerebellar peduncle (Okugawa et al, 2006), and increased mean diffusivity has been detected in the splenium of the corpus callosum (Foong et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Altered Interhemispheric and Temporal Lobe White Matter Microstructural Organization in Severe Chronic Schizophrenia

Holleran

Ahmed

Anderson‐Schmidt

et al. 2013

Neuropsychopharmacol

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Diffusion MRI investigations in schizophrenia provide evidence of abnormal white matter (WM) microstructural organization as indicated by reduced fractional anisotropy (FA) primarily in interhemispheric, left frontal and temporal WM. Using tract-based spatial statistics (TBSS), we examined diffusion parameters in a sample of patients with severe chronic schizophrenia. Diffusion MRI data were acquired on 19 patients with chronic severe schizophrenia and 19 age-and gender-matched healthy controls using a 64 gradient direction sequence, (b ¼ 1300 s/mm 2 ) collected on a Siemens 1.5T MRI scanner. Diagnosis of schizophrenia was determined by Diagnostic and Statistical Manual for Mental Disorders 4th Edition (DSM-IV) Structured Clinical Interview for DSM disorder (SCID). Patients were treatment resistance, having failed to respond to at least two antipsychotic medications, and had prolonged periods of moderate to severe positive or negative symptoms. Analysis of diffusion parameters was carried out using TBSS. Individuals with chronic severe schizophrenia had significantly reduced FA with corresponding increased radial diffusivity in the genu, body, and splenium of the corpus callosum, the right posterior limb of the internal capsule, right external capsule, and the right temporal inferior longitudinal fasciculus. There were no voxels of significantly increased FA in patients compared with controls. A decrease in splenium FA was shown to be related to a longer illness duration. We detected widespread abnormal diffusivity properties in the callosal and temporal lobe WM regions in individuals with severe chronic schizophrenia who have not previously been exposed to clozapine. These deficits can be driven by a number of factors that are indistinguishable using in vivo diffusion-weighted imaging, but may be related to reduced axonal number or packing density, abnormal glial cell arrangement or function, and reduced myelin.

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Fornix Integrity and Hippocampal Volume in Male Schizophrenic Patients

Cited by 138 publications

References 62 publications

Stereologic investigation of the posterior part of the hippocampus in schizophrenia

Stereologic investigation of the posterior part of the hippocampus in schizophrenia

Estudos transcriptômicos no contexto da conectividade perturbada em esquizofrenia

Altered Interhemispheric and Temporal Lobe White Matter Microstructural Organization in Severe Chronic Schizophrenia

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