Disruption of hippocampal connectivity in children and adolescents with schizophrenia — A voxel-based diffusion tensor imaging study☆

White, Tonya; Kendi, Ayşe Tuba Karagülle; Lehericy, Stéphane; Kendi, Mustafa; Karatekin, Canan; Guimaraes, A T L; Davenport, Nicholas D.; Schulz, S. Charles; Lim, Kelvin O.

doi:10.1016/j.schres.2006.09.032

Cited by 95 publications

(71 citation statements)

References 44 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%

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%

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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“…This is not the first study pointing to altered diffusion parameters in the thalamus or thalamocortical pathways. DTI findings supporting altered integrity of thalamocortical connectivity in schizophrenia include controversial alterations of fractional anisotropy in the anterior limb of the internal capsule (ALIC) Kubicki et al, 2005;Mamah et al, 2010;Sprooten et al, 2009;Sussmann et al, 2009;Zhang et al, 2010;Zhou et al, 2008, but see Ashtari et al, 2007;Kito et al, 2009;Kyriakopoulos et al, 2008;Szeszko et al, 2005;White et al, 2007 for negative findings in younger individuals and Beasley et al, 2009 for lack of evidence of myelin abnormalities post-mortem), of the tracts connecting to the LPFC (Kim et al, 2008;Oh et al, 2009) and altered FA (Hashimoto et al, 2009) or mean diffusivity in the thalamus itself (Agarwal et al, 2008;Rose et al, 2006;Spoletini et al, 2011). Kim et al (2007) have performed a similar DTI study, with an identical a-priori hypothesis, but found only differences in the thalamic CDR defined by connectivity to the orbitofrontal, parietal, and medial prefrontal cortices.…”

Section: Discussionmentioning

confidence: 99%

Investigation of Anatomical Thalamo-Cortical Connectivity and fMRI Activation in Schizophrenia

Marenco

Stein

Savostyanova

et al. 2011

Neuropsychopharmacol

143

101

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The purpose of this study was to examine measures of anatomical connectivity between the thalamus and lateral prefrontal cortex (LPFC) in schizophrenia and to assess their functional implications. We measured thalamocortical connectivity with diffusion tensor imaging (DTI) and probabilistic tractography in 15 patients with schizophrenia and 22 age-and sex-matched controls. The relationship between thalamocortical connectivity and prefrontal cortical blood-oxygenation-level-dependent (BOLD) functional activity as well as behavioral performance during working memory was examined in a subsample of 9 patients and 18 controls. Compared with controls, schizophrenia patients showed reduced total connectivity of the thalamus to only one of six cortical regions, the LPFC. The size of the thalamic region with at least 25% of model fibers reaching the LPFC was also reduced in patients compared with controls. The total thalamocortical connectivity to the LPFC predicted working memory task performance and also correlated with LPFC BOLD activation. Notably, the correlation with BOLD activation was accentuated in patients as compared with controls in the ventral LPFC. These results suggest that thalamocortical connectivity to the LPFC is altered in schizophrenia with functional consequences on working memory processing in LPFC.

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Disruption of hippocampal connectivity in children and adolescents with schizophrenia — A voxel-based diffusion tensor imaging study☆

Cited by 95 publications

References 44 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

Investigation of Anatomical Thalamo-Cortical Connectivity and fMRI Activation in Schizophrenia

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