Morphometric analysis of the cerebral expression of ATP-binding cassette transporter protein ABCB1 in chronic schizophrenia: Circumscribed deficits in the habenula

Bernstein, Hans‐Gert; Hildebrandt, Jens; Dobrowolny, Henrik; Steiner, Johann; Bogerts, Bernhard; Pahnke, Jens

doi:10.1016/j.schres.2016.02.036

Cited by 27 publications

(18 citation statements)

References 65 publications

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“…We found that the absolute volume of both the left and right Hb was smaller in the SCH patients, whereas the TIV was not significantly different between two groups. This finding is consistent with previous observations that compared with normal individuals, patients with SCH exhibited a higher proportion of epithalamic calcification (Sandyk, 1992 ) and lower capillary density in the bilateral Hb (Bernstein et al, 2016 ). The administration of antipsychotics for treating SCH has been shown to increase glucose metabolism in the LHb (Dedeurwaerdere et al, 2011 ), and these results further support our findings in the current study.…”

Section: Discussionsupporting

confidence: 93%

“…Interestingly, the above-mentioned trend was obvious only for the left Hb, which is consistent with a previous study showing that compared with the right Hb, the left Hb had more dramatic decreases in the quantity of ATP-binding cassette subfamily B member 1, which is involved in maintaining the steadiness of neural function in patients with SCH (Bernstein et al, 2016 ). The seemingly left-larger-than-right lateralized changes of the Hb volume may be due to the leftward lateralization of the globuspallidus in SCH (Okada et al, 2016 ), one of the most important upstream brain regions influencing Hb activity (Herkenham and Nauta, 1977 ).…”

Section: Discussionsupporting

confidence: 90%

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Altered Volume and Functional Connectivity of the Habenula in Schizophrenia

Zhang

Wang

Luan

et al. 2017

Front. Hum. Neurosci.

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The pathogenesis of schizophrenia (SCH) is associated with the dysfunction of monoamine neurotransmitters, the synthesis and release of which are mainly regulated by a key structure, the habenular (Hb) nucleus. However, little is known regarding whether SCH is associated with structural or functional alterations in the Hb. In this study, we combined structural and resting-state functional magnetic resonance imaging to investigate the changes in volume and functional connectivity of the Hb in 15 patients with SCH vs. 16 age- and gender-matched healthy controls (HCs). Morphologically, the absolute volume of the bilateral Hb was significantly lower in the SCH patients than in the HCs. Functionally, the bilateral Hb showed significantly enhanced functional connectivity with the left medial prefrontal cortex (mPFC) in the SCH patients. Additionally, the SCH patients exhibited increased functional connectivity of the left Hb with the left lingual gyrus and right inferior frontal gyrus (IFG). A further exploratory analysis revealed that the SCH patients showed increased functional connectivity between the right Hb and several subcortical regions related to dopaminergic pathways, including the left ventral striatum, caudate and putamen. Finally, the increased functional connectivity of the right Hb with the mPFC was positively correlated with the Brief Psychiatric Rating Scale (BPRS) scores in the patients. Together, these results suggest that the altered volume and functional connectivity of the Hb may be involved in the pathogenesis of SCH and thus that the Hb may serve as a potential target in developing new therapeutic strategies in SCH.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 90%

Altered Volume and Functional Connectivity of the Habenula in Schizophrenia

Zhang

Wang

Luan

et al. 2017

Front. Hum. Neurosci.

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“…32, 33 The most commonly used markers to identify microglia, such as HLA-DR and CD68, do not clearly distinguish between the different myeloid cells populations, 32, 34, 35 in particular microglia and macrophages. Although under general discussion within the field, 36 the blood–brain barrier is often hypothesized to be intact in patients with schizophrenia. 37 Therefore, the most likely explanation of increased number of myeloid cells demonstrated in this study is an increase in the number of microglia resulting from local expansion in the CNS.…”

Section: Discussionmentioning

confidence: 99%

Immune involvement in the pathogenesis of schizophrenia: a meta-analysis on postmortem brain studies

et al. 2017

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Although the precise pathogenesis of schizophrenia is unknown, genetic, biomarker and imaging studies suggest involvement of the immune system. In this study, we performed a systematic review and meta-analysis of studies investigating factors related to the immune system in postmortem brains of schizophrenia patients and healthy controls. Forty-one studies were included, reporting on 783 patients and 762 controls. We divided these studies into those investigating histological alterations of cellular composition and those assessing molecular parameters; meta-analyses were performed on both categories. Our pooled estimate on cellular level showed a significant increase in the density of microglia (P=0.0028) in the brains of schizophrenia patients compared with controls, albeit with substantial heterogeneity between studies. Meta-regression on brain regions demonstrated this increase was most consistently observed in the temporal cortex. Densities of macroglia (astrocytes and oligodendrocytes) did not differ significantly between schizophrenia patients and healthy controls. The results of postmortem histology are paralleled on the molecular level, where we observed an overall increase in expression of proinflammatory genes on transcript and protein level (P=0.0052) in patients, while anti-inflammatory gene expression levels were not different between schizophrenia and controls. The results of this meta-analysis strengthen the hypothesis that components of the immune system are involved in the pathogenesis of schizophrenia.

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“…Jungerius et al [87] found a weak but significant association between PIK3C2G gene and schizophrenia. Functional analysis of rare variants found in schizophrenia implicates a critical role of GIT1-PAK3 signaling in neuroplasticity [88]. Their study provided the first line of direct evidence suggesting that the CHRM5 gene, together with the CHRNA7 gene may be linked to schizophrenia [89].…”

Section: Experiments and Discussionmentioning

confidence: 99%

Integrating Imaging Genomic Data in the Quest for Biomarkers of Schizophrenia Disease

Deng¹,

Hu²,

Calhoun³

et al. 2018

IEEE/ACM Trans. Comput. Biol. and Bioinf.

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It's increasingly important but difficult to determine potential biomarkers of schizophrenia (SCZ) disease, owing to the complex pathophysiology of this disease. In this study, a network-fusion based framework was proposed to identify genetic biomarkers of the SCZ disease. A three-step feature selection was applied to single nucleotide polymorphisms (SNPs), DNA methylation, and functional magnetic resonance imaging (fMRI) data to select important features, which were then used to construct two gene networks in different states for the SNPs and DNA methylation data, respectively. Two health networks (one is for SNP data and the other is for DNA methylation data) were combined into one health network from which health minimum spanning trees (MSTs) were extracted. Two disease networks also followed the same procedures. Those genes with significant changes were determined as SCZ biomarkers by comparing MSTs in two different states and they were finally validated from five aspects. The effectiveness of the proposed discovery framework was also demonstrated by comparing with other network-based discovery methods. In summary, our approach provides a general framework for discovering gene biomarkers of the complex diseases by integrating imaging genomic data, which can be applied to the diagnosis of the complex diseases in the future.

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Morphometric analysis of the cerebral expression of ATP-binding cassette transporter protein ABCB1 in chronic schizophrenia: Circumscribed deficits in the habenula

Cited by 27 publications

References 65 publications

Altered Volume and Functional Connectivity of the Habenula in Schizophrenia

Altered Volume and Functional Connectivity of the Habenula in Schizophrenia

Immune involvement in the pathogenesis of schizophrenia: a meta-analysis on postmortem brain studies

Integrating Imaging Genomic Data in the Quest for Biomarkers of Schizophrenia Disease

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