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  • 1
    Abstract: Neurological disorders often occur because of failure of proper brain development and/or appropriate maintenance of neuronal circuits. In order to understand roles of causative factors (e.g. genes, cell types) in disease development, generation of solid animal models has been one of straight-forward approaches. Recent next generation sequencing studies on human patient-derived clinical samples have identified various types of recurrent mutations in individual neurological diseases. While these discoveries have prompted us to evaluate impact of mutated genes on these neurological diseases, a feasible but flexible genome editing tool had remained to be developed. An advance of genome editing technology using the clustered regularly interspaced short palindromic repeats (CRISPR) with the CRISPR-associated protein (Cas) offers us a tremendous potential to create a variety of mutations in the cell, leading to "next generation" disease models carrying disease-associated mutations. We will here review recent progress of CRISPR-based brain disease modeling studies and discuss future requirement to tackle current difficulties in usage of these technologies.
    Type of Publication: Journal article published
    PubMed ID: 28536069
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  • 2
    Keywords: VOLUME ; MRI ; BRAIN MORPHOLOGY ; METAANALYSIS ; SENSORIMOTOR CORTEX ; psychosis ; COGNITIVE FUNCTION ; 1ST-EPISODE SCHIZOPHRENIA ; GREY-MATTER ; FUNCTIONAL TOPOGRAPHY
    Abstract: BACKGROUND: Previous structural neuroimaging studies linked cerebellar deficits to neurological soft signs (NSS) in schizophrenia. However, no studies employed a methodology specifically designed to assess cerebellar morphology. In this study, we evaluated the relationship between NSS levels and abnormalities of the human cerebellum in patients with recent-onset schizophrenia and healthy individuals using an exclusive cerebellar atlas. METHODS: A group of 26 patients with recent-onset schizophrenia and 26 healthy controls were included. All participants underwent a high-resolution T1-weighted MRI scan on a 3 Tesla scanner. We used a voxel-based morphometry (VBM) approach utilizing the Spatially Unbiased Infratentorial (SUIT) toolbox to provide an optimized and fine-grained exploration of cerebellar structural alterations associated with NSS. RESULTS: Compared with healthy controls, patients had significantly smaller cerebellar volumes for both hemispheres. In the patients' group, we identified a significant negative correlation between NSS levels and gray matter volume in the left lobule VI and the right lobule VIIa, corrected for multiple comparisons. Further, NSS performance was significantly associated with white matter volume in the left midbrain and corpus medullare and the right lobule VIIa. In contrast, no significant associations between NSS scores and cerebellar subregions in healthy subjects arose. CONCLUSION: Our results demonstrate the benefits of SUIT when investigating cerebellar correlates of NSS. These results support the view that distinct parts of sensorimotor and cognitive cerebellum play an important role in the pathogenesis of NSS in schizophrenia.
    Type of Publication: Journal article published
    PubMed ID: 25640318
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  • 3
    Abstract: Electroconvulsive therapy (ECT) is remarkably effective in severe major depressive disorder (MDD). Growing evidence has accumulated for brain structural and functional changes in response to ECT, primarily within cortico-limbic regions that have been considered in current neurobiological models of MDD. Despite increasing evidence for important cerebellar contributions to affective, cognitive and attentional processes, investigations on cerebellar effects of ECT in depression are yet lacking. In this study, using cerebellum-optimized voxel-based analysis methods, we investigated cerebellar volume in 12 MDD patients who received right-sided unilateral ECT. 16 healthy controls (HC) were included. Structural MRI data was acquired before and after ECT and controls were scanned once. Baseline structural differences in MDD compared to HC were located within the "cognitive cerebellum" and remained unchanged with intervention. ECT led to gray matter volume increase of left cerebellar area VIIa crus I, a region ascribed to the "affective/limbic cerebellum". The effects of ECT on cerebellar structure correlated with overall symptom relief. These findings provide preliminary evidence that structural change of the cerebellum in response to ECT may be related to the treatment's antidepressant effects.
    Type of Publication: Journal article published
    PubMed ID: 27665684
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