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Polygenic risk scores, based on risk variants identified in genome-wide-association-studies (GWAS), explain a considerable portion of the heritability for schizophrenia (SZ) and bipolar disorder (BD). However, little is known about the combined effects of these variants, although polygenic neuroimaging has developed into a powerful tool of translational neuroscience. In this study, we used genome wide significant SZ risk variants to test the predictive capacity of the polygenic model and explored potential associations with white matter volume, a key candidate in imaging phenotype for psychotic disorders.
By calculating the combined additive schizophrenia risk of seven SNPs (significant hits from a recent schizophrenia GWAS study), we show that increased additive genetic risk for SZ was associated with reduced white matter volume in a group of participants (n = 94) consisting of healthy individuals, SZ first-degree relatives, SZ patients and BD patients. This effect was also seen in a second independent sample of healthy individuals (n = 89). We suggest that a moderate portion of variance (~4%) of white matter volume can be explained by the seven hits from the recent schizophrenia GWAS.
These results provide evidence for associations between cumulative genetic risk for schizophrenia and intermediate neuroimaging phenotypes in models of psychosis. Our work contributes to a growing body of literature suggesting that polygenic risk may help to explain white matter alterations associated with familial risk for psychosis.
Hintergrund: Aphasien gehören nicht zu den typischen klinischen Manifestationen lakunärer Hirninfarkte, sind jedoch im Rahmen seltener atypischer lakunärer Syndrome beschrieben.
Ziel der Arbeit: Beschreibung von Aphasiemustern und betroffener Fasertrakte bei lakunären Infarkten.
Material und Methoden: Fallserie von drei Patienten mit in der Magnetresonanztomographie nachgewiesenen lakunären Hirninfarkten und Aphasie. Identifikation betroffener Faserbahnen mittels Fasertraktographie der koregistrierten Schädigungsorte in Gehirnen zweier gesunder Probanden.
Ergebnisse: Radiologisch waren die Lakunen, die Aphasien hervorriefen, weit lateral im Marklager der linken Hemisphäre gelegen und befanden sich im Vergleich zu der Lakune eines nichtaphasischen Kontrollpatienten weiter rostrodorsal. Klinisch fand sich trotz Aussparung des Kortex, Thalamus und weiter Teile der Basalganglien eine leichte bis moderate nichtflüssige Aphasie mit syntaktischen Defiziten. In der Fasertraktographie zeigten die aphasischen im Vergleich zum nichtaphasischen Patienten eine stärkere Affektion der Fasern des linken Fasciculus arcuatus sowie eine Beteiligung des frontostriatalen und frontalen Aslant-Trakts.
Diskussion: Links lateral gelegene lakunäre Infarkte können durch Beteiligung sprachrelevanter Fasertrakte eine klinisch relevante Aphasie hervorrufen.
A potential clinical and etiological overlap between schizophrenia (SZ) and bipolar disorder (BD) has long been a subject of discussion. Imaging studies imply functional and structural alterations of the hippocampus in both diseases. Thus, imaging this core memory region could provide insight into the pathophysiology of these disorders and the associated cognitive deficits. To examine possible shared alterations in the hippocampus, we conducted a multi-modal assessment, including functional and structural imaging as well as neurobehavioral measures of memory performance in BD and SZ patients compared with healthy controls. We assessed episodic memory performance, using tests of verbal and visual learning (HVLT, BVMT) in three groups of participants: BD patients (n = 21), SZ patients (n = 21) and matched (age, gender, education) healthy control subjects (n = 21). In addition, we examined hippocampal resting state functional connectivity, hippocampal volume using voxel-based morphometry (VBM) and fibre integrity of hippocampal connections using diffusion tensor imaging (DTI). We found memory deficits, changes in functional connectivity within the hippocampal network as well as volumetric reductions and altered white matter fibre integrity across patient groups in comparison with controls. However, SZ patients when directly compared with BD patients were more severely affected in several of the assessed parameters (verbal learning, left hippocampal volumes, mean diffusivity of bilateral cingulum and right uncinated fasciculus). The results of our study suggest a graded expression of verbal learning deficits accompanied by structural alterations within the hippocampus in BD patients and SZ patients, with SZ patients being more strongly affected. Our findings imply that these two disorders may share some common pathophysiological mechanisms. The results could thus help to further advance and integrate current pathophysiological models of SZ and BD.
Purpose: In secondary progressive Multiple Sclerosis (SPMS), global neurodegeneration as a driver of disability gains importance in comparison to focal inflammatory processes. However, clinical MRI does not visualize changes of tissue composition outside MS lesions. This quantitative MRI (qMRI) study investigated cortical and deep gray matter (GM) proton density (PD) values and T1 relaxation times to explore their potential to assess neuronal damage and its relationship to clinical disability in SPMS.
Materials and Methods: 11 SPMS patients underwent quantitative T1 and PD mapping. Parameter values across the cerebral cortex and deep GM structures were compared with 11 healthy controls, and correlation with disability was investigated for regions exhibiting significant group differences.
Results: PD was increased in the whole GM, cerebral cortex, thalamus, putamen and pallidum. PD correlated with disability in the whole GM, cerebral cortex, putamen and pallidum. T1 relaxation time was prolonged and correlated with disability in the whole GM and cerebral cortex.
Conclusion: Our study suggests that the qMRI parameters GM PD (which likely indicates replacement of neural tissue with water) and cortical T1 (which reflects cortical damage including and beyond increased water content) are promising qMRI candidates for the assessment of disease status, and are related to disability in SPMS.
Alzheimeŕs disease (AD) represents the most prevalent neurodegenerative disorder that causes cognitive decline in old age. In its early stages, AD is associated with microstructural abnormalities in white matter (WM). In the current study, multiple indices of diffusion tensor imaging (DTI) and brain volumetric measurements were employed to comprehensively investigate the landscape of AD pathology. The sample comprised 58 individuals including cognitively normal subjects (controls), amnestic mild cognitive impairment (MCI) and AD patients. Relative to controls, both MCI and AD subjects showed widespread changes of anisotropic fraction (FA) in the corpus callosum, cingulate and uncinate fasciculus. Mean diffusivity and radial changes were also observed in AD patients in comparison with controls. After controlling for the gray matter atrophy the number of regions of significantly lower FA in AD patients relative to controls was decreased; nonetheless, unique areas of microstructural damage remained, e.g., the corpus callosum and uncinate fasciculus. Despite sample size limitations, the current results suggest that a combination of secondary and primary degeneration occurrs in MCI and AD, although the secondary degeneration appears to have a more critical role during the stages of disease involving dementia.