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      Increased Cerebral Water Content in Hemodialysis Patients

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          Abstract

          Little information is available on the impact of hemodialysis on cerebral water homeostasis and its distribution in chronic kidney disease. We used a neuropsychological test battery, structural magnetic resonance imaging (MRI) and a novel technique for quantitative measurement of localized water content using 3T MRI to investigate ten hemodialysis patients (HD) on a dialysis-free day and after hemodialysis (2.4±2.2 hours), and a matched healthy control group with the same time interval. Neuropsychological testing revealed mainly attentional and executive cognitive dysfunction in HD. Voxel-based-morphometry showed only marginal alterations in the right inferior medial temporal lobe white matter in HD compared to controls. Marked increases in global brain water content were found in the white matter, specifically in parietal areas, in HD patients compared to controls. Although the global water content in the gray matter did not differ between the two groups, regional increases of brain water content in particular in parieto-temporal gray matter areas were observed in HD patients. No relevant brain hydration changes were revealed before and after hemodialysis. Whereas longer duration of dialysis vintage was associated with increased water content in parieto-temporal-occipital regions, lower intradialytic weight changes were negatively correlated with brain water content in these areas in HD patients. Worse cognitive performance on an attention task correlated with increased hydration in frontal white matter. In conclusion, long-term HD is associated with altered brain tissue water homeostasis mainly in parietal white matter regions, whereas the attentional domain in the cognitive dysfunction profile in HD could be linked to increased frontal white matter water content.

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          Most cited references35

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          Decreased volume of left and total anterior insular lobule in schizophrenia.

          The insula is anatomically situated to be critically involved in many bio-behavioral functions impaired in schizophrenia. Furthermore, its total volume has been shown to be reduced in schizophrenia. In the present study, we tested the hypothesis that in schizophrenia it is the anterior insular lobule (aINS(lbl)) rather than the posterior insular lobule (pINS(lbl)) that is smaller, given that limbic system abnormalities are central in schizophrenia and that the affiliations of the limbic system are principally with the anterior insular lobule. We used T1-weighted high resolution magnetic resonance imaging (MRI) to measure the cortical volume of the left and right anterior and posterior insular subdivisions. The subjects included a sample of healthy community controls (N=40) and chronic patients with DSM-III-R schizophrenia (N=41). We correlated insula volumes with positive and negative symptoms. We found that the total aINS(lbl), and the left aINS(lbl) in particular, were significantly volumetrically smaller in schizophrenia compared to controls, and significantly correlated with bizarre behavior. Given that the anterior insular lobule offers anatomic features that allow for MRI-based morphometric analysis, namely its central and circular sulci, this brain structure provides a useful model to test hypotheses regarding genotype-phenotype relationships in schizophrenia using the anterior insular lobule as a candidate endophenotype.
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            Structural brain magnetic resonance imaging of limbic and thalamic volumes in pediatric bipolar disorder.

            Youths with bipolar disorder are ideal for studying illness pathophysiology given their early presentation, lack of extended treatment, and high genetic loading. Adult bipolar disorder MRI studies have focused increasingly on limbic structures and the thalamus because of their role in mood and cognition. On the basis of adult studies, the authors hypothesized a priori that youths with bipolar disorder would have amygdalar, hippocampal, and thalamic volume abnormalities. Forty-three youths 6-16 years of age with DSM-IV bipolar disorder (23 male, 20 female) and 20 healthy comparison subjects (12 male, eight female) similar in age and sex underwent structured and clinical interviews, neurological examination, and cognitive testing. Differences in limbic and thalamic brain volumes, on the logarithmic scale, were tested using a two-way (diagnosis and sex) univariate analysis of variance, with total cerebral volume and age controlled. The subjects with bipolar disorder had smaller hippocampal volumes. Further analysis revealed that this effect was driven predominantly by the female bipolar disorder subjects. In addition, both male and female youths with bipolar disorder had significantly smaller cerebral volumes. No significant hemispheric effects were seen. These findings support the hypothesis that the limbic system, in particular the hippocampus, may be involved in the pathophysiology of pediatric bipolar disorder. While this report may represent the largest MRI study of pediatric bipolar disorder to date, more work is needed to confirm these findings and to determine if they are unique to pediatric bipolar disorder.
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              Hypothalamic abnormalities in schizophrenia: sex effects and genetic vulnerability.

              This is a unique hypothalamic magnetic resonance imaging (MRI) study in schizophrenia, an important region in the limbic system. We hypothesized abnormal volumetric increases, with greater severity in multiplex families (more than one ill member) compared with simplex families (one ill). We tested the hypothesis that normal hypothalamic sexual dimorphism is disrupted in schizophrenia. Eighty-eight DSM-III-R schizophrenia cases (40 simplex and 48 multiplex), 43 first-degree nonpsychotic relatives, and 48 normal comparisons systematically were compared. A 1.5-Tesla General Electric scanner was used to acquire structural MRI scans, and contiguous 3.1-mm slices were used to segment anterior and posterior hypothalamus. General linear model for correlated data and generalized estimating equations were used to compare cases, relatives, and controls on right and left hypothalamus, controlled for age, sex, and total cerebral volume. Spearman's correlations of hypothalamic volumes with anxiety were calculated to begin to examine arousal correlates with structural abnormalities. Findings demonstrated significantly increased hypothalamic volume in cases and nonpsychotic relatives, particularly in regions of paraventricular and mammillary body nuclei, respectively. This increase was linear from simplex to multiplex cases, was positively correlated with anxiety, and had a greater propensity in women. Findings suggest important implications for understanding genetic vulnerability of schizophrenia and the high rate of endocrine abnormalities.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                31 March 2015
                2015
                : 10
                : 3
                : e0122188
                Affiliations
                [1 ]Department of Neurology, RWTH Aachen University Hospital, Germany
                [2 ]Institute of Neuroscience and Medicine (INM-4), Research Centre Jülich GmbH, Jülich, Germany
                [3 ]Jülich Aachen Research Alliance (JARA)—Translational Brain Medicine, Jülich and Aachen, Germany
                [4 ]KfH Kuratorium für Dialyse und Nierentransplantation e.V., Stolberg, Germany
                [5 ]Department of Internal Medicine, St.-Antonius-Hospital Eschweiler, Eschweiler, Germany
                [6 ]Dialysezentrum Aachen, Praxis und Dialyse, Aachen, Germany
                [7 ]Division of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany
                West China Hospital of Sichuan University, CHINA
                Author notes

                Competing Interests: The authors have the following interests. This study is partly supported by the Helmholtz Alliance ICEMED. Thilo Krüger and Frank Eitner are now employed by Bayer Pharma AG. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

                Conceived and designed the experiments: KR NJS JBS ZA AC. Performed the experiments: ZA AC SM KR. Analyzed the data: ZA AC KR FTR. Contributed reagents/materials/analysis tools: ZA VG SM JF BH RDF AV TK FE TG KR. Wrote the paper: KR ZA AC. Revision of manuscript: KR ZA AC VG FTR SM BH RDF AV TK FE TG JBS JF NJS.

                [¤a]

                Current address: Bayer Pharma AG, Global Drug Discovery, Kidney Diseases Research, Wuppertal, Germany

                [¤b]

                Current address: Department of Internal Medicine, Dresden-Friedreichstadt Hospital, Dresden, Germany

                Article
                PONE-D-14-35319
                10.1371/journal.pone.0122188
                4380497
                25826269
                798804e4-4b8e-4b1c-a408-8115889bcff8
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 6 August 2014
                : 10 February 2015
                Page count
                Figures: 3, Tables: 3, Pages: 18
                Funding
                Sources of support: This work was supported in part by the Excellence Initiative of the German Research Foundation [DFG ZUK32/1] and the German Federal Ministry of Education and Research [BMBF 01GQ1402] to KR; and by a PhD fellowship (SFRH/BD/65743 2009) from the Fundação para a Ciência e Tecnologia (FCT), financed by the POPH – QREN Program to ASC. NJS and JBS were in part funded by the Helmholtz Alliance ICEMED - Imaging and Curing Environmental Metabolic Diseases [HA-314], through the Initiative and Network Fund of the Helmholtz Association. The sponsors had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. Bayer Pharma AG provided support for the authors TK and FE, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper and its Supporting Information files. Nevertheless, the correspondence author Dr. Kathrin Reetz can be contacted at kreetz@ 123456ukaachen.de for further questions.

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