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  1. Article ; Online: Opposing brain signatures of sleep in task-based and resting-state conditions

    Mohamed Abdelhack / Peter Zhukovsky / Milos Milic / Shreyas Harita / Michael Wainberg / Shreejoy J. Tripathy / John D. Griffiths / Sean L. Hill / Daniel Felsky

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 14

    Abstract: Abstract Sleep and depression have a complex, bidirectional relationship, with sleep-associated alterations in brain dynamics and structure impacting a range of symptoms and cognitive abilities. Previous work describing these relationships has provided ... ...

    Abstract Abstract Sleep and depression have a complex, bidirectional relationship, with sleep-associated alterations in brain dynamics and structure impacting a range of symptoms and cognitive abilities. Previous work describing these relationships has provided an incomplete picture by investigating only one or two types of sleep measures, depression, or neuroimaging modalities in parallel. We analyze the correlations between brainwide neural signatures of sleep, cognition, and depression in task and resting-state data from over 30,000 individuals from the UK Biobank and Human Connectome Project. Neural signatures of insomnia and depression are negatively correlated with those of sleep duration measured by accelerometer in the task condition but positively correlated in the resting-state condition. Our results show that resting-state neural signatures of insomnia and depression resemble that of rested wakefulness. This is further supported by our finding of hypoconnectivity in task but hyperconnectivity in resting-state data in association with insomnia and depression. These observations dispute conventional assumptions about the neurofunctional manifestations of hyper- and hypo-somnia, and may explain inconsistent findings in the literature.
    Keywords Science ; Q
    Subject code 150
    Language English
    Publishing date 2023-12-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Association of accelerometer-derived sleep measures with lifetime psychiatric diagnoses

    Michael Wainberg / Samuel E Jones / Lindsay Melhuish Beaupre / Sean L Hill / Daniel Felsky / Manuel A Rivas / Andrew S P Lim / Hanna M Ollila / Shreejoy J Tripathy

    PLoS Medicine, Vol 18, Iss 10, p e

    A cross-sectional study of 89,205 participants from the UK Biobank.

    2021  Volume 1003782

    Abstract: Background Sleep problems are both symptoms of and modifiable risk factors for many psychiatric disorders. Wrist-worn accelerometers enable objective measurement of sleep at scale. Here, we aimed to examine the association of accelerometer-derived sleep ... ...

    Abstract Background Sleep problems are both symptoms of and modifiable risk factors for many psychiatric disorders. Wrist-worn accelerometers enable objective measurement of sleep at scale. Here, we aimed to examine the association of accelerometer-derived sleep measures with psychiatric diagnoses and polygenic risk scores in a large community-based cohort. Methods and findings In this post hoc cross-sectional analysis of the UK Biobank cohort, 10 interpretable sleep measures-bedtime, wake-up time, sleep duration, wake after sleep onset, sleep efficiency, number of awakenings, duration of longest sleep bout, number of naps, and variability in bedtime and sleep duration-were derived from 7-day accelerometry recordings across 89,205 participants (aged 43 to 79, 56% female, 97% self-reported white) taken between 2013 and 2015. These measures were examined for association with lifetime inpatient diagnoses of major depressive disorder, anxiety disorders, bipolar disorder/mania, and schizophrenia spectrum disorders from any time before the date of accelerometry, as well as polygenic risk scores for major depression, bipolar disorder, and schizophrenia. Covariates consisted of age and season at the time of the accelerometry recording, sex, Townsend deprivation index (an indicator of socioeconomic status), and the top 10 genotype principal components. We found that sleep pattern differences were ubiquitous across diagnoses: each diagnosis was associated with a median of 8.5 of the 10 accelerometer-derived sleep measures, with measures of sleep quality (for instance, sleep efficiency) generally more affected than mere sleep duration. Effect sizes were generally small: for instance, the largest magnitude effect size across the 4 diagnoses was β = -0.11 (95% confidence interval -0.13 to -0.10, p = 3 × 10-56, FDR = 6 × 10-55) for the association between lifetime inpatient major depressive disorder diagnosis and sleep efficiency. Associations largely replicated across ancestries and sexes, and accelerometry-derived measures were concordant with self-reported sleep properties. Limitations include the use of accelerometer-based sleep measurement and the time lag between psychiatric diagnoses and accelerometry. Conclusions In this study, we observed that sleep pattern differences are a transdiagnostic feature of individuals with lifetime mental illness, suggesting that they should be considered regardless of diagnosis. Accelerometry provides a scalable way to objectively measure sleep properties in psychiatric clinical research and practice, even across tens of thousands of individuals.
    Keywords Medicine ; R
    Subject code 150
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Neuropathological correlates and genetic architecture of microglial activation in elderly human brain

    Daniel Felsky / Tina Roostaei / Kwangsik Nho / Shannon L. Risacher / Elizabeth M. Bradshaw / Vlad Petyuk / Julie A. Schneider / Andrew Saykin / David A. Bennett / Philip L. De Jager

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 12

    Abstract: The consequences of microglial activation in the aging human brain remain unknown. This study quantified microglial morphology and density in the elderly human brain to show that cortical microglial activation strongly associates with AD pathogenesis and ...

    Abstract The consequences of microglial activation in the aging human brain remain unknown. This study quantified microglial morphology and density in the elderly human brain to show that cortical microglial activation strongly associates with AD pathogenesis and may be an upstream contributor to cognitive decline via the accumulation of tau pathology.
    Keywords Science ; Q
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  4. Article ; Online: Proximal and distal effects of genetic susceptibility to multiple sclerosis on the T cell epigenome

    Tina Roostaei / Hans-Ulrich Klein / Yiyi Ma / Daniel Felsky / Pia Kivisäkk / Sarah M. Connor / Alexandra Kroshilina / Christina Yung / Belinda J. Kaskow / Xiaorong Shao / Brooke Rhead / José M. Ordovás / Devin M. Absher / Donna K. Arnett / Jia Liu / Nikolaos Patsopoulos / Lisa F. Barcellos / Howard L. Weiner / Philip L. De Jager

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 12

    Abstract: Integrating functional data with GWAS loci can help interpret the function of genetic variants associated with disease. Here the authors map cis and trans methylation QTL in CD4 + T cells from patients and colocalize with GWAS loci in order to interpret ... ...

    Abstract Integrating functional data with GWAS loci can help interpret the function of genetic variants associated with disease. Here the authors map cis and trans methylation QTL in CD4 + T cells from patients and colocalize with GWAS loci in order to interpret genetic variants associated with multiple sclerosis.
    Keywords Science ; Q
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Atlas of RNA editing events affecting protein expression in aged and Alzheimer’s disease human brain tissue

    Yiyi Ma / Eric B. Dammer / Daniel Felsky / Duc M. Duong / Hans-Ulrich Klein / Charles C. White / Maotian Zhou / Benjamin A. Logsdon / Cristin McCabe / Jishu Xu / Minghui Wang / Thomas S. Wingo / James J. Lah / Bin Zhang / Julie Schneider / Mariet Allen / Xue Wang / Nilüfer Ertekin-Taner / Nicholas T. Seyfried /
    Allan I. Levey / David A. Bennett / Philip L. De Jager

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 16

    Abstract: Resources reporting RNA editing sites from brain tissue have been published. Here, the authors provide an atlas of RNA editing events found in the aged and Alzheimer’s disease human brain tissue resulting in changes at protein level. ...

    Abstract Resources reporting RNA editing sites from brain tissue have been published. Here, the authors provide an atlas of RNA editing events found in the aged and Alzheimer’s disease human brain tissue resulting in changes at protein level.
    Keywords Science ; Q
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  6. Article ; Online: White matter deficits in psychopathic offenders and correlation with factor structure.

    Sylco S Hoppenbrouwers / Arash Nazeri / Danilo R de Jesus / Tania Stirpe / Daniel Felsky / Dennis J L G Schutter / Zafiris J Daskalakis / Aristotle N Voineskos

    PLoS ONE, Vol 8, Iss 8, p e

    2013  Volume 72375

    Abstract: Psychopathic offenders show a persistent pattern of emotional unresponsivity to the often horrendous crimes they perpetrate. Recent studies have related psychopathy to alterations in white matter. Therefore, diffusion tensor imaging followed by tract- ... ...

    Abstract Psychopathic offenders show a persistent pattern of emotional unresponsivity to the often horrendous crimes they perpetrate. Recent studies have related psychopathy to alterations in white matter. Therefore, diffusion tensor imaging followed by tract-based spatial statistics (TBSS) analysis in 11 psychopathic offenders matched to 11 healthy controls was completed. Fractional anisotropy was calculated within each voxel and comparisons were made between groups using a permutation test. Any clusters of white matter voxels different between groups were submitted to probabilistic tractography. Significant differences in fractional anisotropy were found between psychopathic offenders and healthy controls in three main white matter clusters. These three clusters represented two major networks: an amygdalo-prefrontal network, and a striato-thalamo-frontal network. The interpersonal/affective component of the PCL-R correlated with white matter deficits in the orbitofrontal cortex and frontal pole whereas the antisocial component correlated with deficits in the striato-thalamo-frontal network. In addition to replicating earlier work concerning disruption of an amygdala-prefrontal network, we show for the first time that white matter integrity in a striato-thalamo-frontal network is disrupted in psychopathic offenders. The novelty of our findings lies in the two dissociable white matter networks that map directly onto the two major factors of psychopathy.
    Keywords Medicine ; R ; Science ; Q
    Subject code 150
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  7. Article ; Online: Identification of genes associated with dissociation of cognitive performance and neuropathological burden

    Charles C White / Hyun-Sik Yang / Lei Yu / Lori B Chibnik / Robert J Dawe / Jingyun Yang / Hans-Ulrich Klein / Daniel Felsky / Alfredo Ramos-Miguel / Konstantinos Arfanakis / William G Honer / Reisa A Sperling / Julie A Schneider / David A Bennett / Philip L De Jager

    PLoS Medicine, Vol 14, Iss 4, p e

    Multistep analysis of genetic, epigenetic, and transcriptional data.

    2017  Volume 1002287

    Abstract: Introduction The molecular underpinnings of the dissociation of cognitive performance and neuropathological burden are poorly understood, and there are currently no known genetic or epigenetic determinants of the dissociation. Methods and findings " ... ...

    Abstract Introduction The molecular underpinnings of the dissociation of cognitive performance and neuropathological burden are poorly understood, and there are currently no known genetic or epigenetic determinants of the dissociation. Methods and findings "Residual cognition" was quantified by regressing out the effects of cerebral pathologies and demographic characteristics on global cognitive performance proximate to death. To identify genes influencing residual cognition, we leveraged neuropathological, genetic, epigenetic, and transcriptional data available for deceased participants of the Religious Orders Study (n = 492) and the Rush Memory and Aging Project (n = 487). Given that our sample size was underpowered to detect genome-wide significance, we applied a multistep approach to identify genes influencing residual cognition, based on our prior observation that independent genetic and epigenetic risk factors can converge on the same locus. In the first step (n = 979), we performed a genome-wide association study with a predefined suggestive p < 10-5, and nine independent loci met this threshold in eight distinct chromosomal regions. Three of the six genes within 100 kb of the lead SNP are expressed in the dorsolateral prefrontal cortex (DLPFC): UNC5C, ENC1, and TMEM106B. In the second step, in the subset of participants with DLPFC DNA methylation data (n = 648), we found that residual cognition was related to differential DNA methylation of UNC5C and ENC1 (false discovery rate < 0.05). In the third step, in the subset of participants with DLPFC RNA sequencing data (n = 469), brain transcription levels of UNC5C and ENC1 were evaluated for their association with residual cognition: RNA levels of both UNC5C (estimated effect = -0.40, 95% CI -0.69 to -0.10, p = 0.0089) and ENC1 (estimated effect = 0.0064, 95% CI 0.0033 to 0.0096, p = 5.7 × 10-5) were associated with residual cognition. In secondary analyses, we explored the mechanism of these associations and found that ENC1 may be related to the previously documented effect of depression on cognitive decline, while UNC5C may alter the composition of presynaptic terminals. Of note, the TMEM106B allele identified in the first step as being associated with better residual cognition is in strong linkage disequilibrium with rs1990622A (r2 = 0.66), a previously identified protective allele for TDP-43 proteinopathy. Limitations include the small sample size for the genetic analysis, which was underpowered to detect genome-wide significance, the evaluation being limited to a single cortical region for epigenetic and transcriptomic data, and the use of categorical measures for certain non-amyloid-plaque, non-neurofibrillary-tangle neuropathologies. Conclusions Through a multistep analysis of cognitive, neuropathological, genomic, epigenomic, and transcriptomic data, we identified ENC1 and UNC5C as genes with convergent genetic, epigenetic, and transcriptomic evidence supporting a potential role in the dissociation of cognition and neuropathology in an aging population, and we expanded our understanding of the TMEM106B haplotype that is protective against TDP-43 proteinopathy.
    Keywords Medicine ; R
    Subject code 120
    Language English
    Publishing date 2017-04-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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