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Schizophrenia Imaging Genetics

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https://www.readbyqxmd.com/read/27896966/enforcing-co-expression-in-multimodal-regression-framework
#1
Pascal Zille, Vince D Calhoun, Yu-Ping Wang
We consider the problem of multimodal data integration for the study of complex neurological diseases (e.g. schizophrenia). Among the challenges arising in such situation, estimating the link between genetic and neurological variability within a population sample has been a promising direction. A wide variety of statistical models arose from such applications. For example, Lasso regression and its multitask extension are often used to fit a multivariate linear relationship between given phenotype(s) and associated observations...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27872267/endophenotypes-epigenetics-polygenicity-and-more-irv-gottesman-s-dynamic-legacy
#2
David L Braff, Carol A Tamminga
First, we describe the hallmark contributions of Irv Gottesman's pioneering scholarship for schizophrenia research including concepts of polygenicity, gene × environment interactions, epigenetics and the endophenotype concept. Gottesman and colleagues' twin studies showed that genes, not social factors, mediate schizophrenia risk. He then showed that schizophrenia is highly polygenic. Next, he introduced the concept of epigenetics into schizophrenia research. Gottesman then introduced the quantitative endophenotype concept...
November 21, 2016: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/27847593/contribution-of-oxytocin-receptor-polymorphisms-to-amygdala-activation-in-schizophrenia-spectrum-disorders
#3
Marit Haram, Francesco Bettella, Christine Lycke Brandt, Daniel S Quintana, Mari Nerhus, Thomas Bjella, Srdjan Djurovic, Lars T Westlye, Ole A Andreassen, Ingrid Melle, Martin Tesli
BACKGROUND: Oxytocin has been proposed to mediate amygdala dysfunction associated with altered emotion processing in schizophrenia, but the contribution of oxytocin pathway genes is yet to be investigated. AIMS: To identify potential different contributions of three oxytocin receptor polymorphisms (rs53576, rs237902 and rs2254298) between patients with schizophrenia spectrum disorders (SCZ), affective spectrum disorders (AD) and healthy controls (HC). METHOD: In a total of 346 participants (104 with SCZ, 100 with AD, and 142 HC) underwent genotyping and functional magnetic resonance imaging (fMRI) during an emotional faces matching paradigm...
November 2016: BJPsych Open
https://www.readbyqxmd.com/read/27842943/raloxifene-increases-prefrontal-activity-during-emotional-inhibition-in-schizophrenia-based-on-estrogen-receptor-genotype
#4
Jochen Kindler, Cynthia Shannon Weickert, Peter R Schofield, Rhoshel Lenroot, Thomas W Weickert
People with schizophrenia show decreased prefrontal cortex (PFC) activity during emotional response inhibition, a cognitive process sensitive to hormonal influences. Raloxifene, a selective estrogen receptor modulator, binds estrogen receptor alpha (ESR-α), improves memory, attention and normalizes cortical and hippocampal activity during learning and emotional face recognition in schizophrenia. Here, we tested the extent to which raloxifene restores neuronal activity during emotional response inhibition in schizophrenia...
December 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27819315/sustained-synchronized-neuronal-network-activity-in-a-human-astrocyte-co-culture-system
#5
Jacobine Kuijlaars, Tutu Oyelami, Annick Diels, Jutta Rohrbacher, Sofie Versweyveld, Giulia Meneghello, Marianne Tuefferd, Peter Verstraelen, Jan R Detrez, Marlies Verschuuren, Winnok H De Vos, Theo Meert, Pieter J Peeters, Miroslav Cik, Rony Nuydens, Bert Brône, An Verheyen
Impaired neuronal network function is a hallmark of neurodevelopmental and neurodegenerative disorders such as autism, schizophrenia, and Alzheimer's disease and is typically studied using genetically modified cellular and animal models. Weak predictive capacity and poor translational value of these models urge for better human derived in vitro models. The implementation of human induced pluripotent stem cells (hiPSCs) allows studying pathologies in differentiated disease-relevant and patient-derived neuronal cells...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27791105/dynamic-brain-network-reconfiguration-as-a-potential-schizophrenia-genetic-risk-mechanism-modulated-by-nmda-receptor-function
#6
Urs Braun, Axel Schäfer, Danielle S Bassett, Franziska Rausch, Janina I Schweiger, Edda Bilek, Susanne Erk, Nina Romanczuk-Seiferth, Oliver Grimm, Lena S Geiger, Leila Haddad, Kristina Otto, Sebastian Mohnke, Andreas Heinz, Mathias Zink, Henrik Walter, Emanuel Schwarz, Andreas Meyer-Lindenberg, Heike Tost
Schizophrenia is increasingly recognized as a disorder of distributed neural dynamics, but the molecular and genetic contributions are poorly understood. Recent work highlights a role for altered N-methyl-d-aspartate (NMDA) receptor signaling and related impairments in the excitation-inhibitory balance and synchrony of large-scale neural networks. Here, we combined a pharmacological intervention with novel techniques from dynamic network neuroscience applied to functional magnetic resonance imaging (fMRI) to identify alterations in the dynamic reconfiguration of brain networks related to schizophrenia genetic risk and NMDA receptor hypofunction...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27786353/longitudinal-study-of-cerebral-surface-morphology-in-youth-with-22q11-2-deletion-syndrome-and-association-with-positive-symptoms-of-psychosis
#7
Petya D Radoeva, Ravi Bansal, Kevin M Antshel, Wanda Fremont, Bradley S Peterson, Wendy R Kates
BACKGROUND: 22q11.2 deletion syndrome (22q11DS) is a genetic disorder that greatly increases risk of developing schizophrenia. We previously characterized cerebral surface morphology trajectories from late childhood to mid adolescence in a cohort of youth with 22q11DS. Herein, we extend the study period into early adulthood, and describe further the trajectories associated with severe psychiatric symptoms in this cohort. METHODS: Participants included 76 youth with 22q11DS and 30 unaffected siblings, assessed at three timepoints, during which high resolution, anatomic magnetic resonance images were acquired...
October 27, 2016: Journal of Child Psychology and Psychiatry, and Allied Disciplines
https://www.readbyqxmd.com/read/27770667/altered-cortical-processing-of-motor-inhibition-in-schizophrenia
#8
Påvel G Lindberg, Maxime Térémetz, Sylvain Charron, Oussama Kebir, Agathe Saby, Narjes Bendjemaa, Stéphanie Lion, Benoît Crépon, Raphaël Gaillard, Catherine Oppenheim, Marie-Odile Krebs, Isabelle Amado
Inhibition is considered a key mechanism in schizophrenia. Short-latency intracortical inhibition (SICI) in the motor cortex is reduced in schizophrenia and is considered to reflect locally deficient γ-aminobutyric acid (GABA)-ergic modulation. However, it remains unclear how SICI is modulated during motor inhibition and how it relates to neural processing in other cortical areas. Here we studied motor inhibition Stop signal task (SST) in stabilized patients with schizophrenia (N = 28), healthy siblings (N = 21) and healthy controls (n = 31) matched in general cognitive status and educational level...
September 30, 2016: Cortex; a Journal Devoted to the Study of the Nervous System and Behavior
https://www.readbyqxmd.com/read/27690184/are-reprogrammed-cells-a-useful-tool-for-studying-dopamine-dysfunction-in-psychotic-disorders-a-review-of-the-current-evidence
#9
Ulrich Sauerzopf, Roberto Sacco, Gaia Novarino, Marco Niello, Ana Weidenauer, Nicole Praschak-Rieder, Harald Sitte, Matthäus Willeit
Since 2006, reprogrammed cells have increasingly been used as a biomedical research technique in addition to neuro-psychiatric methods. These rapidly evolving techniques allow for the generation of neuronal sub-populations, and have sparked interest not only in monogenetic neuro-psychiatric diseases, but also in poly-genetic and poly-etiological disorders such as schizophrenia (SCZ) and bipolar disorder (BPD). This review provides a summary of 19 publications on reprogrammed adult somatic cells derived from patients with SCZ, and 5 publications using this technique in patients with BPD...
September 30, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27689884/knockdown-of-the-schizophrenia-susceptibility-gene-tcf4-alters-gene-expression-and-proliferation-of-progenitor-cells-from-the-developing-human-neocortex
#10
Matthew J Hill, Richard Killick, Katherinne Navarrete, Aleksandra Maruszak, Gemma M McLaughlin, Brenda P Williams, Nicholas J Bray
BACKGROUND: Common variants in the TCF4 gene are among the most robustly supported genetic risk factors for schizophrenia. Rare TCF4 deletions and loss-of-function point mutations cause Pitt-Hopkins syndrome, a developmental disorder associated with severe intellectual disability. METHODS: To explore molecular and cellular mechanisms by which TCF4 perturbation could interfere with human cortical development, we experimentally reduced the endogenous expression of TCF4 in a neural progenitor cell line derived from the developing human cerebral cortex using RNA interference...
September 29, 2016: Journal of Psychiatry & Neuroscience: JPN
https://www.readbyqxmd.com/read/27646261/myelination-of-parvalbumin-interneurons-a-parsimonious-locus-of-pathophysiological-convergence-in-schizophrenia
#11
J Stedehouder, S A Kushner
Schizophrenia is a debilitating psychiatric disorder characterized by positive, negative and cognitive symptoms. Despite more than a century of research, the neurobiological mechanism underlying schizophrenia remains elusive. White matter abnormalities and interneuron dysfunction are the most widely replicated cellular neuropathological alterations in patients with schizophrenia. However, a unifying model incorporating these findings has not yet been established. Here, we propose that myelination of fast-spiking parvalbumin (PV) interneurons could be an important locus of pathophysiological convergence in schizophrenia...
September 20, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27623121/-advocacy-for-the-establishment-of-a-comprehensive-strategy-to-reduce-the-burden-of-schizophrenic-disorders
#12
D Leguay
This article attempts to identify and put into perspective the different approaches that could globally prevent the suffering induced by schizophrenia, from the detection of early psychosis to the impact on individual and family functioning and emotional health. Schizophrenia causes, at the community level, a number of difficult consequences and associated costs, which likely could be reduced if specific strategies, already known and documented internationally, were applied. Two areas not explored in this article: the role of medication and the issue of suicide prevention...
September 9, 2016: L'Encéphale
https://www.readbyqxmd.com/read/27593442/understanding-the-impact-of-5-httlpr-antidepressants-and-acute-tryptophan-depletion-on-brain-activation-during-facial-emotion-processing-a-review-of-the-imaging-literature
#13
REVIEW
Kyeon Raab, Peter Kirsch, Daniela Mier
Detecting and evaluating emotional information from facial expressions as a basis for behavioural adaption belong to the core social-cognitive abilities of mankind. Dysfunctions in emotional face processing are observed in several major psychiatric disorders like depression and schizophrenia. In search for psychiatric disease biomarkers using the imaging genetics approach, serotonergic gene polymorphisms have been associated with altered brain circuit activation during emotional face processing. Especially the 5-HTTLPR gene polymorphism has been extensively investigated in association with emotion regulation processes...
December 2016: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/27511297/multimodal-mri-reveals-structural-connectivity-differences-in-22q11-deletion-syndrome-related-to-impaired-spatial-working-memory
#14
Erik O'Hanlon, Sarah Howley, Sarah Prasad, Jane McGrath, Alexander Leemans, Colm McDonald, Hugh Garavan, Kieran C Murphy
INTRODUCTION: Impaired spatial working memory is a core cognitive deficit observed in people with 22q11 Deletion syndrome (22q11DS) and has been suggested as a candidate endophenotype for schizophrenia. However, to date, the neuroanatomical mechanisms describing its structural and functional underpinnings in 22q11DS remain unclear. We quantitatively investigate the cognitive processes and associated neuroanatomy of spatial working memory in people with 22q11DS compared to matched controls...
December 2016: Human Brain Mapping
https://www.readbyqxmd.com/read/27505231/impact-of-polygenic-schizophrenia-related-risk-and-hippocampal-volumes-on-the-onset-of-psychosis
#15
F Harrisberger, R Smieskova, C Vogler, T Egli, A Schmidt, C Lenz, A E Simon, A Riecher-Rössler, A Papassotiropoulos, S Borgwardt
Alterations in hippocampal volume are a known marker for first-episode psychosis (FEP) as well as for the clinical high-risk state. The Polygenic Schizophrenia-related Risk Score (PSRS), derived from a large case-control study, indicates the polygenic predisposition for schizophrenia in our clinical sample. A total of 65 at-risk mental state (ARMS) and FEP patients underwent structural magnetic resonance imaging. We used automatic segmentation of hippocampal volumes using the FSL-FIRST software and an odds-ratio-weighted PSRS based on the publicly available top single-nucleotide polymorphisms from the Psychiatric Genomics Consortium genome-wide association study (GWAS)...
2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27466625/joint-sparse-canonical-correlation-analysis-for-detecting-differential-imaging-genetics-modules
#16
Jian Fang, Dongdong Lin, S Charles Schulz, Zongben Xu, Vince D Calhoun, Yu-Ping Wang
MOTIVATION: Imaging genetics combines brain imaging and genetic information to identify the relationships between genetic variants and brain activities. When the data samples belong to different classes (e.g. disease status), the relationships may exhibit class-specific patterns that can be used to facilitate the understanding of a disease. Conventional approaches often perform separate analysis on each class and report the differences, but ignore important shared patterns. RESULTS: In this paper, we develop a multivariate method to analyze the differential dependency across multiple classes...
November 15, 2016: Bioinformatics
https://www.readbyqxmd.com/read/27458342/function-over-form-modeling-groups-of-inherited-neurological-conditions-in-zebrafish
#17
REVIEW
Robert A Kozol, Alexander J Abrams, David M James, Elena Buglo, Qing Yan, Julia E Dallman
Zebrafish are a unique cell to behavior model for studying the basic biology of human inherited neurological conditions. Conserved vertebrate genetics and optical transparency provide in vivo access to the developing nervous system as well as high-throughput approaches for drug screens. Here we review zebrafish modeling for two broad groups of inherited conditions that each share genetic and molecular pathways and overlap phenotypically: neurodevelopmental disorders such as Autism Spectrum Disorders (ASD), Intellectual Disability (ID) and Schizophrenia (SCZ), and neurodegenerative diseases, such as Cerebellar Ataxia (CATX), Hereditary Spastic Paraplegia (HSP) and Charcot-Marie Tooth Disease (CMT)...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27440007/changes-in-white-matter-organization-in-adolescent-offspring-of-schizophrenia-patients
#18
Max de Leeuw, Marc M Bohlken, René Cw Mandl, Manon Hj Hillegers, René S Kahn, Matthijs Vink
Schizophrenia is associated with fronto-striatal network impairments underlying clinical and cognitive symptoms. We previously found disruptions in anatomical pathways, including the tract connecting the left nucleus accumbens and left dorsolateral prefrontal cortex (DLPFC). Similar deficits are observed in unaffected siblings of schizophrenia patients indicating that these deficits are linked to a genetic vulnerability for the disorder. Fronto-striatal tract disruptions may arise during adolescence, preceding the clinical manifestation of the disorder...
July 21, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27396334/somatostatin-interneurons-control-a-key-component-of-mismatch-negativity-in-mouse-visual-cortex
#19
Jordan P Hamm, Rafael Yuste
Patients with schizophrenia have deficient sensory processing, undermining how they perceive and relate to a changing environment. This impairment can be captured by the reduced mismatch negativity (MMN) index, an electroencephalographic biomarker of psychosis. The biological factors contributing to MMN are unclear, though mouse research, in which genetic and optical methods could be applied, has given some insight. Using fast two-photon calcium imaging and multielectrode recordings in awake mice, we find that visual cortical circuits display adapted (decreased) responses to repeated stimuli and amplified responses to a deviant stimulus, the key component of human MMN...
July 19, 2016: Cell Reports
https://www.readbyqxmd.com/read/27378904/stimulation-of-synaptic-vesicle-exocytosis-by-the-mental-disease-gene-disc1-is-mediated-by-n-type-voltage-gated-calcium-channels
#20
Willcyn Tang, Jervis Vermal Thevathasan, Qingshu Lin, Kim Buay Lim, Keisuke Kuroda, Kozo Kaibuchi, Marcel Bilger, Tuck Wah Soong, Marc Fivaz
Lesions and mutations of the DISC1 (Disrupted-in-schizophrenia-1) gene have been linked to major depression, schizophrenia, bipolar disorder and autism, but the influence of DISC1 on synaptic transmission remains poorly understood. Using two independent genetic approaches-RNAi and a DISC1 KO mouse-we examined the impact of DISC1 on the synaptic vesicle (SV) cycle by population imaging of the synaptic tracer vGpH in hippocampal neurons. DISC1 loss-of-function resulted in a marked decrease in SV exocytic rates during neuronal stimulation and was associated with reduced Ca(2+) transients at nerve terminals...
2016: Frontiers in Synaptic Neuroscience
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