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Schizophrenia Imaging Genetics

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https://www.readbyqxmd.com/read/28072415/functional-neuroimaging-effects-of-recently-discovered-genetic-risk-loci-for-schizophrenia-and-polygenic-risk-profile-in-five-rdoc-subdomains
#1
S Erk, S Mohnke, S Ripke, T A Lett, I M Veer, C Wackerhagen, O Grimm, N Romanczuk-Seiferth, F Degenhardt, H Tost, M Mattheisen, T W Mühleisen, K Charlet, N Skarabis, F Kiefer, S Cichon, S H Witt, M M Nöthen, M Rietschel, A Heinz, A Meyer-Lindenberg, H Walter
Recently, 125 loci with genome-wide support for association with schizophrenia were identified. We investigated the impact of these variants and their accumulated genetic risk on brain activation in five neurocognitive domains of the Research Domain Criteria (working memory, reward processing, episodic memory, social cognition and emotion processing). In 578 healthy subjects we tested for association (i) of a polygenic risk profile score (RPS) including all single-nucleotide polymorphisms (SNPs) reaching genome-wide significance in the recent genome-wide association studies (GWAS) meta-analysis and (ii) of all independent genome-wide significant loci separately that showed sufficient distribution of all allelic groups in our sample (105 SNPs)...
January 10, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28067006/addressing-reverse-inference-in-psychiatric-neuroimaging-meta-analyses-of-task-related-brain-activation-in-common-mental-disorders
#2
Emma Sprooten, Alexander Rasgon, Morgan Goodman, Ariella Carlin, Evan Leibu, Won Hee Lee, Sophia Frangou
Functional magnetic resonance imaging (fMRI) studies in psychiatry use various tasks to identify case-control differences in the patterns of task-related brain activation. Differently activated regions are often ascribed disorder-specific functions in an attempt to link disease expression and brain function. We undertook a systematic meta-analysis of data from task-fMRI studies to examine the effect of diagnosis and study design on the spatial distribution and direction of case-control differences on brain activation...
January 9, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28027496/allostatic-load-and-reduced-cortical-thickness-in-schizophrenia
#3
Joshua Chiappelli, Peter Kochunov, Anya Savransky, Feven Fisseha, Krista Wisner, Xiaoming Du, Laura M Rowland, L Elliot Hong
Structural imaging studies have consistently found reduced gray matter thickness of the cerebral cortex in schizophrenia, a finding that is evident in first episode psychosis and may be progressive in some cases. Although genetic predisposition and medication effects may contribute to cortical thinning, we hypothesize that the cumulative effects of stress may represent an environmental factor impacting brain morphology in schizophrenia. We examined the relationship between allostatic load, an index of peripheral biomarkers representing the cumulative effects of stress, and cortical thickness...
November 24, 2016: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28025777/brain-development-and-akt-signaling-the-crossroads-of-signaling-pathway-and-neurodevelopmental-diseases
#4
REVIEW
Long Wang, Kai Zhou, Zhi Fu, Di Yu, Hesuyuan Huang, Xiaodong Zang, Xuming Mo
Neurodevelopmental biology, coupled with the application of advanced histological, imaging, molecular, cellular, biochemical, and genetic approaches, has provided new insights into these intricate genetic, cellular, and molecular events. During telencephalic development, specific neural progenitor cells (NPCs) proliferate, differentiate into numerous cell types, migrate to their apposite positions, and form an integrated circuitry. Critical disturbance to this dynamic process via genetic and environmental risk can cause neurological disorders and disability...
December 26, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28017919/relationship-of-a-common-oxtr-gene-variant-to-brain-structure-and-default-mode-network-function-in-healthy-humans
#5
Junping Wang, Meredith N Braskie, George W Hafzalla, Joshua Faskowitz, Katie L McMahon, Greig I de Zubicaray, Margaret J Wright, Chunshui Yu, Paul M Thompson
A large body of research suggests that oxytocin receptor (OXTR) gene polymorphisms may influence both social behaviors and psychiatric conditions related to social deficits, such as autism spectrum disorders (ASDs), schizophrenia, and mood and anxiety disorders. However, the neural mechanism underlying these associations is still unclear. Relative to controls, patients with these psychiatric conditions show differences in brain structure, and in resting state fMRI (rs-fMRI) signal synchronicity among default mode network (DMN) regions (also known as functional connectivity)...
December 23, 2016: NeuroImage
https://www.readbyqxmd.com/read/28012640/white-matter-integrity-and-symptom-dimensions-of-schizophrenia-a-diffusion-tensor-imaging-study
#6
Miriam H A Bopp, Rebecca Zöllner, Andreas Jansen, Bruno Dietsche, Axel Krug, Tilo T J Kircher
Impaired fiber bundle connectivity between brain regions is a key neuropathological finding in schizophrenia. Symptom dimensions in schizophrenia can be clustered into factor models. Single syndromes have been related to grey and white matter brain structure alterations. We associated all core syndromes of schizophrenia in a single patient group with changes in white matter integrity. Diffusion weighted images (3T MRI) and SAPS/SANS scores were measured in 26 male patients and 26 healthy controls. First, group differences in fractional anisotropy (FA) were calculated with TBSS...
December 21, 2016: Schizophrenia Research
https://www.readbyqxmd.com/read/27994220/structural-dysconnectivity-of-key-cognitive-and-emotional-hubs-in-young-people-at-high-genetic-risk-for-bipolar-disorder
#7
G Roberts, A Perry, A Lord, A Frankland, V Leung, E Holmes-Preston, F Levy, R K Lenroot, P B Mitchell, M Breakspear
Emerging evidence suggests that psychiatric disorders are associated with disturbances in structural brain networks. Little is known, however, about brain networks in those at high risk (HR) of bipolar disorder (BD), with such disturbances carrying substantial predictive and etiological value. Whole-brain tractography was performed on diffusion-weighted images acquired from 84 unaffected HR individuals with at least one first-degree relative with BD, 38 young patients with BD and 96 matched controls (CNs) with no family history of mental illness...
December 20, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27942861/decreased-white-matter-fa-values-in-the-left-inferior-frontal-gyrus-is-a-possible-intermediate-phenotype-of-schizophrenia-evidences-from-a-novel-group-strategy
#8
Jianjun Ou, Hailong Lyu, Maorong Hu, Jun Li, Wenbin Guo, Xiaofeng Guo, Lihua Li, Junjie Zheng, Qinling Wei, Feng Liu, Zhong He, Juan Wang, Fang Liu, Renrong Wu, Jindong Chen, Lehua Li, Bin Hu, Huafu Chen, Jingping Zhao
Intermediate phenotype could be used to investigate genetic susceptibility. However, genetic and environmental heterogeneity may interfere with identification of intermediate phenotypes. In this study, we minimized these interferences by using a novel group strategy. A total of 22 drug-naive and first-episode schizophrenia (FES) patients, along with 22 of their kin healthy siblings (HS), 22 non-kin healthy siblings (nHS) of other schizophrenia patients and 22 healthy controls (HC), were recruited. Brain imaging was acquired from the participants...
December 9, 2016: European Archives of Psychiatry and Clinical Neuroscience
https://www.readbyqxmd.com/read/27896966/enforcing-co-expression-in-multimodal-regression-framework
#9
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
#10
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...
January 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/27847593/contribution-of-oxytocin-receptor-polymorphisms-to-amygdala-activation-in-schizophrenia-spectrum-disorders
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
REVIEW
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-aetiological 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 five publications using this technique in patients with BPD...
January 2017: 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
#18
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
#19
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...
January 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/27623121/-advocacy-for-the-establishment-of-a-comprehensive-strategy-to-reduce-the-burden-of-schizophrenic-disorders
#20
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...
October 2016: L'Encéphale
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