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Schizophrenia Imaging Genetics

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https://www.readbyqxmd.com/read/28195569/rare-damaging-variants-in-dna-repair-and-cell-cycle-pathways-are-associated-with-hippocampal-and-cognitive-dysfunction-a-combined-genetic-imaging-study-in-first-episode-treatment-naive-patients-with-schizophrenia
#1
Z Yang, M Li, X Hu, B Xiang, W Deng, Q Wang, Y Wang, L Zhao, X Ma, P C Sham, G Northoff, T Li
Schizophrenia is a complex neurodevelopmental disorder where changes in both hippocampus and memory-related cognitive functions are central. However, the exact relationship between neurodevelopmental-genetic factors and hippocampal-cognitive dysfunction remains unclear. The general aim of our study is to link the occurrence of rare damaging mutations involved in susceptibility gene pathways to the structure and function of hippocampus in order to define genetically and phenotypically based subgroups in schizophrenia...
February 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28188958/potassium-channel-gene-associations-with-joint-processing-speed-and-white-matter-impairments-in-schizophrenia
#2
Heather A Bruce, Peter Kochunov, Sara A Paciga, Craig L Hyde, Xing Chen, Zhiyong Xie, Baohong Zhang, Hualin S Xi, Patricio O'Donnell, Christopher Whelan, Christian R Schubert, Alfredo Bellon, Seth A Ament, Dinesh K Shukla, Xiaoming Du, Laura M Rowland, Hugh O'Neill, L Elliot Hong
Patients with schizophrenia show decreased processing speed on neuropsychological testing and decreased white matter integrity as measured by diffusion tensor imaging, two traits shown to be both heritable and genetically associated indicating that there may be genes that influence both traits as well as schizophrenia disease risk. The potassium channel gene family is a reasonable candidate to harbor such a gene given the prominent role potassium channels play in the central nervous system in signal transduction, particularly in myelinated axons...
February 11, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28186152/association-of-polygenic-risk-for-major-psychiatric-illness-with-subcortical-volumes-and-white-matter-integrity-in-uk-biobank
#3
L M Reus, X Shen, J Gibson, E Wigmore, L Ligthart, M J Adams, G Davies, S R Cox, S P Hagenaars, M E Bastin, I J Deary, H C Whalley, A M McIntosh
Major depressive disorder (MDD), schizophrenia (SCZ) and bipolar disorder (BP) are common, disabling and heritable psychiatric diseases with a complex overlapping polygenic architecture. Individuals with these disorders, as well as their unaffected relatives, show widespread structural differences in corticostriatal and limbic networks. Structural variation in many of these brain regions is also heritable and polygenic but whether their genetic architecture overlaps with that of major psychiatric disorders is unknown...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28170004/inflammation-and-the-neural-diathesis-stress-hypothesis-of-schizophrenia-a-reconceptualization
#4
REVIEW
O D Howes, R McCutcheon
An interaction between external stressors and intrinsic vulnerability is one of the longest standing pathoaetiological explanations for schizophrenia. However, novel lines of evidence from genetics, preclinical studies, epidemiology and imaging have shed new light on the mechanisms that may underlie this, implicating microglia as a key potential mediator. Microglia are the primary immune cells of the central nervous system. They have a central role in the inflammatory response, and are also involved in synaptic pruning and neuronal remodeling...
February 7, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28152990/reduced-functional-connectivity-between-bilateral-precuneus-and-contralateral-parahippocampus-in-schizotypal-personality-disorder
#5
Yikang Zhu, Yunxiang Tang, Tianhong Zhang, Hui Li, Yingying Tang, Chunbo Li, Xingguang Luo, Yongguang He, Zheng Lu, Jijun Wang
BACKGROUND: Schizotypal personality disorder (SPD) is linked to schizophrenia in terms of shared genetics, biological markers and phenomenological characteristics. In the current study, we aimed to determine whether the previously reported altered functional connectivity (FC) with precuneus in patients with schizophrenia could be extended to individuals with SPD. METHODS: Twenty subjects with SPD and 19 healthy controls were recruited from 4461 freshmen at a university in Shanghai and received a resting-state scan of MRI...
February 2, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28117840/mir-137-derived-polygenic-risk-effects-on-cognitive-performance-in-patients-with-schizophrenia-and-controls
#6
D Cosgrove, D Harold, O Mothersill, R Anney, M J Hill, N J Bray, G Blokland, T Petryshen, A Richards, K Mantripragada, M Owen, M C O'Donovan, M Gill, A Corvin, D W Morris, G Donohoe
Variants at microRNA-137 (MIR137), one of the most strongly associated schizophrenia risk loci identified to date, have been associated with poorer cognitive performance. As microRNA-137 is known to regulate the expression of ~1900 other genes, including several that are independently associated with schizophrenia, we tested whether this gene set was also associated with variation in cognitive performance. Our analysis was based on an empirically derived list of genes whose expression was altered by manipulation of MIR137 expression...
January 24, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28104410/the-drd2-rs1076560-polymorphism-and-schizophrenia-related-intermediate-phenotypes-a-systematic-review-and-meta-analysis
#7
REVIEW
Jurjen J Luykx, Juliette L Broersen, Max de Leeuw
Intermediate phenotypes may contribute to elucidate the genetic determinants of schizophrenia. A regulatory dopamine 2-receptor gene (DRD2) polymorphism (rs1076560; G>T) has been identified as a genetic risk factor for schizophrenia. Studies report conflicting results on its involvement in schizophrenia intermediate phenotypes and no systematic review on this topic has been published. Therefore, we aimed to assess whether this polymorphism is implicated in schizophrenia intermediate phenotypes by performing a systematic review and meta-analysis...
January 16, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28102528/alteration-of-gray-matter-microstructure-in-schizophrenia
#8
Seitz Johanna, Rathi Yogesh, Lyall Amanda, Pasternak Ofer, Del Re Elisabetta C, Niznikiewicz Margaret, Nestor Paul, J Seidman Larry, L Petryshen Tracey, I Mesholam-Gately Raquelle, Wojcik Joanne, W McCarley Robert, E Shenton Martha, K Koerte Inga, Kubicki Marek
Neuroimaging studies demonstrate gray matter (GM) macrostructural abnormalities in patients with schizophrenia (SCZ). While ex-vivo and genetic studies suggest cellular pathology associated with abnormal neurodevelopmental processes in SCZ, few in-vivo measures have been proposed to target microstructural GM organization. Here, we use diffusion heterogeneity- to study GM microstructure in SCZ. Structural and diffusion magnetic resonance imaging (MRI) were acquired on a 3 Tesla scanner in 46 patients with SCZ and 37 matched healthy controls (HC)...
January 19, 2017: Brain Imaging and Behavior
https://www.readbyqxmd.com/read/28094815/drd2-co-expression-network-and-a-related-polygenic-index-predict-imaging-behavioral-and-clinical-phenotypes-linked-to-schizophrenia
#9
G Pergola, P Di Carlo, E D'Ambrosio, B Gelao, L Fazio, M Papalino, A Monda, G Scozia, B Pietrangelo, M Attrotto, J A Apud, Q Chen, V S Mattay, A Rampino, G Caforio, D R Weinberger, G Blasi, A Bertolino
Genetic risk for schizophrenia (SCZ) is determined by many genetic loci whose compound biological effects are difficult to determine. We hypothesized that co-expression pathways of SCZ risk genes are associated with system-level brain function and clinical phenotypes of SCZ. We examined genetic variants related to the dopamine D2 receptor gene DRD2 co-expression pathway and associated them with working memory (WM) behavior, the related brain activity and treatment response. Using two independent post-mortem prefrontal messenger RNA (mRNA) data sets (total N=249), we identified a DRD2 co-expression pathway enriched for SCZ risk genes...
January 17, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28093278/similar-patterns-of-brain-activation-abnormalities-during-emotional-and-non-emotional-judgments-of-faces-in-a-schizophrenia-family-study
#10
Michael J Spilka, Vina M Goghari
Schizophrenia patients have impaired performance and abnormal brain activation during facial emotion recognition, which may represent a marker of genetic liability to schizophrenia. However, it remains unclear whether the impairment is specific to recognizing emotion from faces or is instead attributable to more generalized dysfunction. The current study aimed to distinguish between specific and generalized neural dysfunction underlying impaired facial emotion recognition in schizophrenia and examine associations with genetic liability...
February 2017: Neuropsychologia
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
#11
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
#12
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
#13
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
#14
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
#15
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)...
February 15, 2017: NeuroImage
https://www.readbyqxmd.com/read/28012640/white-matter-integrity-and-symptom-dimensions-of-schizophrenia-a-diffusion-tensor-imaging-study
#16
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
#17
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
#18
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
#19
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
#20
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
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