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Schizophrenia Imaging Genetics

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https://www.readbyqxmd.com/read/28507321/pet-imaging-of-dopamine-d2-receptor-internalization-in-schizophrenia
#1
J J Weinstein, E van de Giessen, R J Rosengard, X Xu, N Ojeil, G Brucato, R B Gil, L S Kegeles, M Laruelle, M Slifstein, A Abi-Dargham
Recent genetic, molecular and post-mortem studies suggest impaired dopamine (DA)-D2 receptor (D2R) trafficking in patients with schizophrenia (SZ). Imaging and preclinical studies have shown agonist-induced D2R internalization can be imaged with positron emission tomography (PET) using D2R radiotracers combined with psychostimulant challenge. This is feasible if radiotracer binding is measured when postchallenge DA levels have returned to baseline, following the initial competition phase between DA and radiotracer for binding to D2R...
May 16, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28416205/the-link-between-schizophrenia-and-substance-use-disorder-a-unifying-hypothesis
#2
REVIEW
Jibran Y Khokhar, Lucas L Dwiel, Angela M Henricks, Wilder T Doucette, Alan I Green
Substance use disorders occur commonly in patients with schizophrenia and dramatically worsen their overall clinical course. While the exact mechanisms contributing to substance use in schizophrenia are not known, a number of theories have been put forward to explain the basis of the co-occurrence of these disorders. We propose here a unifying hypothesis that combines recent evidence from epidemiological and genetic association studies with brain imaging and pre-clinical studies to provide an updated formulation regarding the basis of substance use in patients with schizophrenia...
April 14, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28401151/white-matter-integrity-in-genetic-high-risk-individuals-and-first-episode-schizophrenia-patients-similarities-and-disassociations
#3
Yifang Zhou, Jie Liu, Naomi Driesen, Fay Womer, Kaiyuan Chen, Ye Wang, Xiaowei Jiang, Qian Zhou, Chuan Bai, Dahai Wang, Yanqing Tang, Fei Wang
White matter (WM) neuroimaging studies have shown varied findings at different stages of schizophrenia (SZ). Understanding these variations may elucidate distinct markers of genetic vulnerability and conversion to psychosis. To examine the similarities and differences in WM connectivity between those at-risk for and in early stages of SZ, a cross-sectional diffusion tensor imaging study of 48 individuals diagnosed with first-episode SZ (FE-SZ), 37 nonpsychotic individuals at a high genetic risk of SZ (GHR-SZ), and 67 healthy controls (HC) was conducted...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28384469/altered-cortical-ensembles-in-mouse-models-of-schizophrenia
#4
Jordan P Hamm, Darcy S Peterka, Joseph A Gogos, Rafael Yuste
In schizophrenia, brain-wide alterations have been identified at the molecular and cellular levels, yet how these phenomena affect cortical circuit activity remains unclear. We studied two mouse models of schizophrenia-relevant disease processes: chronic ketamine (KET) administration and Df(16)A(+/-), modeling 22q11.2 microdeletions, a genetic variant highly penetrant for schizophrenia. Local field potential recordings in visual cortex confirmed gamma-band abnormalities similar to patient studies. Two-photon calcium imaging of local cortical populations revealed in both models a deficit in the reliability of neuronal coactivity patterns (ensembles), which was not a simple consequence of altered single-neuron activity...
April 5, 2017: Neuron
https://www.readbyqxmd.com/read/28369257/neuroimaging-and-clinical-features-in-adults-with-a-22q11-2-deletion-at-risk-of-parkinson-s-disease
#5
Nancy J Butcher, Connie Marras, Margarita Pondal, Pablo Rusjan, Erik Boot, Leigh Christopher, Gabriela M Repetto, Rosemarie Fritsch, Eva W C Chow, Mario Masellis, Antonio P Strafella, Anthony E Lang, Anne S Bassett
The recurrent 22q11.2 deletion is a genetic risk factor for early-onset Parkinson's disease. Adults with the associated 22q11.2 deletion syndrome (22q11.2DS) may exhibit phenotypes that could help identify those at highest risk and reveal disease trajectories. We investigated clinical and neuroimaging features relevant to Parkinson's disease in 26 adults: 13 with 22q11.2DS at genetic risk of Parkinson's disease (mean age = 41.5 years, standard deviation = 9.7), 12 healthy age and sex-matched controls, and a 22q11...
March 24, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28350400/immune-involvement-in-the-pathogenesis-of-schizophrenia-a-meta-analysis-on-postmortem-brain-studies
#6
C F M G van Kesteren, H Gremmels, L D de Witte, E M Hol, A R Van Gool, P G Falkai, R S Kahn, I E C Sommer
Although the precise pathogenesis of schizophrenia is unknown, genetic, biomarker and imaging studies suggest involvement of the immune system. In this study, we performed a systematic review and meta-analysis of studies investigating factors related to the immune system in postmortem brains of schizophrenia patients and healthy controls. Forty-one studies were included, reporting on 783 patients and 762 controls. We divided these studies into those investigating histological alterations of cellular composition and those assessing molecular parameters; meta-analyses were performed on both categories...
March 28, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28342832/optimized-clarity-technique-detects-reduced-parvalbumin-density-in-a-genetic-model-of-schizophrenia
#7
Joakim Bastrup, Peter H Larsen
BACKGROUND: Novel tissue clearing technologies have, for the first time, made it possible to study intact tissue samples. This approach provides a tool for further clarifying findings from animal models of schizophrenia by studying parvalbumin-positive (PV+) interneuron density from a 3D perspective. NEW METHOD: This study has developed an optimised CLARITY protocol, including an improved electrophoretic tissue clearing (ETC) chamber, an evaluation of antibody diffusion into cleared tissue slices, and a computational method for detecting PV+ interneurons in 3D...
March 23, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28338738/task-related-functional-connectivity-analysis-of-emotion-discrimination-in-a-family-study-of-schizophrenia
#8
Vina M Goghari, Nicole Sanford, Michael J Spilka, Todd S Woodward
Poor emotion recognition is a core deficit in schizophrenia and is associated with poor functional outcome. Functional magnetic resonance imaging (fMRI) multivariate analysis methods were used to elucidate the neural underpinnings of face and emotion processing associated with both genetic liability and disease-specific effects. Schizophrenia patients, relatives, and controls completed a task that included 4 facial emotion discrimination conditions and an age discrimination condition during fMRI. Three functional networks were derived from the data: the first involved in visual attention and response generation, the second a default mode network (DMN), and a third involved in face and emotion processing...
February 16, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/28297590/insight-into-illness-and-cognition-in-schizophrenia-in-earlier-and-later-life
#9
Philip Gerretsen, Aristotle N Voineskos, Ariel Graff-Guerrero, Mahesh Menon, Bruce G Pollock, David C Mamo, Benoit H Mulsant, Tarek K Rajji
OBJECTIVE: Impaired insight into illness in schizophrenia is associated with illness severity and deficits in premorbid intellectual function, executive function, and memory. A previous study of patients aged 60 years and older found that illness severity and premorbid intellectual function accounted for variance in insight impairment. As such, we aimed to test whether similar relationships would be observed in earlier life. METHODS: A retrospective analysis was performed on 1 large sample of participants (n = 171) with a DSM-IV-TR diagnosis of schizophrenia aged 19 to 79 years acquired from 2 studies: (1) a psychosocial intervention trial for older persons with schizophrenia (June 2008 to May 2014) and (2) a diffusion tensor imaging and genetics study of psychosis across the life span (February 2007 to December 2013)...
April 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28289280/biochemical-physiological-and-clinical-effects-of-l-methylfolate-in-schizophrenia-a-randomized-controlled-trial
#10
J L Roffman, L J Petruzzi, A S Tanner, H E Brown, H Eryilmaz, N F Ho, M Giegold, N J Silverstein, T Bottiglieri, D S Manoach, J W Smoller, D C Henderson, D C Goff
Folic acid supplementation confers modest benefit in schizophrenia, but its effectiveness is influenced by common genetic variants in the folate pathway that hinder conversion to its active form. We examined physiological and clinical effects of l-methylfolate, the fully reduced and bioactive form of folate, in schizophrenia. In this randomized, double-blind trial, outpatients with schizophrenia (n=55) received l-methylfolate 15 mg or placebo for 12 weeks. Patients were maintained on stable doses of antipsychotic medications...
March 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28269013/integration-of-snps-fmri-methylation-data-with-sparse-multi-cca-for-schizophrenia-study
#11
Wenxing Hu, Dongdong Lin, Vince D Calhoun, Yu-Ping Wang
Schizophrenia (SZ) is a complex mental disorder associated with genetic variations, brain development and activities, and environmental factors. There is an increasing interest in combining genetic, epigenetic and neuroimaging datasets to explore different level of biomarkers for the correlation and interaction between these diverse factors. Sparse Multi-Canonical Correlation Analysis (sMCCA) is a powerful tool that can analyze the correlation of three or more datasets. In this paper, we propose the sMCCA model for imaging genomics study...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28227225/integration-of-snps-fmri-methylation-data-with-sparse-multi-cca-for-schizophrenia-study
#12
Wenxing Hu, Dongdong Lin, Vince D Calhoun, Yu-Ping Wang, Wenxing Hu, Dongdong Lin, Vince D Calhoun, Yu-Ping Wang, Vince D Calhoun, Yu-Ping Wang, Wenxing Hu, Dongdong Lin
Schizophrenia (SZ) is a complex mental disorder associated with genetic variations, brain development and activities, and environmental factors. There is an increasing interest in combining genetic, epigenetic and neuroimaging datasets to explore different level of biomarkers for the correlation and interaction between these diverse factors. Sparse Multi-Canonical Correlation Analysis (sMCCA) is a powerful tool that can analyze the correlation of three or more datasets. In this paper, we propose the sMCCA model for imaging genomics study...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
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
#13
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
#14
H A Bruce, P Kochunov, S A Paciga, C L Hyde, X Chen, Z Xie, B Zhang, H S Xi, P O'Donnell, C Whelan, C R Schubert, A Bellon, S A Ament, D K Shukla, X Du, L M Rowland, H O'Neill, L E 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
Johanna Seitz, Yogesh Rathi, Amanda Lyall, Ofer Pasternak, Elisabetta C Del Re, Margaret Niznikiewicz, Paul Nestor, Larry J Seidman, Tracey L Petryshen, Raquelle I Mesholam-Gately, Joanne Wojcik, Robert W McCarley, Martha E Shenton, Inga K Koerte, Marek Kubicki
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
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