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Schizophrenia Imaging Genetics

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https://www.readbyqxmd.com/read/29895892/large-scale-mapping-of-cortical-alterations-in-22q11-2-deletion-syndrome-convergence-with-idiopathic-psychosis-and-effects-of-deletion-size
#1
Daqiang Sun, Christopher R K Ching, Amy Lin, Jennifer K Forsyth, Leila Kushan, Ariana Vajdi, Maria Jalbrzikowski, Laura Hansen, Julio E Villalon-Reina, Xiaoping Qu, Rachel K Jonas, Therese van Amelsvoort, Geor Bakker, Wendy R Kates, Kevin M Antshel, Wanda Fremont, Linda E Campbell, Kathryn L McCabe, Eileen Daly, Maria Gudbrandsen, Clodagh M Murphy, Declan Murphy, Michael Craig, Jacob Vorstman, Ania Fiksinski, Sanne Koops, Kosha Ruparel, David R Roalf, Raquel E Gur, J Eric Schmitt, Tony J Simon, Naomi J Goodrich-Hunsaker, Courtney A Durdle, Anne S Bassett, Eva W C Chow, Nancy J Butcher, Fidel Vila-Rodriguez, Joanne Doherty, Adam Cunningham, Marianne B M van den Bree, David E J Linden, Hayley Moss, Michael J Owen, Kieran C Murphy, Donna M McDonald-McGinn, Beverly Emanuel, Theo G M van Erp, Jessica A Turner, Paul M Thompson, Carrie E Bearden
The 22q11.2 deletion (22q11DS) is a common chromosomal microdeletion and a potent risk factor for psychotic illness. Prior studies reported widespread cortical changes in 22q11DS, but were generally underpowered to characterize neuroanatomic abnormalities associated with psychosis in 22q11DS, and/or neuroanatomic effects of variability in deletion size. To address these issues, we developed the ENIGMA (Enhancing Neuro Imaging Genetics Through Meta-Analysis) 22q11.2 Working Group, representing the largest analysis of brain structural alterations in 22q11DS to date...
June 13, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29794033/prediction-of-response-to-drug-therapy-in-psychiatric-disorders
#2
REVIEW
Shani Stern, Sara Linker, Krishna C Vadodaria, Maria C Marchetto, Fred H Gage
Personalized medicine has become increasingly relevant to many medical fields, promising more efficient drug therapies and earlier intervention. The development of personalized medicine is coupled with the identification of biomarkers and classification algorithms that help predict the responses of different patients to different drugs. In the last 10 years, the Food and Drug Administration (FDA) has approved several genetically pre-screened drugs labelled as pharmacogenomics in the fields of oncology, pulmonary medicine, gastroenterology, haematology, neurology, rheumatology and even psychiatry...
May 2018: Open Biology
https://www.readbyqxmd.com/read/29778275/quantifying-the-effects-of-16p11-2-copy-number-variants-on-brain-structure-a-multisite-genetic-first-study
#3
Sandra Martin-Brevet, Borja Rodríguez-Herreros, Jared A Nielsen, Clara Moreau, Claudia Modenato, Anne M Maillard, Aurélie Pain, Sonia Richetin, Aia E Jønch, Abid Y Qureshi, Nicole R Zürcher, Philippe Conus, Wendy K Chung, Elliott H Sherr, John E Spiro, Ferath Kherif, Jacques S Beckmann, Nouchine Hadjikhani, Alexandre Reymond, Randy L Buckner, Bogdan Draganski, Sébastien Jacquemont
BACKGROUND: 16p11.2 breakpoint 4 to 5 copy number variants (CNVs) increase the risk for developing autism spectrum disorder, schizophrenia, and language and cognitive impairment. In this multisite study, we aimed to quantify the effect of 16p11.2 CNVs on brain structure. METHODS: Using voxel- and surface-based brain morphometric methods, we analyzed structural magnetic resonance imaging collected at seven sites from 78 individuals with a deletion, 71 individuals with a duplication, and 212 individuals without a CNV...
March 27, 2018: Biological Psychiatry
https://www.readbyqxmd.com/read/29773754/a-critical-neurodevelopmental-role-for-l-type-voltage-gated-calcium-channels-in-neurite-extension-and-radial-migration
#4
Satoshi Kamijo, Yuichiro Ishii, Shin-Ichiro Horigane, Kanzo Suzuki, Masamichi Ohkura, Junichi Nakai, Hajime Fujii, Sayaka Takemoto-Kimura, Haruhiko Bito
In spite of many association studies linking gene polymorphisms and mutations of L-type Voltage-Gated Ca2+ Channels (VGCC) in neurodevelopmental disorders, such as autism and schizophrenia, specific L-type VGCC roles during brain development remain unclear. Yet, calcium signaling has been shown to be essential for neurodevelopmental processes such as sculpting of neurites, functional wiring and fine tuning of growing networks. To bridge this gap, we performed submembraneous calcium imaging using a membrane-tethered genetically-encoded calcium indicator (GECI) Lck-G-CaMP7...
May 17, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29748770/a-systematic-review-of-associations-between-functional-mri-activity-and-polygenic-risk-for-schizophrenia-and-bipolar-disorder
#5
REVIEW
Zalina Dezhina, Siri Ranlund, Marinos Kyriakopoulos, Steve C R Williams, Danai Dima
Genetic factors account for up to 80% of the liability for schizophrenia (SCZ) and bipolar disorder (BD). Genome-wide association studies have successfully identified several genes associated with increased risk for both disorders. This has allowed researchers to model the aggregate effect of genes associated with disease status and create a polygenic risk score (PGRS) for each individual. The interest in imaging genetics using PGRS has grown in recent years, with several studies now published. We have conducted a systematic review to examine the effects of PGRS of SCZ, BD and cross psychiatric disorders on brain function and connectivity using fMRI data...
May 10, 2018: Brain Imaging and Behavior
https://www.readbyqxmd.com/read/29730826/using-coordinate-based-meta-analyses-to-explore-structural-imaging-genetics
#6
Hildegard Janouschek, Claudia R Eickhoff, Thomas W Mühleisen, Simon B Eickhoff, Thomas Nickl-Jockschat
Imaging genetics has become a highly popular approach in the field of schizophrenia research. A frequently reported finding is that effects from common genetic variation are associated with a schizophrenia-related structural endophenotype. Genetic contributions to a structural endophenotype may be easier to delineate, when referring to biological rather than diagnostic criteria. We used coordinate-based meta-analyses, namely the anatomical likelihood estimation (ALE) algorithm on 30 schizophrenia-related imaging genetics studies, representing 44 single-nucleotide polymorphisms at 26 gene loci investigated in 4682 subjects...
May 5, 2018: Brain Structure & Function
https://www.readbyqxmd.com/read/29730044/association-between-catechol-o-methyltransferase-genetic-variation-and-functional-connectivity-in-patients-with-first-episode-schizophrenia
#7
Hongyan Wang, Bin Zhang, Botao Zeng, Yingying Tang, Tianhong Zhang, Shanshan Zhao, Chunbo Li, Jijun Wang, Donald C Goff
Dopamine in the prefrontal cortex (PFC) plays an important role in cognitive performance and regulates by catechol-O-methyltransferase (COMT) expression. To clarify the effect of COMT genotype on cognitive function in patients with schizophrenia, we performed DNA genotyping, cognitive evaluations, and functional magnetic resonance imaging (fMRI) in antipsychotic-naïve patients with first-episode schizophrenia (FES) and matched healthy control subjects. We found that all cognitive domains were impaired in patients with FES compared with healthy subjects...
May 3, 2018: Schizophrenia Research
https://www.readbyqxmd.com/read/29728906/altered-voxel-wise-gray-matter-structural-brain-networks-in-schizophrenia-association-with-brain-genetic-expression-pattern
#8
Feng Liu, Hongjun Tian, Jie Li, Shen Li, Chuanjun Zhuo
Previous seed- and atlas-based structural covariance/connectivity analyses have demonstrated that patients with schizophrenia is accompanied by aberrant structural connection and abnormal topological organization. However, it remains unclear whether this disruption is present in unbiased whole-brain voxel-wise structural covariance networks (SCNs) and whether brain genetic expression variations are linked with network alterations. In this study, ninety-five patients with schizophrenia and 95 matched healthy controls were recruited and gray matter volumes were extracted from high-resolution structural magnetic resonance imaging scans...
May 4, 2018: Brain Imaging and Behavior
https://www.readbyqxmd.com/read/29721851/deconstructing-schizophrenia-advances-in-preclinical-models-for-biomarker-identification
#9
Judith A Pratt, Brian Morris, Neil Dawson
Schizophrenia is considered to develop as a consequence of genetic and environmental factors impacting on brain neural systems and circuits during vulnerable neurodevelopmental periods, thereby resulting in symptoms in early adulthood. Understanding of the impact of schizophrenia risk factors on brain biology and behaviour can help in identifying biologically relevant pathways that are attractive for informing clinical studies and biomarker development. In this chapter, we emphasize the importance of adopting a reciprocal forward and reverse translation approach that is iteratively updated when additional new information is gained, either preclinically or clinically, for offering the greatest opportunity for discovering panels of biomarkers for the diagnosis, prognosis and treatment of schizophrenia...
May 3, 2018: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/29704525/opportunities-and-challenges-for-using-the-zebrafish-to-study-neuronal-connectivity-as-an-endpoint-of-developmental-neurotoxicity
#10
REVIEW
Galen W Miller, Vidya Chandrasekaran, Bianca Yaghoobi, Pamela J Lein
Chemical exposures have been implicated as environmental risk factors that interact with genetic susceptibilities to influence individual risk for complex neurodevelopmental disorders, including autism spectrum disorder, schizophrenia, attention deficit hyperactivity disorder and intellectual disabilities. Altered patterns of neuronal connectivity represent a convergent mechanism of pathogenesis for these and other neurodevelopmental disorders, and growing evidence suggests that chemicals can interfere with specific signaling pathways that regulate the development of neuronal connections...
April 25, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29700391/effects-of-autozygosity-and-schizophrenia-polygenic-risk-on-cognitive-and-brain-developmental-trajectories
#11
Aldo Córdova-Palomera, Tobias Kaufmann, Francesco Bettella, Yunpeng Wang, Nhat Trung Doan, Dennis van der Meer, Dag Alnæs, Jaroslav Rokicki, Torgeir Moberget, Ida Elken Sønderby, Ole A Andreassen, Lars T Westlye
Cognitive and brain development are determined by dynamic interactions between genes and environment across the lifespan. Aside from marker-by-marker analyses of polymorphisms, biologically meaningful features of the whole genome (derived from the combined effect of individual markers) have been postulated to inform on human phenotypes including cognitive traits and their underlying biological substrate. Here, estimates of inbreeding and genetic susceptibility for schizophrenia calculated from genome-wide data-runs of homozygosity (ROH) and schizophrenia polygenic risk score (PGRS)-are analyzed in relation to cognitive abilities (n = 4183) and brain structure (n = 516) in a general-population sample of European-ancestry participants aged 8-22, from the Philadelphia Neurodevelopmental Cohort...
April 27, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29696604/genomic-and-imaging-biomarkers-in-schizophrenia
#12
J T Reddaway, J L Doherty, T Lancaster, D Linden, J T Walters, J Hall
Recent large-scale genomic studies have confirmed that schizophrenia is a polygenic syndrome and have implicated a number of biological pathways in its aetiology. Both common variants individually of small effect and rarer but more penetrant genetic variants have been shown to play a role in the pathogenesis of the disorder. No simple Mendelian forms of the condition have been identified, but progress has been made in stratifying risk on the basis of the polygenic burden of common variants individually of small effect, and the contribution of rarer variants of larger effect such as Copy Number Variants (CNVs)...
April 26, 2018: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/29678679/formal-thought-disorders-from-phenomenology-to-neurobiology
#13
REVIEW
Tilo Kircher, Henrike Bröhl, Felicitas Meier, Jennifer Engelen
Formal thought disorder (FTD) is present in most psychiatric disorders and in some healthy individuals. In this Review, we present a comprehensive, integrative, and multilevel account of what is known about FTD, covering genetic, cellular, and neurotransmitter effects, environmental influences, experimental psychology and neuropsychology, brain imaging, phenomenology, linguistics, and treatment. FTD is a dimensional, phenomenologically defined construct, which can be clinically subdivided into positive versus negative and objective versus subjective symptom clusters...
June 2018: Lancet Psychiatry
https://www.readbyqxmd.com/read/29626338/imaging-and-genetic-biomarkers-predicting-transition-to-psychosis
#14
Stuart A Hunter, Stephen M Lawrie
The search for diagnostic and prognostic biomarkers in schizophrenia care and treatment is the focus of many within the research community. Longitudinal cohorts of patients presenting at elevated genetic and clinical risk have provided a wealth of data that has informed our understanding of the development of schizophrenia and related psychotic disorders.Imaging follow-up of high-risk cohorts has demonstrated changes in cerebral grey matter of those that eventually transition to schizophrenia that predate the onset of symptoms and evolve over the course of illness...
April 7, 2018: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/29608775/structural-and-functional-neuroimaging-of-polygenic-risk-for-schizophrenia-a-recall-by-genotype-based-approach
#15
Thomas M Lancaster, Stavros L Dimitriadis, Katherine E Tansey, Gavin Perry, Niklas Ihssen, Derek K Jones, Krish D Singh, Peter Holmans, Andrew Pocklington, George Davey Smith, Stan Zammit, Jeremy Hall, Michael C O'Donovan, Michael J Owen, David E Linden
Risk profile scores (RPS) derived from genome-wide association studies (GWAS) explain a considerable amount of susceptibility for schizophrenia (SCZ). However, little is known about how common genetic risk factors for SCZ influence the structure and function of the human brain, largely due to the constraints of imaging sample sizes. In the current study, we use a novel recall-by-genotype (RbG) methodological approach, where we sample young adults from a population cohort (Avon Longitudinal Study of Parents and Children: N genotyped = 8365) based on their SCZ-RPS...
March 28, 2018: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/29545739/variability-in-resting-state-network-and-functional-network-connectivity-associated-with-schizophrenia-genetic-risk-a-pilot-study
#16
Jiayu Chen, Barnaly Rashid, Qingbao Yu, Jingyu Liu, Dongdong Lin, Yuhui Du, Jing Sui, Vince D Calhoun
Imaging genetics posits a valuable strategy for elucidating genetic influences on brain abnormalities in psychiatric disorders. However, association analysis between 2D genetic data (subject × genetic variable) and 3D first-level functional magnetic resonance imaging (fMRI) data (subject × voxel × time) has been challenging given the asymmetry in data dimension. A summary feature needs to be derived for the imaging modality to compute inter-modality association at subject level. In this work, we propose to use variability in resting state networks (RSNs) and functional network connectivity (FNC) as potential features for purpose of association analysis...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29527499/visual-processing-deficits-in-22q11-2-deletion-syndrome
#17
Marjan Biria, Miralena I Tomescu, Anna Custo, Lucia M Cantonas, Kun-Wei Song, Maude Schneider, Micah M Murray, Stephan Eliez, Christoph M Michel, Tonia A Rihs
Carriers of the rare 22q11.2 microdeletion present with a high percentage of positive and negative symptoms and a high genetic risk for schizophrenia. Visual processing impairments have been characterized in schizophrenia, but less so in 22q11.2 Deletion Syndrome (DS). Here, we focus on visual processing using high-density EEG and source imaging in 22q11.2DS participants (N = 25) and healthy controls (N = 26) with an illusory contour discrimination task. Significant differences between groups emerged at early and late stages of visual processing...
2018: NeuroImage: Clinical
https://www.readbyqxmd.com/read/29527495/orbitofrontal-sulcogyral-morphology-is-a-transdiagnostic-indicator-of-brain-dysfunction
#18
Marisa A Patti, Vanessa Troiani
Atypical sulcogyral patterns in the orbitofrontal cortex (OFC) are associated with increased risk for schizophrenia, as well as with quantitative traits associated with schizophrenia, such as anhedonia. Here we conduct a cross-diagnostic comparison to assess whether atypical OFC sulcogyral patterns confer risk for multiple brain disorders. We examined structural images from 4 groups of adult participants (N = 189), including those diagnosed with schizophrenia (SZ; N = 49), bipolar disorder (BP; N = 46), attention deficit hyperactivity disorder (ADHD; N = 41), and controls (N = 53)...
2018: NeuroImage: Clinical
https://www.readbyqxmd.com/read/29496125/reduced-functional-brain-activation-and-connectivity-during-a-working-memory-task-in-childhood-onset-schizophrenia
#19
Frances F Loeb, Xueping Zhou, Kirsten E S Craddock, Lorie Shora, Diane D Broadnax, Peter Gochman, Liv S Clasen, Francois M Lalonde, Rebecca A Berman, Karen F Berman, Judith L Rapoport, Siyuan Liu
OBJECTIVE: Working memory (WM) deficits are consistently reported in schizophrenia and are related to poor functional outcomes. Functional magnetic resonance imaging studies of adult-onset schizophrenia have reported decreased functional activations and connectivity in the WM network, but no prior functional magnetic resonance imaging study has examined WM in childhood-onset schizophrenia (COS). The aim of this study was to examine the neural correlates of WM in COS. METHOD: Adult patients with COS (n = 32, 21...
March 2018: Journal of the American Academy of Child and Adolescent Psychiatry
https://www.readbyqxmd.com/read/29485852/functionally-biased-d2r-antagonists-targeting-the-%C3%AE-arrestin-pathway-to-improve-antipsychotic-treatment
#20
Michel Weïwer, Qihong Xu, Jennifer P Gale, Michael Lewis, Arthur J Campbell, Frederick A Schroeder, Genevieve C Van de Bittner, Michelle Walk, Aldo Amaya, Ping Su, Luka D Ordevic, Joshua R Sacher, Adam Skepner, David Fei, Kelly Dennehy, Shannon Nguyen, Patrick W Faloon, Jose Perez, Jeffrey R Cottrell, Fang Liu, Michelle Palmer, Jen Q Pan, Jacob M Hooker, Yan-Ling Zhang, Edward Scolnick, Florence F Wagner, Edward B Holson
Schizophrenia is a severe neuropsychiatric disease that lacks completely effective and safe therapies. As a polygenic disorder, genetic studies have only started to shed light on its complex etiology. To date, the positive symptoms of schizophrenia are well-managed by antipsychotic drugs, which primarily target the dopamine D2 receptor (D2R). However, these antipsychotics are often accompanied by severe side effects, including motoric symptoms. At D2R, antipsychotic drugs antagonize both G-protein dependent (Gαi/o ) signaling and G-protein independent (β-arrestin) signaling...
April 20, 2018: ACS Chemical Biology
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