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Schizophrenia Imaging Genetics

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
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
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
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
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...
September 1, 2016: Neuroscience and Biobehavioral Reviews
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...
August 11, 2016: Human Brain Mapping
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
Jian Fang, Dongdong Lin, 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...
July 27, 2016: Bioinformatics
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
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
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
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
Hye Yoon Park, Je-Yeon Yun, Na Young Shin, So-Yeon Kim, Wi Hoon Jung, Ye Seul Shin, Kang Ik K Cho, Youngwoo Bryan Yoon, Kyung-Ok Lim, Sung Nyun Kim, Jun Soo Kwon
BACKGROUND: Patients with schizophrenia show impairment in facial emotion processing which is essential for successful social cognition. Using a functional magnetic resonance imaging (fMRI), this study aimed to investigate the implicit facial emotion recognition processing in participants with high genetic load for schizophrenia (GHR) as a possible trait marker of developing schizophrenia. METHODS: Block design fMRI of implicit facial emotion processing was used in 20 participants with GHR aged 16-35, and 17 age, sex, and education year-matched healthy controls (HC)...
November 3, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
Christiane Mühle, Jakob Kreczi, Cosima Rhein, Tanja Richter-Schmidinger, Panagiotis Alexopoulos, Arnd Doerfler, Bernd Lenz, Johannes Kornhuber
The disrupted-in-schizophrenia-1 (DISC1) gene is known for its role in the development of mental disorders. It is also involved in neurodevelopment, cognition, and memory. To investigate the association between DISC1 variants and brain morphology, we analyzed the influence of the three common non-synonymous polymorphisms in DISC1 on specific brain structures in healthy young adults. The volumes of brain regions were determined in 145 subjects by magnetic resonance imaging and automated analysis using FreeSurfer...
July 1, 2016: Brain Structure & Function
Andrea Schmitt, Dan Rujescu, Micha Gawlik, Alkomiet Hasan, Kenji Hashimoto, Sylvain Iceta, Marek Jarema, Joseph Kambeitz, Siegfried Kasper, Daniel Keeser, Johannes Kornhuber, Nikolaos Koutsouleris, Rupert Lanzenberger, Berend Malchow, Mohamed Saoud, Marie Spies, Gerald Stöber, Florence Thibaut, Peter Riederer, Peter Falkai
OBJECTIVES: Schizophrenia is a group of severe psychiatric disorders with high heritability but only low odds ratios of risk genes. Despite progress in the identification of pathophysiological processes, valid biomarkers of the disease are still lacking. METHODS: This comprehensive review summarises recent efforts to identify genetic underpinnings, clinical and cognitive endophenotypes and symptom dimensions of schizophrenia and presents findings from neuroimaging studies with structural, functional and spectroscopy magnetic resonance imaging and positron emission tomography...
September 2016: World Journal of Biological Psychiatry
Lisa Buchy, Daniel H Mathalon, Tyrone D Cannon, Kristin S Cadenhead, Barbara A Cornblatt, Thomas H McGlashan, Diana O Perkins, Larry J Seidman, Ming T Tsuang, Elaine F Walker, Scott W Woods, Carrie E Bearden, Jean Addington
Among people at genetic risk of schizophrenia, those who use cannabis show smaller thalamic and hippocampal volumes. We evaluated this relationship in people at clinical high risk (CHR) of psychosis. The Alcohol and Drug Use Scale was used to identify 132 CHR cannabis users, the majority of whom were non-dependent cannabis users, 387 CHR non-users, and 204 healthy control non-users, and all participants completed magnetic resonance imaging scans. Volumes of the thalamus, hippocampus and amygdala were extracted with FreeSurfer, and compared across groups...
August 30, 2016: Psychiatry Research
Yi Shin Chang, Julia P Owen, Nicholas J Pojman, Tony Thieu, Polina Bukshpun, Mari L J Wakahiro, Elysa J Marco, Jeffrey I Berman, John E Spiro, Wendy K Chung, Randy L Buckner, Timothy P L Roberts, Srikantan S Nagarajan, Elliott H Sherr, Pratik Mukherjee
Copy number variants at the 16p11.2 chromosomal locus are associated with several neuropsychiatric disorders, including autism, schizophrenia, bipolar disorder, attention-deficit hyperactivity disorder, and speech and language disorders. A gene dosage dependence has been suggested, with 16p11.2 deletion carriers demonstrating higher body mass index and head circumference, and 16p11.2 duplication carriers demonstrating lower body mass index and head circumference. Here, we use diffusion tensor imaging to elucidate this reciprocal relationship in white matter organization, showing widespread increases of fractional anisotropy throughout the supratentorial white matter in pediatric deletion carriers and, in contrast, extensive decreases of white matter fractional anisotropy in pediatric and adult duplication carriers...
August 2016: Human Brain Mapping
Claire M Kaplan, Debjani Saha, Juan L Molina, William D Hockeimer, Elizabeth M Postell, Jose A Apud, Daniel R Weinberger, Hao Yang Tan
SEE STEPHAN ET AL DOI101093/AWW120 FOR A SCIENTIFIC COMMENTARY ON THIS WORK: Real world information is often abstract, dynamic and imprecise. Deciding if changes represent random fluctuations, or alterations in underlying contexts involve challenging probability estimations. Dysfunction may contribute to erroneous beliefs, such as delusions. Here we examined brain function during inferences about context change from noisy information. We examined cortical-subcortical circuitry engaging anterior and dorsolateral prefrontal cortex, and midbrain...
July 2016: Brain: a Journal of Neurology
Soumee Bhattacharya, Rodrigo Herrera-Molina, Victor Sabanov, Tariq Ahmed, Emilia Iscru, Franziska Stöber, Karin Richter, Klaus-Dieter Fischer, Frank Angenstein, Jürgen Goldschmidt, Philip W Beesley, Detlef Balschun, Karl-Heinz Smalla, Eckart D Gundelfinger, Dirk Montag
BACKGROUND: Neuroplastin cell recognition molecules have been implicated in synaptic plasticity. Polymorphisms in the regulatory region of the human neuroplastin gene (NPTN) are correlated with cortical thickness and intellectual abilities in adolescents and in individuals with schizophrenia. METHODS: We characterized behavioral and functional changes in inducible conditional neuroplastin-deficient mice. RESULTS: We demonstrate that neuroplastins are required for associative learning in conditioning paradigms, e...
April 11, 2016: Biological Psychiatry
Patrick Domen, Sanne Peeters, Stijn Michielse, Ed Gronenschild, Wolfgang Viechtbauer, Alard Roebroeck, Jim van Os, Machteld Marcelis
BACKGROUND: Although widespread reduced white matter (WM) integrity is a consistent finding in cross-sectional diffusion tensor imaging (DTI) studies of schizophrenia, little is known about the course of these alterations. This study examined to what degree microstructural WM alterations display differential trajectories over time as a function of level of psychosis liability. METHODS: Two DTI scans with a 3-year time interval were acquired from 159 participants (55 patients with a psychotic disorder, 55 nonpsychotic siblings and 49 healthy controls) and processed with tract-based spatial statistics...
May 17, 2016: Schizophrenia Bulletin
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