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Schizophrenia etiology

Joaquín C Martín, María J Acuña, José Labrador, Matilde Blanco, Cristina Casas
INTRODUCTION: Despite the high prevalence of sexual dysfunction in patients with schizophrenia, its origins are still unclear. THE AIM OF THIS STUDY: to determine the prevalence and causal factors of sexual dysfunction in a group of outpatients with schizophrenia. METHODS: The study was designed to be cross-sectional and naturalistic, including outpatients with schizophrenia undergoing second generation antipsychotic monotherapy. Patients receiving antidepressants and/or mood stabilisers were excluded...
November 2018: Actas Españolas de Psiquiatría
Mark Z Kos, Jubao Duan, Alan R Sanders, Lucy Blondell, Eugene I Drigalenko, Melanie A Carless, Pablo V Gejman, Harald H H Göring
The dopaminergic hypothesis of schizophrenia (SZ) postulates that positive symptoms of SZ, in particular psychosis, are due to disturbed neurotransmission via the dopamine (DA) receptor D2 (DRD2). However, DA is a reactive molecule that yields various oxidative species, and thus has important non-receptor-mediated effects, with empirical evidence of cellular toxicity and neurodegeneration. Here we examine non-receptor-mediated effects of DA on gene co-expression networks and its potential role in SZ pathology...
December 13, 2018: Translational Psychiatry
Chun Chieh Fan, John J McGrath, Vivek Appadurai, Alfonso Buil, Michael J Gandal, Andrew J Schork, Preben Bo Mortensen, Esben Agerbo, Sandy A Geschwind, Daniel Geschwind, Thomas Werge, Wesley K Thompson, Carsten Bøcker Pedersen
Spatial mapping is a promising strategy to investigate the mechanisms underlying the incidence of psychosis. We analyzed a case-cohort study (n = 24,028), drawn from the 1.47 million Danish persons born between 1981 and 2005, using a novel framework for decomposing the geospatial risk for schizophrenia based on locale of upbringing and polygenic scores. Upbringing in a high environmental risk locale increases the risk for schizophrenia by 122%. Individuals living in a high gene-by-environmental risk locale have a 78% increased risk compared to those who have the same genetic liability but live in a low-risk locale...
December 13, 2018: Nature Communications
Artur Reginia, Jolanta Kucharska-Mazur, Marcin Jabłoński, Marta Budkowska, Barbara Dołȩgowska, Leszek Sagan, Błazej Misiak, Mariusz Z Ratajczak, Janusz K Rybakowski, Jerzy Samochowiec
Introduction: The immune system is undoubtedly involved in the pathogenesis of various psychiatric disorders, such as schizophrenia, bipolar disorder, or depression. Although its role is not fully understood, it appears that this area of research can help to understand the etiology of mental illness. One of the components of the human immune system is the complement system, which forms a part of the innate immune response. Physiologically, except for its essential protective role, it is a vital element in the regeneration processes, including neurogenesis...
2018: Frontiers in Psychiatry
Monika Mak, Jerzy Samochowiec, Dorota Frydecka, Justyna Pełka-Wysiecka, Elżbieta Szmida, Paweł Karpiński, Maria M Sąsiadek, Patryk Piotrowski, Agnieszka Samochowiec, Błażej Misiak
Human endogenous retroviruses (HERV) have been widely associated with schizophrenia etiology. Aberrant epigenetic processes may play a role in the etiology of schizophrenia. In this study, we tested whether schizophrenia patients at different stages of illness might present alterations in the levels of HERV-K methylation. We recruited 49 first-episode schizophrenia (FES) patients with 47 age- and sex-matched healthy controls (HCs), and 100 multi-episode schizophrenia (MES) patients with 50 age- and sex-matched HCs...
December 3, 2018: Psychiatry Research
Xianjun Chen, Huifeng Duan, Lan Xiao, Jingli Gan
Numerous genetic risk loci are found to associate with major neuropsychiatric disorders represented by schizophrenia. The pathogenic roles of genetic risk loci in psychiatric diseases are further complicated by the association with cell lineage- and/or developmental stage-specific epigenetic alterations. Besides aberrant assembly and malfunction of neuronal circuitry, an increasing volume of discoveries clearly demonstrate impairment of oligodendroglia and disruption of white matter integrity in psychiatric diseases...
2018: Frontiers in Genetics
Ole Köhler-Forsberg, Liselotte Petersen, Christiane Gasse, Preben B Mortensen, Soren Dalsgaard, Robert H Yolken, Ole Mors, Michael E Benros
Importance: Infections have been associated with increased risks for mental disorders, such as schizophrenia and depression. However, the association between all infections requiring treatment and the wide range of mental disorders is unknown to date. Objective: To investigate the association between all treated infections since birth and the subsequent risk of development of any treated mental disorder during childhood and adolescence. Design, Setting, and Participants: Population-based cohort study using Danish nationwide registers...
December 5, 2018: JAMA Psychiatry
Liang Ma, Edmund T Rolls, Xiuqin Liu, Yuting Liu, Zeyu Jiao, Yue Wang, Weikang Gong, Zhiming Ma, Fuzhou Gong, Lin Wan
Analysis linking directly genomics, neuroimaging phenotypes and clinical measurements is crucial for understanding psychiatric disorders, but remains rare. Here, we describe a multi-scale analysis using genome-wide SNPs, gene-expression, grey matter volume (GMV) and the Positive and Negative Syndrome Scale scores (PANSS) to explore the etiology of schizophrenia. With 72 drug-naive schizophrenic first episode patients (FEPs) and 73 matched heathy controls, we identified 108 genes, from schizophrenia risk genes, that correlated significantly with GMV, which are highly co-expressed in the brain during development...
December 3, 2018: Journal of Molecular Cell Biology
Sakthivel Sekar, Joanes Grandjean, Joanne Fv Garnell, Roland Willems, Hilde Duytschaever, Sankar Seramani, Huang Su, Luc Ver Donck, Kishore K Bhakoo
Neuroimaging endophenotypes in animal models provide an objective and translationally-relevant alternative to cognitive/behavioral traits in human psychopathologies. Metabolic alterations, such as those involved in the glutamate-cycle, have been proposed to play a preponderant role in both depression and schizophrenia. Chronic Mild Unpredictable Stress (CMUS) and sub-chronic administration of NMDA receptor antagonist generate animal models of depression and schizophrenia, respectively. The models are based on etiologically-relevant factors related to the induction and support of these psychopathologies...
November 22, 2018: Neuropharmacology
Emily G Severance, Robert H Yolken
The body's microbiome represents an actively regulated network of novel mechanisms that potentially underlie the etiology and pathophysiology of a wide range of diseases. For complex brain disorders such as schizophrenia, understanding the cellular and molecular pathways that intersect the bidirectional gut-brain axis is anticipated to lead to new methods of treatment. The means by which the microbiome might differ across neuropsychiatric and neurological disorders are not known. Brain disorders as diverse as schizophrenia, major depression, Parkinson's disease and multiple sclerosis appear to share a common pathology of an imbalanced community of commensal microbiota, often measured in terms of a leaky gut phenotype accompanied by low level systemic inflammation...
November 21, 2018: Neurobiology of Disease
Alish B Palmos, Gerome Breen, Laura Goodwin, Souci Frissa, Stephani L Hatch, Matthew Hotopf, Sandrine Thuret, Cathryn M Lewis, Timothy R Powell
Background: Previous studies have revealed associations between psychiatric disorder diagnosis and shorter telomere length. Here, we attempt to discern whether genetic risk for psychiatric disorders, or use of pharmacological treatments (i.e., antidepressants), predict shorter telomere length and risk for aging-related disease in a United Kingdom population sample. Methods: DNA samples from blood were available from 351 participants who were recruited as part of the South East London Community Health (SELCoH) Study, and for which whole-genome genotype data was available...
2018: Frontiers in Genetics
Danhong Wang, Meiling Li, Meiyun Wang, Franziska Schoeppe, Jianxun Ren, Huafu Chen, Dost Öngür, Justin T Baker, Hesheng Liu
Neuroimaging studies of psychotic disorders have demonstrated abnormalities in structural and functional connectivity involving widespread brain networks. However, these group-level observations have failed to yield any biomarkers that can provide confirmatory evidence of a patient's current symptoms, predict future symptoms, or predict a treatment response. Lack of precision in both neuroanatomical and clinical boundaries have likely contributed to the inability of even well-powered studies to resolve these key relationships...
November 15, 2018: Molecular Psychiatry
Elena Minakova, Barbara B Warner
Maternal immune activation (MIA) refers to a maternal immune system triggered by infectious or infectious-like stimuli. A cascade of cytokines and immunologic alterations are transmitted to the fetus, resulting in adverse phenotypes most notably in the central nervous system. Epidemiologic studies implicate maternal infections in a variety of neuropsychiatric disorders, most commonly autism spectrum disorders and schizophrenia. In animal models, MIA causes neurochemical and anatomic changes in the brain that correspond to those found in humans with the disorders...
November 14, 2018: Birth Defects Research
In Wook Hwang, Bit Na Kwon, Hyung Jun Kim, Seung Hun Han, Noo Ri Lee, Myung Ho Lim, Ho Jang Kwon, Han Jun Jin
Attention deficit hyperactivity disorder (ADHD) is a multifactorial disorder with multiple environmental and biological etiologies, including genetic factors. Until now, several genetic variants have been reported to be significantly associated with ADHD. Recently, the relationship between mitochondrial DNA (mtDNA) haplogroups and psychiatric disorders such as schizophrenia has also been reported. However, currently there are no reports pertaining to the genetic association between mtDNA haplogroups and ADHD...
November 10, 2018: Mitochondrion
Samane Abbasy, Fazlollah Shahraki, Arvin Haghighatfard, Masoume Ghasemzadeh Qazvini, Sahel Towfigh Rafiei, Elnaz Noshadirad, Mahdi Farhadi, Horie Rezvani Asl, Atena Alsadat Shiryazdi, Rana Ghamari, Zeinab Tabrizi, Rashed Mehrfard, Fereshteh Esmaili Kakroudi, Mahsima Azarnoosh, Faeghe Younesi, Narges Parsamehr, Nooriyeh Garaei, Soroush Abyari, Maede Salehi, Maryam Gholami, Pardis Zolfaghari, Seyede Mahsa Bagheri, Melika Pourmehrabi, Elham Rastegarimogaddam, Elnaz Nobakht, Elmira Nobakht, Rayan Partovi
BACKGROUND: Autism spectrum disorder (ASD) is a pediatric heterogeneous psychiatric and neurodevelopmental disorder with social and communication deficits, language impairment and ritualistic or repetitive behaviors. ASD has significant genetic bases but candidate genes and molecular mechanisms of disorder are not clarified. Neuregulin1 (NRG1) gene, located in 8p12 is involved in development of central nervous system and was indicated as candidate gene in schizophrenia. METHODS: mRNA level of types I, II and III of NRG1 gene were studied in peripheral blood of 1540 ASD patients (IQ > 70) and 1490 control children by quantitative Real Time PCR...
November 8, 2018: EBioMedicine
Anna Racioppi, Tamara Sheinbaum, Georgina M Gross, Sergi Ballespí, Thomas R Kwapil, Neus Barrantes-Vidal
The present study extends previous cross-sectional findings by examining the predictive validity of positive and negative schizotypy in a young adult sample at a three-year follow-up. Schizotypy and schizophrenia share a comparable multidimensional structure with positive and negative dimensions being the most strongly supported factors. Previous cross-sectional and longitudinal studies employing the psychometric high-risk strategy indicated that schizotypy is a useful method for identifying risk and resilience factors for the development of schizophrenia-spectrum psychopathology...
2018: PloS One
Erbo Dong, Valentina Locci, Eleonora Gatta, Dennis R Grayson, Alessandro Guidotti
Schizophrenia (SZ), schizoaffective (SZA), and bipolar (BP) are neurodevelopmental psychopathological conditions related, in part, to genetic load and, in part, to environmentally-induced epigenetic dysregulation of chromatin structure and function in neocortical GABAergic, glutamatergic and monoaminergic neurons. In order to test the above hypothesis, we targeted our scientific efforts on identifying whether the molecular epigenetic signature of post-mortem brains of SZ, SZA, and BP disorder patients are also present in the brains of adult mice born from dams prenatally restraint-stressed during gestation...
November 5, 2018: Molecular Pharmacology
Matthew L MacDonald, Daley Favo, Megan Garver, Zhe Sun, Dominique Arion, Ying Ding, Nathan Yates, Robert A Sweet, David A Lewis
The mammalian neocortex is organized into layers distinguished by the size, packing density, and connectivity of their constituent neurons. Many neuropsychiatric illnesses are complex trait disorders with etiologic factors converging on neuronal protein networks. Cortical pathology of neuropsychiatric diseases, such as schizophrenia, is often restricted to, or more pronounced in, certain cortical layers, suggesting that genetic vulnerabilities manifest with laminar specificity. Thus, the ability to investigate cortical layer-specific protein levels in human postmortem brain is highly desirable...
November 2, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Andreas Heinz, Graham K Murray, Florian Schlagenhauf, Philipp Sterzer, Anthony A Grace, James A Waltz
Psychotic experiences may be understood as altered information processing due to aberrant neural computations. A prominent example of such neural computations is the computation of prediction errors (PEs), which signal the difference between expected and experienced events. Among other areas showing PE coding, hippocampal-prefrontal-striatal neurocircuits play a prominent role in information processing. Dysregulation of dopaminergic signaling, often secondary to psychosocial stress, is thought to interfere with the processing of biologically important events (such as reward prediction errors) and result in the aberrant attribution of salience to irrelevant sensory stimuli and internal representations...
November 2, 2018: Schizophrenia Bulletin
Özlem Miman, Özlem Özcan, Süheyla Ünal, Metin Atambay
BACKGROUND AND AIM: Obsessive-compulsive disorder (OCD) is a common neuropsychiatric illness. Although the etiology of OCD is still unknown, recent investigations have associated development of OCD with infectious illness. Toxoplasma gondii (T. gondii) is a neurotropic protozoan parasite that causes infection of the central nervous system. In the last decade, a lot of researches have focused on the possible relationship between exposure to T. gondii and neuropsychiatric disorders such as schizophrenia...
November 1, 2018: Nordic Journal of Psychiatry
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