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Schizophrenia etiology

Travis T Mallard, K Paige Harden, Kim Fromme
BACKGROUND: Emerging adulthood is a peak period of risk for alcohol and illicit drug use. Recent advances in psychiatric genetics suggest that the co-occurrence of substance use and psychopathology arises, in part, from a shared genetic etiology. We sought to extend this research by investigating the influence of genetic risk for schizophrenia on trajectories of four substance use behaviors as they occurred across emerging adulthood. METHOD: Young adult participants of non-Hispanic European descent provided DNA samples and completed daily reports of substance use for 1 month per year across 4 years (N = 30 085 observations of N = 342 participants)...
October 12, 2018: Psychological Medicine
Timothy Hughes, Ida E Sønderby, Tatiana Polushina, Lars Hansson, Asbjørn Holmgren, Lavinia Athanasiu, Christian Melbø-Jørgensen, Sahar Hassani, Louise K Hoeffding, Stefan Herms, Sarah E Bergen, Robert Karlsson, Jie Song, Marcella Rietschel, Markus M Nöthen, Andreas J Forstner, Per Hoffmann, Christina M Hultman, Mikael Landén, Sven Cichon, Thomas Werge, Ole A Andreassen, Stephanie Le Hellard, Srdjan Djurovic
Ankyrin-3 (ANK3) is one of the few genes that have been consistently identified as associated with bipolar disorder by multiple genome-wide association studies. However, the exact molecular basis of the association remains unknown. A rare loss-of-function splice-site SNP (rs41283526*G) in a minor isoform of ANK3 (incorporating exon ENSE00001786716) was recently identified as protective of bipolar disorder and schizophrenia. This suggests that an elevated expression of this isoform may be involved in the etiology of the disorders...
October 8, 2018: Translational Psychiatry
Jia-Hui Ma, Xiao-Yu Sun, Tong-Jun Guo, Emily Barot, Dong-Fang Wang, Lai-Lai Yan, Da-Wei Ni, Ning-Hua Huang, Qing Xie, Jing Zeng, Li Ou-Yang, Ya-Qiong Liu, Qing-Bin Lu
Schizophrenia is a major psychiatric disorder with complex genetic, environmental, and psychological etiologies. Although DISC1 gene has been shown as a risk factor for schizophrenia in some reports, there is a lack of a consensus. We therefore performed separate meta-analyses aiming to assess the associations between DISC1 SNPs and schizophrenia risk. We found that SNP rs821597 is significantly associated with schizophrenia risk in terms of both allelic and genotypic distribution, while SNP rs821616 is associated with schizophrenia in terms of genotypic distribution, especially in cases above 40 years old...
September 23, 2018: Psychiatry Research
Antígona Martínez, Pablo A Gaspar, Steven A Hillyard, Søren K Andersen, Javier Lopez-Calderon, Cheryl M Corcoran, Daniel C Javitt
OBJECTIVE: The ability to perceive the motion of biological objects, such as faces, is a critical component of daily function and correlates with the ability to successfully navigate social situations (social cognition). Deficits in motion perception in schizophrenia were first demonstrated about 20 years ago but remain understudied, especially in the early, potentially prodromal, stages of the illness. The authors examined the neural bases of visual sensory processing impairments, including motion, in patients with schizophrenia (N=63) and attenuated psychosis (clinical high risk) (N=32) compared with age-matched healthy control subjects (N=67)...
October 3, 2018: American Journal of Psychiatry
Hatice Altun, Nilfer Şahin, Ergül Belge Kurutaş, Olcay Güngör
BACKGROUND: In our study, we aimed to evaluate the serum homocysteine levels, pyridoxine, folate and vitamin B12 levels in children with attention deficit hyperactivity disorders (ADHD). SUBJECTS AND METHODS: This study included 30 newly diagnosed drug-naive children with ADHD (23 males and 7 female, mean age 9.3±1.8 years) and 30 sex-and age matched healthy controls. The diagnosis of ADHD was made according to DSM-V criteria. Children and adolescents were administered the Schedule for Affective Disorders and Schizophrenia for School Aged Children, Present and Lifetime Version, the Conners' Parent Rating Scale-Revised, Long Form, the Conners' Teacher Rating Scale and the Wechsler Intelligence Scale for Children Revised (WISC-R) for all participants...
September 2018: Psychiatria Danubina
Tilo Kircher, Markus Wöhr, Igor Nenadic, Rainer Schwarting, Gerhard Schratt, Judith Alferink, Carsten Culmsee, Holger Garn, Tim Hahn, Bertram Müller-Myhsok, Astrid Dempfle, Maik Hahmann, Andreas Jansen, Petra Pfefferle, Harald Renz, Marcella Rietschel, Stephanie H Witt, Markus Nöthen, Axel Krug, Udo Dannlowski
Genetic (G) and environmental (E) factors are involved in the etiology and course of the major psychoses (MP), i.e. major depressive disorder (MDD), bipolar disorder (BD), schizoaffective disorder (SZA) and schizophrenia (SZ). The neurobiological correlates by which these predispositions exert their influence on brain structure, function and course of illness are poorly understood. In the FOR2107 consortium, animal models and humans are investigated. A human cohort of MP patients, healthy subjects at genetic and/or environmental risk, and control subjects (N = 2500) has been established...
September 28, 2018: European Archives of Psychiatry and Clinical Neuroscience
Jiaxian Zhang, Yu Jing, Hu Zhang, David K Bilkey, Ping Liu
Microglia, the resident immune cells in the central nervous system, play critical roles in neurodevelopment, synaptic pruning and neuronal wiring. Early in development, microglia migrate via the tangential and radial migration pathways to their final destinations and mature gradually, a process that includes morphological changes. Recent research has implicated microglial abnormality in the etiology of schizophrenia. Since prenatal exposure to viral or bacterial infections due to maternal immune activation (MIA) leads to increased risk of schizophrenia in offspring during adulthood, the present study systematically investigated how MIA induced by polyinosinic:polycytidilic acid (a mimic of viral double stranded RNA) affected microglial immunoreactivity along the migration and maturation trajectories in the brains of male and female rat offspring at postnatal day (PND) 2...
September 26, 2018: Synapse
Cassandra Hoffmann, Tamsyn E Van Rheenen, Serafino G Mancuso, Andrew Zalesky, Jason Bruggemann, Rhoshel K Lenroot, Suresh Sundram, Cynthia Shannon Weickert, Thomas W Weickert, Christos Pantelis, Vanessa Cropley, Chad A Bousman
Genetic and environmental etiologies may contribute to schizophrenia and its associated neurobiological profile. We examined the interaction between dopaminergic polymorphisms, childhood adversity and diagnosis (schizophrenia/schizoaffective disorder) on dopamine-related brain structures. Childhood adversity histories and structural MRI data were obtained from 249 (153 schizophrenia/schizoaffective, 96 controls) participants registered in the Australian Schizophrenia Research Bank. Polymorphisms in DRD2 and COMT were genotyped and a dopaminergic risk allelic load (RAL) was calculated...
September 13, 2018: Psychiatry research. Neuroimaging
Philip R Jansen, Ryan L Muetzel, Tinca J C Polderman, Vincent W Jaddoe, Frank C Verhulst, Aad van der Lugt, Henning Tiemeier, Danielle Posthuma, Tonya White
BACKGROUND: Genome-wide association studies have identified numerous genetic variants that predispose to neuropsychiatric traits. Identification of mechanisms in the brain that underlie these associations is essential for understanding manifestations of genetic predisposition within the general population. Here, we investigated the association between polygenic scores (PGSs) for seven neuropsychiatric traits and white matter microstructure of the brain on diffusion tensor imaging in the pediatric population...
August 3, 2018: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Christiane Ziegler, Katharina Domschke
Epigenetic processes such as DNA methylation are considered key mechanisms at the crossroads between genetics and environment in the etiology of mental disorders. The monoamine oxidases A and B (MAOA/MAOB) are prime candidates for the investigation into the role of DNA methylation in mental disorders, given their pivotal role in the metabolism of monoamines and as pharmacological targets of potent antidepressant drugs such as tranylcypromine, phenelzine or moclobemide. The present mini-review aims at summarizing and critically discussing the growing body of the literature supporting a role of DNA methylation of the MAOA gene promoter/exon I/intron I region and its interaction with environmental factors in several mental disorders, i...
September 21, 2018: Journal of Neural Transmission
Benjamin A E Hunt, Elizabeth B Liddle, Lauren E Gascoyne, Lorenzo Magazzini, Bethany C Routley, Krish D Singh, Peter G Morris, Matthew J Brookes, Peter F Liddle
Introduction: Schizophrenia and schizotypal personality disorder (SPD) lie on a single spectrum of mental illness and converging evidence suggests similarities in the etiology of the 2 conditions. However, schizotypy is a heterogeneous facet of personality in the healthy population and so may be seen as a bridge between health and mental illness. Neural evidence for such a continuity would have implications for the characterization and treatment of schizophrenia. Based on our previous work identifying a relationship between symptomology in schizophrenia and abnormal movement-induced electrophysiological response (the post-movement beta rebound [PMBR]), we predicted that if subclinical schizotypy arises from similar neural mechanisms to schizophrenia, schizotypy in healthy individuals would be associated with reduced PMBR...
September 18, 2018: Schizophrenia Bulletin
Qiguang Li, Jiansong Zhou, Xia Cao, Qiang Liu, Qi Li, Wen Li, Xiaoping Wang
Background: Activated or impaired T-cell function in inflammatory and degenerative process can contribute to the risk and progression of schizophrenia. This study used immune repertoire sequencing to investigate the T-cell receptor beta variable chain (TRBV) presence in blood mononuclear cells in the violent or non-violent schizophrenic patients. Methods: Ten violent and 10 non-violent schizophrenic patients and 8 matched healthy controls were enrolled. The Brief Psychiatric Rating Scale (BPRS) was used to evaluate patients' psychiatric symptoms...
2018: Frontiers in Psychiatry
Xi Xia, Mei Ding, Jin-Feng Xuan, Jia-Xin Xing, Hao Pang, Bao-Jie Wang, Jun Yao
BACKGROUND: Schizophrenia is associated with multiple neurotransmitter disorders, including serotonin (5-hydroxytryptamine, 5-HT). The neuromodulatory action of serotonin on brain function largely depends on the action of specific subtypes of serotonin receptors. The serotonin receptor 1B (HTR1B) gene has been proposed to play putative roles in the development of multiple emotional and psychiatric disorders. METHODS: To study the relationship of HTR1B polymorphisms and schizophrenia, gene information was drawn from a cohort of 310 schizophrenic patients (152 men and 158 women) and 313 healthy controls (153 men and 160 women) of northern Han Chinese descent...
September 19, 2018: BMC Psychiatry
E Pettersson, P Lichtenstein, H Larsson, J Song, A Agrawal, A D Børglum, C M Bulik, M J Daly, L K Davis, D Demontis, H J Edenberg, J Grove, J Gelernter, B M Neale, A F Pardiñas, E Stahl, J T R Walters, R Walters, P F Sullivan, D Posthuma, T J C Polderman
BACKGROUND: Most studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders. METHODS: We assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls)...
September 17, 2018: Psychological Medicine
Alan S Brown, Urs Meyer
Epidemiologic studies, including prospective birth cohort investigations, have implicated maternal immune activation in the etiology of neuropsychiatric disorders. Maternal infectious pathogens and inflammation are plausible risk factors for these outcomes and have been associated with schizophrenia, autism spectrum disorder, and bipolar disorder. Concurrent with epidemiologic research are animal models of prenatal immune activation, which have documented behavioral, neurochemical, neuroanatomic, and neurophysiologic disruptions that mirror phenotypes observed in these neuropsychiatric disorders...
September 17, 2018: American Journal of Psychiatry
Sarojini M Sengupta, Nellie Fotopoulos, Gabriel A Devenyi, Marie-Ève Fortier, Marina Ter-Stepanian, Saba Sagliker, Sherif Karama, M Mallar Chakravarty, Aurelie Labbe, Natalie Grizenko, Ridha Joober
Several epidemiological and genetic studies have provided evidence of an overlap between neurodevelopmental disorders. However, the details of the etiological pathways remain to be elucidated. In this study, we garnered the findings of previous GWAS, conducted with schizophrenia and bipolar disorder. We conducted an exploratory study to examine the association between these SNPs and quantitative clinical/ behavioural/ cognitive/ structural brain parameters, as well as response to treatment with a fixed dose of methylphenidate, in a relatively large sample of children with ADHD...
August 28, 2018: Psychiatry Research
C Luckhaus, G Juckel, R Hurlemann
Neurobiological results from animal models as well as biochemical and genetic findings in patients indicate that the oxytocin (OT) system may be dysfunctional in schizophrenia. On this pathogenetic basis transnasally administered OT (tnOT) could be an innovative treatment option for schizophrenia. Experimental data from animal studies are also suggestive of a particular effectiveness in treatment-resistant schizophrenia. To date, clinical data on tnOT treatment of schizophrenia patients does not unequivocally support a general therapeutic effect on the psychopathology but suggests positive effects on higher integrated social cognitive performance, such as empathy and mentalization...
September 13, 2018: Der Nervenarzt
Sridhar T Narla, Brandon Decker, Pinaki Sarder, Ewa K Stachowiak, Michal K Stachowiak
Schizophrenia is a neurodevelopmental disorder characterized by complex aberrations in the structure, wiring, and chemistry of multiple neuronal systems. The abnormal developmental trajectory of the brain is established during gestation, long before clinical manifestation of the disease. Over 200 genes and even greater numbers of single nucleotide polymorphisms and copy number variations have been linked with schizophrenia. How does altered function of such a variety of genes lead to schizophrenia? We propose that the protein products of these altered genes converge on a common neurodevelopmental pathway responsible for the development of brain neural circuit and neurotransmitter systems...
2018: Results and Problems in Cell Differentiation
Subhashree Devasenapathy, Rashi Midha, Teesta Naskar, Anuradha Mehta, Bharat Prajapati, Mariam Ummekulsum, Rajesh Sagar, Nandini C Singh, Subrata Sinha
Dyslexia is a neurodevelopmental disorder that manifests as a reading disability despite normal intelligence and adequate educational opportunity. Twin and family studies have indicated a genetic component, while genome-wide studies have implicated a number of susceptibility genes, most of which have direct or indirect roles in neuronal migration. Reelin (RELN) has important biological functions facilitating migration of neurons. Polymorphisms in RELN have been implicated in related disorders like autism and schizophrenia but have not been examined in dyslexia...
August 25, 2018: Asian Journal of Psychiatry
Daniel G Ehlinger, Kathryn G Commons
Human genetic variation in the gene CACNA1C, which codes for the alpha-1c subunit of Cav1.2 L-type calcium channels (LTCCs), has been broadly associated with enhanced risk for neuropsychiatric disorders including major depression, bipolar and schizophrenia. Little is known about the specific neural circuits through which CACNA1C and Cav1.2 LTCCs impact disease etiology. However, serotonin (5-HT) neurotransmission has been consistently implicated in these neuropsychiatric disorders and Cav1.2 LTCCs may influence 5-HT neuron activity during relevant behavioral states such as stress...
August 31, 2018: Neuropharmacology
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