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https://www.readbyqxmd.com/read/29027751/the-emerging-role-of-mrna-methylation-in-normal-and-pathological-behavior
#1
REVIEW
Mareen Engel, Alon Chen
Covalent RNA modifications were recently rediscovered as abundant RNA chemical tags. Similarly to DNA epigenetic modifications, they have been proposed as essential regulators of gene expression. Here we focus on two of the most abundant adenosine methylations: N6-methyladenosine (m(6) A), N6,2'-O-dimethyladenosine (m(6) Am) and N1-methyladenosine (m(1) A). We review the potential role of these modifications on mature mRNA in regulating gene expression within the adult brain, nervous system function and normal and pathological behavior...
October 13, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/29025271/psychotropic-drugs-and-cyp2d6-in-late-life-psychiatric-and-neurological-disorders-what-do-we-know
#2
Davide Seripa, Madia Lozupone, Eleonora Stella, Giulia Paroni, Paola Bisceglia, Maddalena La Montagna, Grazia D'onofrio, Carolina Gravina, Maria Urbano, Maria Giovanna Priore, Angela Lamanna, Antonio Daniele, Antonello Bellomo, Giancarlo Logroscino, Antonio Greco, Francesco Panza
Late-life psychiatric and neurological disorders (LLPND) are interesting models to understand the potential role of pharmacogenetics in drug management, since several pharmacological approaches for treating LLPND have proven to be ineffective or deleterious, thus resulting in therapeutic failures (TF) and adverse drug reactions (ADR). Common variants in the genes encoding the cytochrome P450 (CYP) enzyme system, the 'engine room' of drug metabolism, together with well-known age-related increased polypharmacy also contributed to the prevalence of TF and ADR observed in these patients, also rising number and time of hospital readmissions and rate of institutionalizations...
October 12, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29022873/adolescent-thc-exposure-in-female-rats-leads-to-cognitive-deficits-through-a-mechanism-involving-chromatin-modifications-in-the-prefrontal-cortex
#3
Pamela Prini, Franceso Rusconi, Erica Zamberletti, Marina Gabaglio, Federica Penna, Mauro Fasano, Elena Battaglioli, Daniela Parolaro, Tiziana Rubino
BACKGROUND: Increasing cannabis consumption among adolescents, studies that link its early use with mental illnesses, and the political debate on cannabis legalization together call for an urgent need to study molecular underpinnings of adolescent brain vulnerability. The emerging role of epigenetic mechanisms in psychiatric diseases led us to hypothesize that epigenetic alterations could play a role in causes and subsequent development of the depressive/psychotic-like phenotype induced by adolescent, but not adult, Δ9-tetrahydrocannabinol (THC) exposure in female rats...
October 12, 2017: Journal of Psychiatry & Neuroscience: JPN
https://www.readbyqxmd.com/read/29021832/pharmacogenomics-in-the-treatment-of-mood-disorders-strategies-and-opportunities-for-personalized-psychiatry
#4
REVIEW
Azmeraw T Amare, Klaus Oliver Schubert, Bernhard T Baune
Personalized medicine (personalized psychiatry in a specific setting) is a new model towards individualized care, in which knowledge from genomics and other omic pillars (microbiome, epigenomes, proteome, and metabolome) will be combined with clinical data to guide efforts to new drug development and targeted prescription of the existing treatment options. In this review, we summarize pharmacogenomic studies in mood disorders that may lay the foundation towards personalized psychiatry. In addition, we have discussed the possible strategies to integrate data from omic pillars as a future path to personalized psychiatry...
September 2017: EPMA Journal
https://www.readbyqxmd.com/read/29020615/a-scaled-framework-for-crispr-editing-of-human-pluripotent-stem-cells-to-study-psychiatric-disease
#5
Dane Z Hazelbaker, Amanda Beccard, Anne M Bara, Nicole Dabkowski, Angelica Messana, Patrizia Mazzucato, Daisy Lam, Danielle Manning, Kevin Eggan, Lindy E Barrett
Scaling of CRISPR-Cas9 technology in human pluripotent stem cells (hPSCs) represents an important step for modeling complex disease and developing drug screens in human cells. However, variables affecting the scaling efficiency of gene editing in hPSCs remain poorly understood. Here, we report a standardized CRISPR-Cas9 approach, with robust benchmarking at each step, to successfully target and genotype a set of psychiatric disease-implicated genes in hPSCs and provide a resource of edited hPSC lines for six of these genes...
October 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29020418/striatal-n-acetylaspartate-synthetase-shati-nat8l-regulates-depression-like-behaviors-via-mglur3-mediated-serotonergic-suppression-in-mice
#6
Yoshiaki Miyamoto, Noriyuki Iegaki, Kequan Fu, Yudai Ishikawa, Kazuyuki Sumi, Sota Azuma, Kyosuke Uno, Shin-Ichi Muramatsu, Atsumi Nitta
Background: Several clinical studies have suggested that N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) levels in the human brain are associated with various psychiatric disorders, including major depressive disorder. We have previously identified Shati/Nat8l, an N-acetyltransferase, in the brain using an animal model of psychosis. Shati/Nat8l synthesizes NAA from L-aspartate and acetyl-coenzyme A. Further, NAA is converted into NAAG, a neurotransmitter for metabotropic glutamate receptor 3 (mGluR3)...
August 31, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29019003/role-of-dynein-axonemal-heavy-chain-6-gene-expression-as-a-possible-biomarker-for-huntington-s-disease-a-translational-study
#7
Lorena B Areal, Lorraine P Pereira, Fabiola M Ribeiro, Isabella G Olmo, Marcelo R Muniz, Maria do Carmo Rodrigues, Patrik F Costa, Cristina Martins-Silva, Stephen S G Ferguson, Daniela A M Guimarães, Rita G W Pires
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor dysfunction, cognitive deficits, and psychiatric symptoms. The primary genetic cause is an expansion of cytosine adenine guanine (CAG) nucleotides of the huntingtin gene, which codes an important protein involved with neuronal signaling. The severity of HD correlates with the number of CAG repeats and individuals with longer expansions have an earlier onset and more severe symptoms. A microarray study conducted by our research group showed alteration in DNAH6 gene (encoding dynein axonemal heavy chain 6)...
October 10, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29017764/dna-methylation-and-antipsychotic-treatment-mechanisms-in-schizophrenia-progress-and-future-directions
#8
REVIEW
Ellen S Ovenden, Nathaniel W McGregor, Robin A Emsley, Louise Warnich
Antipsychotic response in schizophrenia is a complex, multifactorial trait influenced by pharmacogenetic factors. With genetic studies thus far providing little biological insight or clinical utility, the field of pharmacoepigenomics has emerged to tackle the so-called "missing heritability" of drug response in disease. Research on psychiatric disorders has only recently started to assess the link between epigenetic alterations and treatment outcomes. DNA methylation, the best characterised epigenetic mechanism to date, is discussed here in the context of schizophrenia and antipsychotic treatment outcomes...
October 7, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29016262/association-of-5-httlpr-polymorphism-with-the-nursing-diagnoses-and-the-achievement-of-nursing-outcomes-in-patients-with-major-depression
#9
Margarita Prokofieva, Georgia Karadima, Evmorfia Koukia, Vassiliki Michou, Chrysoula Kyprianidou, Chrysovalantis V Papageorgiou, Evangelos Alexiadis, Pantelis Constantoulakis, Dimitris Dikeos
The aim of this study is to investigate whether a 44-base-pair insertion/deletion polymorphism in the upstream regulatory region of the serotonin transporter gene (5-HTTLPR) is associated with the nursing diagnoses and the achievement of the desired nursing outcomes in inpatients with major depression. Thirty five patients were evaluated. The nursing diagnoses of risk for suicide and imbalanced nutrition are reported less often in homozygotes of the high-expressing gene (LA). Carriers of the low-expressing genes (LG or S) have a worse response to interventions which aim to increase low self-esteem, indicating that they may need more intensive care in order to achieve the desired outcome...
October 2017: Issues in Mental Health Nursing
https://www.readbyqxmd.com/read/28993723/bace1-dependent-neuregulin-1-signaling-an-implication-for-schizophrenia
#10
REVIEW
Zhengrong Zhang, Jing Huang, Yong Shen, Rena Li
Schizophrenia is a chronic psychiatric disorder with a lifetime prevalence of about 1% in the general population. Recent studies have shown that Neuregulin-1 (Nrg1) is a candidate gene for schizophrenia. At least 15 alternative splicing of NRG1 isoforms all contain an extracellular epidermal growth factor (EGF)-like domain, which is sufficient for Nrg1 biological activity including the formation of myelin sheaths and the regulation of synaptic plasticity. It is known that Nrg1 can be cleaved by β-secretase (BACE1) and the resulting N-terminal fragment (Nrg1-ntf) binds to receptor tyrosine kinase ErbB4, which activates Nrg1/ErbB4 signaling...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28990639/pharmacogenomics-and-psychiatric-clinical-care
#11
Russell J Amato, Joseph Boland, Nicole Myer, Lauren Few, Daniel Dowd
Approximately one in five individuals in the United States experiences mental health issues in any given year, and these disorders are consistently among the leading causes of years lived with disability. Unfortunately, many mental illnesses are lifelong conditions that require medication and therapy to improve quality of life, yet clinical trial data show that many patients fail to achieve remission or require several pharmacological interventions prior to remission. These results indicate a need to address the variability among patients in their response to medication, in addition to developing treatment plans tailored to the individual...
October 6, 2017: Journal of Psychosocial Nursing and Mental Health Services
https://www.readbyqxmd.com/read/28990359/ancestry-specific-and-sex-specific-risk-alleles-identified-in-a-genome-wide-gene-by-alcohol-dependence-interaction-study-of-risky-sexual-behaviors
#12
Renato Polimanti, Hongyu Zhao, Lindsay A Farrer, Henry R Kranzler, Joel Gelernter
We previously mapped loci for the genome-wide association studies (GWAS) and genome-wide gene-by-alcohol dependence interaction (GW-GxAD) analyses of risky sexual behaviors (RSB). This study extends those findings by analyzing the ancestry- and sex-specific AD-stratified effects on RSB. We examined the concordance of findings for the AD-stratified GWAS and the GW-GxAD analysis of RSB, with concordance defined as genome-wide significance in one analysis and at least nominal significance in the second analysis...
October 9, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28989100/pleiotropic-genes-in-psychiatry-calcium-channels-and-the-stress-related-fkbp5-gene-in-antidepressant-resistance
#13
Chiara Fabbri, Filippo Corponi, Diego Albani, Ilaria Raimondi, Gianluigi Forloni, Koen Schruers, Siegfried Kasper, Alexander Kautzky, Joseph Zohar, Daniel Souery, Stuart Montgomery, Carlotta Pia Cristalli, Vilma Mantovani, Julien Mendlewicz, Alessandro Serretti
A candidate gene and a genome-wide approach were combined to study the pharmacogenetics of antidepressant response and resistance. Investigated genes were selected on the basis of pleiotropic effect across psychiatric phenotypes in previous genome-wide association studies and involvement in antidepressant response. Three samples with major depressive disorder (total=671) were genotyped for 44 SNPs in 8 candidate genes (CACNA1C, CACNB2, ANK3, GRM7, TCF4, ITIH3, SYNE1, FKBP5). Phenotypes were response/remission after 4weeks of treatment and treatment-resistant depression (TRD)...
October 5, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28988019/acute-intermittent-porphyria-after-right-hemi-colectomy
#14
Shadi Alshammary, Reem Al Dulaijan, Khaldoon Saleh, Hazem Zakaria, Ahmed Eldamati, Norah Alwakeel, Abdulmohsen Al-Mulhim
INTRODUCTION: Acute intermittent porphyria is a rare autosomal dominant metabolic disease. It is caused by a genetic mutation that results in deficiency of porphobilinogen deaminase enzyme, the third enzyme in heme biosynthesis. Acute intermittent porphyria precipitated by surgery is very rare. CASE PRESENTATION: We present a 24 year-old woman who developed acute intermittent porphyria five days after right hemi-colectomy. Her presentation included neuro-visceral and psychiatric manifestations, and severe hyponatremia...
September 28, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/28987167/nutritional-and-systemic-metabolic-disorders
#15
Serge Weis, Andreas Büttner
Vitamin deficiency disorders display a wide variety of neurologic signs and symptoms, the pathogenesis of which is not clearly understood. Metabolic encephalopathies (hepatic, hypoglycemic, and uremic) have to be considered in the differential diagnosis of patients with cognitive impairment, motor disturbances, psychiatric symptoms, seizures, and neuropathies. Calcifications (vascular wall and parenchymal) occur in the normal aging brain and in neurodegeneration; some associated genes are already described.
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/28981898/overexpression-of-truncated-human-disc1-induces-appearance-of-hindbrain-oligodendroglia-in-the-forebrain-during-development
#16
Pavel Katsel, Peter Fam, Weilun Tan, Sonia Khan, Chunxia Yang, Yan Jouroukhin, Sergei Rudchenko, Mikhail V Pletnikov, Vahram Haroutunian
Genetic, neuroimaging, and gene expression studies suggest a role for oligodendrocyte (OLG) dysfunction in schizophrenia (SZ). Disrupted-in-schizophrenia 1 (DISC1) is a risk gene for major psychiatric disorders, including SZ. Overexpression of mutant truncated (hDISC1), but not full-length sequence of human DISC1 in forebrain influenced OLG differentiation and proliferation of glial progenitors in the developing cerebral cortex concurrently with reduction of OLG progenitor markers in the hindbrain. We examined gene and protein expression of the molecular determinants of hindbrain OLG development and their interactions with DISC1 in mutant hDISC1 mice...
August 18, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/28980151/epidemiology-diagnosis-and-treatment-of-cerebrotendinous-xanthomatosis-ctx
#17
REVIEW
Gerald Salen, Robert D Steiner
Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder of bile acid synthesis caused by mutations in the cytochrome P450 CYP27A1 gene that result in production of a defective sterol 27-hydroxylase enzyme. CTX is associated with abnormally high levels of cholestanol in the blood and accumulation of cholestanol and cholesterol in the brain, tendon xanthomas, and bile. Hallmark clinical manifestations of CTX include chronic diarrhea, bilateral cataracts, tendon xanthomas, and neurologic dysfunction...
October 4, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28979981/genome-wide-association-studies-of-a-broad-spectrum-of-antisocial-behavior
#18
Jorim J Tielbeek, Ada Johansson, Tinca J C Polderman, Marja-Riitta Rautiainen, Philip Jansen, Michelle Taylor, Xiaoran Tong, Qing Lu, Alexandra S Burt, Henning Tiemeier, Essi Viding, Robert Plomin, Nicholas G Martin, Andrew C Heath, Pamela A F Madden, Grant Montgomery, Kevin M Beaver, Irwin Waldman, Joel Gelernter, Henry R Kranzler, Lindsay A Farrer, John R B Perry, Marcus Munafò, Devon LoParo, Tiina Paunio, Jari Tiihonen, Sabine E Mous, Irene Pappa, Christiaan de Leeuw, Kyoko Watanabe, Anke R Hammerschlag, Jessica E Salvatore, Fazil Aliev, Tim B Bigdeli, Danielle Dick, Stephen V Faraone, Arne Popma, Sarah E Medland, Danielle Posthuma
Importance: Antisocial behavior (ASB) places a large burden on perpetrators, survivors, and society. Twin studies indicate that half of the variation in this trait is genetic. Specific causal genetic variants have, however, not been identified. Objectives: To estimate the single-nucleotide polymorphism-based heritability of ASB; to identify novel genetic risk variants, genes, or biological pathways; to test for pleiotropic associations with other psychiatric traits; and to reevaluate the candidate gene era data through the Broad Antisocial Behavior Consortium...
October 4, 2017: JAMA Psychiatry
https://www.readbyqxmd.com/read/28979198/schizophrenia-what-s-arc-got-to-do-with-it
#19
REVIEW
Francesca Managò, Francesco Papaleo
Human studies of schizophrenia are now reporting a previously unidentified genetic convergence on postsynaptic signaling complexes such as the activity-regulated cytoskeletal-associated (Arc) gene. However, because this evidence is still very recent, the neurobiological implication of Arc in schizophrenia is still scattered and unrecognized. Here, we first review current and developing findings connecting Arc in schizophrenia. We then highlight recent and previous findings from preclinical mouse models that elucidate how Arc genetic modifications might recapitulate schizophrenia-relevant behavioral phenotypes following the novel Research Domain Criteria (RDoC) framework...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28979185/the-membrane-glycoprotein-m6a-endocytic-recycling-pathway-involves-clathrin-mediated-endocytosis-and-affects-neuronal-synapses
#20
Micaela D Garcia, Karina Formoso, Gabriela I Aparicio, Alberto C C Frasch, Camila Scorticati
Single point mutations or variations in the expression of the gene encoding the neuronal glycoprotein M6a have been associated with psychiatric disorders such as Alzheimer's disease, depression and schizophrenia. In cultured neurons, M6a positively contributes to neurite extension, axon guidance, filopodia/spine outgrowth, and synapse formation. The endocytic processes of neuronal membrane proteins are linked to the differentiation, growth, signaling and plasticity of neurons. However, the roles of M6a and the precise mechanisms through which M6a internalizes and recycles back to the neuronal membrane are unknown...
2017: Frontiers in Molecular Neuroscience
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