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https://www.readbyqxmd.com/read/27911745/the-role-of-epigenetic-mechanisms-in-the-regulation-of-gene-expression-in-the-nervous-system
#1
Justyna Cholewa-Waclaw, Adrian Bird, Melanie von Schimmelmann, Anne Schaefer, Huimei Yu, Hongjun Song, Ram Madabhushi, Li-Huei Tsai
Neuroepigenetics is a newly emerging field in neurobiology that addresses the epigenetic mechanism of gene expression regulation in various postmitotic neurons, both over time and in response to environmental stimuli. In addition to its fundamental contribution to our understanding of basic neuronal physiology, alterations in these neuroepigenetic mechanisms have been recently linked to numerous neurodevelopmental, psychiatric, and neurodegenerative disorders. This article provides a selective review of the role of DNA and histone modifications in neuronal signal-induced gene expression regulation, plasticity, and survival and how targeting these mechanisms could advance the development of future therapies...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27911743/synaptic-actin-dysregulation-a-convergent-mechanism-of-mental-disorders
#2
Zhen Yan, Eunjoon Kim, Dibyadeep Datta, David A Lewis, Scott H Soderling
Actin polymerization governs activity-dependent modulation of excitatory synapses, including their morphology and functionality. It is clear from human genetics that neuropsychiatric and neurodevelopmental disturbances are multigenetic in nature, highlighting the need to better understand the critical neural pathways associated with these disorders and how they are altered by genetic risk alleles. One such signaling pathway that is heavily implicated by candidate genes for psychiatric and neurodevelopmental disorders are regulators of signaling to the actin cytoskeleton, suggesting that its disruption and the ensuring abnormalities of spine structures and postsynaptic complexes is a commonly affected pathway in brain disorders...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27903723/cerebellar-shank2-regulates-excitatory-synapse-density-motor-coordination-and-specific-repetitive-and-anxiety-like-behaviors
#3
Seungmin Ha, Dongwon Lee, Yi Sul Cho, Changuk Chung, Ye-Eun Yoo, Jihye Kim, Jiseok Lee, Woohyun Kim, Hyosang Kim, Yong Chul Bae, Keiko Tanaka-Yamamoto, Eunjoon Kim
: Shank2 is a multidomain scaffolding protein implicated in the structural and functional coordination of multiprotein complexes at excitatory postsynaptic sites as well as in psychiatric disorders, including autism spectrum disorders. While Shank2 is strongly expressed in the cerebellum, whether Shank2 regulates cerebellar excitatory synapses, or contributes to the behavioral abnormalities observed in Shank2(-/-) mice, remains unexplored. Here we show that Shank2(-/-) mice show reduced excitatory synapse density in cerebellar Purkinje cells in association with reduced levels of excitatory postsynaptic proteins, including GluD2 and PSD-93, and impaired motor coordination in the Erasmus test...
November 30, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27902989/plasma-levels-of-leptin-and-adiponectin-in-fragile-x-syndrome
#4
Małgorzata Zofia Lisik, Ewa Gutmajster, Aleksander L Sieroń
: Fragile X syndrome (FXS) is the most common form of familial mental retardation and one of the leading known causes of autism. The mutation responsible for FXS is a large expansion of the CGG repeats in the promoter region of the FMR1 gene, resulting in the transcriptional silencing of the gene. Leptin may be considered a cytokine-like hormone with pleiotropic actions since it may be involved in the regulation of neuroendocrine functions and the immune system response, in addition to playing a role in development...
December 1, 2016: Neuroimmunomodulation
https://www.readbyqxmd.com/read/27900577/neuroleptic-drugs-and-pacap-differentially-affect-the-mrna-expression-of-genes-encoding-pac1-vpac-type-receptors
#5
Marta Jóźwiak-Bębenista, Edward Kowalczyk
Several lines of evidence suggest that pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide playing an important role as a neuromodulator. It has been indicated that PACAP is associated with mental diseases, and that regulation of the PACAPergic signals could be a potential target for the treatment of such psychiatric states as schizophrenia. Recent studies have suggested that action of neuroleptic drugs is mediated not only by dopaminergic and serotonergic neurotransmission, but also via neuropeptides which may act both as neurotransmitters and as neuromodulators...
November 30, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27894002/polymorphism-in-crhr1-gene-affects-the-il-1%C3%AE-levels-in-suicidal-attempters
#6
Clarissa R Bastos, Marta Gazal, Luciana de A Quevedo, Joice Luisa Costa, Carolina D Wiener, Karen Jansen, Christian Loret de Mola, Jean P Oses, Luciano D M Souza, Luiz Valmor Portela, Ricardo T Pinheiro, Ricardo A da Silva, Diogo R Lara, Gabriele Ghisleni
Approximately one million people commit suicide every year, being suicide attempts and ideation even more common. Changes in stress response and activation of the immune system have been associated with suicide risk. Here we investigated the interaction between immune system and HPA axis alterations in the suicide risk, looking for the influence of rs110402 CRHR1 SNP in the IL-1β levels according to suicide ideation and attempt. This study evaluated 171 subjects of which 15 had suicidal ideation, 20 had suicide attempt and 136 were controls...
November 18, 2016: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/27890662/a-genetic-association-study-of-csmd1-and-csmd2-with-cognitive-function
#7
Lavinia Athanasiu, Sudheer Giddaluru, Carla Fernandes, Andrea Ivar Astri J Christoforou Reinvang Lundervold, Lars-Göran Nilsson, Karolina Kauppi, Rolf Adolfsson, Elias Eriksson, Kjetil Sundet, Srdjan Djurovic, Thomas Espeseth, Lars Nyberg, Vidar M Steen, Ole Andreassen, Stephanie Le Hellard
The complement cascade plays a role in synaptic pruning and synaptic plasticity, which seem to be involved in cognitive functions and psychiatric disorders. Genetic variants in the closely related CSMD1 and CSMD2 genes, which are implicated in complement regulation, are associated with schizophrenia. Since patients with schizophrenia often show cognitive impairments, we tested whether variants in CSMD1 and CSMD2 are also associated with cognitive functions per se. We took a discovery-replication approach, using well-characterized Scandinavian cohorts...
November 24, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27890541/the-expression-of-plasticity-related-genes-in-an-acute-model-of-stress-is-modulated-by-chronic-desipramine-in-a-time-dependent-manner-within-medial-prefrontal-cortex
#8
Nicoletta Nava, Giulia Treccani, Heidi Kaastrup Müller, Maurizio Popoli, Gregers Wegener, Betina Elfving
It is well established that stress plays a major role in the pathogenesis of neuropsychiatric diseases. Stress-induced alteration of synaptic plasticity has been hypothesized to underlie the morphological changes observed by neuroimaging in psychiatric patients in key regions such as hippocampus and prefrontal cortex (PFC). We have recently shown that a single acute stress exposure produces significant short-term alterations of structural plasticity within medial PFC. These alterations were partially prevented by previous treatment with chronic desipramine (DMI)...
November 24, 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27888502/a-novel-c132-134del-mutation-in-unverricht-lundborg-disease-and-the-review-of-literature-of-heterozygous-compound-patients
#9
Giovanni Assenza, Antonella Benvenga, Elena Gennaro, Mario Tombini, Chiara Campana, Federica Assenza, Giovanni Di Pino, Vincenzo Di Lazzaro
Unverricht-Lundborg disease or progressive myoclonic epilepsy type 1 (EPM1) is an autosomal recessive disease caused by mutation of the cystatin B gene (CSTB), located on chromosome 21q22.3. The most common mutation is an expansion of unstable dodecamer repetition (CCCCGCCCCGCG), whereas other types of mutations are rare. Among these, heterozygous compound mutations are described to induce a more severe phenotype than that of homozygous dodecameric repetition. We report two siblings affected by heterozygous compound mutations carrying a novel mutation of the deletion of three nucleotides in exon 2 of the gene in position 132-134 of the coding sequence (c...
November 26, 2016: Epilepsia
https://www.readbyqxmd.com/read/27888397/synaptosome-associated-protein-25-snap25-gene-association-analysis-revealed-risk-variants-for-asd-in-iranian-population
#10
Mohammad Reza Safari, Mir Davood Omrani, Rezvan Noroozi, Arezou Sayad, Shaghayegh Sarrafzadeh, Alireza Komaki, Fateme Asadzadeh Manjili, Mehrdokht Mazdeh, Ali Ghaleiha, Mohammad Taheri
Autism spectrum disorder (ASD) is a common, complex neurological condition, affecting approximately 1% of people worldwide. Monogenic neurodevelopmental disorders which showed autistic behavior patterns have suggested synaptic dysfunction, as a key mechanism in the pathophysiology of ASD. Subsequently, genes involved in synaptic signaling have been investigated with a priority for candidate gene studies. A synaptosomal-associated protein 25 (SNAP25) gene plays a crucial role in the central nervous system, contributing to exocytosis by targeting and fusion of vesicles to the cell membrane...
November 26, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27881965/fundamental-role-of-methylenetetrahydrofolate-reductase-677-c%C3%A2-%C3%A2-%C3%A2-t-genotype-and-flavin-compounds-in-biochemical-phenotypes-for-schizophrenia-and-schizoaffective-psychosis
#11
Stephanie Fryar-Williams
The Mental Health Biomarker Project (2010-2016) explored variables for psychosis in schizophrenia and schizoaffective disorder. Blood samples from 67, highly characterized symptomatic cases and 67 gender and age matched control participants were analyzed for methyl tetrahydrofolate reductase (MTHFR) 677C → T gene variants and for vitamin B6, B12 and D, folate, unbound copper, zinc cofactors for enzymes in the methylation cycle, and related catecholamine pathways. Urine samples were analyzed for indole-catecholamines, their metabolites, and oxidative-stress marker, hydroxylpyrolline-2-one (HPL)...
2016: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/27880876/an-integrative-review-of-methylation-at-the-serotonin-transporter-gene-and-its-dialogue-with-environmental-risk-factors-psychopathology-and-5-httlpr
#12
REVIEW
H Palma-Gudiel, L Fañanás
Gene-environment (GxE) interactions have largely been regarded as the root of many complex disorders, including several psychiatric disorders. In this regard, it has been hypothesized that epigenetic mechanisms may be the main mediators of such interactions. Of particular interest is the previously described interaction between psychosocial stress and genetic variability of the serotonin transporter gene (SLC6A4) in its polymorphic region 5-HTTLPR. Here we review the literature concerning SLC6A4 methylation in association with environmental, clinical or genetic variables...
November 20, 2016: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/27878759/loss-of-adenylyl-cyclase-type-5-in-the-dorsal-striatum-produces-autistic-like-behaviors
#13
Hannah Kim, Yunjin Lee, Jin-Young Park, Ji-Eun Kim, Tae-Kyung Kim, Juli Choi, Jung-Eun Lee, Eun-Hwa Lee, Daesoo Kim, Kyoung-Shim Kim, Pyung-Lim Han
Autism spectrum disorders (ASDs) are a heterogeneous group of psychiatric illness characterized by common core symptoms including sociability deficits and stereotyped behaviors. ASD is caused by various genetic and non-genetic factors. The genetic effects of autism-related genes are usually global and are presented with multiple symptoms, which hamper understanding of the mechanism through which the diverse causes of ASD produce common symptoms. In the present study, we demonstrate that genetic or molecular disruption of an array of molecular networks centered on adenylyl cyclase type-5 (AC5 or ADCY5) in the dorsal striatum produces autistic-like behaviors...
November 23, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27874848/the-human-bdnf-gene-peripheral-gene-expression-and-protein-levels-as-biomarkers-for-psychiatric-disorders
#14
REVIEW
A Cattaneo, N Cattane, V Begni, C M Pariante, M A Riva
Brain-derived neurotrophic factor (BDNF) regulates the survival and growth of neurons, and influences synaptic efficiency and plasticity. The human BDNF gene consists of 11 exons, and distinct BDNF transcripts are produced through the use of alternative promoters and splicing events. The majority of the BDNF transcripts can be detected not only in the brain but also in the blood cells, although no study has yet investigated the differential expression of BDNF transcripts at the peripheral level. This review provides a description of the human BDNF gene structure as well as a summary of clinical and preclinical evidence supporting the role of BDNF in the pathogenesis of psychiatric disorders...
November 22, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27870452/sex-hormones-and-genotype-interact-to-influence-psychiatric-disease-treatment-and-behavioral-research
#15
REVIEW
Aarthi R Gobinath, Elena Choleris, Liisa A M Galea
Sex differences exist in the vulnerability, incidence, manifestation, and treatment of numerous neurological and psychiatric diseases. Despite this observation prominent in the literature, little consideration has been given to possible sex differences in outcome in both preclinical and clinical research. This Mini-Review highlights evidence supporting why studying sex differences matter for advances in brain health as well as improving treatment for neurological and psychiatric disease. Additionally, we discuss some statistical and methodological considerations in evaluating sex differences as well as how differences in the physiology of the sexes can contribute to sex difference in disease incidence and manifestation...
January 2, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27869829/contribution-of-copy-number-variants-to-schizophrenia-from-a-genome-wide-study-of-41-321-subjects
#16
(no author information available yet)
Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 × 10(-15)), which persisted after excluding loci implicated in previous studies (OR = 1...
November 21, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27863250/histone-acetylome-wide-association-study-of-autism-spectrum-disorder
#17
Wenjie Sun, Jeremie Poschmann, Ricardo Cruz-Herrera Del Rosario, Neelroop N Parikshak, Hajira Shreen Hajan, Vibhor Kumar, Ramalakshmi Ramasamy, T Grant Belgard, Bavani Elanggovan, Chloe Chung Yi Wong, Jonathan Mill, Daniel H Geschwind, Shyam Prabhakar
The association of histone modification changes with autism spectrum disorder (ASD) has not been systematically examined. We conducted a histone acetylome-wide association study (HAWAS) by performing H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) on 257 postmortem samples from ASD and matched control brains. Despite etiological heterogeneity, ≥68% of syndromic and idiopathic ASD cases shared a common acetylome signature at >5,000 cis-regulatory elements in prefrontal and temporal cortex. Similarly, multiple genes associated with rare genetic mutations in ASD showed common "epimutations...
November 17, 2016: Cell
https://www.readbyqxmd.com/read/27859490/genetically-modified-rodent-models-of-sca17
#18
REVIEW
Yiting Cui, Su Yang, Xiao-Jiang Li, Shihua Li
Spinocerebellar ataxia type 17 (SCA17) is a type of autosomal dominant cerebellar ataxia (ADCA) characterized by variable manifestations, including cerebellar ataxia, dementia, and psychiatric symptoms. Since the identification of a CAG repeat expansion in the TATA-box binding protein (TBP) gene in a patient with ataxia in 1999 and then verification of this expansion in patients with SCA17 in 2001, several SCA17 rodent models, including both knock-in and transgenic models in mice and rats, have been established to explore the phenotypic features and pathogenesis of SCA17...
November 18, 2016: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27857683/in-vitro-magnetic-stimulation-a-simple-stimulation-device-to-deliver-defined-low-intensity-electromagnetic-fields
#19
Stephanie Grehl, David Martina, Catherine Goyenvalle, Zhi-De Deng, Jennifer Rodger, Rachel M Sherrard
Non-invasive brain stimulation (NIBS) by electromagnetic fields appears to benefit human neurological and psychiatric conditions, although the optimal stimulation parameters and underlying mechanisms remain unclear. Although, in vitro studies have begun to elucidate cellular mechanisms, stimulation is delivered by a range of coils (from commercially available human stimulation coils to laboratory-built circuits) so that the electromagnetic fields induced within the tissue to produce the reported effects are ill-defined...
2016: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/27856950/the-role-of-epigenetics-in-social-psychiatry
#20
REVIEW
Jacob Peedicayil
BACKGROUND: Epigenetics refers to the study of heritable changes in gene expression not involving changes in DNA sequence and is presently an active area of research in biology and medicine. There is increasing evidence that epigenetics is involved in the pathogenesis of psychiatric disorders. AIMS AND METHODS: Several studies conducted to date have suggested that psychosocial factors act by modifying epigenetic mechanisms of gene expression in the brain in the pathogenesis of psychiatric disorders...
November 16, 2016: International Journal of Social Psychiatry
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