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Molecular Neuropsychiatry

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https://www.readbyqxmd.com/read/28879201/wnt-%C3%AE-catenin-pathway-and-epigenetic-mechanisms-regulate-the-pitt-hopkins-syndrome-and-schizophrenia-risk-gene-tcf4
#1
Krista M Hennig, Daniel M Fass, Wen-Ning Zhao, Steven D Sheridan, Ting Fu, Serkan Erdin, Alexei Stortchevoi, Diane Lucente, Jannine D Cody, David Sweetser, James F Gusella, Michael E Talkowski, Stephen J Haggarty
Genetic variation within the transcription factor TCF4 locus can cause the intellectual disability and developmental disorder Pitt-Hopkins syndrome (PTHS), whereas single-nucleotide polymorphisms within noncoding regions are associated with schizophrenia. These genetic findings position TCF4 as a link between transcription and cognition; however, the neurobiology of TCF4 remains poorly understood. Here, we quantitated multiple distinct TCF4 transcript levels in human induced pluripotent stem cell-derived neural progenitors and differentiated neurons, and PTHS patient fibroblasts...
July 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/28879200/the-nuclear-proteome-of-white-and-gray-matter-from-schizophrenia-postmortem-brains
#2
Verônica M Saia-Cereda, Aline G Santana, Andrea Schmitt, Peter Falkai, Daniel Martins-de-Souza
Schizophrenia (SCZ) is a serious neuropsychiatric disorder that manifests through several symptoms from early adulthood. Numerous studies over the last decades have led to significant advances in increasing our understanding of the factors involved in SCZ. For example, mass spectrometry-based proteomic analysis has provided important insights by uncovering protein dysfunctions inherent to SCZ. Here, we present a comprehensive analysis of the nuclear proteome of postmortem brain tissues from corpus callosum (CC) and anterior temporal lobe (ATL)...
July 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/28879199/low-density-neuronal-cultures-from-human-induced-pluripotent-stem-cells
#3
Peter Dimitrion, Yun Zhi, Dennis Clayton, Gerard L Apodaca, Madeleine R Wilcox, Jon W Johnson, Vishwajit Nimgaonkar, Leonardo D'Aiuto
Induced pluripotent stem cell (iPSC)-based technologies offer an unprecedented possibility to investigate defects occurring during neuronal differentiation in neuropsychiatric and neurodevelopmental disorders, but the density and intricacy of intercellular connections in neuronal cultures challenge currently available analytic methods. Low-density neuronal cultures facilitate the morphometric and functional analysis of neurons. We describe a differentiation protocol to generate low-density neuronal cultures (∼2,500 neurons/cm(2)) from human iPSC-derived neural stem cells/early neural progenitor cells...
July 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/28879198/complement-c3-expression-is-decreased-in-autism-spectrum-disorder-subjects-and-contributes-to-behavioral-deficits-in-rodents
#4
Kiley Fagan, Amanda Crider, Anthony O Ahmed, Anilkumar Pillai
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with hallmark symptoms including social deficits, communication deficits and repetitive behaviors. Accumulating evidence suggests a potential role of the immune system in the pathophysiology of ASD. The complement system represents one of the major effector mechanisms of the innate immune system, and regulates inflammation, and orchestrates defense against pathogens. However, the role of CNS complement system in ASD is not well understood. In the present study, we found a significant increase in C2, C5, and MASP1, but a decrease in C1q, C3, and C4 mRNA levels in the middle frontal gyrus of ASD subjects compared to controls...
July 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/28879197/a-preliminary-study-of-the-opioid-system-and-personality-traits-using-positron-emission-tomography
#5
Alexandra M Rodman, Thilo Deckersbach, Tina Chou, Jian Kong, Randy L Gollub, Darin D Dougherty
BACKGROUND: Personality traits, such as Neuroticism and Extraversion, have been implicated in the processing of emotion. The neural correlates most often associated with Neuroticism and Extraversion are the insular cortex, orbitofrontal cortex, amygdala, and ventral striatum. OBJECTIVE: The aim of the current study was to explore neurotransmitter systems underlying those neural correlates and investigate the relationship between personality traits and opioid receptor binding potential...
July 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/28879196/assessment-of-whole-exome-sequence-data-in-attempted-suicide-within-a-bipolar-disorder-cohort
#6
Eric T Monson, Mehdi Pirooznia, Jennifer Parla, Melissa Kramer, Fernando S Goes, Marie E Gaine, Sophia C Gaynor, Kelly de Klerk, Dubravka Jancic, Rachel Karchin, W Richard McCombie, Peter P Zandi, James B Potash, Virginia L Willour
Suicidal behavior is a complex and devastating phenotype with a heritable component that has not been fully explained by existing common genetic variant analyses. This study represents the first large-scale DNA sequencing project designed to assess the role of rare functional genetic variation in suicidal behavior risk. To accomplish this, whole-exome sequencing data for ∼19,000 genes were generated for 387 bipolar disorder subjects with a history of suicide attempt and 631 bipolar disorder subjects with no prior suicide attempts...
July 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/28277568/neurodevelopmental-perspectives-on-wnt-signaling-in-psychiatry
#7
REVIEW
Kimberly A Mulligan, Benjamin N R Cheyette
Mounting evidence indicates that Wnt signaling is relevant to pathophysiology of diverse mental illnesses including schizophrenia, bipolar disorder, and autism spectrum disorder. In the 35 years since Wnt ligands were first described, animal studies have richly explored how downstream Wnt signaling pathways affect an array of neurodevelopmental processes and how their disruption can lead to both neurological and behavioral phenotypes. Recently, human induced pluripotent stem cell (hiPSC) models have begun to contribute to this literature while pushing it in increasingly translational directions...
February 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/28277567/evidence-of-as3mt-d2d3-associated-variants-within-10q24-32-33-in-the-genetic-risk-of-major-affective-disorders
#8
Lingyi Li, Hong Chang, Tao Peng, Ming Li, Xiao Xiao
Genome-wide association studies suggest that 10q24.32-33 is a risk region for schizophrenia (SCZ). Considering the substantial genetic overlap between SCZ and major affective disorders, we would like to investigate whether the 10q24.32-33 region confers risk of affective disorders. We chose three SCZ genome-wide significant SNPs (rs7914558, rs7085104, and rs11191580) in 10q24.32-33 and collected the statistical data from European and Asian populations to perform systematic meta-analyses, which finally included up to 26,413 cases with affective disorders and 24,849 controls...
February 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/28277566/positive-traits-in-the-bipolar-spectrum-the-space-between-madness-and-genius
#9
REVIEW
Tiffany A Greenwood
Bipolar disorder is a severe, lifelong mood disorder for which little is currently understood of the genetic mechanisms underlying risk. By examining related dimensional phenotypes, we may further our understanding of the disorder. Creativity has a historical connection with the bipolar spectrum and is particularly enhanced among unaffected first-degree relatives and those with bipolar spectrum traits. This suggests that some aspects of the bipolar spectrum may confer advantages, while more severe expressions of symptoms negatively influence creative accomplishment...
February 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/28277565/pharmacogenetic-analysis-of-functional-glutamate-system-gene-variants-and-clinical-response-to-clozapine
#10
Danielle L Taylor, Arun K Tiwari, Jeffrey A Lieberman, Steven G Potkin, Herbert Y Meltzer, Joanne Knight, Gary Remington, Daniel J Müller, James L Kennedy
Altered glutamate neurotransmission is implicated in the etiology of schizophrenia (SCZ) and the pharmacogenetics of response to clozapine (CLZ), which is the drug of choice for treatment-resistant SCZ. Response to antipsychotic therapy is highly variable, although twin studies suggest a genetic component. We investigated the association of 10 glutamate system gene variants with CLZ response using standard genotyping procedures. GRM2 (rs4067 and rs2518461), SLC1A2 (rs4354668, rs4534557, and rs2901534), SLC6A9 (rs12037805, rs1978195, and rs16831558), GRIA1 (rs2195450), and GAD1 (rs3749034) were typed in 163 European SCZ/schizoaffective disorder patients deemed resistant or intolerant to previous pharmacotherapy...
February 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/28277564/analysis-of-shared-haplotypes-amongst-palauans-maps-loci-for-psychotic-disorders-to-4q28-and-5q23-q31
#11
Corneliu A Bodea, Frank A Middleton, Nadine M Melhem, Lambertus Klei, Youeun Song, Josepha Tiobech, Pearl Marumoto, Victor Yano, Stephen V Faraone, Kathryn Roeder, Marina Myles-Worsley, Bernie Devlin, William Byerley
To localize genetic variation affecting risk for psychotic disorders in the population of Palau, we genotyped DNA samples from 203 Palauan individuals diagnosed with psychotic disorders, broadly defined, and 125 control subjects using a genome-wide single nucleotide polymorphism array. Palau has unique features advantageous for this study: due to its population history, Palauans are substantially interrelated; affected individuals often, but not always, cluster in families; and we have essentially complete ascertainment of affected individuals...
February 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27867941/familial-influences-on-mismatch-negativity-and-its-association-with-plasma-glutamate-level-a-magnetoencephalographic-study-in-twins
#12
Yukika Nishimura, Yuki Kawakubo, Motomu Suga, Kenji Hashimoto, Yuichi Takei, Kunio Takei, Hideyuki Inoue, Masato Yumoto, Ryu Takizawa, Kiyoto Kasai
Mismatch negativity (MMN) or its magnetic counterpart (magnetic mismatch negativity; MMNm) is regarded as a promising biomarker for schizophrenia. Previous electroencephalographic studies of MMN have demonstrated a moderate-to-high heritability for MMN amplitudes. N-methyl-D-aspartate receptor-dependent glutamatergic neurotransmission is implicated in MMN generation. We hypothesized that the differences between identical twins in MMNm variables might be associated with differences in plasma levels of amino acids involved in glutamatergic neurotransmission...
October 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27867940/oxytocin-receptor-oxtr-methylation-and-cognition-in-psychotic-disorders
#13
Tyler B Grove, Kyle J Burghardt, A Zarina Kraal, Ryan J Dougherty, Stephan F Taylor, Vicki L Ellingrod
Previous reports have identified an association between cognitive impairment and genetic variation in psychotic disorders. In particular, this association may be related to abnormal regulation of genes responsible for broad cognitive functions such as the oxytocin receptor (OXTR). Within psychotic disorders, it is unknown if OXTR methylation, which can have important implications for gene regulation, is related to cognitive function. The current study examined peripheral blood OXTR methylation and general cognition in people with schizophrenia, schizoaffective disorder, and psychotic disorder not otherwise specified (N = 101)...
October 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27867939/a-rare-variant-in-cacna1d-segregates-with-7-bipolar-i-disorder-cases-in-a-large-pedigree
#14
Jessica Ross, Erika Gedvilaite, Judith A Badner, Carolyn Erdman, Lisa Baird, Nori Matsunami, Mark Leppert, Jinchuan Xing, William Byerley
Whole-genome sequencing was performed on 3 bipolar I disorder (BPI) cases from a multiplex pedigree of European ancestry with 7 BPI cases. Within CACNA1D, a gene implicated by genome-wide association studies, a G to C nucleotide transversion at 53,835,340 base pairs (bps) was found predicting the substitution of proline for alanine at amino acid position 1751 (A1751P). Using Sanger sequencing, the DNA variant was shown to co-segregate with the remaining 4 BPI cases within the pedigree. A high-resolution DNA denaturing curve method was then used to screen for the presence of the A1751P change in 4,150 BPI cases from the NIMH Genetics Initiative...
October 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27867938/a-mutation-in-npas3-that-segregates-with-schizophrenia-in-a-small-family-leads-to-protein-aggregation
#15
Leslie G Nucifora, YeeWen Candace Wu, Brian J Lee, Li Sha, Russell L Margolis, Christopher A Ross, Akira Sawa, Frederick C Nucifora
Schizophrenia and other major mental illnesses result from a complex interplay of genetic and environmental factors. We previously identified a mutation in NPAS3 that results in a valine to isoleucine (V304I) amino acid substitution segregating with schizophrenia in a small family. The amino acid change occurs in a potentially critical region for protein function. Furthermore, the same amino acid substitution in proteins related to familial Alzheimer's disease and transthyretin amyloidosis has been associated with protein aggregation...
October 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27867937/dopamine-d2l-receptor-is-required-for-visual-discrimination-and-reversal-learning
#16
Makiko Morita, Yanyan Wang, Toshikuni Sasaoka, Kinya Okada, Minae Niwa, Akira Sawa, Takatoshi Hikida
The corticostriatothalamic circuit regulates learning behaviors via dopamine neurotransmission. D2 long (D2L) receptors are an isoform of dopamine D2 receptors (D2Rs) and may act mainly at postsynaptic sites. It is well known that D2Rs influence high brain functions, but the roles of individual D2R isoforms are still unclear. To assess the influence of D2L receptors in visual discrimination learning, we performed visual discrimination and reversal tasks with D2L knockout mice using a touchscreen operant system...
October 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27867936/effects-of-lithium-monotherapy-for-bipolar-disorder-on-gene-expression-in-peripheral-lymphocytes
#17
Amit Anand, Jeanette N McClintick, Jill Murrell, Harish Karne, John I Nurnberger, Howard J Edenberg
BACKGROUND: This study investigated the effect of lithium monotherapy on peripheral lymphocyte gene expression in bipolar disorder (BD). METHOD: Twenty-two medication-free bipolar subjects (11 hypomanic, 11 depressed) were started on lithium monotherapy. Closely matched healthy subjects (n = 15) were included as controls but did not receive treatment. Blood RNA samples were collected at baseline and after 2 and 8 weeks of treatment. RNA expression was measured using the Affymetrix GeneChip® Human Gene 1...
October 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27606324/the-planar-cell-polarity-transmembrane-protein-vangl2-promotes-dendrite-spine-and-glutamatergic-synapse-formation-in-the-mammalian-forebrain
#18
Nathan D Okerlund, Robert E Stanley, Benjamin N R Cheyette
The transmembrane protein Vangl2, a key regulator of the Wnt/planar cell polarity (PCP) pathway, is involved in dendrite arbor elaboration, dendritic spine formation and glutamatergic synapse formation in mammalian central nervous system neurons. Cultured forebrain neurons from Vangl2 knockout mice have simpler dendrite arbors, fewer total spines, less mature spines and fewer glutamatergic synapse inputs on their dendrites than control neurons. Neurons from mice heterozygous for a semidominant Vangl2 mutation have similar but not identical phenotypes, and these phenotypes are also observed in Golgi-stained brain tissue from adult mutant mice...
July 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27606323/perturbational-profiling-of-metabolites-in-patient-fibroblasts-implicates-%C3%AE-aminoadipate-as-a-potential-biomarker-for-bipolar-disorder
#19
Joanne H Huang, Shaunna S Berkovitch, Jonathan Iaconelli, Bradley Watmuff, Hyoungjun Park, Shrikanta Chattopadhyay, Donna McPhie, Dost Öngür, Bruce M Cohen, Clary B Clish, Rakesh Karmacharya
Many studies suggest the presence of aberrations in cellular metabolism in bipolar disorder. We studied the metabolome in bipolar disorder to gain insight into cellular pathways that may be dysregulated in bipolar disorder and to discover evidence of novel biomarkers. We measured polar and nonpolar metabolites in fibroblasts from subjects with bipolar I disorder and matched healthy control subjects, under normal conditions and with two physiologic perturbations: low-glucose media and exposure to the stress-mediating hormone dexamethasone...
July 2016: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/27606322/neuregulin-3-knockout-mice-exhibit-behaviors-consistent-with-psychotic-disorders
#20
Lindsay N Hayes, Alexey Shevelkin, Mariela Zeledon, Gary Steel, Pei-Lung Chen, Cassandra Obie, Ann Pulver, Dimitrios Avramopoulos, David Valle, Akira Sawa, Mikhail V Pletnikov
Neuregulin 3 (NRG3) is a paralog of NRG1. Genetic studies in schizophrenia demonstrate that risk variants in NRG3 are associated with cognitive and psychotic symptom severity, and several intronic single nucleotide polymorphisms in NRG3 are associated with delusions in patients with schizophrenia. In order to gain insights into the biological function of the gene, we generated a novel Nrg3 knockout (KO) mouse model and tested for neurobehavioral phenotypes relevant to psychotic disorders. KO mice displayed novelty-induced hyperactivity, impaired prepulse inhibition of the acoustic startle response, and deficient fear conditioning...
July 2016: Molecular Neuropsychiatry
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