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https://www.readbyqxmd.com/read/29154903/in-vitro-mesenchymal-epithelial-transition-in-nih3t3-fibroblasts-results-in-onset-of-low-dose-radiation-hypersensitivity-coupled-with-attenuated-connexin-43-response
#1
Ankit Mathur, Ashish Kumar, Bincy Babu, Sudhir Chandna
BACKGROUND: Mesenchymal-to-epithelial transition (MET) is associated with altered cell adhesion patterns. Independent studies showed that cellular adhesion regulates low-dose hyper-radiosensitivity (HRS), a phenomenon reported widely in tumour cells. Therefore, present study aimed to investigate whether MET and associated cellular adhesion alterations affect cellular radiosensitivity. METHODS: We established multiple stages of MET by in vitro transformation of NIH3T3 mouse embryonic fibroblasts...
November 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29139167/the-zinc-finger-gene-nolz1-regulates-the-formation-of-retinal-progenitor-cells-and-suppresses-the-lim3-lhx3-phenotype-of-retinal-bipolar-cells-in-chicken-retina
#2
Maria K E Blixt, Dardan Konjusha, Henrik Ring, Finn Hallböök
BACKGROUND: The zinc-finger transcription factor Nolz1 regulates spinal cord neuron development by interacting with the transcription factors Isl1, Lim1 and Lim3, which are also important for photoreceptors, horizontal and bipolar cells during retinal development. We therefore studied Nolz1 during retinal development. RESULTS: Nolz1 expression was seen in two waves during development: one early (peak at embryonic day 3-4.5) in retinal progenitors and one late (embryonic day 8) in newly differentiated cells in the inner nuclear layer...
November 15, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/29129507/the-use-of-polygenic-risk-scores-to-identify-phenotypes-associated-with-genetic-risk-of-schizophrenia-systematic-review
#3
REVIEW
Sumit Mistry, Judith R Harrison, Daniel J Smith, Valentina Escott-Price, Stanley Zammit
Studying the phenotypic manifestations of increased genetic liability for schizophrenia can increase our understanding of this disorder. Specifically, information from alleles identified in genome-wide association studies can be collapsed into a polygenic risk score (PRS) to explore how genetic risk is manifest within different samples. In this systematic review, we provide a comprehensive assessment of studies examining associations between schizophrenia PRS (SZ-PRS) and several phenotypic measures. We searched EMBASE, Medline and PsycINFO (from August 2009-14th March 2016) plus references of included studies, following PRISMA guidelines...
November 9, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/29112195/face-and-predictive-validity-of-the-clock%C3%AE-19-mouse-as-an-animal-model-for-bipolar-disorder-a-systematic-review
#4
REVIEW
M Kristensen, A A Nierenberg, S D Østergaard
Mice carrying the circadian locomotor output cycles Kaput delta 19 N-ethyl-N-nitrosoure (ENU) mutation (ClockΔ19) are used as an animal model for bipolar disorder (BD). We aimed to systematically review the face validity (phenotypical and pathophysiological resemblance with BD) and predictive validity (responsiveness to treatments used in BD) of this model in adherence with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. We carried out a systematic search of the databases PubMed and Embase, combining search terms covering BD and ClockΔ19...
November 7, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29106556/location-matters-distinct-dna-methylation-patterns-in-gabaergic-interneuronal-populations-from-separate-microcircuits-within-the-human-hippocampus
#5
W Brad Ruzicka, Sivan Subburaju, Joseph T Coyle, Francine M Benes
Recent studies describe distinct DNA methylomes among phenotypic subclasses of neurons in the human brain, but variation in DNA methylation between common neuronal phenotypes distinguished by their function within distinct neural circuits remains an unexplored concept. Studies able to resolve epigenetic profiles at the level of microcircuits are needed to illuminate chromatin dynamics in the regulation of specific neuronal populations and circuits mediating normal and abnormal behaviors.The Illumina HumanMethylation450 BeadChip was used to assess genome-wide DNA methylation in stratum oriens GABAergic interneurons sampled by laser-microdissection from two discrete microcircuits along the trisynaptic pathway in postmortem human hippocampus from eight control, eight schizophrenia, and eight bipolar disorder subjects...
November 2, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29101875/dissecting-disease-entities-out-of-the-broad-spectrum-of-bipolar-disorders
#6
Joseph Levine, Lilach Toker, Galila Agam
The etiopathology of bipolar disorders is yet unraveled and new avenues should be pursued. One such avenue may be based on the assumption that the bipolar broad spectrum includes, among others, an array of rare medical disease entities. Towards this aim we propose a dissecting approach based on a search for rare medical diseases with known etiopathology which also exhibit bipolar disorders symptomatology. We further suggest that the etiopathologic mechanisms underlying such rare medical diseases may also underlie a rare variant of bipolar disorder...
November 1, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/29096909/-assessment-of-mood-disorders-by-passive-data-gathering-the-concept-of-digital-phenotype-versus-psychiatrist-s-professional-culture
#7
A Bourla, F Ferreri, L Ogorzelec, C Guinchard, S Mouchabac
OBJECTIVES: The search for objective clinical signs is a constant practitioners' and researchers' concern in psychiatry. New technologies (embedded sensors, artificial intelligence) give an easier access to untapped information such as passive data (i.e. that do not require patient intervention). The concept of "digital phenotype" is emerging in psychiatry: a psychomotor alteration translated by accelerometer's modifications contrasting with the usual functioning of the subject, or the graphorrhea of patients presenting a manic episode which is replaced by an increase of SMS sent...
October 30, 2017: L'Encéphale
https://www.readbyqxmd.com/read/29079138/a-homer-1-gene-variant-influences-brain-structure-and-function-lithium-effects-on-white-matter-and-antidepressant-response-in-bipolar-disorder-a-multimodal-genetic-imaging-study
#8
Francesco Benedetti, Sara Poletti, Clara Locatelli, Elena Mazza, Cristina Lorenzi, Alice Vitali, Martina Riberto, Silvia Brioschi, Benedetta Vai, Irene Bollettini, Elisa Melloni, Veronica Aggio, Andrea Falini, Andrea De Bartolomeis, Cristina Colombo
BACKGROUND: The Homer family of postsynaptic scaffolding proteins plays a crucial role in glutamate-mediated synaptic plasticity, a phenotype associated with Bipolar Disorder (BD). Homer is a target for antidepressants and mood stabilizers. The AA risk genotype of the Homer rs7713917 A>G SNP has been associated with mood disorders and suicide, and in healthy humans with brain function. Despite the evidence linking Homer 1 gene and function to mood disorder, as well as its involvement in animal models of depression, no study has yet investigated the role of Homer in bipolar depression and treatment response...
October 27, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29071070/-massilibactero%C3%A3-des-vaginae-gen-nov-sp-nov-a-new-genus-within-the-family-of-bactero%C3%A3-daceae-isolated-from-a-patient-with-vaginosis
#9
J Jneid, J Y Bou Khalil, S Aherfi, C Blanc-Tailleur, D Raoult, B La Scola, I Pagnier
'Massilibacteroïdes vaginae' sp. nov. strain MV12(T) is the type strain of 'Massilibacteroïdes' gen. nov., a new genus within the family of Porphyromonadaceae. This strain was isolated in Marseille from a patient with vaginosis. 'Massilibacteroïdes vaginae' is a Gram-negative, aero-anaerobic bipolar bacillus. Here we describe the phenotypic characteristics and complete genome sequence of this bacterium. The EMBL accession number is FXDJ00000000 (FXDJ01000001-FXDJ01000009), and its genome consists of nine scaffolds...
January 2018: New Microbes and New Infections
https://www.readbyqxmd.com/read/29064472/genome-wide-association-studies-of-smooth-pursuit-and-antisaccade-eye-movements-in-psychotic-disorders-findings-from-the-b-snip-study
#10
R Lencer, L J Mills, N Alliey-Rodriguez, R Shafee, A M Lee, J L Reilly, A Sprenger, J E McDowell, S A McCarroll, M S Keshavan, G D Pearlson, C A Tamminga, B A Clementz, E S Gershon, J A Sweeney, J R Bishop
Eye movement deviations, particularly deficits of initial sensorimotor processing and sustained pursuit maintenance, and antisaccade inhibition errors, are established intermediate phenotypes for psychotic disorders. We here studied eye movement measures of 849 participants from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study (schizophrenia N=230, schizoaffective disorder N=155, psychotic bipolar disorder N=206 and healthy controls N=258) as quantitative phenotypes in relation to genetic data, while controlling for genetically derived ancestry measures, age and sex...
October 24, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29046483/deficiency-of-shank2-causes-mania-like-behavior-that-responds-to-mood-stabilizers
#11
Andrea L Pappas, Alexandra L Bey, Xiaoming Wang, Mark Rossi, Yong Ho Kim, Haidun Yan, Fiona Porkka, Lara J Duffney, Samantha M Phillips, Xinyu Cao, Jin-Dong Ding, Ramona M Rodriguiz, Henry H Yin, Richard J Weinberg, Ru-Rong Ji, William C Wetsel, Yong-Hui Jiang
Genetic defects in the synaptic scaffolding protein gene, SHANK2, are linked to a variety of neuropsychiatric disorders, including autism spectrum disorders, schizophrenia, intellectual disability, and bipolar disorder, but the molecular mechanisms underlying the pleotropic effects of SHANK2 mutations are poorly understood. We generated and characterized a line of Shank2 mutant mice by deleting exon 24 (Δe24). Shank2Δe24-/- mice engage in significantly increased locomotor activity, display abnormal reward-seeking behavior, are anhedonic, have perturbations in circadian rhythms, and show deficits in social and cognitive behaviors...
October 19, 2017: JCI Insight
https://www.readbyqxmd.com/read/29032150/functional-analysis-of-schizophrenia-genes-using-geneanalytics-program-and-integrated-databases
#12
Tharani Sundararajan, Ann M Manzardo, Merlin G Butler
Schizophrenia (SCZ) is a chronic debilitating neuropsychiatric disorder with multiple risk factors involving numerous complex genetic influences. We examined and updated a master list of clinically relevant and susceptibility genes associated with SCZ reported in the literature and genomic databases dedicated to gene discovery for characterization of SCZ genes. We used the commercially available GeneAnalytics computer-based gene analysis program and integrated genomic databases to create a molecular profile of the updated list of 608 SCZ genes to model their impact in select categories (tissues and cells, diseases, pathways, biological processes, molecular functions, phenotypes and compounds) using specialized GeneAnalytics algorithms...
October 12, 2017: Gene
https://www.readbyqxmd.com/read/28966986/intra-atrial-conduction-delay-revealed-by-multisite-incremental-atrial-pacing-is-an-independent-marker-of-remodeling-in-human-atrial-fibrillation
#13
Steven E Williams, Nick W F Linton, James Harrison, Henry Chubb, John Whitaker, Jaswinder Gill, Christopher A Rinaldi, Reza Razavi, Steven Niederer, Matthew Wright, Mark O'Neill
OBJECTIVES: This study sought to characterize direction-dependent and coupling interval-dependent changes in left atrial conduction and electrogram morphology in uniformly classified patients with paroxysmal atrial fibrillation (AF) and normal bipolar voltage mapping. BACKGROUND: Although AF classifications are based on arrhythmia duration, the clinical course, and treatment response vary between patients within these groups. Electrophysiological mechanisms responsible for this variability are incompletely described...
September 2017: JACC. Clinical Electrophysiology
https://www.readbyqxmd.com/read/28964912/functional-coding-variation-in-the-presynaptic-dopamine-transporter-associated-with-neuropsychiatric-disorders-drives-enhanced-motivation-and-context-dependent-impulsivity-in-mice
#14
Gwynne L Davis, Adele Stewart, Gregg D Stanwood, Raajaram Gowrishankar, Maureen K Hahn, Randy D Blakely
Recent genetic analyses have provided evidence that clinical commonalities associated with different psychiatric diagnoses often have shared mechanistic underpinnings. The development of animal models expressing functional genetic variation attributed to multiple disorders offers a salient opportunity to capture molecular, circuit and behavioral alterations underlying this hypothesis. In keeping with studies suggesting dopaminergic contributions to attention-deficit hyperactivity disorder (ADHD), bipolar disorder (BPD) and autism spectrum disorder (ASD), subjects with these diagnoses have been found to express a rare, functional coding substitution in the dopamine (DA) transporter (DAT), Ala559Val...
January 30, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/28963116/phelan-mcdermid-syndrome-due-to-shank3-mutation-in-an-intellectually-disabled-adult-male-successful-treatment-with-lithium
#15
Jos I M Egger, Willem M A Verhoeven, Renske Groenendijk-Reijenga, Sarina G Kant
For 30 years, Phelan and co-workers described a syndrome characterised by neonatal hypotonia, global developmental delay, strongly impaired speech, sleep disturbances and hyperreactivity to sensory stimuli. This Phelan-McDermid syndrome (PMS), also presenting with symptoms from the autism spectrum and a higher risk of developing seizure disorders, may be caused by a deletion of chromosome 22q13 or by a mutation in the SHANK3 gene. Its core psychopathological phenotype comprises symptoms from the bipolar spectrum for which generally treatment with a mood-stabilising anticonvulsant in combination with an atypical antipsychotic seems to be most effective...
September 28, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28937707/meta-analysis-of-the-antidepressant-effects-of-acute-sleep-deprivation
#16
Elaine M Boland, Hengyi Rao, David F Dinges, Rachel V Smith, Namni Goel, John A Detre, Mathias Basner, Yvette I Sheline, Michael E Thase, Philip R Gehrman
OBJECTIVE: To provide a quantitative meta-analysis of the antidepressant effects of sleep deprivation to complement qualitative reviews addressing response rates. DATA SOURCES: English-language studies from 1974 to 2016 using the keywords sleep deprivation and depression searched through PubMed and PsycINFO databases. STUDY SELECTION: A total of 66 independent studies met criteria for inclusion: conducted experimental sleep deprivation, reported the percentage of the sample that responded to sleep deprivation, provided a priori definition of antidepressant response, and did not seamlessly combine sleep deprivation with other therapies (eg, chronotherapeutics, repetitive transcranial magnetic stimulation)...
September 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28918256/transgene-is-specifically-and-functionally-expressed-in-retinal-inhibitory-interneurons-in-the-vgat-chr2-eyfp-mouse
#17
Guo-Zhong Xu, Ling-Jie Cui, Ai-Lin Liu, Wei Zhou, Xue Gong, Yong-Mei Zhong, Xiong-Li Yang, Shi-Jun Weng
Ectopic transgene expression in the retina has been reported in various transgenic mice, indicating the importance of characterizing retinal phenotypes. We examined transgene expression in the VGAT-ChR2-EYFP mouse retina by fluorescent immunohistochemistry and electrophysiology, with special emphasis on enhanced yellow fluorescent protein (EYFP) localization in retinal neuronal subtypes identified by specific markers. Strong EYFP signals were detected in both the inner and outer plexiform layers. In addition, the ChR2-EYFP fusion protein was also expressed in somata of the great majority of inhibitory interneurons, including horizontal cells and GABAergic and glycinergic amacrine cells...
November 5, 2017: Neuroscience
https://www.readbyqxmd.com/read/28902457/the-role-of-clock-gene-in-psychiatric-disorders-evidence-from-human-and-animal-research
#18
REVIEW
Jaqueline B Schuch, Julia P Genro, Clarissa R Bastos, Gabriele Ghisleni, Luciana Tovo-Rodrigues
The circadian clock system drives daily rhythms in physiology, metabolism, and behavior in mammals. Molecular mechanisms of this system consist of multiple clock genes, with Circadian Locomotor Output Cycles Kaput (CLOCK) as a core member that plays an important role in a wide range of behaviors. Alterations in the CLOCK gene are associated with common psychiatric disorders as well as with circadian disturbances comorbidities. This review addresses animal, molecular, and genetic studies evaluating the role of the CLOCK gene on many psychiatric conditions, namely autism spectrum disorder, schizophrenia, attention-deficit/hyperactivity disorder, major depressive disorder, bipolar disorder, anxiety disorder, and substance use disorder...
September 13, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28894008/genetic-disruption-of-ankyrin-g-in-adult-mouse-forebrain-causes-cortical-synapse-alteration-and-behavior-reminiscent-of-bipolar-disorder
#19
Shanshan Zhu, Zachary A Cordner, Jiali Xiong, Chi-Tso Chiu, Arabiye Artola, Yanning Zuo, Andrew D Nelson, Tae-Yeon Kim, Natalya Zaika, Brian M Woolums, Evan J Hess, Xiaofang Wang, De-Maw Chuang, Mikhail M Pletnikov, Paul M Jenkins, Kellie L Tamashiro, Christopher A Ross
Genome-wide association studies have implicated the ANK3 locus in bipolar disorder, a major human psychotic illness. ANK3 encodes ankyrin-G, which organizes the neuronal axon initial segment (AIS). We generated a mouse model with conditional disruption of ANK3 in pyramidal neurons of the adult forebrain (Ank-G cKO). This resulted in the expected loss of pyramidal neuron AIS voltage-gated sodium and potassium channels. There was also dramatic loss of markers of afferent GABAergic cartridge synapses, resembling the cortical microcircuitry changes in brains from psychotic patients, and suggesting disinhibition...
September 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28879196/assessment-of-whole-exome-sequence-data-in-attempted-suicide-within-a-bipolar-disorder-cohort
#20
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
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