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Lithium genetics

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https://www.readbyqxmd.com/read/29046483/deficiency-of-shank2-causes-mania-like-behavior-that-responds-to-mood-stabilizers
#1
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/29021832/pharmacogenomics-in-the-treatment-of-mood-disorders-strategies-and-opportunities-for-personalized-psychiatry
#2
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/28978660/meta-analysis-of-pharmacogenetic-interactions-in-amyotrophic-lateral-sclerosis-clinical-trials
#3
Ruben P A van Eijk, Ashley R Jones, William Sproviero, Aleksey Shatunov, Pamela J Shaw, P Nigel Leigh, Carolyn A Young, Christopher E Shaw, Gabriele Mora, Jessica Mandrioli, Giuseppe Borghero, Paolo Volanti, Frank P Diekstra, Wouter van Rheenen, Esther Verstraete, Marinus J C Eijkemans, Jan H Veldink, Adriano Chio, Ammar Al-Chalabi, Leonard H van den Berg, Michael A van Es
OBJECTIVE: To assess whether genetic subgroups in recent amyotrophic lateral sclerosis (ALS) trials responded to treatment with lithium carbonate, but that the treatment effect was lost in a large cohort of nonresponders. METHODS: Individual participant data were obtained from 3 randomized trials investigating the efficacy of lithium carbonate. We matched clinical data with data regarding the UNC13A and C9orf72 genotype. Our primary outcome was survival at 12 months...
October 4, 2017: Neurology
https://www.readbyqxmd.com/read/28941093/staging-in-bipolar-disorder-from-theoretical-framework-to-clinical-utility
#4
Michael Berk, Robert Post, Aswin Ratheesh, Emma Gliddon, Ajeet Singh, Eduard Vieta, Andre F Carvalho, Melanie M Ashton, Lesley Berk, Susan M Cotton, Patrick D McGorry, Brisa S Fernandes, Lakshmi N Yatham, Seetal Dodd
Illness staging is widely utilized in several medical disciplines to help predict course or prognosis, and optimize treatment. Staging models in psychiatry in general, and bipolar disorder in particular, depend on the premise that psychopathology moves along a predictable path: an at-risk or latency stage, a prodrome progressing to a first clinical threshold episode, and one or more recurrences with the potential to revert or progress to late or end-stage manifestations. The utility and validity of a staging model for bipolar disorder depend on its linking to clinical outcome, treatment response and neurobiological measures...
October 2017: World Psychiatry: Official Journal of the World Psychiatric Association (WPA)
https://www.readbyqxmd.com/read/28895268/lithium-reduces-the-span-of-g-protein-activated-k-girk-channel-inhibition-in-hippocampal-neurons
#5
Nathan Dascal, Moran Rubinstein
OBJECTIVES: Lithium (Li(+) ) is one of the most widely used treatments for bipolar disorder (BD). However, the molecular and neuronal basis of BD, as well as the mechanisms of Li(+) actions are poorly understood. Cellular and biochemical studies identified G proteins as being among the cellular targets for Li(+) action, while genetic studies indicated an association with the KCNJ3 gene, which encodes the G protein-activated inwardly rectifying K(+) (GIRK) channels. GIRK channels regulate neuronal excitability by mediating the inhibitory effects of multiple neurotransmitters and contribute to the resting potassium conductance...
September 12, 2017: Bipolar Disorders
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
#6
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/28803243/lithium-sensitivity-of-store-operated-ca2-entry-and-survival-of-fibroblasts-isolated-from-chorea-acanthocytosis-patients
#7
Lisann Pelzl, Bhaeldin Elsir, Itishri Sahu, Rosi Bissinger, Yogesh Singh, Basma Sukkar, Sabina Honisch, Ludger Schoels, Mohamed Jemaà, Elisabeth Lang, Alexander Storch, Andreas Hermann, Christos Stournaras, Florian Lang
BACKGROUND: The widely expressed protein chorein fosters activation of the phosphoinositide 3 kinase (PI3K) pathway thus supporting cell survival. Loss of function mutations of the chorein encoding gene VPS13A (vacuolar protein sorting-associated protein 13A) causes chorea-acanthocytosis (ChAc), a neurodegenerative disorder paralleled by deformations of erythrocytes. In mice, genetic knockout of chorein leads to enhanced neuronal apoptosis. PI3K dependent signalling upregulates Orai1, a pore forming channel protein accomplishing store operated Ca2+ entry (SOCE)...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28641149/thyroid-autoimmunity-in-bipolar-disorder-a-systematic-review
#8
REVIEW
Margherita Barbuti, André F Carvalho, Cristiano A Köhler, Andrea Murru, Norma Verdolini, Giovanni Guiso, Ludovic Samalin, Michael Maes, Brendon Stubbs, Giulio Perugi, Eduard Vieta, Isabella Pacchiarotti
BACKGROUND: Accumulating evidence points to the pathophysiological relevance between immune dysfunction and mood disorders. High rates of thyroid dysfunction have been found in patients with bipolar disorder (BD), compared to the general population. A systematic review of the relationship between BD and thyroid autoimmunity was performed. METHODS: Pubmed, EMBASE and PsycINFO databases were searched up till January 28th, 2017. This review has been conducted according to the PRISMA statements...
October 15, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/28639153/genomics-of-lithium-action-and-response
#9
REVIEW
Benjamin S Pickard
Lithium is the most successful mood stabilizer treatment for bipolar disorder. However, unlike conventional drugs that are designed to interact with a specific molecular target, the actions of lithium are distributed across many biological processes and pathways. Treatment response is subject to genetic variation between individuals and similar genetic variation may dictate susceptibility to side effects. Transcriptomic, genomic, and cell-model research strategies have all been deployed in the search for the genetic factors and biological systems that mediate the interaction between genetics and the therapeutic actions of lithium...
July 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28633406/in-saccharomyces-cerevisiae-gene-targeting-fidelity-depends-on-a-transformation-method-and-proportion-of-the-overall-length-of-the-transforming-and-targeted-dna
#10
Anamarija Štafa, Marina Svetec Miklenic, Antonio Zandona, Bojan Žunar, Neža Cadež, Hrvoje Petkovic, Ivan Krešimir Svetec
Gene replacement is one of the most essential approaches in construction of the genetically modified yeast strains. However, the fidelity of gene targeting and the effort needed for construction of a particular strain can vary significantly. We investigated the influence of two important factors-the choice of the transformation method and the design of the transforming DNA fragment, which can vary in overall length (including flanking regions and selectable marker) compared to the length of the targeted region in the genome...
June 1, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/28605600/activin-and-bmp4-signaling-converge-on-wnt-activation-during-odontogenesis
#11
H-J E Kwon, S Jia, Y Lan, H Liu, R Jiang
Previous studies show that both activin and Bmp4 act as crucial mesenchymal odontogenic signals during early tooth development. Remarkably, mice lacking activin-βA ( Inhba(-/-)) and mice with neural crest-specific inactivation of Bmp4 ( Bmp4(ncko/ncko)) both exhibit bud-stage developmental arrest of the mandibular molar tooth germs while their maxillary molar tooth germs completed morphogenesis. In this study, we found that, whereas expression of Inhba and Bmp4 in the developing tooth mesenchyme is independent of each other, Bmp4(ncko/ncko)Inhba(-/-) compound mutant mice exhibit early developmental arrest of all tooth germs...
September 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28574156/prediction-of-lithium-response-in-first-episode-mania-using-the-lithium-intelligent-agent-lithia-pilot-data-and-proof-of-concept
#12
David E Fleck, Nicholas Ernest, Caleb M Adler, Kelly Cohen, James C Eliassen, Matthew Norris, Richard A Komoroski, Wen-Jang Chu, Jeffrey A Welge, Thomas J Blom, Melissa P DelBello, Stephen M Strakowski
OBJECTIVES: Individualized treatment for bipolar disorder based on neuroimaging treatment targets remains elusive. To address this shortcoming, we developed a linguistic machine learning system based on a cascading genetic fuzzy tree (GFT) design called the LITHium Intelligent Agent (LITHIA). Using multiple objectively defined functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy ((1) H-MRS) inputs, we tested whether LITHIA could accurately predict the lithium response in participants with first-episode bipolar mania...
June 2017: Bipolar Disorders
https://www.readbyqxmd.com/read/28567245/confined-space-synthesis-of-nanostructured-anatase-directed-by-genetically-engineered-living-organisms-for-lithium-ion-batteries
#13
Hang Ping, Hao Xie, Mingyu Xiang, Bao-Lian Su, Yucheng Wang, Jinyong Zhang, Fan Zhang, Zhengyi Fu
Biomineral formation processes in nature are temporally and spatially regulated under the functions of biomolecules in a confined space. It is potentially very productive to rationally design a mineralized system by taking into account confined space as well as biomolecules. The laboratory technique of "bacterial cell surface display" is an ideal platform to host catalytically active proteins in a three-dimensionally confined space. In the present study, aiming to regulate the synthesis of nanostructured TiO2 anatase, repeating segments of silaffin were displayed on Escherichia coli surfaces through genetic manipulation...
October 1, 2016: Chemical Science
https://www.readbyqxmd.com/read/28537298/vibrational-and-impedance-spectroscopic-analyses-of-semi-interpenetrating-polymer-networks-as-solid-polymer-electrolytes
#14
Nimai Bar, Pratyay Basak, Yoed Tsur
Semi-interpenetrating polymer networks (semi-IPNs) with significant ionic conductivity (10(-4) S cm(-1) at ambient temperature) were studied by vibrational and impedance spectroscopies coupled with advanced analysis procedures. Vibrational spectroscopy recognized the numbers of free ions, ion pairs, ion-polymers and hydrogen bonds within the solid polymer electrolyte matrices (SPE). Electrochemical impedance spectroscopy (EIS) was used to quantify the bulk resistance and bulk relaxation time. The analyses used discrepancy-complexity plots to assess the number of free parameters properly, and EIS was further analyzed using impedance spectroscopy genetic programming (ISGP)...
June 7, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28474173/-genetics-of-bipolar-disorder
#15
REVIEW
M Budde, A J Forstner, K Adorjan, S K Schaupp, M M Nöthen, T G Schulze
Bipolar disorder (BD) has a multifactorial etiology. Its development is influenced by genetic as well as environmental factors. Large genome-wide association studies (GWAS), in which genetic risk allelic variants for the disorder could be replicated for the first time, marked the breakthrough in the identification of the responsible risk genes. In addition to these common genetic variants with moderate effects identified by GWAS, rare variants with a higher penetrance are expected to play a role in disease development...
July 2017: Der Nervenarzt
https://www.readbyqxmd.com/read/28442992/genetic-deletion-of-akt3-induces-an-endophenotype-reminiscent-of-psychiatric-manifestations-in-mice
#16
Yan Bergeron, Geneviève Bureau, Marie-Élaine Laurier-Laurin, Eric Asselin, Guy Massicotte, Michel Cyr
The protein kinase B (PKB/Akt), found in three distinctive isoforms (PKBα/Akt1, PKBβ/Akt2, PKBγ/Akt3), is implicated in a variety of cellular processes such as cell development, growth and survival. Although Akt3 is the most expressed isoform in the brain, its role in cerebral functions is still unclear. In the present study, we investigated the behavioral, electrophysiological and biochemical consequences of Akt3 deletion in mice. Motor abilities, spatial navigation, recognition memory and LTP are intact in the Akt3 knockout (KO) mice...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28398339/animal-models-to-improve-our-understanding-and-treatment-of-suicidal-behavior
#17
REVIEW
T D Gould, P Georgiou, L A Brenner, L Brundin, A Can, P Courtet, Z R Donaldson, Y Dwivedi, S Guillaume, I I Gottesman, S Kanekar, C A Lowry, P F Renshaw, D Rujescu, E G Smith, G Turecki, P Zanos, C A Zarate, P A Zunszain, T T Postolache
Worldwide, suicide is a leading cause of death. Although a sizable proportion of deaths by suicide may be preventable, it is well documented that despite major governmental and international investments in research, education and clinical practice suicide rates have not diminished and are even increasing among several at-risk populations. Although nonhuman animals do not engage in suicidal behavior amenable to translational studies, we argue that animal model systems are necessary to investigate candidate endophenotypes of suicidal behavior and the neurobiology underlying these endophenotypes...
April 11, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28319150/high-throughput-transformation-of-saccharomyces-cerevisiae-using-liquid-handling-robots
#18
Guangbo Liu, Clayton Lanham, J Ross Buchan, Matthew E Kaplan
Saccharomyces cerevisiae (budding yeast) is a powerful eukaryotic model organism ideally suited to high-throughput genetic analyses, which time and again has yielded insights that further our understanding of cell biology processes conserved in humans. Lithium Acetate (LiAc) transformation of yeast with DNA for the purposes of exogenous protein expression (e.g., plasmids) or genome mutation (e.g., gene mutation, deletion, epitope tagging) is a useful and long established method. However, a reliable and optimized high throughput transformation protocol that runs almost no risk of human error has not been described in the literature...
2017: PloS One
https://www.readbyqxmd.com/read/28242870/neurons-derived-from-patients-with-bipolar-disorder-divide-into-intrinsically-different-sub-populations-of-neurons-predicting-the-patients-responsiveness-to-lithium
#19
S Stern, R Santos, M C Marchetto, A P D Mendes, G A Rouleau, S Biesmans, Q-W Wang, J Yao, P Charnay, A G Bang, M Alda, F H Gage
Bipolar disorder (BD) is a progressive psychiatric disorder with more than 3% prevalence worldwide. Affected individuals experience recurrent episodes of depression and mania, disrupting normal life and increasing the risk of suicide greatly. The complexity and genetic heterogeneity of psychiatric disorders have challenged the development of animal and cellular models. We recently reported that hippocampal dentate gyrus (DG) neurons differentiated from induced pluripotent stem cell (iPSC)-derived fibroblasts of BD patients are electrophysiologically hyperexcitable...
February 28, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28212405/a-simplified-fractional-order-impedance-model-and-parameter-identification-method-for-lithium-ion-batteries
#20
Qingxia Yang, Jun Xu, Binggang Cao, Xiuqing Li
Identification of internal parameters of lithium-ion batteries is a useful tool to evaluate battery performance, and requires an effective model and algorithm. Based on the least square genetic algorithm, a simplified fractional order impedance model for lithium-ion batteries and the corresponding parameter identification method were developed. The simplified model was derived from the analysis of the electrochemical impedance spectroscopy data and the transient response of lithium-ion batteries with different states of charge...
2017: PloS One
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