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https://www.readbyqxmd.com/read/28525603/genome-wide-association-study-of-psychosis-proneness-in-the-finnish-population
#1
Alfredo Ortega-Alonso, Jesper Ekelund, Antti-Pekka Sarin, Jouko Miettunen, Juha Veijola, Marjo-Riitta Järvelin, William Hennah
The current study examined quantitative measures of psychosis proneness in a nonpsychotic population, in order to elucidate their underlying genetic architecture and to observe if there is any commonality to that already detected in the studies of individuals with overt psychotic conditions, such as schizophrenia and bipolar disorder. Heritability, univariate and multivariate genome-wide association (GWAs) tests, including a series of comprehensive gene-based association analyses, were developed in 4269 nonpsychotic persons participating in the Northern Finland Birth Cohort 1966 study with information on the following psychometric measures: Hypomanic Personality, Perceptual Aberration, Physical and Social Anhedonia (also known as Chapman's Schizotypia scales), and Schizoidia scale...
May 19, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/28505127/variability-of-dna-methylation-within-schizophrenia-risk-loci-across-subregions-of-human-hippocampus
#2
W Brad Ruzicka, Sivan Subburaju, Francine M Benes
Identification of 108 genomic regions significantly associated with schizophrenia risk by the Psychiatric Genomics Consortium was a milestone for the field, and much work is now focused on determining the mechanism of risk associated with each locus. Within these regions, we investigated variability of DNA methylation, a low-level cellular phenotype closely linked to genotype, in two highly similar cellular populations sampled from the human hippocampus, to draw inferences about the elaboration of genotype to phenotype within these loci enriched for schizophrenia risk...
May 15, 2017: Genes
https://www.readbyqxmd.com/read/28490646/a-missense-mutation-in-grm6-reduces-but-does-not-eliminate-mglur6-expression-or-rod-depolarizing-bipolar-cell-function
#3
Neal S Peachey, Nazarul Hasan, Bernard FitzMaurice, Samantha Burrill, Gobinda Pangeni, Son Yong Karst, Laura Reinholdt, Melissa L Berry, Marge Strobel, Ronald George Gregg, Maureen A McCall, Bo Chang
GRM6 encodes the metabotropic glutamate receptor 6 (mGluR6) used by retinal depolarizing bipolar cells (DBCs). Mutations in GRM6 lead to DBC dysfunction, and underlie the human condition autosomal recessive complete congenital stationary night blindness. Mouse mutants for Grm6 are important models for this condition. Here we report a new Grm6 mutant, identified in an electroretinogram (ERG) screen of mice maintained at The Jackson Laboratory. The Grm6(nob8) mouse has a reduced amplitude b-wave component of the ERG, which reflects light-evoked DBC activity...
May 10, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28487562/protein-phosphatase-2a-pp2a-regulates-eg5-to-control-mitotic-progression
#4
Yang Liu, Zhong Zhang, Hui Liang, Xuyang Zhao, Ling Liang, Guangxi Wang, Jingyi Yang, Yan Jin, Michael A McNutt, Yuxin Yin
EG5 (KIF11) is a member of the kinesin-like protein family involved in centrosome separation and bipolar spindle formation. When a cell enters mitosis, CDK1 phosphorylates EG5 at Thr926 and promotes EG5 localization on the mitotic spindle which drives bipolar spindle formation. EG5 provides power for spindle movement and thus controls the dynamics of spindle assembly. However, little is known about EG5 regulation or how EG5 detaches from the spindle upon mitotic exit. In this study we identify EG5 as a novel substrate of PP2A phosphatase, and we show that the PP2A/B55α complex plays an important role in mitotic exit by a mechanism involving EG5...
May 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28474173/-genetics-of-bipolar-disorder
#5
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...
May 4, 2017: Der Nervenarzt
https://www.readbyqxmd.com/read/28469556/integrative-analysis-of-brain-region-specific-shank3-interactomes-for-understanding-the-heterogeneity-of-neuronal-pathophysiology-related-to-shank3-mutations
#6
Yeunkum Lee, Hyojin Kang, Bokyoung Lee, Yinhua Zhang, Yoonhee Kim, Shinhyun Kim, Won-Ki Kim, Kihoon Han
Recent molecular genetic studies have identified 100s of risk genes for various neurodevelopmental and neuropsychiatric disorders. As the number of risk genes increases, it is becoming clear that different mutations of a single gene could cause different types of disorders. One of the best examples of such a gene is SHANK3, which encodes a core scaffold protein of the neuronal excitatory post-synapse. Deletions, duplications, and point mutations of SHANK3 are associated with autism spectrum disorders, intellectual disability, schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28467520/transdiagnostic-associations-between-functional-brain-network-integrity-and-cognition
#7
Julia M Sheffield, Sridhar Kandala, Carol A Tamminga, Godfrey D Pearlson, Matcheri S Keshavan, John A Sweeney, Brett A Clementz, Dov B Lerman-Sinkoff, S Kristian Hill, Deanna M Barch
Importance: Cognitive impairment occurs across the psychosis spectrum and is associated with functional outcome. However, it is unknown whether these shared manifestations of cognitive dysfunction across diagnostic categories also reflect shared neurobiological mechanisms or whether the source of impairment differs. Objective: To examine whether the general cognitive deficit observed across psychotic disorders is similarly associated with functional integrity of 2 brain networks widely implicated in supporting many cognitive domains...
May 3, 2017: JAMA Psychiatry
https://www.readbyqxmd.com/read/28454982/dopamine-transporter-dat-genetic-hypofunction-in-mice-produces-alterations-consistent-with-adhd-but-not-schizophrenia-or-bipolar-disorder
#8
M Mereu, G Contarini, E F Buonaguro, G Latte, F Managò, F Iasevoli, A de Bartolomeis, F Papaleo
ADHD, schizophrenia and bipolar disorder are psychiatric diseases with a strong genetic component which share dopaminergic alterations. Dopamine transporter (DAT) genetics might be potentially implicated in all these disorders. However, in contrast to DAT absence, the effects of DAT hypofunction especially in developmental trajectories have been scarcely addressed. Thus, we comprehensively studied DAT hypofunctional mice (DAT+/-) from adolescence to adulthood to disentangle DAT-dependent alterations in the development of psychiatric-relevant phenotypes...
April 26, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28449557/wnt-and-gsk3-signaling-pathways-in-bipolar-disorder-clinical-and-therapeutic-implications
#9
REVIEW
Ather Muneer
The neurobiology of bipolar disorder, a chronic and systemic ailment is not completely understood. The bipolar phenotype manifests in myriad ways, and psychopharmacological agents like lithium have long term beneficial effects. The enzyme glycogen synthase kinase 3 (GSK3) has come into focus, as lithium and several other mood stabilizing medications inhibit its activity. This kinase and its key upstream modulator, Wnt are dysregulated in mood disorders and there is a growing impetus to delineate the chief substrates involved in the development of these illnesses...
May 31, 2017: Clinical Psychopharmacology and Neuroscience: the Official Scientific Journal of the Korean College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28449121/tri-directional-anaphases-as-a-novel-chromosome-segregation-defect-in-human-oocytes
#10
Jenna Haverfield, Nicola L Dean, Diana Nöel, Gaudeline Rémillard-Labrosse, Veronique Paradis, Isaac-Jacques Kadoch, Greg FitzHarris
STUDY QUESTION: What are the chromosome segregation errors in human oocyte meiosis-I that may underlie oocyte aneuploidy? SUMMARY ANSWER: Multiple modes of chromosome segregation error were observed, including tri-directional anaphases, which we attribute to loss of bipolar spindle structure at anaphase-I. WHAT IS KNOWN ALREADY: Oocyte aneuploidy is common and associated with infertility, but mechanistic information on the chromosome segregation errors underlying these defects is scarce...
June 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28439101/largest-gwas-of-ptsd-n-20%C3%A2-070-yields-genetic-overlap-with-schizophrenia-and-sex-differences-in-heritability
#11
L E Duncan, A Ratanatharathorn, A E Aiello, L M Almli, A B Amstadter, A E Ashley-Koch, D G Baker, J C Beckham, L J Bierut, J Bisson, B Bradley, C-Y Chen, S Dalvie, L A Farrer, S Galea, M E Garrett, J E Gelernter, G Guffanti, M A Hauser, E O Johnson, R C Kessler, N A Kimbrel, A King, N Koen, H R Kranzler, M W Logue, A X Maihofer, A R Martin, M W Miller, R A Morey, N R Nugent, J P Rice, S Ripke, A L Roberts, N L Saccone, J W Smoller, D J Stein, M B Stein, J A Sumner, M Uddin, R J Ursano, D E Wildman, R Yehuda, H Zhao, M J Daly, I Liberzon, K J Ressler, C M Nievergelt, K C Koenen
The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h(2)SNP) for European-American females of 29% that is similar to h(2)SNP for schizophrenia and is substantially higher than h(2)SNP in European-American males (estimate not distinguishable from zero)...
April 25, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28421717/cognitive-profiles-in-euthymic-patients-with-bipolar-disorders-results-from-the-face-bd-cohort
#12
Paul Roux, Aurélie Raust, Anne Sophie Cannavo, Valérie Aubin, Bruno Aouizerate, Jean-Michel Azorin, Frank Bellivier, Raoul Belzeaux, Thierry Bougerol, Iréna Cussac, Philippe Courtet, Bruno Etain, Sébastien Gard, Sophie Job, Jean-Pierre Kahn, Marion Leboyer, Emilie Olié, Chantal Henry, Christine Passerieux
OBJECTIVES: Although cognitive deficits are a well-established feature of bipolar disorders (BD), even during periods of euthymia, little is known about cognitive phenotype heterogeneity among patients with BD. METHODS: We investigated neuropsychological performance in 258 euthymic patients with BD recruited via the French network of expert centers for BD. We used a test battery assessing six domains of cognition. Hierarchical cluster analysis of the cross-sectional data was used to determine the optimal number of subgroups and to assign each patient to a specific cognitive cluster...
April 19, 2017: Bipolar Disorders
https://www.readbyqxmd.com/read/28401296/associations-of-specific-psychiatric-disorders-with-isolated-focal-dystonia-and-monogenic-and-idiopathic-parkinson-s-disease
#13
Susanne Steinlechner, Johann Hagenah, Hans-Jürgen Rumpf, Christian Meyer, Ulrich John, Tobias Bäumer, Norbert Brüggemann, Meike Kasten, Alexander Münchau, Christine Klein, Rebekka Lencer
Comorbidity of psychiatric disorders in patients with movement disorders is common. Often, psychiatric symptoms manifest before the onset of the movement disorder, thus not representing a mere reaction to its burden. How the disease mechanisms of psychiatric and movement disorders are related is still poorly understood. The aim of the present study was to compare prevalence rates of specific psychiatric disorders between different movement disorders including isolated focal dystonia (IFD, N = 91), monogenic Parkinson's disease (PD, N = 41), idiopathic PD (N = 45), and a sample from a Northern Germany general population (TACOS Study; N = 4075)...
April 11, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28395208/increased-dopamine-receptor-expression-and-anti-depressant-response-following-deep-brain-stimulation-of-the-medial-forebrain-bundle
#14
Manoj P Dandekar, Dustin Luse, Carson Hoffmann, Patrick Cotton, Travis Peery, Christian Ruiz, Caroline Hussey, Vijayasree V Giridharan, Jair C Soares, Joao Quevedo, Albert J Fenoy
BACKGROUND: Among several potential neuroanatomical targets pursued for deep brain stimulation (DBS) for treating those with treatment-resistant depression (TRD), the superolateral-branch of the medial forebrain bundle (MFB) is emerging as a privileged location. We investigated the antidepressant-like phenotypic and chemical changes associated with reward-processing dopaminergic systems in rat brains after MFB-DBS. METHODS: Male Wistar rats were divided into three groups: sham-operated, DBS-Off, and DBS-On...
April 5, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/28392151/effects-of-risk-for-bipolar-disorder-on-brain-function-a-twin-and-family-study
#15
Genichi Sugihara, Fergus Kane, Marco M Picchioni, Christopher A Chaddock, Eugenia Kravariti, Sridevi Kalidindi, Fruhling Rijsdijk, Timothea Toulopoulou, Vivienne A Curtis, Colm McDonald, Robin M Murray, Philip McGuire
Bipolar disorder (BPD) is associated with altered regional brain function during the performance of cognitive tasks. The relative contribution of genetic and environmental risk factors for BPD to these changes has not yet been quantified. We sought to address this issue in a functional neuroimaging study of people who varied in their risk for BPD. Functional magnetic resonance imaging was used to study 124 subjects (29 twin and 9 sibling pairs with at least one member with BPD, and 24 healthy twin pairs) performing a working memory task...
April 6, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28390849/cognitive-burden-of-anticholinergic-medications-in-psychotic-disorders
#16
Seenae Eum, S Kristian Hill, Leah H Rubin, Ryan M Carnahan, James L Reilly, Elena I Ivleva, Sarah K Keedy, Carol A Tamminga, Godfrey D Pearlson, Brett A Clementz, Elliot S Gershon, Matcheri S Keshavan, Richard S E Keefe, John A Sweeney, Jeffrey R Bishop
BACKGROUND: Patients with psychotic disorders are often treated with numerous medications, many of which have anticholinergic activity. We assessed cognition in relation to the cumulative anticholinergic burden of multiple drugs included in treatment regimens of participants from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study. METHOD: Clinically stable participants with schizophrenia (n=206), schizoaffective disorder (n=131), and psychotic bipolar disorder (n=146) were examined...
April 5, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28382556/acute-progressive-paravascular-placoid-neuroretinopathy-with-negative-type-electroretinography-in-paraneoplastic-retinopathy
#17
Fred K Chen, Avenell L Chew, Dan Zhang, Shang-Chih Chen, Enid Chelva, Erandi Chandrasekera, Eleanor M H Koay, John Forrester, Samuel McLenachan
PURPOSE: Paraneoplastic retinopathy can be the first manifestation of systemic malignancy. A subset of paraneoplastic retinopathy is characterized by negative-type electroretinography (ERG) without fundus abnormality. Here we describe the multimodal imaging and clinico-pathological correlation of a unique case of acute progressive paravascular placoid neuroretinopathy with suspected retinal depolarizing bipolar cell dysfunction preceding the diagnosis of metastatic small cell carcinoma of the prostate...
April 5, 2017: Documenta Ophthalmologica. Advances in Ophthalmology
https://www.readbyqxmd.com/read/28372995/targeting-aggression-in-severe-mental-illness-the-predictive-role-of-genetic-epigenetic-and-metabolomic-markers
#18
REVIEW
Mirko Manchia, Vassilios Fanos
Human aggression is a complex and widespread social behavior that is overrepresented in individuals affected by severe mental illness (SMI), such as schizophrenia (SCZ), bipolar disorder (BD), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). A substantial proportion of the liability threshold for aggressive behavior is determined by genetic factors, and environmental moderators might precipitate the manifestation of this behavioral phenotype through modification of gene expression via the epigenetic machinery...
April 2, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28346060/stem-cell-derived-neurons-in-the-development-of-targeted-treatment-for-schizophrenia-and-bipolar-disorder
#19
Bradley Watmuff, Bangyan Liu, Rakesh Karmacharya
The recent advent of induced pluripotent stem cells has enabled the study of patient-specific and disease-related neurons in vitro and has facilitated new directions of inquiry into disease mechanisms. With these approaches, we now have the possibility of correlating ex vivo cellular phenotypes with individual patient response to treatment and/or side effects, which makes targeted treatments for schizophrenia and bipolar disorder a distinct prospect in the coming years. Here, we briefly review the current state of stem cell-based models and explore studies that are providing new insights into the disease biology of schizophrenia and bipolar disorder, which are laying the foundations for the development of novel targeted therapies...
April 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28342679/pharmacogenomic-aspects-of-bipolar-disorder-an-update
#20
M Budde, D Degner, J Brockmöller, T G Schulze
The hopes for readily implementable precision medicine are high. For many complex disorders, such as bipolar disorder, these hopes critically hinge on tangible successes in pharmacogenetics of treatment response or susceptibility to adverse events. In this article, we review the current state of pharmacogenomics of bipolar disorder including latest results from candidate genes and genome-wide association studies. The majority of studies focus on response to lithium treatment. Although a host of genes has been studied, hardly any replicated findings have emerged so far...
March 22, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
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