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Bipolar phenotype

Antonella Sferra, Fabiana Fattori, Teresa Rizza, Elsabetta Flex, Emanuele Bellacchio, Alessandro Bruselles, Stefania Petrini, Serena Cecchetti, Massimo Teson, Fabrizia Restaldi, Andrea Ciolfi, Filippo M Santorelli, Ginevra Zanni, Sabina Barresi, Claudia Castiglioni, Marco Tartaglia, Enrico Bertini
Microtubules participate in fundamental cellular processes, including chromosomal segregation and cell division, migration, and intracellular trafficking. Their proper function is required for correct central nervous system development and operative preservation, and mutations in genes coding tubulins, the constituting units of microtubules, underlie a family of neurodevelopmental and neurodegenerative diseases, collectively known as "tubulinopathies", characterized by a wide range of neuronal defects resulting from defective proliferation, migration, and function...
March 14, 2018: Human Molecular Genetics
Juliana Brum Moraes, Michael Maes, Chutima Roomruangwong, Kamila Landucci Bonifacio, Decio Sabbatini Barbosa, Heber Odebrecht Vargas, George Anderson, Marta Kubera, Andre F Carvalho, Sandra Odebrecht Vargas Nunes
Early life trauma (ELT) may increase the risk towards bipolar disorder (BD) and major depression (MDD), disorders associated with activated neuro-oxidative and neuro-nitrosative stress (O&NS) pathways. It has remained elusive whether ELTs are associated with O&NS and which ELTs are associated with distinct affective disorder phenotypes. This case-control study examined patients with BD (n = 68) and MDD (n = 37) and healthy controls (n = 66). The Child Trauma Questionnaire (CTQ) was used to assess specific ELT...
March 14, 2018: Metabolic Brain Disease
Eugenia Tomasella, Lucila Bechelli, Mora Belén Ogando, Camilo Mininni, Mariano N Di Guilmi, Fernanda De Fino, Silvano Zanutto, Ana Belén Elgoyhen, Antonia Marin-Burgin, Diego M Gelman
Excessive dopamine neurotransmission underlies psychotic episodes as observed in patients with some types of bipolar disorder and schizophrenia. The dopaminergic hypothesis was postulated after the finding that antipsychotics were effective to halt increased dopamine tone. However, there is little evidence for dysfunction within the dopaminergic system itself. Alternatively, it has been proposed that excessive afferent activity onto ventral tegmental area dopaminergic neurons, particularly from the ventral hippocampus, increase dopamine neurotransmission, leading to psychosis...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Sumit Mistry, Judith R Harrison, Daniel J Smith, Valentina Escott-Price, Stanley Zammit
BACKGROUND: Identifying the phenotypic manifestations of increased genetic liability for depression (MDD) and bipolar disorder (BD) can enhance understanding of their aetiology. The polygenic risk score (PRS) derived using data from genome-wide-association-studies can be used to explore how genetic risk is manifest in different samples. AIMS: In this systematic review, we review studies that examine associations between the MDD and BD polygenic risk scores and phenotypic outcomes...
February 15, 2018: Journal of Affective Disorders
Marisa A Patti, Vanessa Troiani
Atypical sulcogyral patterns in the orbitofrontal cortex (OFC) are associated with increased risk for schizophrenia, as well as with quantitative traits associated with schizophrenia, such as anhedonia. Here we conduct a cross-diagnostic comparison to assess whether atypical OFC sulcogyral patterns confer risk for multiple brain disorders. We examined structural images from 4 groups of adult participants (N = 189), including those diagnosed with schizophrenia (SZ; N = 49), bipolar disorder (BP; N = 46), attention deficit hyperactivity disorder (ADHD; N = 41), and controls (N = 53)...
2018: NeuroImage: Clinical
Michele Fornaro, Annalisa Anastasia, Francesco Monaco, Stefano Novello, Andrea Fusco, Felice Iasevoli, Domenico De Berardis, Nicola Veronese, Marco Solmi, Andrea de Bartolomeis
BACKGROUND: Treatment-emergent affective switch (TEAS), including treatment-emergent mania (TEM), carry significant burden in the clinical management of bipolar depression, whereas the use of antidepressants raises both efficacy, safety and tolerability concerns. The present study assesses the prevalence and clinical correlates of TEM in selected sample of Bipolar Disorder (BD) Type-II (BD-II) acute depression outpatients. METHODS: Post-hoc analysis of the clinical and psychopathological features associated with TEM among 91 BD-II depressed outpatients exposed to antidepressants...
March 1, 2018: Journal of Affective Disorders
E M Peter-Ross
The pathobiological causes, the shared cellular and molecular pathways in catatonia and in catatonic presentation in neuropsychiatric disorders are yet to be determined. The hypotheses in this paper have been deduced from the latest scientific research findings and clinical observations of patients with genetic disorders, behavioral phenotypes and other family members suffering mental disorders. The first hypothesis postulates that catatonia and the heterogeneity of catatonic signs and symptoms involve nucleolar dysfunction arising from abnormalities of the brain-specific, non-coding micro-RNA, SNORD115 genes (either duplications or deletions) which result in pathobiological dysfunction of various combinations in the downstream pathways (possibly along with other genes in these shared pathways)...
April 2018: Medical Hypotheses
Kazuhiko Yamamuro, Sohei Kimoto, Junzo Iida, Naoko Kishimoto, Shohei Tanaka, Michihiro Toritsuka, Daisuke Ikawa, Yasunori Yamashita, Toyosaku Ota, Manabu Makinodan, Hiroki Yoshino, Toshifumi Kishimoto
BACKGROUND: Schizophrenia (SZ) and bipolar disorder (BD) are characterized by different clinical symptoms, and have previously been considered as categorically separate. However, several lines of evidence controversially suggest that these two disorders may run on a continuum. While it is therefore important to evaluate the subtle differences between SZ and BD, few studies have investigated the difference of brain functioning between the two by focusing on the common symptoms of cognitive functioning and impulsivity, rather than positive/negative and mood symptoms...
February 27, 2018: Journal of Affective Disorders
Ravi Kiran Deevi, Arman Javadi, Jane McClements, Jekaterina Vohhodina, Kienan Savage, Maurice Bernard Loughrey, Emma Evergren, Frederick Charles Campbell
Histological grading provides prognostic stratification of colorectal cancer (CRC) by scoring heterogeneous phenotypes. Features of aggressiveness include aberrant mitotic spindle configurations, chromosomal breakage, and bizarre multicellular morphology, but pathobiology is poorly understood. Protein kinase C zeta (PKCz) controls mitotic spindle dynamics, chromosome segregation, and multicellular patterns, but its role in CRC phenotype evolution remains unclear. Here, we show that PKCz couples genome segregation to multicellular morphology through control of interphase centrosome anchoring...
March 9, 2018: Journal of Pathology
Covadonga M Díaz-Caneja, Mª Goretti Morón-Nozaleda, Raquel P Vicente-Moreno, Elisa Rodríguez-Toscano, Laura Pina-Camacho, Elena de la Serna, Gisela Sugranyes, Inmaculada Baeza, Soledad Romero, Vanessa Sánchez-Gistau, Josefina Castro-Fornieles, Carmen Moreno, Dolores Moreno
Shared vulnerability in offspring of individuals with schizophrenia (SzO) and bipolar disorder (BpO) might manifest early during development through common temperament traits. Temperament dimensions in child and adolescent BpO (N = 80), SzO (N = 34) and the offspring of community controls (CcO) (N = 101) were assessed using the Revised Dimensions of Temperament Survey. The association between temperament dimensions and lifetime psychopathology (including threshold and subthreshold DSM-IV-TR diagnoses) and current socio-academic adjustment was assessed using logistic regression...
March 8, 2018: European Child & Adolescent Psychiatry
Anke Hoffmann, Vincenza Sportelli, Michael Ziller, Dietmar Spengler
Bipolar disease (BD) is one of the major public health burdens worldwide and more people are affected every year. Comprehensive genetic studies have associated thousands of single nucleotide polymorphisms (SNPs) with BD risk; yet, very little is known about their functional roles. Induced pluripotent stem cells (iPSCs) are powerful tools for investigating the relationship between genotype and phenotype in disease-relevant tissues and cell types. Neural cells generated from BD-specific iPSCs are thought to capture associated genetic risk factors, known and unknown, and to allow the analysis of their effects on cellular and molecular phenotypes...
March 8, 2018: International Journal of Molecular Sciences
Dominik A Moser, Gaelle E Doucet, Won Hee Lee, Alexander Rasgon, Hannah Krinsky, Evan Leibu, Alex Ing, Gunter Schumann, Natalie Rasgon, Sophia Frangou
Importance: Alterations in multiple neuroimaging phenotypes have been reported in psychotic disorders. However, neuroimaging measures can be influenced by factors that are not directly related to psychosis and may confound the interpretation of case-control differences. Therefore, a detailed characterization of the contribution of these factors to neuroimaging phenotypes in psychosis is warranted. Objective: To quantify the association between neuroimaging measures and behavioral, health, and demographic variables in psychosis using an integrated multivariate approach...
March 7, 2018: JAMA Psychiatry
Robert M Maier, Zhihong Zhu, Sang Hong Lee, Maciej Trzaskowski, Douglas M Ruderfer, Eli A Stahl, Stephan Ripke, Naomi R Wray, Jian Yang, Peter M Visscher, Matthew R Robinson
Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts...
March 7, 2018: Nature Communications
Mathew D Hutchinson, Hyon-He K Garza
As we have witnessed in other arenas of catheter-based therapeutics, ventricular tachycardia (VT) ablation has become increasingly anatomical in its execution. Multi-modality imaging provides anatomical detail in substrate characterization, which is often complex in nonischemic cardiomyopathy patients. Patients with intramural, intraseptal, and epicardial substrates provide challenges in delivering effective ablation to the critical arrhythmia substrate due to the depth of origin or the presence of adjacent critical structures...
February 24, 2018: Current Treatment Options in Cardiovascular Medicine
T M Lancaster
BACKGROUND: Recent genome-wide association studies (GWAS) of striatal volumes and bipolar disorder (BD) indicate these traits are heritable and share common genetic architecture, however little independent work has been conducted to help establish this relationship. METHODS: Subcortical volumes (mm3 ) of young, healthy offspring of BD (N= 32) and major depressive disorder (MDD) patients (N= 158) were compared to larger healthy control sample (NRANGE = 925-1052) adjusting for potential confounds, using data from the latest release (S1200) of the Human Connectome Project...
February 17, 2018: Journal of Affective Disorders
Justin Rustenhoven, Leon C Smyth, Deidre Jansson, Patrick Schweder, Miranda Aalderink, Emma L Scotter, Edward W Mee, Richard L M Faull, Thomas I-H Park, Mike Dragunow
BACKGROUND: Brain pericytes ensheathe the endothelium and contribute to formation and maintenance of the blood-brain-barrier. Additionally, pericytes are involved in several aspects of the CNS immune response including scarring, adhesion molecule expression, chemokine secretion, and phagocytosis. In vitro cultures are routinely used to investigate these functions of brain pericytes, however, these are highly plastic cells and can display differing phenotypes and functional responses depending on their culture conditions...
February 22, 2018: BMC Neuroscience
Ya-Nan Wang, Dwight Figueiredo, Xiang-Dong Sun, Zhao-Qi Dong, Wen-Bing Chen, Wan-Peng Cui, Fang Liu, Hong-Sheng Wang, Hai-Wen Li, Heath Robinson, Er-Kang Fei, Bing-Xing Pan, Bao-Ming Li, Wen-Cheng Xiong, Lin Mei
Neuregulin3 (NRG3) is a growth factor of the neuregulin (NRG) family and a risk gene of various severe mental illnesses including schizophrenia, bipolar disorders, and major depression. However, the physiological function of NRG3 remains poorly understood. Here we show that loss of Nrg3 in GFAP-Nrg3 f/f mice increased glutamatergic transmission, but had no effect on GABAergic transmission. These phenotypes were observed in Nex-Nrg3 f/f mice, where Nrg3 was specifically knocked out in pyramidal neurons, indicating that Nrg3 regulates glutamatergic transmission by a cell-autonomous mechanism...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
Michele Fornaro, Annalisa Anastasia, Stefano Novello, Andrea Fusco, Marco Solmi, Francesco Monaco, Nicola Veronese, Domenico De Berardis, Andrea de Bartolomeis
BACKGROUND: Treatment-emergent mania (TEM) represents a common phenomenon inconsistently reported across primary studies, warranting further assessment. METHODS: A systematic review and meta-analysis following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines were conducted. Major electronic databases were searched from inception to May 2017 to assess the incidence and prevalence rates and clinical features associated with manic switch among bipolar depressed patients receiving antidepressants, using meta-regression and subgroup analysis...
February 14, 2018: Bipolar Disorders
Michael J Gandal, Jillian R Haney, Neelroop N Parikshak, Virpi Leppa, Gokul Ramaswami, Chris Hartl, Andrew J Schork, Vivek Appadurai, Alfonso Buil, Thomas M Werge, Chunyu Liu, Kevin P White, Steve Horvath, Daniel H Geschwind
The predisposition to neuropsychiatric disease involves a complex, polygenic, and pleiotropic genetic architecture. However, little is known about how genetic variants impart brain dysfunction or pathology. We used transcriptomic profiling as a quantitative readout of molecular brain-based phenotypes across five major psychiatric disorders-autism, schizophrenia, bipolar disorder, depression, and alcoholism-compared with matched controls. We identified patterns of shared and distinct gene-expression perturbations across these conditions...
February 9, 2018: Science
Stephanie Thiele, Luciano Furlanetti, Lisa-Marie Pfeiffer, Volker A Coenen, Máté D Döbrössy
BACKGROUND: Clinical trials of supra-lateral medial forebrain bundle (MFB) Deep Brain Stimulation (DBS) in treatment resistant major depressive patients have shown rapid and long-term benefits. OBJECTIVE/HYPOTHESIS: The study used Flinders Sensitive Line (FSL) rats with previously identified depressive-like phenotype to assess the range of behavior modification achieved by MFB DBS. METHODS: Male FSL and wild-type Sprague-Dawley rats as Controls were tested on mood/anxiety/exploration, cognitive and motor behaviors...
February 8, 2018: Experimental Neurology
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