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8. Deletion of TOP3β, a component of FMRP-containing mRNPs, contributes to neurodevelopmental disorders

Author

Stoll, Georg, Pietiläinen, Olli PH, Linder, Bastian, Suvisaari, Jaana, Brosi, Cornelia, Hennah, William, Leppä, Virpi, Torniainen, Minna, Ripatti, Samuli, Ala-Mello, Sirpa, Plöttner, Oliver, Rehnström, Karola, Tuulio-Henriksson, Annamari, Varilo, Teppo, Tallila, Jonna, Kristiansson, Kati, Isohanni, Matti, Kaprio, Jaakko, Eriksson, Johan G, Raitakari, Olli T, Lehtimäki, Terho, Jarvelin, Marjo-Riitta, Salomaa, Veikko, Hurles, Matthew, Stefansson, Hreinn, Peltonen, Leena, Sullivan, Patrick F, Paunio, Tiina, Lönnqvist, Jouko, Daly, Mark J, Fischer, Utz, Freimer, Nelson B, and Palotie, Aarno

Subjects
Neurosciences, Schizophrenia, Intellectual and Developmental Disabilities (IDD), Mental Health, Genetics, Fragile X Syndrome, Rare Diseases, Brain Disorders, Aetiology, 2.1 Biological and endogenous factors, Mental health, Abnormalities, Multiple, Adolescent, Adult, Aged, Chromosome Deletion, Chromosomes, Human, Pair 22, Cognition Disorders, Cohort Studies, DNA Topoisomerases, Type I, DiGeorge Syndrome, Family Health, Female, Finland, Fragile X Mental Retardation Protein, Gene Expression Profiling, Genetic Association Studies, Genotype, HEK293 Cells, Health Surveys, Humans, Male, Middle Aged, Models, Molecular, Proteins, Ribonucleoproteins, Sequence Deletion, Young Adult, Psychology, Cognitive Sciences, Neurology & Neurosurgery
Abstract

Implicating particular genes in the generation of complex brain and behavior phenotypes requires multiple lines of evidence. The rarity of most high-impact genetic variants typically precludes the possibility of accruing statistical evidence that they are associated with a given trait. We found that the enrichment of a rare chromosome 22q11.22 deletion in a recently expanded Northern Finnish sub-isolate enabled the detection of association between TOP3B and both schizophrenia and cognitive impairment. Biochemical analysis of TOP3β revealed that this topoisomerase was a component of cytosolic messenger ribonucleoproteins (mRNPs) and was catalytically active on RNA. The recruitment of TOP3β to mRNPs was independent of RNA cis-elements and was coupled to the co-recruitment of FMRP, the disease gene product in fragile X mental retardation syndrome. Our results indicate a previously unknown role for TOP3β in mRNA metabolism and suggest that it is involved in neurodevelopmental disorders.

Published
2013

13. m-RESIST, a Mobile Therapeutic Intervention for Treatment-Resistant Schizophrenia: Feasibility, Acceptability, and Usability Study

Author

Grasa, Eva, Seppälä, Jussi, Alonso, Anna, Haapea, Marianne, Isohanni, Matti, Miettunen, Jouko, Caro Mendivelso, Johanna, Almazán, Cari, Reixach, Elisenda, [Grassa E] Mental Health, Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Barcelona, Spain. Centro de Investigación Biomédica en Red de Salud Mental, Instituto de Salud Carlos III, Madrid, Spain. [Seppälä J] Social Insurance Institution of Finland, Kuopio, Finland. Research Unit of Population Health, University of Oulu, Oulu, Finland. [Alonso-Solis A] Centro de Investigación Biomédica en Red de Salud Mental, Instituto de Salud Carlos III, Madrid, Spain. Mental Health Division, Fundació Althaia, Xarxa Assistencial Universitaria de Manresa, Manresa, Spain. [Haapea M] Research Unit of Population Health, University of Oulu, Oulu, Finland. Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland. Department of Psychiatry, Oulu University Hospital, Oulu, Finland. [Isohanni M] Research Unit of Population Health, University of Oulu, Oulu, Finland. [Miettunen J] Research Unit of Population Health, University of Oulu, Oulu, Finland. Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland. [Caro Mendivelso J, Almazan C] Agència de Qualitat i Avaluació Sanitàries de Catalunya (AQUAS), Departament de Salut, Generalitat de Catalunya, Barcelona, Spain. [Reixach E] Fundació TIC Salut Social, Departament de Salut, Generalitat de Catalunya, Barcelona, Spain, and Departament de Salut

Subjects
administración de los servicios de salud::gestión de la atención al paciente::prestación sanitaria::telemedicina [ATENCIÓN DE SALUD], Other subheadings::Other subheadings::/therapy [Other subheadings], Health Services Administration::Patient Care Management::Delivery of Health Care::Telemedicine [HEALTH CARE], Otros calificadores::Otros calificadores::/terapia [Otros calificadores], Esquizofrènia - Tractament, Telemedicina, Mental Disorders::Schizophrenia Spectrum and Other Psychotic Disorders::Schizophrenia [PSYCHIATRY AND PSYCHOLOGY], trastornos mentales::espectro de la esquizofrenia y otros trastornos psicóticos::esquizofrenia [PSIQUIATRÍA Y PSICOLOGÍA]
Abstract

Mental disorder; Schizophrenia; Treatment-resistant Trastorno mental; Esquizofrenia; Resistentencia al tratamiento Malaltia mental; Esquizofrènia; Resistència al tractament Background: In the European Union, around 5 million people are affected by psychotic disorders, and approximately 30%-50% of people with schizophrenia have treatment-resistant schizophrenia (TRS). Mobile health (mHealth) interventions may be effective in preventing relapses, increasing treatment adherence, and managing some of the symptoms of schizophrenia. People with schizophrenia seem willing and able to use smartphones to monitor their symptoms and engage in therapeutic interventions. mHealth studies have been performed with other clinical populations but not in populations with TRS. Objective: The purpose of this study was to present the 3-month prospective results of the m-RESIST intervention. This study aims to assess the feasibility, acceptability, and usability of the m-RESIST intervention and the satisfaction among patients with TRS after using this intervention. Methods: A prospective multicenter feasibility study without a control group was undertaken with patients with TRS. This study was performed at 3 sites: Sant Pau Hospital (Barcelona, Spain), Semmelweis University (Budapest, Hungary), and Sheba Medical Center and Gertner Institute of Epidemiology and Health Policy Research (Ramat-Gan, Israel). The m-RESIST intervention consisted of a smartwatch, a mobile app, a web-based platform, and a tailored therapeutic program. The m-RESIST intervention was delivered to patients with TRS and assisted by mental health care providers (psychiatrists and psychologists). Feasibility, usability, acceptability, and user satisfaction were measured. Results: This study was performed with 39 patients with TRS. The dropout rate was 18% (7/39), the main reasons being as follows: loss to follow-up, clinical worsening, physical discomfort of the smartwatch, and social stigma. Patients' acceptance of m-RESIST ranged from moderate to high. The m-RESIST intervention could provide better control of the illness and appropriate care, together with offering user-friendly and easy-to-use technology. In terms of user experience, patients indicated that m-RESIST enabled easier and quicker communication with clinicians and made them feel more protected and safer. Patients' satisfaction was generally good: 78% (25/32) considered the quality of service as good or excellent, 84% (27/32) reported that they would use it again, and 94% (30/32) reported that they were mostly satisfied. Conclusions: The m-RESIST project has provided the basis for a new modular program based on novel technology: the m-RESIST intervention. This program was well-accepted by patients in terms of acceptability, usability, and satisfaction. Our results offer an encouraging starting point regarding mHealth technologies for patients with TRS. This work has been supported by the Horizon 2020 Framework Programme of the European Union (grant 643552) and partly funded by CERCA (Centres de Recerca de Catalunya) Programme/Generalitat de Catalunya.

Published
2023

23. MAINTENANCE OF GENETIC VARIATION IN HUMAN PERSONALITY: TESTING EVOLUTIONARY MODELS BY ESTIMATING HERITABILITY DUE TO COMMON CAUSAL VARIANTS AND INVESTIGATING THE EFFECT OF DISTANT INBREEDING

Author

Verweij, Karin J.H., Yang, Jian, Lahti, Jari, Veijola, Juha, Hintsanen, Mirka, Pulkki-Råback, Laura, Heinonen, Kati, Pouta, Anneli, Pesonen, Anu-Katriina, Widen, Elisabeth, Taanila, Anja, Isohanni, Matti, Miettunen, Jouko, Palotie, Aarno, Penke, Lars, Service, Susan K., Heath, Andrew C., Montgomery, Grant W., Raitakari, Olli, Kähönen, Mika, Viikari, Jorma, Räikkönen, Katri, Eriksson, Johan G, Keltikangas-Järvinen, Liisa, Lehtimäki, Terho, Martin, Nicholas G., Järvelin, Marjo-Riitta, Visscher, Peter M., Keller, Matthew C., and Zietsch, Brendan P.

Published
2012

25. Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption

Author

Schumann, Gunter, Coin, Lachlan J., Lourdusamy, Anbarasu, Charoen, Pimphen, Berger, Karen H., Stacey, David, Desrivières, Sylvane, Aliev, Fazil A., Khan, Anokhi A., Amin, Najaf, Aulchenko, Yurii S., Bakalkin, Georgy, Bakker, Stephan J., Balkau, Beverley, Beulens, Joline W., Bilbao, Ainhoa, de Boer, Rudolf A., Beury, Delphine, Bots, Michiel L., Breetvelt, Elemi J., Cauchi, Stéphane, Cavalcanti-Proença, Christine, Chambers, John C., Clarke, Toni-Kim, Dahmen, Norbert, de Geus, Eco J., Dick, Danielle, Ducci, Francesca, Easton, Alanna, Edenberg, Howard J., Esk, Tõnu, Fernández-Medarde, Alberto, Foroud, Tatiana, Freimer, Nelson B., Girault, Jean-Antoine, Grobbee, Diederick E., Guarrera, Simonetta, Gudbjartsson, Daniel F., Hartikainen, Anna-Liisa, Heath, Andrew C., Hesselbrock, Victor, Hofman, Albert, Hottenga, Jouke-Jan, Isohanni, Matti K., Kaprio, Jaakko, Khaw, Kay-Tee, Kuehnel, Brigitte, Laitinen, Jaana, Lobbens, Stéphane, Luan, Jian'an, Mangino, Massimo, Maroteaux, Matthieu, Matullo, Giuseppe, McCarthy, Mark I., Mueller, Christian, Navis, Gerjan, Numans, Mattijs E., Núñez, Alejandro, Nyholt, Dale R., Onland-Moret, Charlotte N., Oostra, Ben A., O'Reilly, Paul F., Palkovits, Miklos, Penninx, Brenda W., Polidoro, Silvia, Pouta, Anneli, Prokopenko, Inga, Ricceri, Fulvio, Santos, Eugenio, Smit, Johannes H., Soranzo, Nicole, Song, Kijoung, Sovio, Ulla, Stumvoll, Michael, Surakk, Ida, Thorgeirsson, Thorgeir E., Thorsteinsdottir, Unnur, Troakes, Claire, Tyrfingsson, Thorarinn, Tönjes, Anke, Uiterwaal, Cuno S., Uitterlinden, Andre G., van der Harst, Pim, van der Schouw, Yvonne T., Staehlin, Oliver, Vogelzangs, Nicole, Vollenweider, Peter, Waeber, Gerard, Wareham, Nicholas J., Waterworth, Dawn M., Whitfield, John B., Wichmann, Erich H., Willemsen, Gonneke, Witteman, Jacqueline C., Yuan, Xin, Zhai, Guangju, Zhao, Jing H., Zhang, Weihua, Martin, Nicholas G., Metspalu, Andres, Doering, Angela, Scott, James, Spector, Tim D., Loos, Ruth J., Boomsma, Dorret I., Mooser, Vincent, Peltonen, Leena, Stefansson, Kari, van Duijn, Cornelia M., Vineis, Paolo, Sommer, Wolfgang H., Kooner, Jaspal S., Spanagel, Rainer, Heberlein, Ulrike A., Jarvelin, Marjo-Riitta, Elliott, Paul, and Singer, Burton H.

Published
2011

32. Psykoosilääkehoidon ohjaus voi tehostaa skitsofrenian hoitoa

Author

Bergström, Tomi, Hulkko, Anja, Hartikainen, Sirpa, Koponen, Hannu, Lieslehto, Johannes, Jääskeläinen, Erika, Isohanni, Matti, Clinicum, Psykiatrian osasto, and HUS Psykiatria

Subjects
+drug therapy, Medication Therapy Management, 317 Farmasia, Schizophrenia, Antipsychotic Agents, 3124 Neurologia ja psykiatria
Abstract

Vertaisarvioitu. Psykoosilääkkeet lievittävät skitsofrenian psykoosioireita ja vähentävät relapsiriskiä. Psykoosilääkityksen pitkäaikaiskäytön hyöty-haittasuhde skitsofrenian hoidossa on osin tuntematon. Etenkin suurten psykoosilääkeannosten pitkäaikaiskäyttö voi altistaa metabolisille, neurologisille, kognitiivisille ja psykologisille haitoille. Psykoosilääkehoidon haittoja voidaan minimoida systemaattisella lääkehoidon ohjauksella, jossa lääkehoito suunnitellaan ja toteutetaan moniammatillisessa yhteistyössä potilaan ja hänen läheistensä kanssa. Lääkehoidon ohjaus voi auttaa käyttämään pienintä vaikuttavaa hoitoannosta sekä parantaa hoitoon sitoutumista ja hoidon tuloksellisuutta. Skitsofrenian psykoosilääkehoidon ohjauskäytäntöjen toteutus edellyttää eri ammattiryhmien kouluttamista, psykoosilääkehoidosta vastaavaa tiimiä ja organisaatiorajat ylittävää moniammatillista työpari- ja verkostotyötä.

Published
2022

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