umu.sePublikationer
Ändra sökning
Avgränsa sökresultatet
1234 51 - 100 av 180
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Träffar per sida
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
Markera
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 51. Giddaluru, Sudheer
    et al.
    Espeseth, Thomas
    Salami, Alireza
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Aging Research Center, Karolinska Institutet and Stockholm University, 11330 Stockholm, Sweden.
    Westlye, Lars T
    Lundquist, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Christoforou, Andrea
    Cichon, Sven
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Steen, Vidar M
    Reinvang, Ivar
    Nilsson, Lars Göran
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). ARC, Karolinska Institutet, Stockholm, Sweden.
    Le Hellard, Stéphanie
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Genetics of structural connectivity and information processing in the brain2016Ingår i: Brain Structure and Function, ISSN 1863-2653, E-ISSN 1863-2661, Vol. 221, nr 9, s. 4643-4661Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Understanding the genetic factors underlying brain structural connectivity is a major challenge in imaging genetics. Here, we present results from genome-wide association studies (GWASs) of whole-brain white matter (WM) fractional anisotropy (FA), an index of microstructural coherence measured using diffusion tensor imaging. Data from independent GWASs of 355 Swedish and 250 Norwegian healthy adults were integrated by meta-analysis to enhance power. Complementary GWASs on behavioral data reflecting processing speed, which is related to microstructural properties of WM pathways, were performed and integrated with WM FA results via multimodal analysis to identify shared genetic associations. One locus on chromosome 17 (rs145994492) showed genome-wide significant association with WM FA (meta P value = 1.87 × 10(-08)). Suggestive associations (Meta P value <1 × 10(-06)) were observed for 12 loci, including one containing ZFPM2 (lowest meta P value = 7.44 × 10(-08)). This locus was also implicated in multimodal analysis of WM FA and processing speed (lowest Fisher P value = 8.56 × 10(-07)). ZFPM2 is relevant in specification of corticothalamic neurons during brain development. Analysis of SNPs associated with processing speed revealed association with a locus that included SSPO (lowest meta P value = 4.37 × 10(-08)), which has been linked to commissural axon growth. An intergenic SNP (rs183854424) 14 kb downstream of CSMD1, which is implicated in schizophrenia, showed suggestive evidence of association in the WM FA meta-analysis (meta P value = 1.43 × 10(-07)) and the multimodal analysis (Fisher P value = 1 × 10(-07)). These findings provide novel data on the genetics of WM pathways and processing speed, and highlight a role of ZFPM2 and CSMD1 in information processing in the brain.

  • 52. Gothefors, Dan
    et al.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri. Swedish Psychiatric Association. .
    Attvall, Stig
    Erlinge, David
    Jarbin, Håkan
    Lindström, Kjell
    von Hausswolff-Juhlin, Yvonne Linné
    Morgell, Roland
    Toft, Eva
    Osby, Urban
    Swedish clinical guidelines: prevention and management of metabolic risk in patients with severe psychiatric disorders2010Ingår i: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 64, nr 5, s. 294-302Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Individuals with severe psychiatric disorders are more likely than the population at large to develop metabolic derangements such as overweight and diabetes. Cardiovascular disease is also more frequently seen in this group. Contributing factors may include inappropriate diet or lack of physical activity, but antipsychotic medication may also play a role. Seven Swedish specialist medical societies have collaborated in formulating a set of concise clinically applicable guidelines-reproduced here in modified form-for the prevention and management of metabolic risk in this patient group. The importance of implementation is emphasized.

  • 53. Hagg, S.
    et al.
    Zhan, Y.
    Karlsson, R.
    Gerritsen, L.
    Ploner, A.
    van der Lee, S. J.
    Broer, L.
    Deelen, J.
    Marioni, R. E.
    Wong, A.
    Lundquist, Anders
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Zhu, G.
    Hansell, N. K.
    Sillanpaa, E.
    Fedko, I. O.
    Amin, N. A.
    Beekman, M.
    de Craen, A. J. M.
    Degerman, Sofie
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Harris, S. E.
    Kan, K-J
    Martin-Ruiz, C. M.
    Montgomery, G. W.
    Adolfsson, Annelie N.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Reynolds, C. A.
    Samani, N. J.
    Suchiman, H. E. D.
    Viljanen, A.
    von Zglinicki, T.
    Wright, M. J.
    Hottenga, J-J
    Boomsma, D. I.
    Rantanen, T.
    Kaprio, J. A.
    Nyholt, D. R.
    Martin, N. G.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Kuh, D.
    Starr, J. M.
    Deary, I. J.
    Slagboom, P. E.
    van Duijn, C. M.
    Codd, V.
    Pedersen, N. L.
    Short telomere length is associated with impaired cognitive performance in European ancestry cohorts2017Ingår i: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 7, artikel-id e1100Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The association between telomere length (TL) dynamics on cognitive performance over the life-course is not well understood. This study meta-analyses observational and causal associations between TL and six cognitive traits, with stratifications on APOE genotype, in a Mendelian Randomization (MR) framework. Twelve European cohorts (N = 17 052; mean age = 59.2 +/- 8.8 years) provided results for associations between qPCR-measuredTL (T/S-ratio scale) and general cognitive function, mini-mental state exam (MMSE), processing speed by digit symbol substitution test (DSST), visuospatial functioning, memory and executive functioning (STROOP). In addition, a genetic risk score (GRS) for TL including seven known genetic variants for TL was calculated, and used in associations with cognitive traits as outcomes in all cohorts. Observational analyses showed that longer telomeres were associated with better scores on DSST (beta = 0.051 per s. d.-increase of TL; 95% confidence interval (CI): 0.024, 0.077; P = 0.0002), and MMSE (beta = 0.025; 95% CI: 0.002, 0.047; P = 0.03), and faster STROOP (beta = -0.053; 95% CI: -0.087, -0.018; P = 0.003). Effects for DSST were stronger in APOE epsilon 4 non-carriers (beta = 0.081; 95% CI: 0.045, 0.117; P = 1.0 x 10(-5)), whereas carriers performed better in STROOP (beta = -0.074; 95% CI: -0.140, -0.009; P = 0.03). Causal associations were found for STROOP only (beta = -0.598 per s. d.-increase of TL; 95% CI: -1.125, -0.072; P = 0.026), with a larger effect in epsilon 4-carriers (beta = -0.699; 95% CI: -1.330, -0.069; P = 0.03). Two-sample replication analyses using CHARGE summary statistics showed causal effects between TL and general cognitive function and DSST, but not with STROOP. In conclusion, we suggest causal effects from longer TL on better cognitive performance, where APOE epsilon 4-carriers might be at differential risk.

  • 54. Hallmans, Göran
    et al.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Granqvist, E
    Johansson, Gunnar
    Nygren, Charlotte
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för kostvetenskap.
    Sandman, P
    Sehlstedt, E
    Winblad, B
    Auswirkungen eines Knäckebrotes mit hohem Kleiegehalt auf die defäkationsgewohnheiten von älteren, obsipierten demenz-patienten sowie jungen personen mit oder ohne obstipation1985Ingår i: Ernärungs-Umschau, Vol. 32, nr 2, s. 44-47Artikel i tidskrift (Refereegranskat)
  • 55.
    Hansson, Patrik
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Eriksson Sörman, Daniel
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Bergdahl, Jan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Institute of Clinical Dentistry, UIT The Arctic Universityof Norway, Tromsø, Norway.
    Bergdahl, Maud
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nilsson, Lars-Goran
    Dental status is unrelated to risk of dementia: a 20-year prospective study2014Ingår i: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 62, nr 5, s. 979-981Artikel i tidskrift (Refereegranskat)
  • 56. Hardy, J
    et al.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Alafuzoff, I
    Bucht, G
    Marcusson, J
    Nyberg, P
    Perdahl, E
    Wester, P
    Winblad, B
    Transmitter deficits in Alzheimer's disease.1985Ingår i: Neurochemistry International, ISSN 0197-0186, E-ISSN 1872-9754, Vol. 7, nr 4, s. 545-63Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The pattern of neurotransmitter pathway losses in Alzheimer's disease are reviewed. Deficits of the cholinergic pathway from the nucleus basalis, the noradrenergic pathway from the locus coeruleus and the serotoninergic pathway from the raphe nuclei are established. Cortical somatostatin interneurons are affected and dopaminergic neurons may be affected although these may be late or secondary phenomena in the disease process. Other neuronal systems, particularly in the hippocampus and temporal cortex, are also damaged. However, the disease is not one of generalised neuronal atrophy since some neurons are selectively spared. The established pathway-specific losses are discussed in relation to the clinical symptomatology and the pathology of the disorder. The biochemical and histological findings are compared with similar measurements made on tissues from other dementing disorders in an attempt to trace features common to dementias. Finally, as an addendum, a hypothesis is briefly outlined which attempts to explain the common features of the affected neurons and the pathogenesis of the disorder.

  • 57. Huckins, Laura M.
    et al.
    Dobbyn, Amanda
    Ruderfer, Douglas M.
    Hoffman, Gabriel
    Wang, Weiqing
    Pardinas, Antonio F.
    Rajagopal, Veera M.
    Als, Thomas D.
    Nguyen, Hoang T.
    Girdhar, Kiran
    Boocock, James
    Roussos, Panos
    Fromer, Menachem
    Kramer, Robin
    Domenici, Enrico
    Gamazon, Eric R.
    Purcell, Shaun
    Demontis, Ditte
    Borglum, Anders D.
    Walters, James T. R.
    O'Donovan, Michael C.
    Sullivan, Patrick
    Owen, Michael J.
    Devlin, Bernie
    Sieberts, Solveig K.
    Cox, Nancy J.
    Im, Hae Kyung
    Sklar, Pamela
    Stahl, Eli A.
    Johnson, Jessica S.
    Shah, Hardik R.
    Klein, Lambertus L.
    Dang, Kristen K.
    Logsdon, Benjamin A.
    Mahajan, Milind C.
    Mangravite, Lara M.
    Toyoshiba, Hiroyoshi
    Gur, Raquel E.
    Hahn, Chang-Gyu
    Schadt, Eric
    Lewis, David A.
    Haroutunian, Vahram
    Peters, Mette A.
    Lipska, Barbara K.
    Buxbaum, Joseph D.
    Hirai, Keisuke
    Perumal, Thanneer M.
    Essioux, Laurent
    Rajagopal, Veera Manikandan
    Mattheisen, Manuel
    Grove, Jakob
    Werge, Thomas
    Mortensen, Preben Bo
    Pedersen, Carsten Bocker
    Agerbo, Esben
    Pedersen, Marianne Giortz
    Mors, Ole
    Nordentoft, Merete
    Hougaard, David M.
    Bybjerg-Grauholm, Jonas
    Baekvad-Hansen, Marie
    Hansen, Christine Soholm
    Ripke, Stephan
    Neale, Benjamin M.
    Corvin, Aiden
    Farh, Kai-How
    Holmans, Peter A.
    Lee, Phil
    Bulik-Sullivan, Brendan
    Collier, David A.
    Huang, Hailiang
    Pers, Tune H.
    Agartz, Ingrid
    Albus, Margot
    Alexander, Madeline
    Amin, Farooq
    Bacanu, Silviu A.
    Begemann, Martin
    Belliveau, Richard A., Jr.
    Bene, Judit
    Bergen, Sarah E.
    Bevilacqua, Elizabeth
    Bigdeli, Tim B.
    Black, Donald W.
    Bruggeman, Richard
    Buccola, Nancy G.
    Buckner, Randy L.
    Byerley, William
    Cahn, Wiepke
    Cai, Guiqing
    Campion, Dominique
    Cantor, Rita M.
    Carr, Vaughan J.
    Carrera, Noa
    Catts, Stanley, V
    Chambert, Kimberly D.
    Chan, Raymond C. K.
    Chen, Ronald Y. L.
    Chen, Eric Y. H.
    Cheng, Wei
    Cheung, Eric F. C.
    Chong, Siow Ann
    Cloninger, C. Robert
    Cohen, David
    Cohen, Nadine
    Cormican, Paul
    Craddock, Nick
    Crowley, James J.
    Curtis, David
    Davidson, Michael
    Davis, Kenneth L.
    Degenhardt, Franziska
    Del Favero, Jurgen
    Dikeos, Dimitris
    Dinan, Timothy
    Djurovic, Srdjan
    Donohoe, Gary
    Drapeau, Elodie
    Duan, Jubao
    Dudbridge, Frank
    Durmishi, Naser
    Eichhammer, Peter
    Eriksson, Johan
    Escott-Price, Valentina
    Fanous, Ayman H.
    Farrell, Martilias S.
    Frank, Josef
    Franke, Lude
    Freedman, Robert
    Freimer, Nelson B.
    Friedl, Marion
    Friedman, Joseph, I
    Genovese, Giulio
    Georgieva, Lyudmila
    Giegling, Ina
    Giusti-Rodriguez, Paola
    Godard, Stephanie
    Goldstein, Jacqueline, I
    Golimbet, Vera
    Gopal, Srihari
    Gratten, Jacob
    de Haan, Lieuwe
    Hammer, Christian
    Hamshere, Marian L.
    Hansen, Mark
    Hansen, Thomas
    Hartmann, Annette M.
    Henskens, Frans A.
    Herms, Stefan
    Hirschhorn, Joel N.
    Hoffmann, Per
    Hofman, Andrea
    Hollegaard, Mads, V
    Ikeda, Masashi
    Joa, Inge
    Julia, Antonio
    Kahn, Rene S.
    Kalaydjieva, Luba
    Karachanak-Yankova, Sena
    Karjalainen, Juha
    Kavanagh, David
    Keller, Matthew C.
    Kennedy, James L.
    Khrunin, Andrey
    Kim, Yunjung
    Klovins, Janis
    Knowles, James A.
    Konte, Bettina
    Kucinskas, Vaidutis
    Kucinskiene, Zita Ausrele
    Kuzelova-Ptackova, Hana
    Kahler, Anna K.
    Laurent, Claudine
    Keong, Jimmy Lee Chee
    Lee, S. Hong
    Legge, Sophie E.
    Lerer, Bernard
    Li, Miaoxin
    Li, Tao
    Liang, Kung-Yee
    Lieberman, Jeffrey
    Limborska, Svetlana
    Loughland, Carmel M.
    Lubinski, Jan
    Lonnqvist, Jouko
    Macek, Milan, Jr.
    Magnusson, Patrik K. E.
    Maher, Brion S.
    Maier, Wolfgang
    Mallet, Jacques
    Marsal, Sara
    Mattingsdal, Morten
    McCarley, Robert W.
    McDonald, Colm
    McIntosh, Andrew M.
    Meier, Sandra
    Meijer, Carin J.
    Melegh, Bela
    Melle, Ingrid
    Mesholam-Gately, Raquelle, I
    Metspalu, Andres
    Michie, Patricia T.
    Milani, Lili
    Milanova, Vihra
    Mokrab, Younes
    Morris, Derek W.
    Murphy, Kieran C.
    Murray, Robin M.
    Myin-Germeys, Inez
    Muller-Myhsok, Bertram
    Nelis, Mari
    Nenadic, Igor
    Nertney, Deborah A.
    Nestadt, Gerald
    Nicodemus, Kristin K.
    Nikitina-Zake, Liene
    Nisenbaum, Laura
    Nordin Adolfsson, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    O'Callaghan, Eadbhard
    O'Dushlaine, Colm
    O'Neill, F. Anthony
    Oh, Sang-Yun
    Olincy, Ann
    Olsen, Line
    Van Os, Jim
    Pantelis, Christos
    Papadimitriou, George N.
    Papiol, Sergi
    Parkhomenko, Elena
    Pato, Michele T.
    Paunio, Tiina
    Pejovic-Milovancevic, Milica
    Perkins, Diana O.
    Pietilainen, Olli
    Pimm, Jonathan
    Pocklington, Andrew J.
    Powell, John
    Price, Alkes
    Pulver, Ann E.
    Purcell, Shaun M.
    Quested, Digby
    Rasmussen, Henrik B.
    Reichenberg, Abraham
    Reimers, Mark A.
    Richards, Alexander L.
    Roffman, Joshua L.
    Salomaa, Veikko
    Sanders, Alan R.
    Schall, Ulrich
    Schubert, Christian R.
    Schulze, Thomas G.
    Schwab, Sibylle G.
    Scolnick, Edward M.
    Scott, Rodney J.
    Seidman, Larry J.
    Shi, Jianxin
    Sigurdsson, Engilbert
    Silagadze, Teimuraz
    Silverman, Jeremy M.
    Sim, Kang
    Slominsky, Petr
    Smoller, Jordan W.
    So, Hon-Cheong
    Spencer, Chris C. A.
    Stefansson, Hreinn
    Steinberg, Stacy
    Stogmann, Elisabeth
    Straub, Richard E.
    Strengman, Eric
    Strohmaier, Jana
    Stroup, T. Scott
    Subramaniam, Mythily
    Suvisaari, Jaana
    Svrakic, Dragan M.
    Szatkiewicz, Jin P.
    Soderman, Erik
    Thirumalai, Srinivas
    Toncheva, Draga
    Tosato, Sarah
    Veijola, Juha
    Waddington, John
    Walsh, Dermot
    Wang, Dai
    Wang, Qiang
    Webb, Bradley T.
    Weiser, Mark
    Wildenauer, Dieter B.
    Williams, Nigel M.
    Williams, Stephanie
    Witt, Stephanie H.
    Wolen, Aaron R.
    Wong, Emily H. M.
    Wormley, Brandon K.
    Xi, Hualin Simon
    Zai, Clement C.
    Zheng, Xuebin
    Zimprich, Fritz
    Wray, Naomi R.
    Stefansson, Kari
    Visscher, Peter M.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Andreassen, Ole A.
    Blackwood, Douglas H. R.
    Bramon, Elvira
    Cichon, Sven
    Darvasi, Ariel
    Ehrenreich, Hannelore
    Esko, Tonu
    Gejman, Pablo, V
    Gill, Michael
    Gurling, Hugh
    Hultman, Christina M.
    Iwata, Nakao
    Jablensky, Assen, V
    Jonsson, Erik G.
    Kendler, Kenneth S.
    Kirov, George
    Knight, Jo
    Lencz, Todd
    Levinson, Douglas F.
    Li, Qingqin S.
    Liu, Jianjun
    Malhotra, Anil K.
    McCarroll, Steven A.
    McQuillin, Andrew
    Moran, Jennifer L.
    Mortensen, Preben B.
    Mowry, Bryan J.
    Nothen, Markus M.
    Ophoff, Roel A.
    Palotie, Aarno
    Pato, Carlos N.
    Petryshen, Tracey L.
    Posthuma, Danielle
    Rietschel, Marcella
    Riley, Brien P.
    Rujescu, Dan
    Sham, Pak C.
    St Clair, David
    Weinberger, Daniel R.
    Wendland, Jens R.
    Daly, Mark J.
    Sullivan, Patrick F.
    Gene expression imputation across multiple brain regions provides insights into schizophrenia risk2019Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, nr 4, s. 659-+Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression.

  • 58.
    Hägg, Staffan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Lindblom, Yvonne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Mjörndal, Tom
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    High prevalence of the metabolic syndrome among a Swedish cohort of patients with schizophrenia2006Ingår i: International Clinical Psychopharmacology, ISSN 0268-1315, E-ISSN 1473-5857, Vol. 21, nr 2, s. 93-98Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Several cardiovascular risk factors have been linked to antipsychotic treatment and cardiovascular mortality is increased in these patients compared to the general population. The full metabolic syndrome (or its components) is associated with an increased risk of cardiovascular disorders. The prevalence of the metabolic syndrome was investigated using a cross-sectional study design in a cohort of 269 patients, aged 20-69 years, with schizophrenia living in Northern Sweden, and was defined according to the criteria of the National Cholesterol Education program. The prevalence of the metabolic syndrome was 34.6% (95% CI = 28.8-40.3) and highest (43%; 95% CI = 32-53) for participants aged 40-49 years. Clozapine treated subjects reached the highest prevalence of the metabolic syndrome (48%; 95% CI = 34-62). The prevalence was similar for men (32.8%; 95% CI = 25.8-39.8) and women (38.0%; 95% CI = 27.9-48.2). Men had a high prevalence of hypertension (49.2%; 95% CI = 41.7-56.6) and women had high prevalence of low high-density lipoprotein cholesterol (40.2%; 95% CI = 30.0-50.4) and abdominal obesity (75.0%; 95% CI = 66.0-84.0). Subjects with the metabolic syndrome had significantly higher mean body mass index (BMI) (P < 0.001), HbA1c (P = 0.002), and fasting serum insulin (P < 0.001) compared to non-metabolic syndrome subject. Subjects with the metabolic syndrome had also significantly more often a positive history of cardiovascular diseases compared to non-metabolic syndrome subjects (25.8% versus 12.5%; P = 0.01). Of all study subjects 36.8% were obese (BMI > 30). These results clearly show that the metabolic syndrome and its components are highly prevalent in patients with schizophrenia. Physicians treating patients with schizophrenia are recommended to monitor the components included in the metabolic syndrome.

  • 59. Johansson, Carolina
    et al.
    Willeit, Matthäeus
    Aron, Liviu
    Smedh, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Ekholm, Jenny
    Paunio, Tiina
    Kieseppa, Tuula
    Lichtermann, Dirk
    Praschak-Rieder, Nicole
    Neumeister, Alexander
    Kasper, Siegfried
    Peltonen, Leena
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Partonen, Timo
    Schalling, Martin
    Seasonal affective disorder and the G-protein beta-3-subunit C825T polymorphism2004Ingår i: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 55, nr 3, s. 317-319Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Guanine nucleotide-binding proteins (G-proteins) have been implicated in affective disorders, with reports of altered signal transduction and G-protein levels. Association with seasonal affective disorder (SAD) has been found for the higher activity T-allele of the G-protein beta-3-subunit C825T polymorphism.

    Methods. European SAD patients (n = 159) and matched controls (n = 159) were genotyped for the C825T. Seasonality and diurnal preference were investigated in subsets of the material (n = 177 and 92, respectively).

    Results. We found no association between C825T and SAD (chi(2) = .09, p = .96) or seasonality (F = 1.76, p = .18). There was some evidence for an effect on diurnal preference but only in the control group (n = 46, t = - 2.8, Bonferroni corrected p = .045).

    Conclusions: These results suggest that the G-protein beta-3-subunit 825 T-allele does not play a major role in susceptibility to seasonal affective disorder in the population studied.

  • 60. Johnstone, Mandy
    et al.
    Maclean, Alan
    Heyrman, Lien
    Lenaerts, An-Sofie
    Nordin, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nilsson, Lars-Göran
    De Rijk, Peter
    Goossens, Dirk
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    St Clair, David M
    Hall, Jeremy
    Lawrie, Stephen M
    McIntosh, Andrew M
    Del-Favero, Jurgen
    Blackwood, Douglas H R
    Pickard, Benjamin S
    Copy number variations in DISC1 and DISC1-interacting partners in major mental illness2015Ingår i: Molecular neuropsychiatry, ISSN 2296-9209, Vol. 1, nr 3, s. 175-190Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Robust statistical, genetic and functional evidence supports a role for DISC1 in the aetiology of major mental illness. Furthermore, many of its protein-binding partners show evidence for involvement in the pathophysiology of a range of neurodevelopmental and psychiatric disorders. Copy number variants (CNVs) are suspected to play an important causal role in these disorders. In this study, CNV analysis of DISC1 and its binding partners PAFAH1B1, NDE1, NDEL1, FEZ1, MAP1A, CIT and PDE4B in Scottish and Northern Swedish population-based samples was carried out using multiplex amplicon quantification. Here, we report the finding of rare CNVs in DISC1, NDE1 (together with adjacent genes within the 16p13.11 duplication), NDEL1 (including the overlapping MYH10 gene) and CIT. Our findings provide further evidence for involvement of DISC1 and its interaction partners in neuropsychiatric disorders and also for a role of structural variants in the aetiology of these devastating diseases.

  • 61.
    Josefsson, Maria
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Larsson, Maria
    Nordin, Steven
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Olofsson, Jonas
    APOE-ɛ4 effects on longitudinal decline in olfactory and non-olfactory cognitive abilities in middle-aged and old adults2017Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, artikel-id 1286Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Characterizing aging-related decline trajectories in mental abilities, and relationships of the ɛ4 allele of the Apolipoprotein gene, helps to identify individuals at high risk for dementia. However, longitudinal changes in olfactory and non-olfactory cognitive abilities have not been investigated in relation to the ɛ4 allele. In the present study, participants from a large population-based study (657 middle-aged and 556 old) were tested over 10 years on their performance on an odor identification task and three non-olfactory cognitive tasks; MMSE, episodic memory, and semantic memory. Our key finding is that in middle-aged participants, odor identification declined twice as fast for ɛ4/4 homozygotes, compared to non-carriers. However, in old participants, the ɛ4/4 homozygotes showed an impaired odor identification ability, but they declined at a similar rate as the non-carriers. Furthermore, in old participants all assessments displayed aging-related declines, but exaggerated declines in ɛ4-carriers were found only in MMSE and episodic memory assessments. In sum, we present evidence that odor identification ability starts to decline already in middle-aged, and that carriers of ɛ4/4, who are at highest risk of developing dementia, decline twice as fast. Our results may have implications for use of odor identification assessment in detection of early-stage dementia.

  • 62.
    Josefsson, Maria
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR). Demographic Data Base.
    Sundström, Anna
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Pudas, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nordin Adolfsson, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Memory profiles predict dementia over 23–28 years in normal but not successful aging2019Ingår i: International psychogeriatrics, ISSN 1041-6102, E-ISSN 1741-203XArtikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Prospective studies suggest that memory deficits are detectable decades before clinical symptoms of dementia emerge. However, individual differences in long-term memory trajectories prior to diagnosis need to be further elucidated. The aim of the current study was to investigate long-term dementia and mortality risk for individuals with different memory trajectory profiles in a well-characterized population-based sample.

    Methods: 1062 adults (aged 45–80 years) who were non-demented at baseline were followed over 23–28 years. Dementia and mortality risk were studied for three previously classified episodic memory trajectory groups: maintained high performance (Maintainers; 26%), average decline (Averages; 64%), and accelerated decline (Decliners; 12%), using multistate modeling to characterize individuals’ transitions from an initial non-demented state, possibly to a state of dementia and/or death.

    Results: The memory groups showed considerable intergroup variability in memory profiles, starting 10–15 years prior to dementia diagnosis, and prior to death. A strong relationship between memory trajectory group and dementia risk was found. Specifically, Decliners had more than a fourfold risk of developing dementia compared to Averages. In contrast, Maintainers had a 2.6 times decreased dementia risk compared to Averages, and in addition showed no detectable memory decline prior to dementia diagnosis. A similar pattern of association was found for the memory groups and mortality risk, although only among non-demented.

    Conclusion: There was a strong relationship between accelerated memory decline and dementia, further supporting the prognostic value of memory decline. The intergroup differences, however, suggest that mechanisms involved in successful memory aging may delay symptom onset.

  • 63.
    Karling, P
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Danielsson, Å
    Pettersson, M
    Söderström, I
    Del-Favero, J
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Norrback, Karl-Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    The val158met Catechol-O-methyl-transferase (COMT) polymorphism is associated with irritable bowel syndrome-like symptomsManuskript (Övrigt vetenskapligt)
  • 64.
    Karling, Pontus
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Danielsson, Åke
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Norrback, Karl-Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    No difference in symptoms of irritable bowel syndrome between healthy subjects and patients with recurrent depression in remission2007Ingår i: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 19, nr 11, s. 896-904Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is bidirectional comorbidity between anxiety/depression and irritable bowel syndrome (IBS). To investigate the prevalence of IBS symptoms, and factors associated with gastrointestinal symptoms in patients with recurrent depressive disorder. Patients (n = 95) with recurrent type of major depression according to DSM-IV criteria and sex- and age-matched controls (n = 190) were sent questionnaires investigating symptoms of IBS [Gastrointestinal Symptom Rating Scale (GSRS)-IBS] and symptoms of anxiety and depression [Hospital Anxiety and Depression Scale (HADS)]. Medical records were checked over a 10-year period for chronic somatic symptoms or diseases. Seventy-three patients with unipolar disorder (mean age 63.6 years SD 13.8; range 23–86 years) and 156 controls (mean age 59.2 years SD 11.6, range 21–85 years) responded. Patients with recurrent depression had higher GSRS-IBS scores and showed a strong correlation between symptoms of IBS and anxiety-depression (rs = 0.54; P < 0.001). IBS symptoms were also associated with multiple pain symptoms, higher health-seeking behaviour and selective-serotonin-reuptake inhibitor intake. However, patients with recurrent depression (n = 46) in remission (HADS-Depression score <8) did not have more symptoms of IBS than controls (GSRS-IBS median score 6.0 vs 6.5; P = 0.46). There is a strong association between symptoms of IBS and symptoms of anxiety and depression, whereas depressive patients in remission do not have more IBS symptoms than controls.

  • 65.
    Karling, Pontus
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Danielsson, Åke
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Wikgren, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Söderström, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Del-Favero, Jurgen
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Norrback, Karl-Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    The relationship between the val158met catechol-o-methyltransferase (COMT) polymorphism and irritable bowel syndrome.2011Ingår i: PloS one, ISSN 1932-6203, Vol. 6, nr 3, s. e18035-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    The catechol-O-methyltransferase (COMT) enzyme has a key function in the degradation of catecholamines and a functional polymorphism is val158met. The val/val genotype results in a three to fourfold higher enzymatic activity compared with the met/met genotype, with the val/met genotype exhibiting intermediate activity. Since pain syndromes as well as anxiety and depression are associated to low and high COMT activity respectively and these conditions are all associated with irritable bowel syndrome (IBS) we wanted for the first time to explore the relationship between the polymorphism and IBS.

    Methodology/Principal Findings

    867 subjects (445 women) representative of the general population and 70 consecutively sampled patients with IBS (61 women) were genotyped for the val158met polymorphism and the IBS patients filled out the Hospital-Anxiety-and-Depression-Scale (HADS) questionnaire, and an IBS symptom diary.

    Results

    There was a significantly higher occurrence of the val/val genotype in patients compared with controls (30% vs 20%; Chi2 (1) 3.98; p = 0.046) and a trend toward a lower occurrence of the val/met genotype in IBS patients compared with controls (39% vs 49%; Chi2 (1) 2.89; p = 0.089). Within the IBS patients the val/val carriers exhibited significantly increased bowel frequency (2.6 vs 1.8 stools per day; Chi2 (1) 5.3; p = 0.03) and a smaller proportion of stools with incomplete defecation (41% vs 68%; Chi2 (1) 4.3; p = 0.04) compared with the rest (val/met+met/met carriers). The val/val carriers also showed a trend for a smaller proportion of hard stools (0% vs 15%; Chi2 (1) 3.2; p = 0.08) and a higher frequency of postprandial defecation (26% vs 21%; Chi2 (1) 3.0; p = 0.08).

    Conclusions/Significance

    In this study we found an association between the val/val genotype of the val158met COMT gene and IBS as well as to specific IBS related bowel pattern in IBS patients.

  • 66.
    Karling, Pontus
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Maripuu, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Wikgren, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Norrback, Karl-Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Association between gastrointestinal symptoms and affectivity in patients with bipolar disorder2016Ingår i: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 22, nr 38, s. 8540-8548Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM: To study if anxiety, depression and experience of stress are associated with gastrointestinal (GI) symptoms in patients with bipolar disorder.

    METHODS: A total of 136 patients with bipolar disorder (mean age 49.9 years; 61% women) and 136 controls from the general population (mean age 51.0 years; 60% women) were included in the study. GI symptoms were assessed with The Gastrointestinal Symptom Rating Scale-irritable bowel syndrome (GSRS-IBS), level of anxiety and depression with The Hospital Anxiety and Depression Scale (HADS) and stress-proneness with Perceived Stress Questionnaire. Over a ten year period, all visits in primary care were retrospectively recorded in order to identify functional GI disorders.

    RESULTS: In subjects with low total HADS-score, there were no significant differences in GI-symptoms between patients and controls (GSRS-IBS 7.0 vs 6.5, P = 0.513). In the patients with bipolar disorder there were significant correlations between all GSRS and HADS subscores for all symptom clusters except for "constipation" and "reflux". Factors associated to GI symptoms in the patient group were female sex (adjusted OR = 2.37, 95%CI: 1.07-5.24) and high HADS-Depression score (adjusted OR = 3.64, 95%CI: 1.07-12.4). These patients had also significantly more visits for IBS than patients with low HADS-Depression scores (29% vs 8%, P = 0.008). However, there was no significant differences in consulting behaviour for functional GI disorders between patients and controls (25% vs 17%, P = 0.108).

    CONCLUSION: Female patients and patients with high HADS depression score reported significantly more GI symptoms, whereas patients with low HADS scores did not differ from control subjects.

  • 67.
    Karling, Pontus
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Norrback, Karl-Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Danielsson, Åke
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Medicin.
    Gastrointestinal symptoms are associated with hypothalamic-pituitary-adrenal axis suppression in healthy individuals.2007Ingår i: Scand J Gastroenterol, ISSN 0036-5521, Vol. 42, nr 11, s. 1294-1301Artikel i tidskrift (Refereegranskat)
  • 68.
    Karling, Pontus
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Wikgren, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Norrback, Karl-Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Hypothalamus-Pituitary-Adrenal Axis Hypersuppression Is Associated with Gastrointestinal Symptoms in Major Depression2016Ingår i: Journal of neurogastroenterology and motility, ISSN 2093-0879, Vol. 22, nr 2, s. 292-303Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background/Aims: Gastrointestinal symptoms and hypothalamus-pituitary-adrenal (HPA) axis dysfunction are frequently observed in patients with major depression. The primary aim of the study was to investigate the relationship between HPA-axis function and self-perceived functional gastrointestinal symptoms in major depression.

    Methods: Patients with major depression (n = 73) and controls representative of the general population (n = 146) underwent a weight-adjusted very low dose dexamethasone suppression test (DST). Patients and controls completed the Gastrointestinal Symptom Rating Scale-Irritable Bowel Syndrome (GSRS-IBS) and the Hospital Anxiety Depression Scale. Medical records of the patients were screened over a ten year period for functional gastrointestinal disorder and pain conditions.

    Results: Patients with high GSRS-IBS scores (above median) exhibited HPA-axis hypersuppression more often than controls (defined by the lowest 10% cutoff of the post-DST cortisol values among controls, adjusted OR 7.25, CI 1.97-26.7) whereas patients with low GSRS-IBS scores did not differ from controls concerning their post-DST cortisol values. Patients who had consulted primary care for functional gastrointestinal disorder (P= 0.039), lumbago (P = 0.006) and chronic multifocal pain (P= 0.057) also exhibited an increased frequency of hypersuppression.

    Conclusions: HPA-axis hypersuppression is associated with functional gastrointestinal symptoms in patients with major depression.

  • 69. Karlsson, Thomas
    et al.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Börjesson, Arne
    Nilsson, Lars-Göran
    Primed word-fragment completion and successive memory test performance in normal aging.2003Ingår i: Scandinavian Journal of Psychology, ISSN 0036-5564, E-ISSN 1467-9450, Vol. 44, nr 4, s. 355-61Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Young and old subjects were investigated to examine whether: the effects of priming are influenced by aging; there is independence between primed word-fragment completion and recognition performances; and the dependence between different tests is influenced by aging. A successive test paradigm was employed involving repeated assessment of to-be-remembered words by means of recognition and primed word-fragment completion. The results show that implicit memory declines with increasing age, and that correlations between different memory tests decrease with age. The outcome suggests that age-related memory decline involves several forms of memory, including primed word-fragment completion, and is reflected in correlations between measures of implicit and explicit memory.

  • 70.
    Katarina, Nordfjäll
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Svenson, Ulrika
    Norrback, Karl-Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Roos, Göran
    The paternal influence on telomere length is stronger than the maternal and the heritable impact diminishes with ageManuskript (Övrigt vetenskapligt)
  • 71.
    Katarina, Nordfjäll
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Ulrika, Svenson
    Norrback, Karl-Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Lenner, Per
    Roos, Göran
    Human blood cell telomere attrition rate is telomere length dependent but not associated to tumour development.Manuskript (Övrigt vetenskapligt)
  • 72.
    Kauppi, Karolina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nilsson, Lars-Göran
    Stockholm University.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Eriksson, Elias
    Gothenburg University.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    KIBRA polymorphism is related to enhanced memory and elevated hippocampal processing2011Ingår i: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 31, nr 40, s. 14218-14222Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Several studies have linked the KIBRA rs17070145 T polymorphism to superior episodic memory in healthy humans. One study investigated the effect of KIBRA on brain activation patterns (Papassotiropoulos et al., 2006) and observed increased hippocampal activation in noncarriers of the T allele during retrieval. Noncarriers were interpreted to need more hippocampal activation to reach the same performance level as T carriers. Using large behavioral (N = 2230) and fMRI (N = 83) samples, we replicated the KIBRA effect on episodic memory performance, but found increased hippocampal activation in T carriers during episodic retrieval. There was no evidence of compensatory brain activation in noncarriers within the hippocampal region. In the main fMRI sample, T carriers performed better than noncarriers during scanning but, importantly, the difference in hippocampus activation remained after post hoc matching according to performance, sex, and age (N = 64). These findings link enhanced memory performance in KIBRA T allele carriers to elevated hippocampal functioning, rather than to neural compensation in noncarriers.

  • 73.
    Kauppi, Karolina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Nilsson, Lars-Göran
    Stockholm University.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Lundquist, Anders
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Eriksson, Elias
    Gothenburg University.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Decreased medial temporal lobe activation in BDNF 66Met allele carriers during memory encoding2013Ingår i: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 51, nr 12, s. 2462-2468Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Met allele of the Brain-derived neurotrophic factor (BDNF) Val(66)Met polymorphism has been associated with impaired activity-dependent secretion of BDNF protein and decreased memory performance. Results from imaging studies relating Val(66)Met to brain activation during memory processing have been inconsistent, with reports of both increased and decreased activation in the Medial Temporal Lobe (MTL) in Met carriers relative to Val homozygotes. Here, we extensively studied BDNF Val(66)Met in relation to brain activation and white matter integrity as well as memory performance in a large imaging (n=194) and behavioral (n=2229) sample, respectively. Functional magnetic resonance imaging (fMRI) was used to investigate MTL activation in healthy participants in the age of 55-75 years during a face-name episodic encoding and retrieval task. White matter integrity was measured using diffusion tensor imaging.

    BDNF Met allele carriers had significantly decreased activation in the MTL during encoding processes, but not during retrieval processes. In contrast to previous proposals, the effect was not modulated by age and the polymorphism was not related to white matter integrity. Met carriers had lower memory performance than Val homozygotes, but differences were subtle and not significant. In conclusion, the BDNF Met allele has a negative influence on MTL functioning, preferentially during encoding processes, which might translate into impaired episodic memory function.

  • 74.
    Kauppi, Karolina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Nilsson, Lars-Göran
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Combined gene effects on hippocampal mnemonic processing: a large-scale imaging-genetics study of APOE, BDNF, KIBRA, and CLSTN22013Ingår i: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 25, nr Suppl., s. S140-S141Artikel i tidskrift (Övrigt vetenskapligt)
  • 75. Lavebratt, Catharina
    et al.
    Sjöholm, Louise K
    Soronen, Pia
    Paunio, Tiina
    Vawter, Marquis P
    Bunney, William E
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Forsell, Yvonne
    Wu, Joseph C
    Kelsoe, John R
    Partonen, Timo
    Schalling, Martin
    CRY2 is associated with depression2010Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, nr 2, artikel-id e9407Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Abnormalities in the circadian clockwork often characterize patients with major depressive and bipolar disorders. Circadian clock genes are targets of interest in these patients. CRY2 is a circadian gene that participates in regulation of the evening oscillator. This is of interest in mood disorders where a lack of switch from evening to morning oscillators has been postulated.

    Principal Findings: We observed a marked diurnal variation in human CRY2 mRNA levels from peripheral blood mononuclear cells and a significant up-regulation (P = 0.020) following one-night total sleep deprivation, a known antidepressant. In depressed bipolar patients, levels of CRY2 mRNA were decreased (P = 0.029) and a complete lack of increase was observed following sleep deprivation. To investigate a possible genetic contribution, we undertook SNP genotyping of the CRY2 gene in two independent population-based samples from Sweden (118 cases and 1011 controls) and Finland (86 cases and 1096 controls). The CRY2 gene was significantly associated with winter depression in both samples (haplotype analysis in Swedish and Finnish samples: OR = 1.8, P = 0.0059 and OR = 1.8, P = 0.00044, respectively).

    Conclusions: We propose that a CRY2 locus is associated with vulnerability for depression, and that mechanisms of action involve dysregulation of CRY2 expression.

  • 76.
    Lind, Johanna
    et al.
    Department of Clinical Neuroscience, Karolinska Institute, MR Research Center, Karolinska Hospital.
    Ingvar, Martin
    Department of Clinical Neuroscience, Karolinska Institute, MR Research Center, Karolinska Hospital.
    Persson, Jonas
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Sleegers, Kristel
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerp, Belgium.
    Van Broeckhoven, Christine
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerp, Belgium.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University, Stockholm.
    Nyberg, Lars
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Parietal cortex activation predicts memory decline in apolipoprotein E-epsilon 4 carriers2006Ingår i: NeuroReport, ISSN 0959-4965, E-ISSN 1473-558X, Vol. 17, nr 16, s. 1683-1686Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Apolipoprotein E-[varepsilon]4 is the main known genetic risk factor for Alzheimer's disease. Functional abnormalities in the parietal cortex have been reported for Alzheimer's disease patients and also for those at risk. Hence, a critical question is whether measurements of parietal cortex integrity may predict negative outcome among at-risk persons. We studied nondementedapolipoprotein E-[varepsilon]4 carriers and found a significant relationship between parietal blood-oxygen-level-dependent functional magnetic resonance imaging response during a word categorization task and subsequent episodic memory performance. Thus, the results show that parietal cortex alterations predict memory decline in nondemented apolipoprotein E-[varepsilon]4 carriers, and hence likely progression to Alzheimer's disease.

  • 77.
    Lind, Johanna
    et al.
    Department of Clinical Neuroscience, MR Research Center, Karolinska Hospital N-8, S-171 76 Stockholm, Sweden.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Persson, Jonas
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Ingvar, Martin
    Department of Clinical Neuroscience, MR Research Center, Karolinska Hospital N-8, S-171 76 Stockholm, Sweden.
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University, S-106 91 Stockholm, Sweden.
    Bäckman, Lars
    National Centre of Aging, Box 6401, S-113 82 Stockholm, Sweden.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Cruts, Marc
    Department of Molecular Genetics, Flanders Interuniversity, Institute of Biotechnology, University of Antwerp, B-2610 Antwerpen, Belgium.
    Sleegers, Kristel
    Department of Molecular Genetics VIB8, University of Antwerp, Campus CDE, Universiteitsplein 1, B-2610 Antwerp, Belgium.
    Van Broeckhoven, Christine
    Department of Molecular Genetics, Flanders Interuniversity, Institute of Biotechnology, University of Antwerp, B-2610 Antwerpen, Belgium.
    Nyberg, Lars
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Reduced hippocampal volume in non-demented carriers fo the apolipoprotein E ε4: Relation to chronological age and recognition memory2006Ingår i: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 396, nr 1, s. 23-27Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Apolipoprotein E ε4 (APOE ε4) is the main known genetic risk factor for Alzheimer's disease (AD). Some previous studies have reported structural brain changes as well as cognitive deficits in non-demented APOE ε4 carriers, but the pattern of results is inconsistent and studies with larger sample sizes have been called for. Here we compared hippocampal volume and recognition–memory performance between AD-symptom-free carriers (N = 30) and non-carriers (N = 30) of the APOE ε4 (age range: 49–79 years). We observed reduced right hippocampal volume in APOE ε4 carriers, and found that the difference was most pronounced before the age of 65. Further, the APOE ε4 carriers made significantly more false alarms in the recognition–memory test, and the number of false alarms correlated significantly with right hippocampus volume. These results indicate that relatively young individuals at genetic risk for AD have smaller hippocampal volume and lower performance on hippocampal-dependent cognitive tasks. A question for the future is whether smaller hippocampal volume represents early-onset hippocampal volume reduction or an inherent trait.

  • 78.
    Lind, Johanna
    et al.
    Department of Clinical Neuroscience, MR Research Center, Karolinska Hospital, Stockholm.
    Persson, Jonas
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Ingvar, Martin
    Department of Clinical Neuroscience, MR Research Center, Karolinska Hospital, Stockholm.
    Larsson, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Cruts, Marc
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerpen, Belgium.
    Van Broeckhoven, Christine
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerpen, Belgium.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Bäckman, Lars
    Stockholm Aging Research Center.
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University, Stockholm.
    Petersson, Karl Magnus
    Department of Clinical Neuroscience, MR Research Center, Karolinska Hospital.
    Nyberg, Lars
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Reduced functional brain activity response in cognitively intact apolipoprotein E ε4 carriers2006Ingår i: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 129, nr 5, s. 1240-1248Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The apolipoprotein E epsilon4 (APOE epsilon4) is the main known genetic risk factor for Alzheimer's disease. Genetic assessments in combination with other diagnostic tools, such as neuroimaging, have the potential to facilitate early diagnosis. In this large-scale functional MRI (fMRI) study, we have contrasted 30 APOE epsilon4 carriers (age range: 49-74 years; 19 females), of which 10 were homozygous for the epsilon4 allele, and 30 non-carriers with regard to brain activity during a semantic categorization task. Test groups were closely matched for sex, age and education. Critically, both groups were cognitively intact and thus symptom-free of Alzheimer's disease. APOE epsilon4 carriers showed reduced task-related responses in the left inferior parietal cortex, and bilaterally in the anterior cingulate region. A dose-related response was observed in the parietal area such that diminution was most pronounced in homozygous compared with heterozygous carriers. In addition, contrasts of processing novel versus familiar items revealed an abnormal response in the right hippocampus in the APOE epsilon4 group, mainly expressed as diminished sensitivity to the relative novelty of stimuli. Collectively, these findings indicate that genetic risk translates into reduced functional brain activity, in regions pertinent to Alzheimer's disease, well before alterations can be detected at the behavioural level.

  • 79. Lindholm, E
    et al.
    Ekholm, B
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Balciuniene, J
    Johansson, G
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Castensson, A
    Koisti, M
    Nylander, P O
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Pettersson, U
    Adolfsson, R
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Jazin, E
    Linkage analysis of a Swedish kindred provides further support for a susceptibility locus for schizophrenia on chromosome 6p231999Ingår i: American Journal of Medical Genetics, ISSN 0148-7299, E-ISSN 1096-8628, Vol. 88, nr 4, s. 369-377Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Several reports have indicated genetic linkage between markers on the short arm of chromosome 6 and schizophrenia. However, significant threshold levels were not always achieved, and the chromosomal regions identified are large and different in different families. One way to decrease the problem of heterogeneity is to study a single extended pedigree. Here we report the analysis of a very large, previously undescribed pedigree from northern Sweden that includes 31 affected individuals. We typed 16 markers spanning 40 cM on the short arm of chromosome 6. Linkage analysis was performed only with the affected individuals. Suggestive lod scores (maximum 2.6) were obtained with markers on chromosome 6p23 in a single branch of the large pedigree indicating possible heterogeneity inside the family. A haplotype comprising markers from D6S309 to D6S1578 was found to segregate with the disease. This chromosomal region is included within a segment proposed to contain a susceptibility gene for schizophrenia by many other investigators. Our results thus give further support for a possible localization of a susceptibility locus for schizophrenia in 6p23 and help to narrow the candidate chromosomal region to the segment included between markers D6S309 and D6S1578. Copyright 1999 Wiley-Liss, Inc.

  • 80. Lindholm, E
    et al.
    Ekholm, B
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Shaw, S
    Jalonen, P
    Johansson, G
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Pettersson, U
    Sherrington, R
    Adolfsson, R
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Jazin, E
    A schizophrenia-susceptibility locus at 6q25, in one of the world´s largest reported pedigree2001Ingår i: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 69, nr 1, s. 96-105Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We have completed a genome scan of a 12-generation, 3,400-member pedigree with schizophrenia. Samples from 210 individuals were collected from the pedigree. We performed an "affecteds-only" genome-scan analysis using 43 members of the pedigree. The affected individuals included 29 patients with schizophrenia, 10 with schizoaffective disorders, and 4 with psychosis not otherwise specified. Two sets of white-European allele frequencies were used-one from a Swedish control population (46 unrelated individuals) and one from the pedigree (210 individuals). All analyses pointed to the same region: D6S264, located at 6q25.2, showed a maximum LOD score of 3.45 when allele frequencies in the Swedish control population were used, compared with a maximum LOD score of 2.59 when the pedigree's allele frequencies were used. We analyzed additional markers in the 6q25 region and found a maximum LOD score of 6.6 with marker D6S253, as well as a 6-cM haplotype (markers D6S253-D6S264) that segregated, after 12 generations, with the majority of the affected individuals. Multipoint analysis was performed with the markers in the 6q25 region, and a maximum LOD score of 7.7 was obtained. To evaluate the significance of the genome scan, we simulated the complete analysis under the assumption of no linkage. The results showed that a LOD score >2.2 should be considered as suggestive of linkage, whereas a LOD score >3.7 should be considered as significant. These results suggest that a common ancestral region was inherited by the affected individuals in this large pedigree.

  • 81. Lindholm, Eva
    et al.
    Åberg, Karolina
    Ekholm, Birgit
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Pettersson, Ulf
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Jazin, Elena E
    Reconstruction of ancestral haplotypes in a 12-generation schizophrenia pedigree2004Ingår i: Psychiatric Genetics, ISSN 0955-8829, E-ISSN 1473-5873, Vol. 14, nr 1, s. 1-8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We searched for candidate chromosomal regions inherited identical by descent in 19 patients suffering from schizophrenia or schizoaffective disorder that are related 12 generations back, to an ancestral couple born in the middle of the seventeenth century. To accomplish this goal, we constructed complete chromosomal haplotypes for each patient using genotype data from 450 markers. In total, 12 haplotype regions (with sizes ranging from 0.6 to 10.9 cM) constituted by three markers each were identical in three or more of the affected individuals. The largest genomic segment was located on 6q25, a region previously shown to be significantly more frequent in patients than controls, and proposed to contain a schizophrenia susceptibility locus. For the remaining 11 candidate haplotypes, we estimated haplotype frequencies from all the 43 affected members collected from the same family and 46 unrelated control individuals. This analysis indicated that at least four of the 11 candidate haplotypes are ancestral, since the frequencies were significantly higher in patients than in controls. Five additional haplotypes showed higher estimated frequencies in the patients but the differences were not significant. Interestingly, five of these 11 genomic regions are located in, or close to, candidate regions previously suggested to contain susceptibility genes for schizophrenia. The regions are 5q21-23, 8p21-22, 1 0p13-15, 13q12-13 and 22q12-13. Several of these haplotypes are probably ancestral linkage disequilibrium blocks inherited from the original couple. There exists, however, the possibility that one or more of these regions harbour schizophrenia susceptibility loci that may have epistatic interactions among them.

  • 82.
    Ljungberg, Jessika K.
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Cardiff University.
    Hansson, Patrik
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nilsson, Lars-Göran
    The effect of language skills on dementia in a Swedish longitudinal cohort2016Ingår i: Linguistic Approaches to Bilingualism, ISSN 1879-9264, E-ISSN 1879-9272, Vol. 6, nr 1-2, s. 190-204Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recent findings indicate that bilingualism delay the onset of dementia. Using data from the Betula longitudinal cohort study on memory, health and aging (www.betula.su.se) the issue of a possible protective effect of bilingualism was addressed.

    Monolingual (n = 736) and bilingual (n = 82) participants (≥ 60 years) without dementia at inclusion were followed for incident dementia over a time-period up to 10 years. In total, 112 participants developed dementia. Analyses were performed with Cox proportional hazards regression adjusted for age, sex, and presence/absence of the Apolipoprotein E (APOE) ɛ4 allele, with dementia outcome as the dependent variable.

    Results showed no delayed onset of dementia in bilinguals compared to monolinguals. However, because of the findings from a study using participants from the same population showing beneficial longitudinal effects of bilingualism on episodic memory; we argue that our results may depend on the frequency of use of the second language after retirement.

  • 83.
    Lundberg, Mattias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Perris, Carlo
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Schlette, Paul
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Transhistorical variations in personality and their association with experiences of parental rearing.1999Ingår i: European psychiatry, ISSN 0924-9338, E-ISSN 1778-3585, Vol. 14, nr 6, s. 303-18Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A population sample comprised of 765 subjects (367 males and 398 females), in the age range of 15-81 years, completed the EMBU, a reliable questionnaire aimed at assessing experiences of parental rearing, and the TCI, a self-report questionnaire aimed at assessing dimensions of temperament and character. The study had three main aims: 1) to verify, on a larger scale, previous findings suggesting the occurrence of significant associations between experiences of parental rearing and aspects of temperament and character, 2) to assess possible variations in temperament and character in cohorts of subjects who have grown up in different historical epochs, and 3) to investigate to what extent transgenerational differences in parental rearing are detectable in different associations with various dimensions of personality. Several, albeit small, significant and meaningful associations between experiences of parental rearing and both temperament and character dimensions have been found, adding support to the robustness of previously reported results obtained in an independent smaller series. Also, several significant differences among subjects in different age groups have been found, both concerning temperament variables and character dimensions. Finally, the results show that associations between experiences of parental rearing and dimensions of temperament and character are most pronounced in subjects belonging to the youngest cohort and almost nil in the cohort comprising the oldest subjects.

  • 84. Lövdén, Martin
    et al.
    Bergman, Lars
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Lindenberger, Ulman
    Nilsson, Lars-Göran
    Studying individual aging in an interindividual context: typical paths of age-related, dementia-related, and mortality-related cognitive development in old age2005Ingår i: Psychology and Aging, ISSN 0882-7974, E-ISSN 1939-1498, Vol. 20, nr 2, s. 303-316Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study has 2 objectives: (a) to explore typical paths of cognitive development associated with aging, terminal decline, and dementia and (b) to promote and illustrate an individual-oriented approach to the study of cognitive aging based on longitudinal panel data from a population-based sample (N = 500; age range(TI) = 60-80, where T refers to time) tested at 3 occasions 5 years apart. Results document interindividual differences in multivariate patterns of change. Although cognitive changes generally covary, the present study indicates that subgroups of individuals develop along different paths characterized by selective changes in subsets of cognitive functions. Typical progression of dementia followed a developmental cascade from low declarative memory, via low functioning across all observed cognitive measures, to dementia diagnosis, and finally, death.

  • 85.
    Lövheim, Hugo
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Gilthorpe, Jonathan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nilsson, Lars-Göran
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Reactivated herpes simplex infection increases the risk of Alzheimer's disease2015Ingår i: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 11, nr 6, s. 593-599Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Previous studies have suggested a link between herpes simplex virus (HSV) type 1 and the development of Alzheimer's disease (AD).

    METHODS: The present analysis included 3432 persons (53.9% women, mean age at inclusion 62.7 ± 14.4 years) with a mean follow-up time of 11.3 years. The number of incident AD cases was 245. Serum samples were analyzed for anti-HSV antibodies (immunoglobulin (Ig)G and IgM) by enzyme-linked immunosorbent assays.

    RESULTS: The presence of anti-HSV IgG antibodies was not associated with an increased risk for AD, controlled for age and sex (hazard ratio, HR, 0.993, P = .979). However, the presence of anti-HSV IgM at baseline was associated with an increased risk of developing AD (HR 1.959, P = .012).

    CONCLUSION: Positivity for anti-HSV IgM, a sign of reactivated infection, was found to almost double the risk for AD, whereas the presence of anti-HSV IgG antibodies did not affect the risk.

  • 86.
    Lövheim, Hugo
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Norman, Tove
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Weidung, Bodil
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Sweden.
    Olsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Josefsson, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Avdelningen för virologi.
    Herpes Simplex Virus, APOE ɛ4, and Cognitive Decline in Old Age: Results from the Betula Cohort Study2019Ingår i: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 67, nr 1, s. 211-220Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Herpes simplex virus (HSV) has been suggested to play a role in Alzheimer’s disease (AD) development.

    Objective: The aim of the present study was to investigate the early AD-related symptom episodic memory decline in relation to HSV and carriage of allele 4 of the apolipoprotein E gene (APOE ɛ4) in a large population-based cohort with a long follow-up time.

    Methods: The study included 3,413 persons, with longitudinal data available for 1,293 persons with a mean follow-up time of 11.6 years. The associations between HSV carriage, APOE ɛ4 carriage, and episodic memory was investigated at baseline, as well as in longitudinal analyses where individuals with and without HSV antibodies (HSV1/2 non-specific) were matched and episodic memory decline compared.

    Results: Cross-sectional analyses revealed an age-dependent association of HSV carriage with lower episodic memory function, particularly among APOE ɛ4 carriers (p = 0.008). Longitudinal analyses showed an increased risk of episodic memory decline in HSV carriers (≥65 years: p < 0.001, all ages: non-significant), and a significant interaction between HSV and APOE ɛ4 for episodic memory decline (p < 0.001).

    Conclusion: In this large population-based cohort study, both cross-sectional and longitudinal results support an association between HSV carriage and declining episodic memory function, especially among APOE ɛ4 carriers. The results strengthen the hypothesis that HSV is associated with AD development.

  • 87.
    Maitland, Scott B
    et al.
    Family Relations and Applied Nutrition, University of Guelph, ON, Canada .
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Bäckman, Lars
    Aging Research Center, Karolinska Institute, Stockholm, Sweden.
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University, Sweden.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    On the structure of personality: are there separate temperament and character factors?2009Ingår i: Personality and Individual Differences, ISSN 0191-8869, E-ISSN 1873-3549, Vol. 47, nr 3, s. 180-184Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Temperament and Character Inventory (TCI) is a widely used measure of psychobiological aspects of personality. Theoretically, the TCI is defined as comprising four temperament and three character factors. Most previous examinations of the factor structure have used exploratory factor methods with mixed results. We used confirmatory factor analyses (CFA) to examine the TCI in a sample of 2423 adults aged 35–90 years (1093 women, 1330 men) from the Betula study. Support for the seven TCI factors was mixed. Models including second-order factors provided no evidence that the seven first-order TCI factors reflect higher-order temperament and character constructs. Our findings provide no support that individual differences on the seven first-order TCI factors reflect distinct temperament or character dimensions of personality. Whereas more complex modeling strategies rejected separate character and temperament models, the simultaneous (seven-factor) model, and the use of second-order factors; the harm avoidance, self-directedness, and cooperativeness factors were acceptable examined individually. Results for novelty seeking were marginal and self-transcendence, reward dependence and/or persistence factors were not acceptable.

  • 88. Malm, J
    et al.
    Kristensen, B
    Ekstedt, J
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Wester, P
    CSF monoamine metabolites, cholinesterases and lactate in the adult hydrocephalus syndrome (normal pressure hydrocephalus) related to CSF hydrodynamic parameters.1991Ingår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 54, nr 3, s. 252-9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Monoamine metabolites, cholinesterases and lactic acid in lumbar cerebrospinal fluid (CSF) were investigated on patients with the adult hydrocephalus syndrome (idiopathic normal pressure syndrome; AHS, n = 15), Alzheimer's disease (AD, n = 14), multi-infarct dementia (MID, n = 13) and controls (n = 21). Patients had clinical and CSF hydrodynamic investigations. Monoamine concentrations were determined by reversed-phase liquid chromatography, cholinesterases and lactate were determined photometrically. In the AHS patients, CSF monoamine concentrations were not significantly different compared with controls, AD or MID patients. AHS and AD patients showed a similar reduction of CSF acetylcholinesterase activity compared with controls. Positive correlations were found in concentrations of CSF homovanillic acid, CSF 5-hydroxyindoleacetic acid and CSF lactic acid versus CSF outflow conductance (that is, resistance against CSF outflow) in the AHS patients. A similar pattern was observed in a subgroup of MID patients characterised by dilated ventricles and disturbed CSF hydrodynamics. These data suggest that a low CSF outflow conductance may facilitate the clearance of acidic substances from the arachnoid space at the probenecid sensitive active transport site. Alternative explanations would be that a pathologically low CSF outflow conductance is accompanied by an inverse caudorostral flow of CSF or a compromised trans-ependymal diffusion.

  • 89.
    Maripuu, Martin Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Wikgren, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Norrback, Karl-Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Relative hypocortisolism is associated with obesity and the metabolic syndrome in recurrent affective disorders2016Ingår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 71, s. 64-65Artikel i tidskrift (Övrigt vetenskapligt)
  • 90.
    Maripuu, Martin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Wikgren, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Norrback, Karl-Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Bipolar patients at risk for developing hypocortisolism: Long-term lithium treatment is preventiveManuskript (preprint) (Övrigt vetenskapligt)
  • 91.
    Maripuu, Martin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Wikgren, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Norrback, Karl-Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Hyper- and hypocortisolism in bipolar disorder: A beneficial influence of lithium on the HPA-axis?2017Ingår i: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 213, s. 161-167Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: A hyperactive hypothalamic-pituitary-adrenal axis (HPA-axis) is a well-known phenomenon in bipolar disorder (BD). However, hypocortisolism has also been described and found associated with depression, low quality of life and cardiovascular risk factors in BD patients. Although the pathophysiology related to hypocortisolism in BD is largely unknown, hypocortisolism is associated with chronic stress exposure and after inducing an initial rise in cortisol long-term stress may result in a transition to hypocortisolism. BD patients are throughout life often exposed to chronic stress. We therefore hypothesized that higher age would be associated with lower HPA-axis activity especially among patients without previous mood stabilizing treatment. Methods: This cross-sectional study consisted of 159 bipolar outpatients and 258 controls. A low-dose-dexamethasone-suppression-test (DST) was used to measure HPA-axis activity. Results: Patients with BD showed a negative association between post DST cortisol and age (-3.0 nmol/l per year; p=0.007). This association gradually increased in subgroups that were naive to lithium (-7.7 nmol/l per year; p=0.001) and "all mood stabilizers" (-11.4 nmol/l per year; p=0.004). Patients exhibiting hypercortisolism were characterized by younger age and female gender, whereas patients exhibiting hypocortisolism were characterized by long disease duration without prophylactic lithium treatment as well as absence of current lithium medication. Limitations: Cross sectional study design. Conclusions: There was a negative association between HPA-axis activity and age in BD, rendering BD patients at risk for developing hypocortisolism. This association was most pronounced among patients without previous or current lithium prophylaxis.

  • 92.
    Maripuu, Martin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Wikgren, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Norrback, Karl-Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Relative hypocortisolism is associated with obesity and the metabolic syndrome in recurrent affective disordersManuskript (preprint) (Övrigt vetenskapligt)
  • 93.
    Maripuu, Martin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Wikgren, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Norrback, Karl-Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Relative hypocortisolism is associated with obesity and the metabolic syndrome in recurrent affective disorders2016Ingår i: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 204, s. 187-196Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Cardiovascular disease (CVD) is one of the main causes of excess deaths in affective disorders. Affective disorders are associated with increased frequencies of CVD risk-factors such as obesity, dyslipidemia, and metabolic syndrome. Stress-induced chronic cortisol excess has been suggested to promote obesity and metabolic syndrome. Chronic stress with frequent or persisting hypothalamic-pituitary-adrenal-axis (HPA-axis) hyperactivity may, over time, lead to a state of low HPA-axis activity, also denoted hypocortisolism. A low-dose weight-adjusted dexamethasone-suppression-test (DST) is considered to be a sensitive measure of hypocortisolism.

    Methods: 245 patients with recurrent depression or bipolar disorder and 258 controls participated in a low-dose DST and were also examined with regard to metabolic status.

    Results: Patients with hypocortisolism (low post-DST cortisol) compared with patients without hypocortisolism (normal or high post-DST cortisol) exhibited increased odds ratios (OR) for obesity (OR=4.0), overweight (OR=4.0), large waist (OR=2.7), high LDL (OR=4.2), low HDL (OR=2.4), high LDL/HDL ratio (OR=3.3), high TC/HDL ratio (OR=3.4) and metabolic syndrome (OR=2.0). A similar pattern but less pronounced was also found in the control sample.

    Limitations: The cross sectional study design and absence of analyses addressing lifestyle factors.

    Conclusions: Our findings suggest that a substantial portion of the metabolic disorders and cardiovascular risk factors seen in recurrent affective disorders are found among individuals exhibiting hypocortisolism. This might indicate that long-term stress is a central contributor to metabolic abnormalities and CVD mortality in recurrent affective disorders.

  • 94.
    Maripuu, Martin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Wikgren, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Norrbäck, Karl-Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Relative Hypo- and Hypercortisolism are Both Associated with Depression and Lower Quality of Life in Bipolar Disorder2016Ingår i: Journal of Psychosomatic Research, ISSN 0022-3999, E-ISSN 1879-1360, Vol. 85, s. 73-74Artikel i tidskrift (Övrigt vetenskapligt)
  • 95.
    Maripuu, Martin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Wikgren, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Karling, Pontus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Norrbäck, Karl-Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Relative Hypo-and Hypercortisolism Are Both Associated with Depression and Lower Quality of Life in Bipolar Disorder: A Cross-Sectional Study2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 6, artikel-id e98682Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Depression in unipolar and bipolar disorders is associated with hypothalamic-pituitary-adrenal-axis (HPA-axis) hyperactivity. Also, unipolar disorder has recently been shown to exhibit HPA-axis hypoactivity. We studied for the first time how HPA-axis hypo-and hyperactivity relate to depression and disease burden in bipolar disorder. We were interested in studying hypocortisolism; characterized by increased HPA-axis negative feedback sensitivity and lower basal cortisol levels together with the opposite HPA-axis regulatory pattern of hypercortisolism. Methods: This cross-sectional study includes 145 type 1 and 2 bipolar outpatients and 145 matched controls. A dexamethasone-suppression-test (DST) measures the negative feedback sensitivity and a weight-adjusted very-low-dose DST was employed, which is sensitive in identifying hypocortisolism and hypercortisolism. The 25th and 75th percentiles of control post-DST values were used as cut-offs identifying patients exhibiting relative hypo-, and hypercortisolism. Self-report questionnaires were employed: Beck-Depression-Inventory (BDI), Montgomery-Asberg-Depression-Rating-Scale (MADRS-S), World-Health-Organization-Quality-of-Life-Assessment-100 and Global-Assessment-of-Functioning. Results: Patients exhibiting relative hypocortisolism expectedly exhibited lowered basal cortisol levels (p = 0.046). Patients exhibiting relative hypercortisolism expectedly exhibited elevated basal levels (p<0.001). Patients exhibiting relative hypocortisolism showed 1.9-2.0 (BDI, p = 0.017, MADRS-S, p = 0.37) and 6.0 (p<0.001) times increased frequencies of depression and low overall life quality compared with patients exhibiting mid post-DST values (eucortisolism). Adjusted Odds Ratios (OR:s) for depression ranged from 3.8-4.1 (BDI, p = 0.006, MADRS-S, p = 0.011) and was 23.4 (p<0.001) for life quality. Patients exhibiting relative hypercortisolism showed 1.9-2.4 (BDI, p = 0.017, MADRS-S, p = 0.003) and 4.7 (p<0.001) times higher frequencies of depression and low overall life quality compared with patients exhibiting eucortisolism. Adjusted OR: s for depression ranged from 2.2-2.7 (BDI, p = 0.068, MADRS-S, p = 0.045) and was 6.3 (p = 0.008) for life quality. Limitations: The cross-sectional design and lack of pre-established reference values of the DST employed. Conclusions: Relative hypocortisolism and relative hypercortisolism were associated with depression and lower life quality, providing novel insights into the detrimental role of stress in bipolar disorder.

  • 96. Marshall, Christian R.
    et al.
    Howrigan, Daniel P.
    Merico, Daniele
    Thiruvahindrapuram, Bhooma
    Wu, Wenting
    Greer, Douglas S.
    Antaki, Danny
    Shetty, Aniket
    Holmans, Peter A.
    Pinto, Dalila
    Gujral, Madhusudan
    Brandler, William M.
    Malhotra, Dheeraj
    Wang, Zhouzhi
    Fajarado, Karin V. Fuentes
    Maile, Michelle S.
    Ripke, Stephan
    Agartz, Ingrid
    Albus, Margot
    Alexander, Madeline
    Amin, Farooq
    Atkins, Joshua
    Bacanu, Silviu A.
    Belliveau, Richard A., Jr.
    Bergen, Sarah E.
    Ertalan, Marcelo
    Bevilacqua, Elizabeth
    Bigdeli, Tim B.
    Black, Donald W.
    Bruggeman, Richard
    Buccola, Nancy G.
    Buckner, Randy L.
    Bulik-Sullivan, Brendan
    Byerley, William
    Cahn, Wiepke
    Cai, Guiqing
    Cairns, Murray J.
    Campion, Dominique
    Cantor, Rita M.
    Carr, Vaughan J.
    Carrera, Noa
    Catts, Stanley V.
    Chambert, Kimberley D.
    Cheng, Wei
    Cloninger, C. Robert
    Cohen, David
    Cormican, Paul
    Craddock, Nick
    Crespo-Facorro, Benedicto
    Crowley, James J.
    Curtis, David
    Davidson, Michael
    Davis, Kenneth L.
    Degenhardt, Franziska
    Del Favero, Jurgen
    DeLisi, Lynn E.
    Dikeos, Dimitris
    Dinan, Timothy
    Djurovic, Srdjan
    Donohoe, Gary
    Drapeau, Elodie
    Duan, Jubao
    Dudbridge, Frank
    Eichhammer, Peter
    Eriksson, Johan
    Escott-Price, Valentina
    Essioux, Laurent
    Fanous, Ayman H.
    Farh, Kai-How
    Farrell, Martilias S.
    Frank, Josef
    Franke, Lude
    Freedman, Robert
    Freimer, Nelson B.
    Friedman, Joseph I.
    Forstner, Andreas J.
    Fromer, Menachem
    Genovese, Giulio
    Georgieva, Lyudmila
    Gershon, Elliot S.
    Giegling, Ina
    Giusti-Rodriguez, Paola
    Godard, Stephanie
    Goldstein, Jacqueline I.
    Gratten, Jacob
    de Haan, Lieuwe
    Hamshere, Marian L.
    Hansen, Mark
    Hansen, Thomas
    Haroutunian, Vahram
    Hartmann, Annette M.
    Henskens, Frans A.
    Herms, Stefan
    Hirschhorn, Joel N.
    Hoffinann, Per
    Hofman, Andrea
    Huang, Hailiang
    Ikeda, Masashi
    Joa, Inge
    Kahler, Anna K.
    Kahn, Rene S.
    Kalaydjieva, Luba
    Karjalainen, Juha
    Kavanagh, David
    Keller, Matthew C.
    Kelly, Brian J.
    Kennedy, James L.
    Kim, Yunjung
    Knowles, James A.
    Konte, Bettina
    Laurent, Claudine
    Lee, Phil
    Lee, S. Hong
    Legge, Sophie E.
    Lerer, Bernard
    Levy, Deborah L.
    Liang, Kung-Yee
    Lieberman, Jeffrey
    Lonnqvist, Jouko
    Loughland, Carmel M.
    Magnusson, Patrik K. E.
    Maher, Brion S.
    Maier, Wolfgang
    Mallet, Jacques
    Mattheisen, Manuel
    Mattingsdal, Morten
    McCarley, Robert W.
    McDonald, Colm
    McIntosh, Andrew M.
    Meier, Sandra
    Meijer, Carin J.
    Melle, Ingrid
    Mesholam-Gately, Raquelle I.
    Metspalu, Andres
    Michie, Patricia T.
    Milani, Lili
    Milanova, Vihra
    Mokrab, Younes
    Morris, Derek W.
    Muller-Myhsok, Bertram
    Murphy, Kieran C.
    Murray, Robin M.
    Myin-Germeys, Inez
    Nenadic, Igor
    Nertney, Deborah A.
    Nestadt, Gerald
    Nicodemus, Kristin K.
    Nisenbaum, Laura
    Nordin, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    O'Callaghan, Eadbhard
    O'Dushlaine, Colm
    Oh, Sang-Yun
    Olincy, Ann
    Olsen, Line
    O'Neill, F. Anthony
    Van Os, Jim
    Pantelis, Christos
    Papadimitriou, George N.
    Parkhomenko, Elena
    Pato, Michele T.
    Paunio, Tiina
    Perkins, Diana O.
    Pers, Tune H.
    Pietilainen, Olli
    Pimm, Jonathan
    Pocklington, Andrew J.
    Powell, John
    Price, Alkes
    Pulver, Ann E.
    Purcell, Shaun M.
    Quested, Digby
    Rasmussen, Henrik B.
    Reichenberg, Abraham
    Reimers, Mark A.
    Richards, Alexander L.
    Roffman, Joshua L.
    Roussos, Panos
    Ruderfer, Douglas M.
    Salomaa, Veikko
    Sanders, Alan R.
    Savitz, Adam
    Schall, Ulrich
    Schulze, Thomas G.
    Schwab, Sibylle G.
    Scolnick, Edward M.
    Scott, Rodney J.
    Seidman, Larry J.
    Shi, Jianxin
    Silverman, Jeremy M.
    Smoller, Jordan W.
    Soderman, Erik
    Spencer, Chris C. A.
    Stahl, Eli A.
    Strengman, Eric
    Strohmaier, Jana
    Stroup, T. Scott
    Suvisaari, Jaana
    Svrakic, Dragan M.
    Szatkiewicz, Jin P.
    Thirumalai, Srinivas
    Tooney, Paul A.
    Veijola, Juha
    Visscher, Peter M.
    Waddington, John
    Walsh, Dermot
    Webb, Bradley T.
    Weiser, Mark
    Wildenauer, Dieter B.
    Williams, Nigel M.
    Williams, Stephanie
    Witt, Stephanie H.
    Wolen, Aaron R.
    Wormley, Brandon K.
    Wray, Naomi R.
    Wu, Jing Qin
    Zai, Clement C.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Andreassen, Ole A.
    Blackwood, Douglas H. R.
    Bramon, Elvira
    Buxbaum, Joseph D.
    Cichon, Sven
    Collier, David A.
    Corvin, Aiden
    Daly, Mark J.
    Darvasi, Ariel
    Domenici, Enrico
    Esko, Tonu
    Gejman, Pablo V.
    Gill, Michael
    Gurling, Hugh
    Hultman, Christina M.
    Iwata, Nakao
    Jablensky, Assen V.
    Jonsson, Erik G.
    Kendler, Kenneth S.
    Kirov, George
    Knight, Jo
    Levinson, Douglas F.
    Li, Qingqin S.
    McCarroll, Steven A.
    McQuillin, Andrew
    Moran, Jennifer L.
    Mowry, Bryan J.
    Nothen, Markus M.
    Ophoff, Roel A.
    Owen, Michael J.
    Palotie, Aarno
    Pato, Carlos N.
    Petryshen, Tracey L.
    Posthuma, Danielle
    Rietschel, Marcella
    Riley, Brien P.
    Rujescu, Dan
    Sklar, Pamela
    St Clair, David
    Walters, James T. R.
    Werge, Thomas
    Siillivan, Patrick F.
    O'Donovan, Michael C.
    Scherer, Stephen W.
    Neale, Benjamin M.
    Sebat, Jonathan
    Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects2017Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 49, nr 1, s. 27-35Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 x 10(-15)), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 x 10(-6)). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 x 10(-11)) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 x 10(-5)). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination.

  • 97. Mendlewicz, Julien
    et al.
    Souery, Daniel
    Del-Favero, Jurgen
    Massat, Isabelle
    Lindblad, Kerstin
    Engström, Christer
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Van den Bossche, Dirk
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Schalling, Martin
    Van Broeckhoven, Christine
    Expanded RED products and loci containing CAG/CTG repeats on chromosome 17 (ERDA1) and chromosome 18 (CTG18.1) in trans-generational pairs with bipolar affective disorder2004Ingår i: American Journal of Medical Genetics, ISSN 0148-7299, E-ISSN 1096-8628, Vol. 128B, nr 1, s. 71-75Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The purpose of the present study was to further test if expanded CAG repeats detected by the repeat expansion detection (RED) method in bipolar affective disorder (BPAD) are correlated with ERDA1 (17q21.3) and/or CTG18.1 (18q21.1) loci expansions, and changes of phenotype severity in successive generations (anticipation). The sample was designed to analyze ERDA1 and CTG18.1 expansions in trans-generational pairs of affected individuals (parent-offspring pairs: G1 and G2). Clinical and genetic information was available on 95 two-generations pairs. We found in our sample no one patient.

  • 98. Meyer, Thomas D
    et al.
    Hammelstein, Philipp
    Nilsson, Lars-Göran
    Skeppar, Peter
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Angst, Jules
    The Hypomania Checklist (HCL-32): its factorial structure and association to indices of impairment in German and Swedish nonclinical samples2007Ingår i: Comprehensive Psychiatry, ISSN 0010-440X, E-ISSN 1532-8384, Vol. 48, nr 1, s. 79-87Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Bipolar disorders are often not recognized. Several instruments were developed but none primarily focused on hypomania. The Hypomania Checklist (HCL) is aimed at the identification of bipolarity in outpatients. Using a German and Swedish sample, we investigated if the factor structure in nonclinical samples is similar to the one reported for outpatient samples. Furthermore, we tested if people who probably had a lifetime history of hypomania report more depression or other signs of impairment and if current depression is associated with lifetime hypomania.

    Method: In the German study, participants completed the HCL-32 as an online questionnaire that also included questions about lifetime and current depression (n = 695), whereas the Swedish data relied on the paper-and-pencil version of the HCL-32 completed by a ranclorn sample from a representative population sample (n = 408).

    Results: The factor structure of the HCL-32 was fairly similar in both samples and to the ones presented by Angst et al (J Affect Disord 2005;88:217-33). People reporting "highs" (>= 4 days and experiencing negative consequences) not only endorsed more HCL-32 symptoms but also had higher rates of current and former depression and psychotherapy. Level of current depression was also associated with lifetime hypomanic symptoms.

    Discussion and limitation: An "active-elated' and "risk-taking/irritable" factor of hypomania can be distinguished with the HCL-32 in clinical and nonclinical samples. Based on our results, the HCL-32 might even be useful as screening toot in nonclinical samples and not only in depressed outpatients. However, our data do not allow estimating sensitivity and specificity of the HCL-32 because structured clinical interviews were not included.

  • 99.
    Moens, Lotte N
    et al.
    Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium.
    Ceulemans, Shana
    Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium.
    Alaerts, Maaike
    Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium.
    Van Den Bossche, Maarten J A
    Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium.
    Lenaerts, An-Sofie
    Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium.
    De Zutter, Sonia
    Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium.
    Norrback, Karl-Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Del-Favero, Jurgen
    Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium.
    PCM1 and schizophrenia: a replication study in the Northern Swedish population2010Ingår i: American Journal of Medical Genetics, ISSN 0148-7299, E-ISSN 1096-8628, Vol. 153B, nr 6, s. 1240-1243Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Previous studies implicated centrosomal dysfunction as a source of various neuropsychiatric disorders, including schizophrenia (SZ). Two recent reports [Gurling et al., 2006; Datta et al., 2008. Mol Psychiatry] described an association between polymorphisms in the PCM1 gene and SZ in a UK/Scottish population. In this study, we aimed to replicate these findings in a Northern Swedish association sample of 486 research subjects with SZ and 512 unrelated control individuals. We genotyped 12 previously described SNP markers and carried out haplotype analyses using the same multi-marker haplotypes previously reported. Though we could not replicate the association with SNPs rs445422 and rs208747, we did observe a significant protective association with intronic SNP rs13276297. Furthermore, we performed a meta-analysis comprising 1,794 SZ patients and 1,553 controls, which confirmed the previously reported association with rs445422 and rs208747. These data provide further evidence that PCM1-though certainly not a major risk factor in the Northern Swedish population-cannot be ruled out as a contributor to SZ risk and/or protection, and deserves further replication in larger populations to elucidate its role in disease etiology.

  • 100.
    Moens, Lotte N.
    et al.
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology (VIB), Flanders, Belgium; University of Antwerp (UA), Antwerp, Belgium.
    De Rijk, Peter
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology (VIB), Flanders, Belgium; University of Antwerp (UA), Antwerp, Belgium.
    Reumers, Joke
    SWITCH Laboratory, Flanders Institute for Biotechnology (VIB), Flanders, Belgium; Vrije Universiteit Brussel (VUB), Brussels, Belgium.
    Van den Bossche, Maarten J. A.
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology (VIB), Flanders, Belgium; University of Antwerp (UA), Antwerp, Belgium.
    Glassee, Wim
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology (VIB), Flanders, Belgium; University of Antwerp (UA), Antwerp, Belgium.
    De Zutter, Sonia
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology (VIB), Flanders, Belgium; University of Antwerp (UA), Antwerp, Belgium.
    Lenaerts, An-Sofie
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology (VIB), Flanders, Belgium; University of Antwerp (UA), Antwerp, Belgium.
    Nordin, Annelie
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University, Stockholm, Sweden.
    Castello, Ignacio Medina
    Functional Genomics Unit, Bioinformatics and Genomics Department, Prince Felipe Research Centre (CIPF), Valencia, Spain.
    Norrback, Karl-Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Goossens, Dirk
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology (VIB), Flanders, Belgium; University of Antwerp (UA), Antwerp, Belgium.
    Van Steen, Kristel
    Systems and Modeling Unit, Montefiore Institute/GIGA, University of Liège, Liège, Belgium.
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Del-Favero, Jurgen
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology (VIB), Flanders, Belgium; University of Antwerp (UA), Antwerp, Belgium.
    Sequencing of DISC1 Pathway Genes Reveals Increased Burden of Rare Missense Variants in Schizophrenia Patients from a Northern Swedish Population2011Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 8, artikel-id e23450Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In recent years, DISC1 has emerged as one of the most credible and best supported candidate genes for schizophrenia and related neuropsychiatric disorders. Furthermore, increasing evidence - both genetic and functional - indicates that many of its protein interaction partners are also involved in the development of these diseases. In this study, we applied a pooled sample 454 sequencing strategy, to explore the contribution of genetic variation in DISC1 and 10 of its interaction partners (ATF5, Grb2, FEZ1, LIS-1, PDE4B, NDE1, NDEL1, TRAF3IP1, YWHAE, and ZNF365) to schizophrenia susceptibility in an isolated northern Swedish population. Mutation burden analysis of the identified variants in a population of 486 SZ patients and 514 control individuals, revealed that non-synonymous rare variants with a MAF<0.01 were significantly more present in patients compared to controls (8.64% versus 4.7%, P = 0.018), providing further evidence for the involvement of DISC1 and some of its interaction partners in psychiatric disorders. This increased burden of rare missense variants was even more striking in a subgroup of early onset patients (12.9% versus 4.7%, P = 0.0004), highlighting the importance of studying subgroups of patients and identifying endophenotypes. Upon investigation of the potential functional effects associated with the identified missense variants, we found that similar to 90% of these variants reside in intrinsically disordered protein regions. The observed increase in mutation burden in patients provides further support for the role of the DISC1 pathway in schizophrenia. Furthermore, this study presents the first evidence supporting the involvement of mutations within intrinsically disordered protein regions in the pathogenesis of psychiatric disorders. As many important biological functions depend directly on the disordered state, alteration of this disorder in key pathways may represent an intriguing new disease mechanism for schizophrenia and related neuropsychiatric diseases. Further research into this unexplored domain will be required to elucidate the role of the identified variants in schizophrenia etiology.

1234 51 - 100 av 180
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf