150 results on '"Schwieler L"'
Search Results
2. LPS-induced cortical kynurenic acid and neurogranin-NFAT signaling is associated with deficits in stimulus processing during Pavlovian conditioning
- Author
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Oliveros, A., Wininger, K., Sens, J., Larsson, M.K., Liu, X.C., Choi, S., Faka, A., Schwieler, L., Engberg, G., Erhardt, S., and Choi, D.S.
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- 2017
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3. Kynurenic acid promotes activity-dependent synaptic pruning and associates with genetic risk variance for schizophrenia
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Orhan, F., primary, Malwade, S., additional, Schwieler, L., additional, Tiihonen, J., additional, Koistinahu, J., additional, Erhardt, S., additional, Engberg, G., additional, Kent, J., additional, Samudyata, S., additional, and Sellgren, C., additional
- Published
- 2023
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4. Repeated LPS Injection Induces Distinct Changes in the Kynurenine Pathway in Mice
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Larsson, M. K., Faka, A., Bhat, M., Imbeault, S., Goiny, M., Orhan, F., Oliveros, A., Ståhl, S., Liu, X. C., Choi, D. S., Sandberg, K., Engberg, G., Schwieler, L., and Erhardt, S.
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- 2016
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5. The genetic architecture of human brainstem structures and their involvement in common brain disorders
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Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K., Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A., Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J., Høgestøl, Einar A., Jonassen, Rune, Jönsson, Erik G., Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, O'Connell, Kevin S., Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A., Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias, Farde, L., Flyckt, L., Engberg, G., Erhardt, S. S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Sellgren, C. M., Elvsåshagen, Torbjørn, Bahrami, Shahram, van der Meer, Dennis, Agartz, Ingrid, Alnæs, Dag, Barch, Deanna M., Baur-Streubel, Ramona, Bertolino, Alessandro, Beyer, Mona K., Blasi, Giuseppe, Borgwardt, Stefan, Boye, Birgitte, Buitelaar, Jan, Bøen, Erlend, Celius, Elisabeth Gulowsen, Cervenka, Simon, Conzelmann, Annette, Coynel, David, Di Carlo, Pasquale, Djurovic, Srdjan, Eisenacher, Sarah, Espeseth, Thomas, Fatouros-Bergman, Helena, Flyckt, Lena, Franke, Barbara, Frei, Oleksandr, Gelao, Barbara, Harbo, Hanne Flinstad, Hartman, Catharina A., Håberg, Asta, Heslenfeld, Dirk, Hoekstra, Pieter J., Høgestøl, Einar A., Jonassen, Rune, Jönsson, Erik G., Kirsch, Peter, Kłoszewska, Iwona, Lagerberg, Trine Vik, Landrø, Nils Inge, Le Hellard, Stephanie, Lesch, Klaus-Peter, Maglanoc, Luigi A., Malt, Ulrik F., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Nordvik, Jan Egil, Nyberg, Lars, O'Connell, Kevin S., Oosterlaan, Jaap, Papalino, Marco, Papassotiropoulos, Andreas, Pauli, Paul, Pergola, Giulio, Persson, Karin, de Quervain, Dominique, Reif, Andreas, Rokicki, Jaroslav, van Rooij, Daan, Shadrin, Alexey A., Schmidt, André, Schwarz, Emanuel, Selbæk, Geir, Soininen, Hilkka, Sowa, Piotr, Steen, Vidar M., Tsolaki, Magda, Vellas, Bruno, Wang, Lei, Westman, Eric, Ziegler, Georg C., Zink, Mathias, Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias, Farde, L., Flyckt, L., Engberg, G., Erhardt, S. S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., and Sellgren, C. M.
- Abstract
Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders. The genetic architecture underlying brainstem regions and how this links to common brain disorders is not well understood. Here, the authors use MRI and GWAS data from 27,034 individuals to identify genetic and morphological brainstem features that influence common brain disorders.
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- 2020
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6. Prostaglandin-mediated control of rat brain kynurenic acid synthesis – opposite actions by COX-1 and COX-2 isoforms
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Schwieler, L., Erhardt, S., Erhardt, C., and Engberg, G.
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- 2005
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7. Brain Age Prediction Reveals Aberrant Brain White Matter in Schizophrenia and Bipolar Disorder: A Multisample Diffusion Tensor Imaging Study
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Tønnesen, Siren, primary, Kaufmann, Tobias, additional, de Lange, Ann-Marie G., additional, Richard, Geneviève, additional, Doan, Nhat Trung, additional, Alnæs, Dag, additional, van der Meer, Dennis, additional, Rokicki, Jaroslav, additional, Moberget, Torgeir, additional, Maximov, Ivan I., additional, Agartz, Ingrid, additional, Aminoff, Sofie R., additional, Beck, Dani, additional, Barch, Deanna M., additional, Beresniewicz, Justyna, additional, Cervenka, Simon, additional, Fatouros-Bergman, Helena, additional, Craven, Alexander R., additional, Flyckt, Lena, additional, Gurholt, Tiril P., additional, Haukvik, Unn K., additional, Hugdahl, Kenneth, additional, Johnsen, Erik, additional, Jönsson, Erik G., additional, Kolskår, Knut K., additional, Kroken, Rune Andreas, additional, Lagerberg, Trine V., additional, Løberg, Else-Marie, additional, Nordvik, Jan Egil, additional, Sanders, Anne-Marthe, additional, Ulrichsen, Kristine, additional, Andreassen, Ole A., additional, Westlye, Lars T., additional, Farde, L., additional, Flyckt, L., additional, Engberg, G., additional, Erhardt, S., additional, Fatouros-Bergman, H., additional, Cervenka, S., additional, Schwieler, L., additional, Piehl, F., additional, Agartz, I., additional, Collste, K., additional, Victorsson, P., additional, Malmqvist, A., additional, Hedberg, M., additional, Orhan, F., additional, and Sellgren, C., additional
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- 2020
- Full Text
- View/download PDF
8. Elevated cerebrospinal fluid kynurenic acid levels in patients with tick-borne encephalitis
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Holtze, M., Mickiené, A., Atlas, A., Lindquist, L., and Schwieler, L.
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- 2012
- Full Text
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9. Common brain disorders are associated with heritable patterns of apparent aging of the brain
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Kaufmann, T., van der Meer, D., Doan, N. T., Schwarz, E., Lund, M. J., Agartz, I., Alnaes, D., Barch, D. M., Baur-Streubel, R., Bertolino, A., Bettella, F., Beyer, M. K., Boen, E., Borgwardt, S., Brandt, C. L., Buitelaar, J., Celius, E. G., Cervenka, S., Conzelmann, A., Cordova-Palomera, A., Dale, A. M., de Quervain, D. J. F., Carlo, P. D., Djurovic, S., Dorum, E. S., Eisenacher, S., Elvsashagen, T., Espeseth, T., Fatouros-Bergman, H., Flyckt, L., Franke, B., Frei, O., Haatveit, B., Haberg, A. K., Harbo, H. F., Hartman, C. A., Heslenfeld, D., Hoekstra, P. J., Hogestol, E. A., Jernigan, T. L., Jonassen, R., Jonsson, E. G., Farde, L., Engberg, G., Erhardt, S., Schwieler, L., Piehl, F., Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Kirsch, P., Kloszewska, I., Kolskar, K. K., Landro, N. I., Hellard, S. L., Lesch, K. -P., Lovestone, S., Lundervold, A., Lundervold, A. J., Maglanoc, L. A., Malt, U. F., Mecocci, P., Melle, I., Meyer-Lindenberg, A., Moberget, T., Norbom, L. B., Nordvik, J. E., Nyberg, L., Oosterlaan, J., Papalino, M., Papassotiropoulos, A., Pauli, P., Pergola, G., Persson, K., Richard, G., Rokicki, J., Sanders, A. -M., Selbaek, G., Shadrin, A. A., Smeland, O. B., Soininen, H., Sowa, P., Steen, V. M., Tsolaki, M., Ulrichsen, K. M., Vellas, B., Wang, L., Westman, E., Ziegler, G. C., Zink, M., Andreassen, O. A., Westlye, L. T., Le Hellard, S., Di Carlo, P., Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), General Paediatrics, ARD - Amsterdam Reproduction and Development, Pediatric surgery, Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience, and RS: MHeNs - R2 - Mental Health
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0301 basic medicine ,Brain age gap, brain disorders, genetic architecture, pleiotropy ,Male ,Aging ,Schizophrenia/genetics ,LOCI ,Genome-wide association study ,Neuropsychological Tests ,0302 clinical medicine ,80 and over ,Brain age gap ,Aging/genetics ,ALZHEIMERS ,Child ,Aged, 80 and over ,Brain Diseases ,Sex Characteristics ,General Neuroscience ,Mental Disorders ,Brain ,MULTIPLE-SCLEROSIS ,brain disorders ,Middle Aged ,Magnetic Resonance Imaging ,3. Good health ,Schizophrenia ,Child, Preschool ,Female ,Alzheimer's disease ,Neurovetenskaper ,Algorithms ,MRI ,Adult ,Adolescent ,Brain Diseases/diagnostic imaging ,Brain Structure and Function ,Mental Disorders/diagnostic imaging ,Biology ,Article ,03 medical and health sciences ,Young Adult ,AGE ,pleiotropy ,Genetic architecture ,Genetic Pleiotropy ,medicine ,Humans ,Preschool ,Brain disorders ,Aged ,Pleiotropy ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,Brain age gaps ,Multiple sclerosis ,Neurosciences ,Infant ,medicine.disease ,Brain/diagnostic imaging ,genetic architecture ,030104 developmental biology ,Pleiotropy (drugs) ,Neuroscience ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3–96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders. The author list between I.A. and M.Z. is in alphabetic order. The authors were funded by the Research Council of Norway (276082 LifespanHealth (T.K.), 213837 (O.A.A), 223273 NORMENT (O.A.A.), 204966 (L.T.W.), 229129 (O.A.A.), 249795 (L.T.W.), 273345 (L.T.W.) and 283798 SYNSCHIZ (O.A.A.)), the South-Eastern Norway Regional Health Authority (2013-123 (O.A.A.), 2014-097 (L.T.W.), 2015-073 (L.T.W.) and 2016083 (L.T.W.)), Stiftelsen Kristian Gerhard Jebsen (SKGJ-MED-008), the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC Starting Grant, Grant agreement No. 802998 BRAINMINT (L.T.W.)), NVIDIA Corporation GPU Grant (T.K.), and the European Commission 7th Framework Programme (602450, IMAGEMEND (A.M.-L.)).
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- 2019
10. Reproducible grey matter patterns index a multivariate, global alteration of brain structure in schizophrenia and bipolar disorder
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Schwarz, E., Doan, N. T., Pergola, G., Westlye, L. T., Kaufmann, T., Wolfers, T., Brecheisen, R., Quarto, T., Ing, A. J., Di Carlo, P., Gurholt, T. P., Harms, R. L., Noirhomme, Q., Moberget, T., Agartz, I., Andreassen, O. A., Bellani, M., Bertolino, A., Blasi, G., Brambilla, P., Buitelaar, J. K., Cervenka, S., Flyckt, L., Frangou, S., Franke, B., Hall, J., Heslenfeld, D. J., Kirsch, P., Mcintosh, A. M., Nothen, M. M., Papassotiropoulos, A., de Quervain, D. J. -F., Rietschel, M., Schumann, G., Tost, H., Witt, S. H., Zink, M., Meyer-Lindenberg, A., Bettella, F., Brandt, C. L., Clarke, T. -K., Coynel, D., Degenhardt, F., Djurovic, S., Eisenacher, S., Fastenrath, M., Fatouros-Bergman, H., Forstner, A. J., Frank, J., Gambi, F., Gelao, B., Geschwind, L., Di Giannantonio, M., Di Giorgio, A., Hartman, C. A., Heilmann-Heimbach, S., Herms, S., Hoekstra, P. J., Hoffmann, P., Hoogman, M., Jonsson, E. G., Loos, E., Maggioni, E., Oosterlaan, J., Papalino, M., Rampino, A., Romaniuk, L., Selvaggi, P., Sepede, G., Sonderby, I. E., Spalek, K., Sussmann, J. E., Thompson, P. M., Vasquez, A. A., Vogler, C., Whalley, H., Farde, L., Engberg, G., Erhardt, S., Schwieler, L., Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Cognitive Psychology, IBBA, Behavioural Sciences, Elvira Brattico / Principal Investigator, Department of Psychology and Logopedics, Cognitive Brain Research Unit, Faculty of Medicine, University of Helsinki, General Paediatrics, ARD - Amsterdam Reproduction and Development, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Multiscale Imaging of Brain Connectivity, RS: FPN CN 11, Vision, and RS: FPN CN 1
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0301 basic medicine ,Male ,Multivariate statistics ,Bipolar Disorder ,SEGMENTATION ,3124 Neurology and psychiatry ,Machine Learning ,0302 clinical medicine ,DEFICITS ,Gray Matter ,Psychiatry ,RISK ,medicine.diagnostic_test ,220 Statistical Imaging Neuroscience ,LIKELIHOOD ESTIMATION ,Middle Aged ,MRI SCANS ,Magnetic Resonance Imaging ,Justice and Strong Institutions ,3. Good health ,Psychiatry and Mental health ,medicine.anatomical_structure ,bipolar disorders ,Schizophrenia ,Female ,brain structural patterns ,MRI ,Adult ,SDG 16 - Peace ,Adolescent ,Brain Structure and Function ,Grey matter ,Psykiatri ,CLASSIFICATION ,Article ,lcsh:RC321-571 ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Young Adult ,Text mining ,medicine ,Humans ,Bipolar disorder ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Biological Psychiatry ,METAANALYSIS ,schizophrenia ,grey matter alterations ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,business.industry ,1ST-EPISODE ,SDG 16 - Peace, Justice and Strong Institutions ,Magnetic resonance imaging ,medicine.disease ,030104 developmental biology ,Sample size determination ,Attention Deficit Disorder with Hyperactivity ,Case-Control Studies ,VOLUME ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Contains fulltext : 202693.pdf (Publisher’s version ) (Open Access) Schizophrenia is a severe mental disorder characterized by numerous subtle changes in brain structure and function. Machine learning allows exploring the utility of combining structural and functional brain magnetic resonance imaging (MRI) measures for diagnostic application, but this approach has been hampered by sample size limitations and lack of differential diagnostic data. Here, we performed a multi-site machine learning analysis to explore brain structural patterns of T1 MRI data in 2668 individuals with schizophrenia, bipolar disorder or attention-deficit/ hyperactivity disorder, and healthy controls. We found reproducible changes of structural parameters in schizophrenia that yielded a classification accuracy of up to 76% and provided discrimination from ADHD, through it lacked specificity against bipolar disorder. The observed changes largely indexed distributed grey matter alterations that could be represented through a combination of several global brain-structural parameters. This multi-site machine learning study identified a brain-structural signature that could reproducibly differentiate schizophrenia patients from controls, but lacked specificity against bipolar disorder. While this currently limits the clinical utility of the identified signature, the present study highlights that the underlying alterations index substantial global grey matter changes in psychotic disorders, reflecting the biological similarity of these conditions, and provide a roadmap for future exploration of brain structural alterations in psychiatric patients.
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- 2019
11. Reproducible grey matter patterns index a multivariate, global alteration of brain structure in schizophrenia and bipolar disorder
- Author
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Schwarz, Emanuel, Doan, Nhat Trung, Pergola, Giulio, Westlye, Lars T., Kaufmann, Tobias, Wolfers, Thomas, Brecheisen, Ralph, Quarto, Tiziana, Ing, Alex J., Di Carlo, Pasquale, Gurholt, Tiril P., Harms, Robbert L., Noirhomme, Quentin, Moberget, Torgeir, Agartz, Ingrid, Andreassen, Ole A., Bellani, Marcella, Bertolino, Alessandro, Blasi, Giuseppe, Brambilla, Paolo, Buitelaar, Jan K., Cervenka, Simon, Flyckt, Lena, Frangou, Sophia, Franke, Barbara, Hall, Jeremy, Heslenfeld, Dirk J., Kirsch, Peter, McIntosh, Andrew M., Noethen, Markus M., Papassotiropoulos, Andreas, de Quervain, Dominique J-F, Rietschel, Marcella, Schumann, Gunter, Tost, Heike, Witt, Stephanie H., Zink, Mathias, Meyer-Lindenberg, Andreas, Bettella, Francesco, Brandt, Christine L., Clarke, Toni-Kim, Coynel, David, Degenhardt, Franziska, Djurovic, Srdjan, Eisenacher, Sarah, Fastenrath, Matthias, Fatouros-Bergman, Helena, Forstner, Andreas J., Frank, Josef, Gambi, Francesco, Gelao, Barbara, Geschwind, Leo, Di Giannantonio, Massimo, Di Giorgio, Annabella, Hartman, Catharina A., Heilmann-Heimbach, Stefanie, Herms, Stefan, Hoekstra, Pieter J., Hoffmann, Per, Hoogman, Martine, Jonsson, Erik G., Loos, Eva, Maggioni, Eleonora, Oosterlaan, Jaap, Papalino, Marco, Rampino, Antonio, Romaniuk, Liana, Selvaggi, Pierluigi, Sepede, Gianna, Sonderby, Ida E., Spalek, Klara, Sussmann, Jessika E., Thompson, Paul M., Vasquez, Alejandro Arias, Vogler, Christian, Whalley, Heather, Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Schwarz, Emanuel, Doan, Nhat Trung, Pergola, Giulio, Westlye, Lars T., Kaufmann, Tobias, Wolfers, Thomas, Brecheisen, Ralph, Quarto, Tiziana, Ing, Alex J., Di Carlo, Pasquale, Gurholt, Tiril P., Harms, Robbert L., Noirhomme, Quentin, Moberget, Torgeir, Agartz, Ingrid, Andreassen, Ole A., Bellani, Marcella, Bertolino, Alessandro, Blasi, Giuseppe, Brambilla, Paolo, Buitelaar, Jan K., Cervenka, Simon, Flyckt, Lena, Frangou, Sophia, Franke, Barbara, Hall, Jeremy, Heslenfeld, Dirk J., Kirsch, Peter, McIntosh, Andrew M., Noethen, Markus M., Papassotiropoulos, Andreas, de Quervain, Dominique J-F, Rietschel, Marcella, Schumann, Gunter, Tost, Heike, Witt, Stephanie H., Zink, Mathias, Meyer-Lindenberg, Andreas, Bettella, Francesco, Brandt, Christine L., Clarke, Toni-Kim, Coynel, David, Degenhardt, Franziska, Djurovic, Srdjan, Eisenacher, Sarah, Fastenrath, Matthias, Fatouros-Bergman, Helena, Forstner, Andreas J., Frank, Josef, Gambi, Francesco, Gelao, Barbara, Geschwind, Leo, Di Giannantonio, Massimo, Di Giorgio, Annabella, Hartman, Catharina A., Heilmann-Heimbach, Stefanie, Herms, Stefan, Hoekstra, Pieter J., Hoffmann, Per, Hoogman, Martine, Jonsson, Erik G., Loos, Eva, Maggioni, Eleonora, Oosterlaan, Jaap, Papalino, Marco, Rampino, Antonio, Romaniuk, Liana, Selvaggi, Pierluigi, Sepede, Gianna, Sonderby, Ida E., Spalek, Klara, Sussmann, Jessika E., Thompson, Paul M., Vasquez, Alejandro Arias, Vogler, Christian, Whalley, Heather, Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., and Orhan, F.
- Abstract
Schizophrenia is a severe mental disorder characterized by numerous subtle changes in brain structure and function. Machine learning allows exploring the utility of combining structural and functional brain magnetic resonance imaging (MRI) measures for diagnostic application, but this approach has been hampered by sample size limitations and lack of differential diagnostic data. Here, we performed a multi-site machine learning analysis to explore brain structural patterns of T1 MRI data in 2668 individuals with schizophrenia, bipolar disorder or attention-deficit/hyperactivity disorder, and healthy controls. We found reproducible changes of structural parameters in schizophrenia that yielded a classification accuracy of up to 76% and provided discrimination from ADHD, through it lacked specificity against bipolar disorder. The observed changes largely indexed distributed grey matter alterations that could be represented through a combination of several global brain-structural parameters. This multi-site machine learning study identified a brain-structural signature that could reproducibly differentiate schizophrenia patients from controls, but lacked specificity against bipolar disorder. While this currently limits the clinical utility of the identified signature, the present study highlights that the underlying alterations index substantial global grey matter changes in psychotic disorders, reflecting the biological similarity of these conditions, and provide a roadmap for future exploration of brain structural alterations in psychiatric patients.
- Published
- 2019
- Full Text
- View/download PDF
12. Reply to: New Meta- and Mega-analyses of Magnetic Resonance Imaging Findings in Schizophrenia: Do They Really Increase Our Knowledge About the Nature of the Disease Process?
- Author
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van Erp, TGM, Walton, E, Hibar, DP, Schmaal, L, Jiang, W, Glahn, DC, Pearlson, GD, Yao, N, Fukunaga, M, Hashimoto, R, Okada, N, Yamamori, H, Clark, VP, Mueller, BA, de Zwarte, SMC, Ophoff, RA, van Haren, NEM, Andreassen, OA, Gurholt, TP, Gruber, O, Kraemer, B, Richter, A, Calhoun, VD, Crespo-Facorro, B, Roiz-Santiañez, R, Tordesillas-Gutiérrez, D, Loughland, C, Catts, S, Fullerton, JM, Green, MJ, Henskens, F, Jablensky, A, Mowry, BJ, Pantelis, C, Quidé, Y, Schall, U, Scott, RJ, Cairns, MJ, Seal, M, Tooney, PA, Rasser, PE, Cooper, G, Shannon Weickert, C, Weickert, TW, Hong, E, Kochunov, P, Gur, RE, Gur, RC, Ford, JM, Macciardi, F, Mathalon, DH, Potkin, SG, Preda, A, Fan, F, Ehrlich, S, King, MD, De Haan, L, Veltman, DJ, Assogna, F, Banaj, N, de Rossi, P, Iorio, M, Piras, F, Spalletta, G, Pomarol-Clotet, E, Kelly, S, Ciufolini, S, Radua, J, Murray, R, Marques, TR, Simmons, A, Borgwardt, S, Schönborn-Harrisberger, F, Riecher-Rössler, A, Smieskova, R, Alpert, KI, Bertolino, A, Bonvino, A, Di Giorgio, A, Neilson, E, Mayer, AR, Yun, JY, Cannon, DM, Lebedeva, I, Tomyshev, AS, Akhadov, T, Kaleda, V, Fatouros-Bergman, H, Flyckt, L, Farde, L, Cervenka, S, Agartz, I, Collste, K, Victorsson, P, Engberg, G, Erhardt, S, Schwieler, L, Malmqvist, A, Hedberg, M, Orhan, F, van Erp, TGM, Walton, E, Hibar, DP, Schmaal, L, Jiang, W, Glahn, DC, Pearlson, GD, Yao, N, Fukunaga, M, Hashimoto, R, Okada, N, Yamamori, H, Clark, VP, Mueller, BA, de Zwarte, SMC, Ophoff, RA, van Haren, NEM, Andreassen, OA, Gurholt, TP, Gruber, O, Kraemer, B, Richter, A, Calhoun, VD, Crespo-Facorro, B, Roiz-Santiañez, R, Tordesillas-Gutiérrez, D, Loughland, C, Catts, S, Fullerton, JM, Green, MJ, Henskens, F, Jablensky, A, Mowry, BJ, Pantelis, C, Quidé, Y, Schall, U, Scott, RJ, Cairns, MJ, Seal, M, Tooney, PA, Rasser, PE, Cooper, G, Shannon Weickert, C, Weickert, TW, Hong, E, Kochunov, P, Gur, RE, Gur, RC, Ford, JM, Macciardi, F, Mathalon, DH, Potkin, SG, Preda, A, Fan, F, Ehrlich, S, King, MD, De Haan, L, Veltman, DJ, Assogna, F, Banaj, N, de Rossi, P, Iorio, M, Piras, F, Spalletta, G, Pomarol-Clotet, E, Kelly, S, Ciufolini, S, Radua, J, Murray, R, Marques, TR, Simmons, A, Borgwardt, S, Schönborn-Harrisberger, F, Riecher-Rössler, A, Smieskova, R, Alpert, KI, Bertolino, A, Bonvino, A, Di Giorgio, A, Neilson, E, Mayer, AR, Yun, JY, Cannon, DM, Lebedeva, I, Tomyshev, AS, Akhadov, T, Kaleda, V, Fatouros-Bergman, H, Flyckt, L, Farde, L, Cervenka, S, Agartz, I, Collste, K, Victorsson, P, Engberg, G, Erhardt, S, Schwieler, L, Malmqvist, A, Hedberg, M, and Orhan, F
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- 2019
13. Increased peripheral levels of TARC/CCL17 in first episode psychosis patients
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Malmqvist, Anna, Schwieler, Lilly, Orhan, Funda, Fatouros-Bergman, Helena, Bauer, Markus, Flyckt, Lena, Cervenka, Simon, Engberg, Goran, Piehl, Fredrik, Erhardt, Sophie, Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Malmqvist, Anna, Schwieler, Lilly, Orhan, Funda, Fatouros-Bergman, Helena, Bauer, Markus, Flyckt, Lena, Cervenka, Simon, Engberg, Goran, Piehl, Fredrik, Erhardt, Sophie, Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I, Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., and Orhan, F.
- Abstract
Background: Evidence for a link between the pathophysiology of schizophrenia and the immune system is mounting. Altered levels of chemokines in plasma have previously been reported in patients with schizophrenia under antipsychotic medication. Here we aimed to study both peripheral and central chemokine levels in drugnaive or short-time medicated first episode psychosis (FEP) patients. Method: We analyzed nine chemokines in plasma and CSF from 41 FEP patients and 22 healthy controls using electrochemiluminescence assay. Results: In plasma four chemokines; TARC/CCL17, eotaxin/CCL11, MDC/CCL22, IP-10/CXCL10 and in CSF one chemokine; IP-10/CXCL10 showed reliable detection in N50% of the cases. FEP patients displayed increased levels of TARC/CCL17 in plasma compared to healthy controls, 89.6 (IQR 66.2-125.8) pg/mL compared to 48.6 (IQR 28.0-71.7) pg/mL (p = 0.001). The difference was not attributed to confounding factors. Plasma TARC/CCL17 was not associated with PANSS, CGI or GAF scores, neither with cognitive functions. The chemokines eotaxin/CCL11, MDC/CCL22, IP-10/CXCL10 in plasma and IP-10/CXCL10 in CSF did not differ between FEP patients and controls. Conclusion: In line with a previous study showing that chronic patients with schizophrenia display increased plasma TARC/CCL17 levels, we here found an elevation in FEP patients suggesting a role of TARC/CCL17 in early stages of schizophrenia. The exactmechanism of this involvement is still unknown and future longitudinal studies as well as studies of central and peripheral chemokine levels would be of great interest. (C) 2018 Elsevier B.V. All rights reserved.
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- 2019
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14. The anaesthetic agent propofol interacts with GABAB-receptors: an electrophysiological study in rat
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Schwieler, L, Delbro, S D., Engberg, G, and Erhardt, S
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- 2003
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15. Cerebrospinal fluid levels of sphingolipids associate with disease severity in first episode psychosis patients
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Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I., Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Checa, Antonio, Malmqvist, Anna, Flyckt, Lena, Schwieler, Lilly, Samuelsson, Martin, Skogh, Elisabeth, Cervenka, Simon, Dahl, Marja-Liisa, Piehl, Fredrik, Erhardt, Sophie, and Wheelock, Craig E.
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- 2018
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16. Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium
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Erp, T.G.M. (Theo G.) van, Walton, E. (Esther), Hibar, D.P. (Derrek P.), Schmaal, L. (Lianne), Jiang, W. (Wenhao), Glahn, D.C. (David), Pearlson, G. (Godfrey), Yao, N. (Nailin), Fukunaga, M. (Masaki), Hashimoto, R. (Ryota), Okada, N. (Naohiro), Yamamori, H. (Hidenaga), Bustillo, J., Clark, V.P., Agartz, I. (Ingrid), Mueller, B.A. (Bryon ), Cahn, W. (Wiepke), de Zwarte, S.M.C. (Sonja M.C.), Hulshoff Pol, H.E. (Hilleke), Kahn, R. (René), Ophoff, R.A. (Roel), van Haren, N.E.M. (Neeltje E.M.), Andreassen, O.A. (Ole), Dale, A.M. (Anders), Doan, N.T. (Nhat Trung), Gurholt, T.P. (Tiril P.), Hartberg, C.B. (Cecilie B.), Haukvik, U.K. (Unn), Jørgensen, K.N. (Kjetil N.), Lagerberg, T.V. (Trine V.), Melle, I. (Ingrid), Westlye, L.T. (Lars), Gruber, O. (Oliver), Kraemer, B. (Bernd), Richter, A. (Anja), Zilles, D. (David), Calhoun, V.D. (Vince), Crespo-Facorro, B. (Benedicto), Roiz-Santiañez, R. (Roberto), Tordesillas-Gutierrez, D. (Diana), Loughland, C.M. (Carmel), Carr, V.J. (Vaughan J.), Catts, S.V. (Stanley), Cropley, V.L. (Vanessa L.), Fullerton, J.M. (Janice M.), Green, M.J. (Melissa J.), Henskens, F.A. (Frans), Jablensky, A. (Assen), Lenroot, R.K. (Rhoshel), Mowry, B.J. (Bryan J), Michie, P.T. (Patricia), Pantelis, C. (Christos), Quidé, Y. (Yann), Schall, J.D. (Jeffrey), Scott, R.J. (Rodney J.), Cairns, M.J. (Murray J.), Seal, M. (Marc), Tooney, P.A. (Paul A.), Rasser, P.E. (Paul E.), Cooper, G. (Gavin), Shannon Weickert, C. (Cynthia), Weickert, T.W. (Thomas W.), Morris, D.W. (Derek W), Hong, E. (Elliot), Kochunov, P. (Peter), Beard, L.M. (Lauren M.), Gur, R.E. (Raquel), Gur, R.C. (Ruben C.), Satterthwaite, T.D. (Theodore), Wolf, D.H. (Daniel H.), Belger, A. (Aysenil), Brown, G.G. (Gregory G.), Ford, J.M. (Judith M.), Macciardi, F. (Fabio), Mathalon, D.H. (Daniel H.), O'Leary, D.S. (Daniel S.), Potkin, S.G. (Steven), Preda, A. (Adrian), Voyvodic, J. (James), Lim, K.O. (Kelvin), McEwen, S. (Sarah), Yang, F. (Fude), Tan, Y. (Yunlong), Tan, S. (Shuping), Wang, Z. (Zhiren), Fan, F. (Fengmei), Chen, J. (Jingxu), Xiang, H. (Hong), Tang, S. (Shiyou), Guo, H. (Hua), Wan, P. (Ping), Wei, D. (Dong), Bockholt, H.J., Ehrlich, S.M. (Stefan), Wolthusen, R.P.F. (Rick P.F.), King, M.D. (Margaret D.), Shoemaker, J.M. (Jody M.), Sponheim, S.R. (Scott), Haan, L. (Lieuwe) de, Koenders, L. (Laura), Machielsen, M.W.J. (Marise), Amelsvoort, T.A.M.J. (Therese) van, Veltman, D.J. (Dick), Assogna, F. (Francesca), Banaj, N. (Nerisa), de Rossi, P. (Pietro), Iorio, M. (Mariangela), Piras, F. (Fabrizio), Spalletta, G. (Gianfranco), McKenna, P.J. (Peter J.), Pomarol-Clotet, E. (Edith), Salvador, R. (Raymond), Corvin, A. (Aiden), Donohoe, D.J. (Dennis), Kelly, S. (Sinead), Whelan, C.D. (Christopher), Dickie, E.W. (Erin W.), Rotenberg, D. (David), Voineskos, A.N. (Aristotle N.), Ciufolini, S. (Simone), Radua, J. (Joaquim), Dazzan, P. (Paola), Murray, R. (Robin), Reis Marques, T. (Tiago), Simmons, A. (Andrew), Borgwardt, S. (Stefan), Egloff, L. (Laura), Harrisberger, F. (Fabienne), Riecher-Rössler, A. (Anita), Smieskova, R. (Renata), Alpert, K. (Kathryn), Wang, L. (Lei), Jönsson, E.G. (Erik), Koops, S. (Sanne), Sommer, I.E.C. (Iris E.C.), Bertolino, A. (Alessandro), Bonvino, A. (Aurora), Di Giorgio, A. (Annabella), Neilson, E. (Emma), Mayer, A.R. (Andrew R.), Stephen, J.M. (Julia M.), Kwon, J.S. (Jun Soo), Yun, J.-Y. (Je-Yeon), Cannon, D.M. (Dara), McDonald, C. (Colm), Lebedeva, I. (Irina), Tomyshev, A.S. (Alexander S.), Akhadov, T. (Tolibjohn), Kaleda, V. (Vasily), Fatouros-Bergman, H. (Helena), Flyckt, L. (Lena), Farde, L. (Lars), Engberg, G. (Göran), Erhardt, S. (Sophie), Cervenka, S. (Simon), Schwieler, L. (Lilly), Piehl, F. (Fredrik), Collste, K. (Karin), Victorsson, P. (Pauliina), Malmqvist, A. (Anna), Hedberg, M. (Mikael), Orhan, F. (Funda), Busatto, G.F. (Geraldo F.), Rosa, P.G.P. (Pedro G.P.), Serpa, M.H. (Mauricio H.), Zanetti, M.V. (Marcus V.), Hoschl, C. (Cyril), Skoch, A. (Antonin), Spaniel, F. (Filip), Tomecek, D. (David), Hagenaars, S. (Saskia), McIntosh, A.M. (Andrew), Whalley, H.C. (Heather C.), Lawrie, S. (Stephen), Knöchel, C. (Christian), Oertel-Knöchel, V. (Viola), Stäblein, M. (Michael), Howells, F.M. (Fleur M.), Stein, D.J. (Dan), Temmingh, H.S. (Henk S.), Uhlmann, A. (Anne), Lopez-Jaramillo, C. (Carlos), Dima, D. (Danai), McMahon, A. (Agnes), Faskowitz, J.I. (Joshua I.), Gutman, B.A. (Boris A.), Jahanshad, N. (Neda), Thompson, P.M. (Paul), Turner, J. (Jessica), Erp, T.G.M. (Theo G.) van, Walton, E. (Esther), Hibar, D.P. (Derrek P.), Schmaal, L. (Lianne), Jiang, W. (Wenhao), Glahn, D.C. (David), Pearlson, G. (Godfrey), Yao, N. (Nailin), Fukunaga, M. (Masaki), Hashimoto, R. (Ryota), Okada, N. (Naohiro), Yamamori, H. (Hidenaga), Bustillo, J., Clark, V.P., Agartz, I. (Ingrid), Mueller, B.A. (Bryon ), Cahn, W. (Wiepke), de Zwarte, S.M.C. (Sonja M.C.), Hulshoff Pol, H.E. (Hilleke), Kahn, R. (René), Ophoff, R.A. (Roel), van Haren, N.E.M. (Neeltje E.M.), Andreassen, O.A. (Ole), Dale, A.M. (Anders), Doan, N.T. (Nhat Trung), Gurholt, T.P. (Tiril P.), Hartberg, C.B. (Cecilie B.), Haukvik, U.K. (Unn), Jørgensen, K.N. (Kjetil N.), Lagerberg, T.V. (Trine V.), Melle, I. (Ingrid), Westlye, L.T. (Lars), Gruber, O. (Oliver), Kraemer, B. (Bernd), Richter, A. (Anja), Zilles, D. (David), Calhoun, V.D. (Vince), Crespo-Facorro, B. (Benedicto), Roiz-Santiañez, R. (Roberto), Tordesillas-Gutierrez, D. (Diana), Loughland, C.M. (Carmel), Carr, V.J. (Vaughan J.), Catts, S.V. (Stanley), Cropley, V.L. (Vanessa L.), Fullerton, J.M. (Janice M.), Green, M.J. (Melissa J.), Henskens, F.A. (Frans), Jablensky, A. (Assen), Lenroot, R.K. (Rhoshel), Mowry, B.J. (Bryan J), Michie, P.T. (Patricia), Pantelis, C. (Christos), Quidé, Y. (Yann), Schall, J.D. (Jeffrey), Scott, R.J. (Rodney J.), Cairns, M.J. (Murray J.), Seal, M. (Marc), Tooney, P.A. (Paul A.), Rasser, P.E. (Paul E.), Cooper, G. (Gavin), Shannon Weickert, C. (Cynthia), Weickert, T.W. (Thomas W.), Morris, D.W. (Derek W), Hong, E. (Elliot), Kochunov, P. (Peter), Beard, L.M. (Lauren M.), Gur, R.E. (Raquel), Gur, R.C. (Ruben C.), Satterthwaite, T.D. (Theodore), Wolf, D.H. (Daniel H.), Belger, A. (Aysenil), Brown, G.G. (Gregory G.), Ford, J.M. (Judith M.), Macciardi, F. (Fabio), Mathalon, D.H. (Daniel H.), O'Leary, D.S. (Daniel S.), Potkin, S.G. (Steven), Preda, A. (Adrian), Voyvodic, J. (James), Lim, K.O. (Kelvin), McEwen, S. (Sarah), Yang, F. (Fude), Tan, Y. (Yunlong), Tan, S. (Shuping), Wang, Z. (Zhiren), Fan, F. (Fengmei), Chen, J. (Jingxu), Xiang, H. (Hong), Tang, S. (Shiyou), Guo, H. (Hua), Wan, P. (Ping), Wei, D. (Dong), Bockholt, H.J., Ehrlich, S.M. (Stefan), Wolthusen, R.P.F. (Rick P.F.), King, M.D. (Margaret D.), Shoemaker, J.M. (Jody M.), Sponheim, S.R. (Scott), Haan, L. (Lieuwe) de, Koenders, L. (Laura), Machielsen, M.W.J. (Marise), Amelsvoort, T.A.M.J. (Therese) van, Veltman, D.J. (Dick), Assogna, F. (Francesca), Banaj, N. (Nerisa), de Rossi, P. (Pietro), Iorio, M. (Mariangela), Piras, F. (Fabrizio), Spalletta, G. (Gianfranco), McKenna, P.J. (Peter J.), Pomarol-Clotet, E. (Edith), Salvador, R. (Raymond), Corvin, A. (Aiden), Donohoe, D.J. (Dennis), Kelly, S. (Sinead), Whelan, C.D. (Christopher), Dickie, E.W. (Erin W.), Rotenberg, D. (David), Voineskos, A.N. (Aristotle N.), Ciufolini, S. (Simone), Radua, J. (Joaquim), Dazzan, P. (Paola), Murray, R. (Robin), Reis Marques, T. (Tiago), Simmons, A. (Andrew), Borgwardt, S. (Stefan), Egloff, L. (Laura), Harrisberger, F. (Fabienne), Riecher-Rössler, A. (Anita), Smieskova, R. (Renata), Alpert, K. (Kathryn), Wang, L. (Lei), Jönsson, E.G. (Erik), Koops, S. (Sanne), Sommer, I.E.C. (Iris E.C.), Bertolino, A. (Alessandro), Bonvino, A. (Aurora), Di Giorgio, A. (Annabella), Neilson, E. (Emma), Mayer, A.R. (Andrew R.), Stephen, J.M. (Julia M.), Kwon, J.S. (Jun Soo), Yun, J.-Y. (Je-Yeon), Cannon, D.M. (Dara), McDonald, C. (Colm), Lebedeva, I. (Irina), Tomyshev, A.S. (Alexander S.), Akhadov, T. (Tolibjohn), Kaleda, V. (Vasily), Fatouros-Bergman, H. (Helena), Flyckt, L. (Lena), Farde, L. (Lars), Engberg, G. (Göran), Erhardt, S. (Sophie), Cervenka, S. (Simon), Schwieler, L. (Lilly), Piehl, F. (Fredrik), Collste, K. (Karin), Victorsson, P. (Pauliina), Malmqvist, A. (Anna), Hedberg, M. (Mikael), Orhan, F. (Funda), Busatto, G.F. (Geraldo F.), Rosa, P.G.P. (Pedro G.P.), Serpa, M.H. (Mauricio H.), Zanetti, M.V. (Marcus V.), Hoschl, C. (Cyril), Skoch, A. (Antonin), Spaniel, F. (Filip), Tomecek, D. (David), Hagenaars, S. (Saskia), McIntosh, A.M. (Andrew), Whalley, H.C. (Heather C.), Lawrie, S. (Stephen), Knöchel, C. (Christian), Oertel-Knöchel, V. (Viola), Stäblein, M. (Michael), Howells, F.M. (Fleur M.), Stein, D.J. (Dan), Temmingh, H.S. (Henk S.), Uhlmann, A. (Anne), Lopez-Jaramillo, C. (Carlos), Dima, D. (Danai), McMahon, A. (Agnes), Faskowitz, J.I. (Joshua I.), Gutman, B.A. (Boris A.), Jahanshad, N. (Neda), Thompson, P.M. (Paul), and Turner, J. (Jessica)
- Abstract
Background: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This
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- 2018
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17. Increased number of monocytes and plasma levels of MCP-1 and YKL-40 in first-episode psychosis
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Orhan, F., Schwieler, L., Fatouros-Bergman, H., Malmqvist, A., Cervenka, Simon, Collste, K., Flyckt, L., Farde, L., Sellgren, C. M., Piehl, F., Engberg, G., Erhardt, S., Orhan, F., Schwieler, L., Fatouros-Bergman, H., Malmqvist, A., Cervenka, Simon, Collste, K., Flyckt, L., Farde, L., Sellgren, C. M., Piehl, F., Engberg, G., and Erhardt, S.
- Abstract
ObjectiveMethodAccumulating evidence implicates immune activation in the development of schizophrenia. Here, monocyte numbers, monocyte chemoattractant protein-1 (MCP-1) and chitinase-3-like protein 1 (YKL-40) were investigated in plasma and cerebrospinal fluid (CSF) in first-episode psychosis (FEP) patients. CSF and blood were sampled from 42 first-episode psychosis (FEP) patients and 22 healthy controls. The levels of YKL-40 and MCP-1 were measured using electrochemiluminescence assay, and blood monocytes were counted using an XN-9000-hematology analyzer. ResultsConclusionWe found higher plasma levels of MCP-1 and YKL-40 in FEP patients compared with healthy controls, a condition that was unrelated to antipsychotic and/or anxiolytic medication. This was combined with an increased number of blood monocytes and a borderline significant increase in YKL-40 levels in the CSF of tobacco-free FEP patients. Plasma or CSF chemokines or blood monocytes did not correlate with the severity of symptoms or the level of functioning. These data demonstrate activation of monocytes in FEP and strengthens the idea of an immune dysfunction of psychotic disorders. Further studies are required to perceive a role of YKL-40 and MCP-1 in the initiation and progression of schizophrenia.
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- 2018
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18. Positive symptoms associate with cortical thinning in the superior temporal gyrus via the enigma schizophrenia consortium
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Walton, E., Hibar, D. P., van Erp, T. G M, Potkin, S. G., Roiz-Santiañez, R., Crespo-Facorro, B., Suarez-Pinilla, P., Van Haren, N. E M, de Zwarte, S. M C, Kahn, R. S., Cahn, W., Doan, N. T., Jørgensen, K. N., Gurholt, T. P., Agartz, I., Andreassen, O. A., Westlye, L. T., Melle, I., Berg, A. O., Mørch-Johnsen, L., Færden, A., Flyckt, L., Fatouros-Bergman, H., Jönsson, E. G., Hashimoto, R., Yamamori, H., Fukunaga, M., Preda, A., De Rossi, P., Piras, F., Banaj, N., Ciullo, V., Spalletta, G., Gur, R. E., Gur, R. C., Wolf, D. H., Satterthwaite, T. D., Beard, L. M., Sommer, I. E., Koops, S., Gruber, O., Richter, A., Krämer, B., Kelly, S., Donohoe, G., McDonald, C., Cannon, D. M., Corvin, A., Gill, M., Di Giorgio, A., Bertolino, A., Lawrie, S., Nickson, T., Whalley, H. C., Neilson, E., Calhoun, V. D., Thompson, P. M., Turner, J. A., Ehrlich, S., Farde, L., Engberg, G., Erhardt, S., Cervenka, S., Schwieler, L., Piehl, F., Ikonen, P., Collste, K., Orhan, F., Malmqvist, A., and Hedberg, M.
- Subjects
Male ,genetic structures ,Planum temporale ,FreeSurfer ,Audiology ,Brain mapping ,Superior temporal gyrus ,0302 clinical medicine ,enigma ,Prospective Studies ,psychosis ,bipolar disorder ,Brain Mapping ,Positive and Negative Syndrome Scale ,positive and negative syndrome scale ,ENIGMA ,Magnetic Resonance Imaging ,Temporal Lobe ,Multicenter Study ,Psychiatry and Mental health ,superior temporal gyrus ,Schizophrenia ,cerebral-cortex ,Female ,Schizophrenic Psychology ,auditory verbal hallucinations ,Psychology ,comprehension ,MRI ,freesurfer ,metaanalysis ,Adult ,medicine.medical_specialty ,Psychosis ,cortical thickness ,positive symptoms ,scale for the assessment of positive symptoms ,schizophrenia ,Humans ,Psychiatric Status Rating Scales ,Psychiatry and Mental Health ,1st-episode schizophrenia ,behavioral disciplines and activities ,Article ,Temporal lobe ,03 medical and health sciences ,Journal Article ,medicine ,Bipolar disorder ,Psychiatry ,mri ,medicine.disease ,thickness ,030227 psychiatry ,planum temporale ,1st episode schizophrenia ,030217 neurology & neurosurgery ,Meta-Analysis - Abstract
OBJECTIVE: Based on the role of the superior temporal gyrus (STG) in auditory processing, language comprehension and self-monitoring, this study aimed to investigate the relationship between STG cortical thickness and positive symptom severity in schizophrenia.METHOD: This prospective meta-analysis includes data from 1987 individuals with schizophrenia collected at seventeen centres around the world that contribute to the ENIGMA Schizophrenia Working Group. STG thickness measures were extracted from T1-weighted brain scans using FreeSurfer. The study performed a meta-analysis of effect sizes across sites generated by a model predicting left or right STG thickness with a positive symptom severity score (harmonized SAPS or PANSS-positive scores), while controlling for age, sex and site. Secondary models investigated relationships between antipsychotic medication, duration of illness, overall illness severity, handedness and STG thickness.RESULTS: Positive symptom severity was negatively related to STG thickness in both hemispheres (left: βstd = -0.052; P = 0.021; right: βstd = -0.073; P = 0.001) when statistically controlling for age, sex and site. This effect remained stable in models including duration of illness, antipsychotic medication or handedness.CONCLUSION: Our findings further underline the important role of the STG in hallmark symptoms in schizophrenia. These findings can assist in advancing insight into symptom-relevant pathophysiological mechanisms in schizophrenia.
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- 2017
19. Lower levels of the glial cell marker TSPO in drug-naive first-episode psychosis patients as measured using PET and [C-11]PBR28
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Anton Forsberg, Ingrid Agartz, Lars Farde, Christer Halldin, A Malmqvist, Nahid Amini, Schwieler L, K. Collste, Pauliina Ikonen Victorsson, Lena Flyckt, Simon Cervenka, Fredrik Piehl, Funda Orhan, Martin Schain, Göran Engberg, Hedberg M, Helena Fatouros-Bergman, Sophie Erhardt, Shahin Aeinehband, and Pontus Plavén-Sigray
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medicine.medical_specialty ,Psychosis ,Neurologi ,medicine.medical_treatment ,Psykiatri ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Internal medicine ,medicine ,Translocator protein ,Radioligand ,Antipsychotic ,Molecular Biology ,Volume of distribution ,Psychiatry ,biology ,Neurosciences ,medicine.disease ,Radioligand Assay ,030227 psychiatry ,Psychiatry and Mental health ,Drug-naïve ,Endocrinology ,Neurology ,Schizophrenia ,biology.protein ,Psychology ,Neuroscience ,030217 neurology & neurosurgery ,Neurovetenskaper ,medicine.drug - Abstract
Several lines of evidence are indicative of a role for immune activation in the pathophysiology of schizophrenia. Nevertheless, studies using positron emission tomography (PET) and radioligands for the translocator protein (TSPO), a marker for glial activation, have yielded inconsistent results. Whereas early studies using a radioligand with low signal-to-noise in small samples showed increases in patients, more recent studies with improved methodology have shown no differences or trend-level decreases. Importantly, all patients investigated thus far have been on antipsychotic medication, and as these compounds may dampen immune cell activity, this factor limits the conclusions that can be drawn. Here, we examined 16 drug-naive, first-episode psychosis patients and 16 healthy controls using PET and the TSPO radioligand [C-11]PBR28. Gray matter (GM) volume of distribution (V-T) derived from a two-tissue compartmental analysis with arterial input function was the main outcome measure. Statistical analyses were performed controlling for both TSPO genotype, which is known to affect [C-11]PBR28 binding, and gender. There was a significant reduction of [C-11]PBR28 V-T in patients compared with healthy controls in GM as well as in secondary regions of interest. No correlation was observed between GM V-T and clinical or cognitive measures after correction for multiple comparisons. The observed decrease in TSPO binding suggests reduced numbers or altered function of immune cells in brain in early-stage schizophrenia.
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- 2017
20. Cerebrospinal fluid levels of sphingolipids associate with disease severity in first episode psychosis patients
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Checa, Antonio, primary, Malmqvist, Anna, additional, Flyckt, Lena, additional, Schwieler, Lilly, additional, Samuelsson, Martin, additional, Skogh, Elisabeth, additional, Cervenka, Simon, additional, Dahl, Marja-Liisa, additional, Piehl, Fredrik, additional, Erhardt, Sophie, additional, Wheelock, Craig E., additional, Farde, L., additional, Flyckt, L., additional, Engberg, G., additional, Erhardt, S., additional, Fatouros-Bergman, H., additional, Cervenka, S., additional, Schwieler, L., additional, Piehl, F., additional, Agartz, I., additional, Collste, K., additional, Victorsson, P., additional, Malmqvist, A., additional, Hedberg, M., additional, and Orhan, F., additional
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- 2018
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21. Positive symptoms associate with cortical thinning in the superior temporal gyrus via the ENIGMA Schizophrenia consortium
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Onderzoeksgroep 4, Brain, Onderzoeksgroep 11, Affectieve & Psychotische Med., Curr. Onderwijs Huisartsgeneeskunde, Affectieve & Psychotisch Ond., Risico & Preventie Ond., Walton, E., Hibar, D. P., van Erp, T. G M, Potkin, S. G., Roiz-Santiañez, R., Crespo-Facorro, B., Suarez-Pinilla, P., Van Haren, N. E M, de Zwarte, S. M C, Kahn, R. S., Cahn, W., Doan, N. T., Jørgensen, K. N., Gurholt, T. P., Agartz, I., Andreassen, O. A., Westlye, L. T., Melle, I., Berg, A. O., Mørch-Johnsen, L., Færden, A., Flyckt, L., Fatouros-Bergman, H., Jönsson, E. G., Hashimoto, R., Yamamori, H., Fukunaga, M., Preda, A., De Rossi, P., Piras, F., Banaj, N., Ciullo, V., Spalletta, G., Gur, R. E., Gur, R. C., Wolf, D. H., Satterthwaite, T. D., Beard, L. M., Sommer, I. E., Koops, S., Gruber, O., Richter, A., Krämer, B., Kelly, S., Donohoe, G., McDonald, C., Cannon, D. M., Corvin, A., Gill, M., Di Giorgio, A., Bertolino, A., Lawrie, S., Nickson, T., Whalley, H. C., Neilson, E., Calhoun, V. D., Thompson, P. M., Turner, J. A., Ehrlich, S., Farde, L., Engberg, G., Erhardt, S., Cervenka, S., Schwieler, L., Piehl, F., Ikonen, P., Collste, K., Orhan, F., Malmqvist, A., Hedberg, M., Onderzoeksgroep 4, Brain, Onderzoeksgroep 11, Affectieve & Psychotische Med., Curr. Onderwijs Huisartsgeneeskunde, Affectieve & Psychotisch Ond., Risico & Preventie Ond., Walton, E., Hibar, D. P., van Erp, T. G M, Potkin, S. G., Roiz-Santiañez, R., Crespo-Facorro, B., Suarez-Pinilla, P., Van Haren, N. E M, de Zwarte, S. M C, Kahn, R. S., Cahn, W., Doan, N. T., Jørgensen, K. N., Gurholt, T. P., Agartz, I., Andreassen, O. A., Westlye, L. T., Melle, I., Berg, A. O., Mørch-Johnsen, L., Færden, A., Flyckt, L., Fatouros-Bergman, H., Jönsson, E. G., Hashimoto, R., Yamamori, H., Fukunaga, M., Preda, A., De Rossi, P., Piras, F., Banaj, N., Ciullo, V., Spalletta, G., Gur, R. E., Gur, R. C., Wolf, D. H., Satterthwaite, T. D., Beard, L. M., Sommer, I. E., Koops, S., Gruber, O., Richter, A., Krämer, B., Kelly, S., Donohoe, G., McDonald, C., Cannon, D. M., Corvin, A., Gill, M., Di Giorgio, A., Bertolino, A., Lawrie, S., Nickson, T., Whalley, H. C., Neilson, E., Calhoun, V. D., Thompson, P. M., Turner, J. A., Ehrlich, S., Farde, L., Engberg, G., Erhardt, S., Cervenka, S., Schwieler, L., Piehl, F., Ikonen, P., Collste, K., Orhan, F., Malmqvist, A., and Hedberg, M.
- Published
- 2017
22. Associations between central chemokine levels and glial activation in first episode psychosis – a positron emission tomography study
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Collste, K., primary, Orhan, F., additional, Erhardt, S., additional, Schwieler, L., additional, Flyckt, L., additional, Farde, L., additional, Engberg, G., additional, and Cervenka, S., additional
- Published
- 2017
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23. Tryptophan Metabolism Along the Kynurenine Pathway Downstream of Toll-like Receptor Stimulation in Peripheral Monocytes
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Orhan, F., Bhat, M., Sandberg, Kristian, Stahl, S., Piehl, F., Svensson, C., Erhardt, S., Schwieler, L., Orhan, F., Bhat, M., Sandberg, Kristian, Stahl, S., Piehl, F., Svensson, C., Erhardt, S., and Schwieler, L.
- Abstract
Tryptophan degradation along the kynurenine pathway is of central importance for the immune function. Toll-like receptors (TLRs), representing the first line of immune defence against pathogens, are expressed in various cell types. The most abundant expression is found on monocytes, macrophages and dendritic cells. The aim of this study was to investigate whether stimulation with different TLR ligands induces the kynurenine pathway in human peripheral monocytes. Cell supernatants were analysed using a liquid chromatography/mass spectrometry to measure kynurenine, kynurenic acid (KYNA), quinolinic acid (QUIN) and tryptophan. Stimulation of TLR-2, TLR-3, TLR-4, TLR-7/8 and TLR-9 was found to induce the production of kynurenine, but only stimulation of TLR-3 increased levels of further downstream metabolites, such as KYNA and QUIN. Stimulation of TLR-1, TLR-5 and TLR-6 did not induce the kynurenine pathway. Taken together, this study provides novel evidence demonstrating that TLR activation induces a pattern of downstream tryptophan degradation along the kynurenine pathway in monocytes. The results of this study may implicate that TLRs can be used as new drug targets for the regulation of aberrant tryptophan metabolism along this pathway, a potential therapeutic strategy that may be of importance in several disorders.
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- 2016
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24. Cognitive Performance in Drug-naÏve First Episode Schizophrenia (FES) Patients
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Fatouros-Bergman, H., primary, Cervenka, C., additional, Flyckt, L., additional, Edman, G., additional, Schwieler, L., additional, Ikonen, P., additional, Collste, K., additional, Piehl, F., additional, Agartz, I., additional, Engberg, G., additional, Erhardt, S., additional, and Farde, L., additional
- Published
- 2015
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25. P.1.i.053 - Associations between central chemokine levels and glial activation in first episode psychosis – a positron emission tomography study
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Collste, K., Orhan, F., Erhardt, S., Schwieler, L., Flyckt, L., Farde, L., Engberg, G., and Cervenka, S.
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- 2017
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26. 57. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections perceived as conversion disorder. A case study of a young woman
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Bejerot, S., primary, Hesselmark, E., additional, Wallén, H., additional, Mobarrez, F., additional, Landén, M., additional, Schwieler, L., additional, Nybom, R., additional, and Wetterberg, L., additional
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- 2013
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27. P.1.014 Intracerebroventricular administration of interleukin-1β elevates brain kynurenic acid and disrupts prepulse inhibition in C57BL/6 mice
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Larsson, M., primary, Schwieler, L., additional, Engberg, G., additional, Powell, S.B., additional, and Erhardt, S., additional
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- 2013
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28. P.1.01 The effect of influenza A/WSN/33 virus infections on the kynurenine pathway
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Asp, L., primary, Holtze, M., additional, Schwieler, L., additional, Engberg, G., additional, and Karlsson, H., additional
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- 2008
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29. S.28.04 Endogenous kynurenate regulates dopaminergic activity: implications for schizophrenia research
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Erhardt, S., primary, Schwieler, L., additional, Nilsson, L.K., additional, Andersson, L.A., additional, Linderholm, K.R., additional, Holtze, M., additional, Olsson, E., additional, Olsson, S.K., additional, and Engberg, G., additional
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- 2007
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30. P.3.b.009 Enhanced amphetamine-induced dopamine release in rat nucleus accumbens following subchronic elevation of kynurenic acid
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Andersson, L.A., primary, Nilsson, L.K., additional, Schwieler, L., additional, Holtze, M., additional, Olsson, S.K., additional, Olsson, E., additional, Linderholm, K., additional, Engberg, G., additional, and Erhardt, S., additional
- Published
- 2007
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31. P.3.b.006 Kynurenine pathway enzymes and levels of brain kynurenic acid following Influenza virus infection
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Holtze, M., primary, Asp, L., additional, Engberg, G., additional, Karlsson, H., additional, and Schwieler, L., additional
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- 2007
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32. P.3.b.004 Subchronic elevation of endogenous levels of kynurenic acid increase dopamine release in rat nucleus accumbens
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Nilsson-Todd, L.K., primary, Andersson, L.A., additional, Schwieler, L., additional, Engberg, G., additional, Holtze, M., additional, Linderholm, K.R., additional, Olsson, E., additional, Olsson, S.K., additional, and Erhardt, S., additional
- Published
- 2007
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33. P.5.d.002 Increased levels of kynurenic acid may account for neuropsychiatric symptoms in patients with tick-borne encephalitis
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Schwieler, L., primary, Mickien´e, A., additional, Holtze, M., additional, Atlas, A., additional, and Engberg, G., additional
- Published
- 2007
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34. P.3.d.012 The response of clozapine on midbrain dopamine neurons depends on endogenous concentration of kynurenic acid
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Schwieler, L., primary, Linderholm, K.R., additional, Nilsson, L.K., additional, Engberg, G., additional, and Erhardt, S., additional
- Published
- 2006
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35. Prostaglandin-mediated control of rat brain kynurenic acid synthesis – opposite actions by COX-1 and COX-2 isoforms
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Schwieler, L., primary, Erhardt, S., additional, Erhardt, C., additional, and Engberg, G., additional
- Published
- 2004
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36. The anaesthetic agent propofol interacts with GABAB-receptors: an electrophysiological study in rat
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Schwieler, L., Delbro, D.S., Engberg, G., and Erhardt, S.
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- *
ANESTHESIA , *DOPAMINE - Abstract
The mode of action by which propofol induces anaesthesia is not fully understood, although several studies suggest that the compound acts via potentiation of brain GABAA-receptors. The aim of the present study is to investigate a putative GABAB-receptor agonistic action of propofol. For this purpose the action of propofol on a GABA-receptor mediated regulation of dopamine neurons was analyzed with extracellular single unit recordings of dopaminergic neurons of the substantia nigra in chloral hydrate anaesthetized rats.Intravenous administration of propofol (1–16 mg/kg) was found to dose-dependently decrease the firing rate and burst firing activity of nigral DA neurons. These effects by propofol were effectively antagonized by pretreatment with the selective GABAB-receptor antagonist CGP 35348 (200 mg/kg, i.v.) but not by pretreatment with the GABAA-receptor antagonist picrotoxin (4.5 mg/kg, i.v.).It is proposed that an activation of central GABAB-receptors may, at least partially, contribute to the anesthetic properties of propofol. [Copyright &y& Elsevier]
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- 2003
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37. Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia--significance for activation of the kynurenine pathway
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Schwieler L, Markus Larsson, Skogh E, Me, Kegel, Orhan F, Abdelmoaty S, Finn A, Bhat M, Samuelsson M, Lundberg K, Ml, Dahl, Sellgren C, Schuppe-Koistinen I, Svensson C, Erhardt S, and Engberg G
38. Mood, Cognitive Function, and Plasma Kynurenine Metabolites Responses Following Severe Changes in Physical Activity.
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Kamandulis S, Lukonaitiene I, Snieckus A, Brazaitis M, Mickevicius M, Cernych M, Ruas J, Schwieler L, Louvrou V, Erhardt S, Westerblad H, and Venckunas T
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- Humans, Female, Male, Adult, Young Adult, Depression blood, Resistance Training, High-Intensity Interval Training, Electroencephalography, Kynurenine blood, Cognition physiology, Affect physiology, Exercise physiology
- Abstract
Purpose: To monitor changes in mood, cognitive function, brain electrical activity, and circulating kynurenine pathway metabolites in response to a 3-wk severe physical activity (PA) restriction, followed by 3 wk of resumed activity adding resistance and high-intensity interval exercise training., Methods: Twenty healthy participants (14 males, 6 females; 25.4 ± 5.2 yr) underwent 3 wk of limited PA using forearm crutches with one leg suspended (INACT) and then 3 wk of resumed activity plus supervised resistance and high-intensity interval training sessions (ACT, three to six sessions per week). At baseline, after INACT, and then after ACT, venous blood was sampled for analysis of major kynurenine pathway metabolites, a short version of the International Physical Activity Questionnaire, Hospital Anxiety and Depression Scale (HADS) and Profile of Mood States (POMS) questionnaires were completed, and cognitive tests with electroencephalography were performed., Results: During INACT, the depression score on the HADS scale tended to increase (3.5 to 6.8; P = 0.065), whereas it was reduced with ACT compared with after INACT (2.8; P = 0.022). On the POMS scale, depression, fatigue, and confusion increased within INACT ( P < 0.05). Notably, subjects exhibited considerable variability, and those experiencing depression symptoms recorded by the HADS scale ( n = 4) displayed distinct mood disturbances on POMS. All HADS and POMS scores were fully restored to baseline with ACT. Neither INACT nor ACT induced significant changes in cognition, brain electrical activity, or kynurenine pathway metabolites ( P > 0.05)., Conclusions: Although young healthy individuals with 3 wk of severely restricted PA do not undergo changes in circulating kynurenine pathway metabolites, cognitive performance, and brain electrical activity, their mood response is quite variable, and depression develops in some. Three weeks of resuming mobility plus exercise training reversed the mood profile., (Copyright © 2024 by the American College of Sports Medicine.)
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- 2024
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39. Long-term neurological and neurocognitive impairments after tick-borne encephalitis in Lithuania - a prospective study.
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Griška V, Pranckevičienė A, Pakalnienė J, Gabrijolavičiūtė D, Veje M, Studahl M, Ahlberg J, Schwieler L, Lindquist L, and Mickienė A
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- Humans, Male, Female, Prospective Studies, Middle Aged, Adult, Lithuania epidemiology, Aged, Cognitive Dysfunction etiology, Cognitive Dysfunction physiopathology, Young Adult, Neuropsychological Tests, Adolescent, Severity of Illness Index, Nervous System Diseases complications, Nervous System Diseases etiology, Encephalitis, Tick-Borne complications
- Abstract
Background: The aim of this study was to characterise long-term neurological and neurocognitive sequelae after tick-borne encephalitis (TBE) in adults., Methods: 98 prospective consecutive TBE patients, classified by disease severity, were included. Immediate outcomes were evaluated with Glasgow Outcome Scale (GOS) and Rankin Scale (RS). After 6 and 18 months, long-term disability was evaluated using Modified Rankin Scale (MRS) and neurocognitive assessment was performed with Matrics Consensus Cognitive Battery (MCCB), measuring processing speed, attention/vigilance, working memory, verbal learning, visual learning, reasoning/problem solving and social cognition. The MCCB results were compared to healthy age, gender and education-matched controls., Results: Mild, moderate, and severe TBE was diagnosed in 53.1%, 38.8%, and 8.2% of cases, respectively. At discharge, 25.5% of the patients had major or moderate impairments (GOS) and various levels of disability in 34.7% (RS). Up to 18 months from the onset of TBE, over 20% remained with slight to moderate disability (MRS). GOS, RS and MRS scores correlated with disease severity. At 6 months after the onset, TBE patients scored significantly lower than controls in processing speed, verbal, and visual learning. Two latter domains were significantly more impaired in patients with mild TBE. Patients aged 18-39 performed significantly worse in attention/vigilance and working memory, whereas aged 60+ in verbal learning. A year later, significant improvement was observed in six of seven cognitive domains., Conclusions: Long-term neurological sequelae persist in a substantial proportion of TBE patients with significant impairment in several cognitive domains, especially in younger patients and even after mild TBE.
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- 2024
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40. The Tryptophan Metabolite Indole-3-Propionic Acid Raises Kynurenic Acid Levels in the Rat Brain In Vivo.
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Sathyasaikumar KV, Blanco-Ayala T, Zheng Y, Schwieler L, Erhardt S, Tufvesson-Alm M, Poeggeler B, and Schwarcz R
- Abstract
Alterations in the composition of the gut microbiota may be causally associated with several brain diseases. Indole-3-propionic acid (IPrA) is a tryptophan-derived metabolite, which is produced by intestinal commensal microbes, rapidly enters the circulation, and crosses the blood-brain barrier. IPrA has neuroprotective properties, which have been attributed to its antioxidant and bioenergetic effects. Here, we evaluate an alternative and/or complementary mechanism, linking IPrA to kynurenic acid (KYNA), another neuroprotective tryptophan metabolite. Adult Sprague-Dawley rats received an oral dose of IPrA (200 mg/kg), and both IPrA and KYNA were measured in plasma and frontal cortex 90 minutes, 6 or 24 hours later. IPrA and KYNA levels increased after 90 minutes and 6 hours (brain IPrA: ~56- and ~7-fold; brain KYNA: ~4- and ~3-fold, respectively). In vivo microdialysis, performed in the medial prefrontal cortex and in the striatum, revealed increased KYNA levels (~2.5-fold) following the administration of IPrA (200 mg/kg, p.o), but IPrA failed to affect extracellular KYNA when applied locally. Finally, treatment with 100 or 350 mg IPrA, provided daily to the animals in the chow for a week, resulted in several-fold increases of IPrA and KYNA levels in both plasma and brain. These results suggest that exogenously supplied IPrA may provide a novel strategy to affect the function of KYNA in the mammalian brain., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: R.S. is co-founder of Kynexis BV, which develops kynurenic acid-related compounds for human use., (© The Author(s) 2024.)
- Published
- 2024
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41. Kynurenine Metabolites in CSF and Plasma in Healthy Males.
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Orhan F, Schwieler L, Engberg G, and Samuelsson M
- Abstract
In recent years, kynurenine metabolites generated by tryptophan catabolism have gained increasing attention in the context of brain diseases. The question of importance is whether there is a relationship between peripheral and central levels of these metabolites. Some of these compounds do not cross the blood-brain barrier; in particular, kynurenic acid, and most analyses of kynurenines from psychiatric patients have been performed using plasma samples. In the present study, we recruited 30 healthy volunteers with no history of psychiatric or neurological diagnosis, to analyze tryptophan, kynurenine, kynurenic acid, and quinolinic acid levels in CSF and plasma. In addition, kynurenic acid was analyzed in urine. The most important finding of this study is that CSF kynurenic acid levels do not correlate with those in plasma or urine. However, we found a correlation between plasma kynurenine and CSF kynurenic acid. Further, plasma kynurenine and plasma quinolinic acid were correlated. Our findings clarify the distribution of tryptophan and its metabolites in various body compartments and may serve as a guide for the analysis of these metabolites in humans. The most significant finding of the present study is that a prediction of brain kynurenic acid by of the analysis of the compound in plasma cannot be made., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)
- Published
- 2024
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42. Preanalytic handling of clinical blood samples in assessing immunological proteins - Role of storage duration.
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Eren F, Schwieler L, Orhan F, Malmqvist A, Piehl F, Cervenka S, Sellgren CM, Fatouros-Bergman H, Engberg G, and Erhardt S
- Abstract
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
- Published
- 2023
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43. Dual administration of lipopolysaccharide induces behavioural changes in rats relevant to psychotic disorders.
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Zheng YR, Tufvesson-Alm M, Trepci A, Imbeault S, Li XQ, Schwieler L, Engberg G, and Erhardt S
- Abstract
Objective: We previously reported that dual injections of lipopolysaccharide (LPS) in mice constitute a valuable tool for investigating the contribution of inflammation to psychotic disorders. The present study investigated how immune activation affects the kynurenine pathway and rat behaviour of relevance for psychotic disorders., Methods: Male Sprague Dawley rats were treated with either dual injections of LPS (0.5 mg/kg + 0.5 mg/kg, i.p.) or dual injections of saline. Twenty-four hours after the second injection, behavioural tests were carried out, including locomotor activity test, fear conditioning test, spontaneous alternation Y-maze test, and novel object recognition test. In a separate batch of animals, in vivo striatal microdialysis was performed, and tryptophan, kynurenine, quinolinic acid, and kynurenic acid (KYNA) in the dialysate were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)., Results: Dual-LPS treatment decreased spontaneous locomotion, exaggerated d-amphetamine-induced locomotor activity, and impaired recognition memory in male Sprague-Dawley rats. In vivo microdialysis showed that dual-LPS treatment elicited metabolic disturbances in the kynurenine pathway with increased extracellular levels of kynurenine and KYNA in the striatum., Conclusion: The present study further supports the feasibility of using the dual-LPS model to investigate inflammation-related psychotic disorders and cognitive impairments.
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- 2023
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44. Lipopolysaccharide-induced changes in the kynurenine pathway and symptoms of sickness behavior in humans.
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Balter LJ, Li X, Schwieler L, Erhardt S, Axelsson J, Olsson MJ, Lasselin J, and Lekander M
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- Humans, Female, Young Adult, Adult, Illness Behavior, Kynurenic Acid metabolism, Niacinamide, Kynurenine metabolism, Lipopolysaccharides pharmacology
- Abstract
Metabolites of the kynurenine pathway are hypothesized to be implicated in inflammation-associated depression, but there is a lack of experimental studies in humans assessing the kinetics of kynurenine metabolites in relation to experimentally-induced sickness. The aim of the present study was to assess changes in the kynurenine pathway and to explore its relation to symptoms of sickness behavior during an acute experimental immune challenge. This double-blind placebo-controlled randomized cross-over study included 22 healthy human participants (n = 21 both sessions, M
age = 23.4, SD = 3.6, nine women) who received an intravenous injection of 2.0 ng/kg lipopolysaccharide (LPS) and saline (placebo) on two different occasions in a randomized order. Blood samples (0 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 5 h, 7 h post-injection) were analyzed for kynurenine metabolites and inflammatory cytokines. The intensity of symptoms of sickness behavior was assessed using the 10-item Sickness Questionnaire at 0 h, 1.5 h, 3 h, 5 h, and 7 h post-injection. LPS induced significantly lower concentrations of plasma tryptophan (at 2 h, 4 h, 5 h, and 7 h post-injection), kynurenine (at 2 h, 3 h, 4 h, and 5 h post-injection), nicotinamide (at 4 h, 5 h, and 7 h post-injection), and higher levels for quinolinic acid at 5 h post-injection as compared to placebo. LPS did not affect kynurenic acid, 3-hydroxykynurenine, and picolinic acid. The development of the sickness symptoms was largely similar across items, with the highest levels around 1.5-3 h post-injection. Changes in plasma levels of kynurenine metabolites seem to coincide rather than precede or follow changes in subjective sickness. Exploratory analyses indicate that higher Sickness Questionnaire total scores at 1.5-5 h post-injection were correlated with lower kynurenic acid and nicotinamide levels. These results lend further support for LPS-induced changes in the kynurenine pathway, but may not, as interpreted from blood levels, causally link to LPS-induced acute symptoms of sickness behavior. Future research may consider a larger sample to further scrutinize the role of the kynurenine pathway in the sickness response., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2023
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45. Immunological protein profiling of first-episode psychosis patients identifies CSF and blood biomarkers correlating with disease severity.
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Eren F, Schwieler L, Orhan F, Malmqvist A, Piehl F, Cervenka S, Sellgren CM, Fatouros-Bergman H, Engberg G, and Erhardt S
- Subjects
- Humans, Biomarkers, Patient Acuity, Sweden, Psychotic Disorders metabolism, Schizophrenia
- Abstract
Background and Hypothesis: Immune activation is suggested to play an important role in psychosis. In this study, a large number of immune-related proteins were analyzed to obtain a more comprehensive picture of immune aberrations in schizophrenia., Study Design: Ninety-two immune markers were analyzed by the Olink Protein Extension Assay (Inflammatory Panel) in plasma and cerebrospinal fluid (CSF) from 77 first-episode psychosis (FEP) patients (of which 43 later received the diagnosis of schizophrenia) and 56 healthy controls, all recruited from the Karolinska Schizophrenia Project (KaSP), Stockholm, Sweden., Study Results: Differential analysis showed that 12 of 92 inflammatory proteins were significantly higher in the plasma of FEP patients (n = 77) than in controls, and several proteins were positively correlated with disease severity. Patients from the same cohort diagnosed with schizophrenia (n = 43), showed significantly higher levels of 15 plasma proteins compared to controls whereas those not receiving this diagnosis showed no significant differences. The presently used OLINK inflammatory panel allowed the detection of only 47 CSF proteins of which only CD5 differed between patients and controls., Conclusions: The levels of several peripheral immune markers, particularly those interfering with WNT/β-catenin signaling, were significantly higher in patients with FEP than in healthy controls and associated with illness severity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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46. CSF dopamine is elevated in first-episode psychosis and associates to symptom severity and cognitive performance.
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Orhan F, Goiny M, Becklén M, Mathé L, Piehl F, Schwieler L, Fatouros-Bergman H, Farde L, Cervenka S, Sellgren CM, Engberg G, and Erhardt S
- Subjects
- Humans, Dopamine metabolism, Brain, Cognition, Psychotic Disorders, Schizophrenia
- Abstract
Background: The hypothesis of dopamine dysfunction in psychosis has evolved since the mid-twentieth century. However, clinical support from biochemical analysis of the transmitter in patients is still missing. The present study assessed dopamine and related metabolites in the cerebrospinal fluid (CSF) of first-episode psychosis (FEP) subjects., Methods: Forty first-episode psychosis subjects and twenty healthy age-matched volunteers were recruited via the Karolinska Schizophrenia Project, a multidisciplinary research consortium that investigates the pathophysiology of schizophrenia. Psychopathology, disease severity, and cognitive performance were rated as well as cerebrospinal fluid concentrations of dopamine and related metabolites were measured using a sensitive high-pressure liquid chromatography assay., Results: CSF dopamine was reliably detected in 50 % of healthy controls and in 65 % of first-episode psychosis subjects and significantly higher in first-episode psychosis subjects compared to age-matched healthy controls. No difference in CSF dopamine levels was observed between drug-naive subjects and subjects with short exposure to antipsychotics. The dopamine concentrations were positively associated with illness severity and deficits in executive functioning., Conclusions: Dopamine dysfunction has long been considered a cornerstone of the pathophysiology of schizophrenia, although biochemical support for elevated brain dopamine levels has been lacking. The results of the present study, showing that FEP subjects have increased CSF dopamine levels that correlate to disease symptoms, should fill the knowledge gap in this regard., Competing Interests: Declaration of competing interest All authors declare they have no competing interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
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47. Cognitive impairments correlate with increased central nervous system immune activation after allogeneic haematopoietic stem cell transplantation.
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Boberg E, Kadri N, Hagey DW, Schwieler L, El Andaloussi S, Erhardt S, Iacobaeus E, and Le Blanc K
- Subjects
- Humans, Mice, Animals, Proteomics, Central Nervous System, Fatigue, Cognitive Dysfunction etiology, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods
- Abstract
Murine studies indicate that, after allogeneic haematopoietic stem cell transplantation (aHSCT), donor-derived macrophages replace damaged microglia and alloreactive T-cells invade the central nervous system (CNS). The clinical relevance of this is unknown. We assessed CNS immune surveillance and metabolic activity involved in neuronal survival, in relation to fatigue and cognitive dysfunction in 25 long-term survivors after aHSCT. Patients with cognitive dysfunction exhibited increased proportions of activated T-cells and CD16 + NK-cells in the cerebrospinal fluid (CSF). Immune cell activation was paralleled with reduced levels of anti-inflammatory factors involved in T-cell suppression (transforming growth factor-β, programmed death ligand-1), NK-cell regulation (poliovirus receptor, nectin-2), and macrophage and microglia activation (CD200, chemokine [C-X3-C motif] ligand-1). Additionally, the CSF mRNA expression pattern was associated with neuroinflammation and oxidative stress. Furthermore, proteomic, and transcriptomic studies demonstrated decreased levels of neuroprotective factors, and an upregulation of apoptosis pathway genes. The kynurenine pathway of tryptophan metabolism was activated in the CNS of all aHSCT patients, resulting in accumulation of neurotoxic and pro-inflammatory metabolites. Cognitive decline and fatigue are overlooked but frequent complications of aHSCT. This study links post-transplant CNS inflammation and neurotoxicity to our previously reported hypoactivation in the prefrontal cortex during cognitive testing, suggesting novel treatment targets., (© 2023. The Author(s).)
- Published
- 2023
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48. Cerebrospinal fluid concentration of complement component 4A is increased in first episode schizophrenia.
- Author
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Gracias J, Orhan F, Hörbeck E, Holmén-Larsson J, Khanlarkani N, Malwade S, Goparaju SK, Schwieler L, Demirel İŞ, Fu T, Fatourus-Bergman H, Pelanis A, Goold CP, Goulding A, Annerbrink K, Isgren A, Sparding T, Schalling M, Yañez VAC, Göpfert JC, Nilsson J, Brinkmalm A, Blennow K, Zetterberg H, Engberg G, Piehl F, Sheridan SD, Perlis RH, Cervenka S, Erhardt S, Landen M, and Sellgren CM
- Subjects
- Humans, Complement C4a genetics, Complement C4a cerebrospinal fluid, Risk Factors, Schizophrenia genetics, Schizophrenia metabolism, Psychotic Disorders genetics
- Abstract
Postsynaptic density is reduced in schizophrenia, and risk variants increasing complement component 4A (C4A) gene expression are linked to excessive synapse elimination. In two independent cohorts, we show that cerebrospinal fluid (CSF) C4A concentration is elevated in patients with first-episode psychosis (FEP) who develop schizophrenia (FEP-SCZ: median 0.41 fmol/ul [CI = 0.34-0.45], FEP-non-SCZ: median 0.29 fmol/ul [CI = 0.22-0.35], healthy controls: median 0.28 [CI = 0.24-0.33]). We show that the CSF elevation of C4A in FEP-SCZ exceeds what can be expected from genetic risk variance in the C4 locus, and in patient-derived cellular models we identify a mechanism dependent on the disease-associated cytokines interleukin (IL)-1beta and IL-6 to selectively increase neuronal C4A mRNA expression. In patient-derived CSF, we confirm that IL-1beta correlates with C4A controlled for genetically predicted C4A RNA expression (r = 0.39; CI: 0.01-0.68). These results suggest a role of C4A in early schizophrenia pathophysiology., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
49. Two-day fasting affects kynurenine pathway with additional modulation of short-term whole-body cooling: a quasi-randomised crossover trial.
- Author
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Solianik R, Schwieler L, Trepci A, Erhardt S, and Brazaitis M
- Abstract
Metabolites of the kynurenine (KYN) pathway of tryptophan (TRP) degradation have attracted interest as potential pathophysiological mediators and future diagnostic biomarkers. A greater knowledge of the pathological implications of the metabolites is associated with a need for a better understanding of how the normal behaviour and physiological activities impact their concentrations. This study aimed to investigate whether fasting (FAST) and whole-body cold-water immersion (CWI) affect KYN pathway metabolites. Thirteen young women were randomly assigned to receive the 2-d FAST with two 10-min CWI on separate days (FAST-CWI), 2-d FAST without CWI (FAST-CON), 2-d two CWI on separate days without FAST (CON-CWI) or the 2-d usual diet without CWI (CON-CON) in a randomised crossover fashion. Changes in plasma concentrations of TRP, kynurenic acid (KYNA), 3-hydroxy-kynurenine (3-HK), picolinic acid (PIC), quinolinic acid (QUIN) and nicotinamide (NAA) were determined with ultra-performance liquid chromatography-tandem mass spectrometer. FAST-CWI and FAST-CON lowered TRP concentration ( P < 0·05, η
p 2 = 0·24), and increased concentrations of KYNA, 3-HK and PIC ( P < 0·05, ηp 2 = 0·21-0·71) with no additional effects of CWI. The ratio of PIC/QUIN increased after FAST-CWI and FAST-CON trials ( P < 0·05) but with a blunted effect in the FAST-CWI trial ( P < 0·05) compared with the FAST-CON trials ( ηp 2 = 0·67). Concentrations of QUIN and NAA were unaltered. This study demonstrated that fasting for 2 d considerably impacts the concentration of several metabolites in the KYN pathway. This should be considered when discussing the potential of KYN pathway metabolites as biomarkers.- Published
- 2022
- Full Text
- View/download PDF
50. Identification of cerebrospinal fluid and serum metabolomic biomarkers in first episode psychosis patients.
- Author
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Shang P, Ho AM, Tufvesson-Alm M, Lindberg DR, Grant CW, Orhan F, Eren F, Bhat M, Engberg G, Schwieler L, Fatouros-Bergman H, Imbeault S, Iverson RM, Dasari S, Piehl F, Cervenka S, Sellgren CM, Erhardt S, and Choi DS
- Subjects
- Biomarkers, Humans, Metabolomics, Serotonin, Psychotic Disorders pathology, Schizophrenia
- Abstract
Psychotic disorders are currently diagnosed by examining the patient's mental state and medical history. Identifying reliable diagnostic, monitoring, predictive, or prognostic biomarkers would be useful in clinical settings and help to understand the pathophysiology of schizophrenia. Here, we performed an untargeted metabolomics analysis using ultra-high pressure liquid chromatography coupled with time-of-flight mass spectroscopy on cerebrospinal fluid (CSF) and serum samples of 25 patients at their first-episode psychosis (FEP) manifestation (baseline) and after 18 months (follow-up). CSF and serum samples of 21 healthy control (HC) subjects were also analyzed. By comparing FEP and HC groups at baseline, we found eight CSF and 32 serum psychosis-associated metabolites with non-redundant identifications. Most remarkable was the finding of increased CSF serotonin (5-HT) levels. Most metabolites identified at baseline did not differ between groups at 18-month follow-up with significant improvement of positive symptoms and cognitive functions. Comparing FEP patients at baseline and 18-month follow-up, we identified 20 CSF metabolites and 90 serum metabolites that changed at follow-up. We further utilized Ingenuity Pathway Analysis (IPA) and identified candidate signaling pathways involved in psychosis pathogenesis and progression. In an extended cohort, we validated that CSF 5-HT levels were higher in FEP patients than in HC at baseline by reversed-phase high-pressure liquid chromatography. To conclude, these findings provide insights into the pathophysiology of psychosis and identify potential psychosis-associated biomarkers., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
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