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1. Brain Age Prediction Reveals Aberrant Brain White Matter in Schizophrenia and Bipolar Disorder: A Multisample Diffusion Tensor Imaging Study

Author

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., Sellgren, C., Tønnesen, Siren, Kaufmann, Tobias, de Lange, Ann-Marie G., Richard, Geneviève, Doan, Nhat Trung, Alnæs, Dag, van der Meer, Dennis, Rokicki, Jaroslav, Moberget, Torgeir, Maximov, Ivan I., Agartz, Ingrid, Aminoff, Sofie R., Beck, Dani, Barch, Deanna M., Beresniewicz, Justyna, Cervenka, Simon, Fatouros-Bergman, Helena, Craven, Alexander R., Flyckt, Lena, Gurholt, Tiril P., Haukvik, Unn K., Hugdahl, Kenneth, Johnsen, Erik, Jönsson, Erik G., Kolskår, Knut K., Kroken, Rune Andreas, Lagerberg, Trine V., Løberg, Else-Marie, Nordvik, Jan Egil, Sanders, Anne-Marthe, Ulrichsen, Kristine, Andreassen, Ole A., and Westlye, Lars T.

Published
2020
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2. Esperanto for histones: CENP-A, not CenH3, is the centromeric histone H3 variant.

Author

Earnshaw, WC, Allshire, RC, Black, BE, Bloom, K, Brinkley, BR, Brown, W, Cheeseman, IM, Choo, KHA, Copenhaver, GP, Deluca, JG, Desai, A, Diekmann, S, Erhardt, S, Fitzgerald-Hayes, M, Foltz, D, Fukagawa, T, Gassmann, R, Gerlich, DW, Glover, DM, Gorbsky, GJ, Harrison, SC, Heun, P, Hirota, T, Jansen, LET, Karpen, G, Kops, GJPL, Lampson, MA, Lens, SM, Losada, A, Luger, K, Maiato, H, Maddox, PS, Margolis, RL, Masumoto, H, McAinsh, AD, Mellone, BG, Meraldi, P, Musacchio, A, Oegema, K, O'Neill, RJ, Salmon, ED, Scott, KC, Straight, AF, Stukenberg, PT, Sullivan, BA, Sullivan, KF, Sunkel, CE, Swedlow, JR, Walczak, CE, Warburton, PE, Westermann, S, Willard, HF, Wordeman, L, Yanagida, M, Yen, TJ, Yoda, K, and Cleveland, DW

Subjects
Centromere, Kinetochores, Humans, Scleroderma, Systemic, Chromosomal Proteins, Non-Histone, Histones, Autoantigens, Terminology as Topic, Centromere Protein A, centromere, CENP-A, histone, kinetochore, CenH3, Developmental Biology, Biochemistry and Cell Biology, Genetics
Abstract

The first centromeric protein identified in any species was CENP-A, a divergent member of the histone H3 family that was recognised by autoantibodies from patients with scleroderma-spectrum disease. It has recently been suggested to rename this protein CenH3. Here, we argue that the original name should be maintained both because it is the basis of a long established nomenclature for centromere proteins and because it avoids confusion due to the presence of canonical histone H3 at centromeres.

Published
2013

4. Twelve-week physical exercise does not have a long-lasting effect on kynurenines in plasma of depressed patients

Author

Millischer V, Erhardt S, Ekblom Ö, Forsell Y, and Lavebratt C

Subjects
Kynurenine pathway, kynurenine, kynurenic acid, depression, physical exercise, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Vincent Millischer,1,2 Sophie Erhardt,3 Örjan Ekblom,4 Yvonne Forsell,5 Catharina Lavebratt1,2 1Department of Molecular Medicine and Surgery, Karolinska Institutet, 2Center for Molecular Medicine, Karolinska University Hospital, 3Department of Physiology and Pharmacology, Karolinska Institutet, 4Department of Sport Sciences, The Swedish School of Sport and Health Sciences, GIH, 5Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden Background: Physical exercise has well-characterized positive effects on depressive symptoms. The underlying biologic mechanisms are, however, far from established. A recently discovered mechanism has linked the enhanced conversion of kynurenine to kynurenic acid (KYNA) to an increased resilience toward stress-induced depression in mice. The aim of this study was to translate these findings to humans.Materials and methods: Kynurenine and KYNA levels were measured by high-performance liquid chromatography in plasma samples from 117 patients affected by mild-to-moderate depression before and within a week after a 12-week training period at three different intensities. The patients were part of the Regassa study.Results: No differences in plasma levels of kynurenine and KYNA or in their ratio could be detected between before and after training. No effect of the intensity group could be observed. No correlation with the improvement in cardiovascular fitness (Åstrand score) or the improvement in mood (Montgomery Åsberg Depression Rating Scale score) could be observed.Limitations: As the Regassa study is based on an intention-to-treat protocol, the exact time and the exact intensity of the physical exercise are not known. Analyses of pulse data as well as personal interviews, however, were used to control the exercise protocols. Furthermore, the observations reflect chronic changes.Conclusion: Physical exercise positively affects mood and cardiovascular fitness, but does not lead to long-lasting changes in plasma levels of kynurenine and KYNA in patients affected by mild-to-moderate depression. Keywords: kynurenine pathway, kynurenine, kynurenic acid, depression, physical exercise

Published
2017

7. Epidemiological, genetic, and clinical characterization by age of newly diagnosed acute myeloid leukemia based on an academic population-based registry study (AMLSG BiO)

Author

Nagel, Gabriele, Weber, D., Fromm, E., Erhardt, S., Lübbert, M., Fiedler, W., Kindler, T., Krauter, J., Brossart, P., Kündgen, A., Salih, H. R., Westermann, J., Wulf, G., Hertenstein, B., Wattad, M., Götze, K., Kraemer, D., Heinicke, T., Girschikofsky, M., Derigs, H.G., Horst, H. A., Rudolph, C., Heuser, M., Göhring, G., Teleanu, V., Bullinger, L., Thol, F., Gaidzik, V. I., Paschka, P., Döhner, K., Ganser, A., Döhner, Hartmut, Schlenk, R. F., and German-Austrian AML Study Group (AMLSG)

Published
2017
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9. Logic Mill - A Knowledge Navigation System, arXiv preprint 2301.00200

Author

Erhardt, S., Ghosh, M., Buunk, E., Rose, M., and Harhoff, D.

Abstract

Logic Mill is a scalable and openly accessible software system that identifies semantically similar documents within either one domain-specific corpus or multi-domain corpora. It uses advanced Natural Language Processing (NLP) techniques to generate numerical representations of documents. Currently it leverages a large pre-trained language model to generate these document representations. The system focuses on scientific publications and patent documents and contains more than 200 million documents. It is easily accessible via a simple Application Programming Interface (API) or via a web interface. Moreover, it is continuously being updated and can be extended to text corpora from other domains. We see this system as a general-purpose tool for future research applications in the social sciences and other domains.

Published
2022

10. List of Contributors

Author

Agarwal, P., primary, Bade, D., additional, Bannister, A.J., additional, Belden, W.J., additional, Berdasco, M., additional, Brossas, C., additional, Cacchione, S., additional, Castelo-Branco, G., additional, Cicconi, A., additional, Doenecke, D., additional, Donohoe, M.E., additional, Duriez, B., additional, Erhardt, S., additional, Esteller, M., additional, Falcão, A.M., additional, Fiszbein, A., additional, Galati, A., additional, Godoy Herz, M.A., additional, Gomez Acuña, L.I., additional, Göndör, A., additional, Kornblihtt, A.R., additional, Lennartsson, A., additional, Lezzerini, M., additional, Linder, S.J., additional, Margueron, R., additional, Martino, M., additional, Micheli, E., additional, Millán-Ariño, L., additional, Miller, K.M., additional, Mostoslavsky, R., additional, Östlund Farrants, A-.K., additional, Prioleau, M-.N., additional, Riedel, C.G., additional, Scholz, B.A., additional, Tzelepis, I., additional, Valton, A-.L., additional, and Wassef, M., additional

Published
2017
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16. Esperanto for histones: CENP-A, not CenH3, is the centromeric histone H3 variant

Author

Earnshaw, W. C., Allshire, R. C., Black, B. E., Bloom, K., Brinkley, B. R., Brown, W., Cheeseman, I. M., Choo, K. H. A., Copenhaver, G. P., DeLuca, J. G., Desai, A., Diekmann, S., Erhardt, S., Fitzgerald-Hayes, M., Foltz, D., Fukagawa, T., Gassmann, R., Gerlich, D. W., Glover, D. M., Gorbsky, G. J., Harrison, S. C., Heun, P., Hirota, T., Jansen, L. E. T., Karpen, G., Kops, G. J. P. L., Lampson, M. A., Lens, S. M., Losada, A., Luger, K., Maiato, H., Maddox, P. S., Margolis, R. L., Masumoto, H., McAinsh, A. D., Mellone, B. G., Meraldi, P., Musacchio, A., Oegema, K., O’Neill, R. J., Salmon, E. D., Scott, K. C., Straight, A. F., Stukenberg, P. T., Sullivan, B. A., Sullivan, K. F., Sunkel, C. E., Swedlow, J. R., Walczak, C. E., Warburton, P. E., Westermann, S., Willard, H. F., Wordeman, L., Yanagida, M., Yen, T. J., Yoda, K., and Cleveland, D. W.

Published
2013
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20. The genetic architecture of human brainstem structures and their involvement in common brain disorders

Author

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.

Published
2020
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26. Brain Age Prediction Reveals Aberrant Brain White Matter in Schizophrenia and Bipolar Disorder: A Multisample Diffusion Tensor Imaging Study

Author

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

Published
2020
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30. Common brain disorders are associated with heritable patterns of apparent aging of the brain

Author

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

Subjects
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.)).

Published
2019
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31. Reproducible grey matter patterns index a multivariate, global alteration of brain structure in schizophrenia and bipolar disorder

Author

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

Subjects
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.

Published
2019
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32. Reproducible grey matter patterns index a multivariate, global alteration of brain structure in schizophrenia and bipolar disorder

Author

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
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33. 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

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

Published
2019

34. Neurogranin as a potential synaptic marker in the cerebrospinal fluid of patients with a first episode psychosis

Author

Santillo, A. F., Lundgren, S., Xu, C., Orhan, F., Fatouros-Bergman, H., Blennow, K., Zetterberg, H., Portelius, E., Cervenka, Simon, Jonsson, E. G., Erhardt, S., Engberg, G., Santillo, A. F., Lundgren, S., Xu, C., Orhan, F., Fatouros-Bergman, H., Blennow, K., Zetterberg, H., Portelius, E., Cervenka, Simon, Jonsson, E. G., Erhardt, S., and Engberg, G.

Published
2019
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35. Increased peripheral levels of TARC/CCL17 in first episode psychosis patients

Author

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.

Published
2019
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37. Cerebrospinal fluid levels of sphingolipids associate with disease severity in first episode psychosis patients

Author

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.

Published
2018
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40. CSF GABA is reduced in first-episode psychosis and associates to symptom severity

Author

Orhan, F, Fatouros-Bergman, H, Goiny, M, Malmqvist, A, Piehl, F, Cervenka, Simon, Collste, K, Victorsson, P, Sellgren, C M, Flyckt, L, Erhardt, S, Engberg, G, Orhan, F, Fatouros-Bergman, H, Goiny, M, Malmqvist, A, Piehl, F, Cervenka, Simon, Collste, K, Victorsson, P, Sellgren, C M, Flyckt, L, Erhardt, S, and Engberg, G

Abstract

Schizophrenia is characterized by a multiplicity of symptoms arising from almost all domains of mental function. γ-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain and is increasingly recognized to have a significant role in the pathophysiology of the disorder. In the present study, cerebrospinal fluid (CSF) concentrations of GABA were analyzed in 41 first-episode psychosis (FEP) patients and 21 age- and sex-matched healthy volunteers by high-performance liquid chromatography. We found lower CSF GABA concentration in FEP patients compared with that in the healthy volunteers, a condition that was unrelated to antipsychotic and/or anxiolytic medication. Moreover, lower CSF GABA levels were associated with total and general score of Positive and Negative Syndrome Scale, illness severity and probably with a poor performance in a test of attention. This study offers clinical in vivo evidence for a potential role of GABA in early-stage schizophrenia.

Published
2018
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41. Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium

Author

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

Published
2018
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42. Increased number of monocytes and plasma levels of MCP-1 and YKL-40 in first-episode psychosis

Author

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.

Published
2018
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43. Metformin selectively targets redox control of complex I energy transduction

Author

Cameron, A. R. (Amy R.), Logie, L. (Lisa), Patel, K. (Kashyap), Erhardt, S. (Stefan), Bacon, S. (Sandra), Middleton, P. (Paul), Harthill, J. (Jean), Forteath, C. (Calum), Coats, J. T. (Josh T.), Kerr, C. (Calum), Curry, H. (Heather), Stewart, D. (Derek), Sakamoto, K. (Kei), Repiščák, P. (Peter), Paterson, M. J. (Martin J.), Hassinen, I. (Ilmo), McDougall, G. (Gordon), Rena, G. (Graham), Cameron, A. R. (Amy R.), Logie, L. (Lisa), Patel, K. (Kashyap), Erhardt, S. (Stefan), Bacon, S. (Sandra), Middleton, P. (Paul), Harthill, J. (Jean), Forteath, C. (Calum), Coats, J. T. (Josh T.), Kerr, C. (Calum), Curry, H. (Heather), Stewart, D. (Derek), Sakamoto, K. (Kei), Repiščák, P. (Peter), Paterson, M. J. (Martin J.), Hassinen, I. (Ilmo), McDougall, G. (Gordon), and Rena, G. (Graham)

Abstract

Many guanide-containing drugs are antihyperglycaemic but most exhibit toxicity, to the extent that only the biguanide metformin has enjoyed sustained clinical use. Here, we have isolated unique mitochondrial redox control properties of metformin that are likely to account for this difference. In primary hepatocytes and H4IIE hepatoma cells we found that antihyperglycaemic diguanides DG5-DG10 and the biguanide phenformin were up to 1000-fold more potent than metformin on cell signalling responses, gluconeogenic promoter expression and hepatocyte glucose production. Each drug inhibited cellular oxygen consumption similarly but there were marked differences in other respects. DG5 and phenformin but not metformin inhibited NADH oxidation in submitochondrial particles, indicative of complex I inhibition, which also corresponded closely with dehydrogenase activity in living cells measured by WST-1. Consistent with these findings, in isolated mitochondria, DG8 but not metformin caused the NADH/NAD+ couple to become more reduced over time and mitochondrial deterioration ensued, suggesting direct inhibition of complex I and mitochondrial toxicity of DG8. In contrast, metformin exerted a selective oxidation of the mitochondrial NADH/NAD+ couple, without triggering mitochondrial deterioration. Together, our results suggest that metformin suppresses energy transduction by selectively inducing a state in complex I where redox and proton transfer domains are no longer efficiently coupled.

Published
2018

44. Positive symptoms associate with cortical thinning in the superior temporal gyrus via the enigma schizophrenia consortium

Author

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.

Published
2017
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45. Cerebrospinal fluid levels of sphingolipids associate with disease severity in first episode psychosis patients

Author

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

Published
2018
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46. Lower levels of the glial cell marker TSPO in drug-naive first-episode psychosis patients as measured using PET and [C-11]PBR28

Author

Collste, K., Plaven-Sigray, P., Fatouros-Bergman, H., Victorsson, P., Schain, M., Forsberg, A., Amini, N., Aeinehband, S., Erhardt, S., Halldin, C., Flyckt, L., Farde, L., Cervenka, Simon, Collste, K., Plaven-Sigray, P., Fatouros-Bergman, H., Victorsson, P., Schain, M., Forsberg, A., Amini, N., Aeinehband, S., Erhardt, S., Halldin, C., Flyckt, L., Farde, L., and Cervenka, Simon

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.

Published
2017
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47. Positive symptoms associate with cortical thinning in the superior temporal gyrus via the ENIGMA Schizophrenia consortium

Author

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

49. Tryptophan Metabolism Along the Kynurenine Pathway Downstream of Toll-like Receptor Stimulation in Peripheral Monocytes

Author

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.

Published
2016
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50. An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation

Author

Brundin, L., Sellgren, C. M., Lim, C. K., Grit, J., Palsson, E., Landen, M., Samuelsson, Martin, Lundgren, Kristoffer, Brundin, P., Fuchs, D., Postolache, T. T., Traskman-Bendz, L., Guillemin, G. J., Erhardt, S., Brundin, L., Sellgren, C. M., Lim, C. K., Grit, J., Palsson, E., Landen, M., Samuelsson, Martin, Lundgren, Kristoffer, Brundin, P., Fuchs, D., Postolache, T. T., Traskman-Bendz, L., Guillemin, G. J., and Erhardt, S.

Abstract

Emerging evidence suggests that inflammation has a key role in depression and suicidal behavior. The kynurenine pathway is involved in neuroinflammation and regulates glutamate neurotransmission. In the cerebrospinal fluid (CSF) of suicidal patients, levels of inflammatory cytokines and the kynurenine metabolite quinolinic acid (QUIN), an N-methyl-D-aspartate receptor agonist, are increased. The enzyme amino-beta-carboxymuconate-semialdehyde-decarboxylase (ACMSD) limits QUIN formation by competitive production of the neuroprotective metabolite picolinic acid (PIC). Therefore, decreased ACMSD activity can lead to excess QUIN. We tested the hypothesis that deficient ACMSD activity underlies suicidal behavior. We measured PIC and QUIN in CSF and plasma samples from 137 patients exhibiting suicidal behavior and 71 healthy controls. We used DSM-IV and the Montgomery-Asberg Depression Rating Scale and Suicide Assessment Scale to assess behavioral changes. Finally, we genotyped ACMSD tag single nucleotide polymorphisms (SNPs) in 77 of the patients and 150 population-based controls. Suicide attempters had reduced PIC and a decreased PIC/QUIN ratio in both CSF (Pamp;lt;0.001) and blood (P=0.001 and Pamp;lt;0.01, respectively). The reductions of PIC in CSF were sustained over 2 years after the suicide attempt based on repeated measures. The minor C allele of the ACMSD SNP rs2121337 was more prevalent in suicide attempters and associated with increased CSF QUIN. Taken together, our data suggest that increased QUIN levels may result from reduced activity of ACMSD in suicidal subjects. We conclude that measures of kynurenine metabolites can be explored as biomarkers of suicide risk, and that ACMSD is a potential therapeutic target in suicidal behavior., Funding Agencies|Swedish Research Council (VR) [2009-4284, 2011-4787, 2002-5297, 2008-2922, 2009-7052, 2013-2838]; Province of Scania clinical state grants; Swedish Research Council [K2014-62X-14647-12-51]; Swedish Federal Government [ALF 20130032]; NIH [1R01MH104622-01]; American Foundation for Suicide Prevention [DIG 1-162-12]; Michigan State University; Van Andel Research Institute; Australian Research Council; National Health and Medical Research Council, Australia; Rocky Mountain MIRECC; Merit Review CSRD grant [1 I01 CX001310- 01A1]; Joint Institute for Food Safety and Applied Nutrition/ UMD [FDU.001418]

Published
2016
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