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8. Excitatory/inhibitory imbalance in autism: the role of glutamate and GABA gene-sets in symptoms and cortical brain structure

Author

Hollestein, Viola, Poelmans, Geert, Forde, Natalie J, Beckmann, Christian F, Ecker, Christine, Mann, Caroline, Schäfer, Tim, Moessnang, Carolin, Baumeister, Sarah, Banaschewski, Tobias, Bourgeron, Thomas, Loth, Eva, Dell'Acqua, Flavio, Murphy, Declan GM, Puts, Nicolaas A, Tillmann, Julian, Charman, Tony, Jones, Emily JH, Mason, Luke, Ambrosino, Sara, Holt, Rosemary, Bölte, Sven, Buitelaar, Jan K, Naaijen, Jilly, Hollestein, Viola [0000-0002-6326-4172], Poelmans, Geert [0000-0001-7039-6985], Banaschewski, Tobias [0000-0003-4595-1144], Loth, Eva [0000-0001-9458-9167], Murphy, Declan GM [0000-0002-6664-7451], Puts, Nicolaas A [0000-0003-1024-1927], Charman, Tony [0000-0003-1993-6549], Bölte, Sven [0000-0002-4579-4970], Buitelaar, Jan K [0000-0001-8288-7757], Apollo - University of Cambridge Repository, Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], Radboud University Medical Center [Nijmegen], Goethe-Universität Frankfurt am Main, King‘s College London, Universität Heidelberg [Heidelberg] = Heidelberg University, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Sackler Institute of Translational Neurodevelopment [London], F. Hoffmann-La Roche [Basel], University of London [London], Utrecht University [Utrecht], University of Cambridge [UK] (CAM), Karolinska Institutet [Stockholm], Curtin University [Perth], Planning and Transport Research Centre (PATREC), Karakter Child and Adolescent Psychiatry University Centre [Nijmegen], This work has been supported by the EU-AIMS (European Autism Interventions) and AIMS-2-TRIALS programmes which receive support from Innovative Medicines Initiative Joint Undertaking Grant No. 115300 and 777394, the resources of which are composed of financial contributions from the European Union’s FP7 and Horizon2020 Programmes, and from the European Federation of Pharmaceutical Industries and Associations (EFPIA) companies’ in-kind contributions, and AUTISM SPEAKS, Autistica and SFARI, by the Horizon2020 supported programme CANDY Grant No. 847818 and a Veni grant from the Netherlands organization for scientific research (NWO) under grant number VI.Veni.194.032 awarded to JN. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results. Any views expressed are those of the authors and not necessarily those of the funders., European Project: 115300,EC:FP7:SP1-JTI,IMI-JU-03-2010,EU-AIMS(2012), European Project: 777394,H2020-JTI-IMI2-2016-10-two-stage,AIMS-2-TRIALS(2018), and European Project: 101069276,CANDY

Subjects
Adult, Male, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Adolescent, Autism Spectrum Disorder, article, Glutamic Acid, Brain, 692/699/476/1373, Cellular and Molecular Neuroscience, Psychiatry and Mental health, All institutes and research themes of the Radboud University Medical Center, 692/53, 59/57, Humans, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Autistic Disorder, 631/378, Transcriptome, gamma-Aminobutyric Acid, Biological Psychiatry
Abstract

Funder: AIMS-2TRIALS/EU-AIMS which receive support from Innovative Medicines Initiative Joint Undertaking grant numbers 115300 and 777394, Funder: Horizon2020 CANDY programme grant number 847818, Funder: Dutch NWO Veni grant grant number VI.Veni.194.032, The excitatory/inhibitory (E/I) imbalance hypothesis posits that imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) mechanisms underlies the behavioral characteristics of autism. However, how E/I imbalance arises and how it may differ across autism symptomatology and brain regions is not well understood. We used innovative analysis methods-combining competitive gene-set analysis and gene-expression profiles in relation to cortical thickness (CT) to investigate relationships between genetic variance, brain structure and autism symptomatology of participants from the AIMS-2-TRIALS LEAP cohort (autism = 359, male/female = 258/101; neurotypical control participants = 279, male/female = 178/101) aged 6-30 years. Using competitive gene-set analyses, we investigated whether aggregated genetic variation in glutamate and GABA gene-sets could be associated with behavioral measures of autism symptoms and brain structural variation. Further, using the same gene-sets, we corelated expression profiles throughout the cortex with differences in CT between autistic and neurotypical control participants, as well as in separate sensory subgroups. The glutamate gene-set was associated with all autism symptom severity scores on the Autism Diagnostic Observation Schedule-2 (ADOS-2) and the Autism Diagnostic Interview-Revised (ADI-R) within the autistic group. In adolescents and adults, brain regions with greater gene-expression of glutamate and GABA genes showed greater differences in CT between autistic and neurotypical control participants although in opposing directions. Additionally, the gene expression profiles were associated with CT profiles in separate sensory subgroups. Our results suggest complex relationships between E/I related genetics and autism symptom profiles as well as brain structure alterations, where there may be differential roles for glutamate and GABA.

Published
2023

9. In search of environmental risk factors for obsessive-compulsive disorder: study protocol for the OCDTWIN project

Author

Mataix-Cols, David, primary, Fernández de la Cruz, Lorena, additional, De Schipper, Elles, additional, Kuja-Halkola, Ralf, additional, Bulik, Cynthia M., additional, Crowley, James J., additional, Neufeld, Janina, additional, Rück, Christian, additional, Tammimies, Kristiina, additional, Lichtenstein, Paul, additional, Bölte, Sven, additional, and Beucke, Jan C., additional

Published
2023
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19. Emerging Verbal Functions in Early Infancy: Lessons from Observational and Computational Approaches on Typical Development and Neurodevelopmental Disorders

Author

Marschik, Peter B., primary, Widmann, Claudius A. A., additional, Lang, Sigrun, additional, Kulvicius, Tomas, additional, Boterberg, Sofie, additional, Nielsen-Saines, Karin, additional, Bölte, Sven, additional, Esposito, Gianluca, additional, Nordahl-Hansen, Anders, additional, Roeyers, Herbert, additional, Wörgötter, Florentin, additional, Einspieler, Christa, additional, Poustka, Luise, additional, and Zhang, Dajie, additional

Published
2022
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20. The efficacy of the “Talk-to-Me” suicide prevention and mental health education program for tertiary students: a crossover randomised control trial

Author

Afsharnejad, Bahareh, primary, Milbourn, Ben, additional, Hayden-Evans, Maya, additional, Baker-Young, Ellie, additional, Black, Melissa H., additional, Thompson, Craig, additional, McGarry, Sarah, additional, Grobler, Melissa, additional, Clifford, Rhonda, additional, Zimmermann, Frank, additional, Kacic, Viktor, additional, Hasking, Penelope, additional, Bölte, Sven, additional, Romanos, Marcel, additional, Machingura, Tawanda, additional, and Girdler, Sonya, additional

Published
2022
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23. Resting state EEG power spectrum and functional connectivity in autism: a cross-sectional analysis

Author

Garcés, Pilar, Baumeister, Sarah, Mason, Luke, Chatham, Christopher, Holiga, Stefan, Dukart, Juergen, Jones, Emily, Banaschewski, Tobias, Baron-Cohen, Simon, Bölte, Sven, Buitelaar, Jan, Durston, Sarah, Oranje, Bob, Persico, Antonio, Beckmann, Christian, Bougeron, Thomas, Dell’acqua, Flavio, Ecker, Christine, Moessnang, Carolin, Charman, Tony, Tillmann, Julian, Murphy, Declan, Johnson, Mark, Loth, Eva, Brandeis, Daniel, Hipp, Joerg, Ahmad, Jumana, Ambrosino, Sara, Auyeung, Bonnie, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brogna, Claudia, de Bruijn, Yvette, Chakrabarti, Bhismadev, Cornelissen, Ineke, Crawley, Daisy, Dumas, Guillaume, Faulkner, Jessica, Frouin, Vincent, Goyard, David, Ham, Lindsay, Hayward, Hannah, Holt, Rosemary, Kundu, Prantik, Lai, Meng-Chuan, Ardhuy, Xavier Liogier D’, Lombardo, Michael, Lythgoe, David, Mandl, René, Marquand, Andre, Mennes, Maarten, Meyer-Lindenberg, Andreas, Mueller, Nico, Oakley, Bethany, O’dwyer, Laurence, Oldehinkel, Marianne, Pandina, Gahan, Ruggeri, Barbara, Ruigrok, Amber, Sabet, Jessica, Sacco, Roberto, Cáceres, Antonia San José, Simonoff, Emily, Spooren, Will, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams, Steve, Wooldridge, Caroline, Zwiers, Marcel, Leap Group, The Eu-Aims, Garcés, Pilar [0000-0003-4989-0123], Apollo - University of Cambridge Repository, Roche Innovation Center [Basel, Switzerland], Heidelberg University, University Hospital Mannheim | Universitätsmedizin Mannheim, University of London [London], Institute of Neuroscience and Medicine, Brain and Behaviour [Jülich, Germany] (INM-7), Jülich Research Centre, Autism Research Centre [Cambridge, Royaume-Uni], University of Cambridge [UK] (CAM), Centre for Psychiatry Research [Stockholm], Karolinska Institutet [Stockholm], Curtin University [Perth], Planning and Transport Research Centre (PATREC), Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], University Medical Center [Utrecht], Università degli Studi di Messina = University of Messina (UniMe), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), King‘s College London, Goethe-University Frankfurt am Main, Central Institute of Mental Health [Mannheim], This work was supported by EU-AIMS (European Autism Interventions), which receives support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115300, the resources of which are composed of financial contributions from the European Union’s Seventh Framework Programme (grant FP7/2007–2013), from the European Federation of Pharmaceutical Industries and Associations companies’ in-kind contributions and from Autism Speaks. AIMS-2-TRIALS is funded by the Innovative Medicines Initiative 2 Joint Undertaking (IMI 2 JU) under grant agreement no. 777394. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation program, EFPIA, Autism Speaks, Autistica, and SFARI. PG was supported by the Roche Postdoctoral Fellowship (RPF) program., European Project: 115300,EC:FP7:SP1-JTI,IMI-JU-03-2010,EU-AIMS(2012), European Project: 777394,H2020-JTI-IMI2-2016-10-two-stage,AIMS-2-TRIALS(2018), and University of Zurich

Subjects
Adult, Adolescent, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], Autism spectrum disorder, EEG, Resting state, Power spectrum, Functional connectivity, 610 Medicine & health, 1309 Developmental Biology, 2806 Developmental Neuroscience, 2738 Psychiatry and Mental Health, Developmental Neuroscience, 130 000 Cognitive Neurology & Memory, 1312 Molecular Biology, Humans, ddc:610, 10064 Neuroscience Center Zurich, Autistic Disorder, Child, Molecular Biology, Brain Mapping, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Research, 220 Statistical Imaging Neuroscience, Brain, Reproducibility of Results, Electroencephalography, 10058 Department of Child and Adolescent Psychiatry, Magnetic Resonance Imaging, Psychiatry and Mental health, Cross-Sectional Studies, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Developmental Biology
Abstract

Background Understanding the development of the neuronal circuitry underlying autism spectrum disorder (ASD) is critical to shed light into its etiology and for the development of treatment options. Resting state EEG provides a window into spontaneous local and long-range neuronal synchronization and has been investigated in many ASD studies, but results are inconsistent. Unbiased investigation in large and comprehensive samples focusing on replicability is needed. Methods We quantified resting state EEG alpha peak metrics, power spectrum (PS, 2–32 Hz) and functional connectivity (FC) in 411 children, adolescents and adults (n = 212 ASD, n = 199 neurotypicals [NT], all with IQ > 75). We performed analyses in source-space using individual head models derived from the participants’ MRIs. We tested for differences in mean and variance between the ASD and NT groups for both PS and FC using linear mixed effects models accounting for age, sex, IQ and site effects. Then, we used machine learning to assess whether a multivariate combination of EEG features could better separate ASD and NT participants. All analyses were embedded within a train-validation approach (70%–30% split). Results In the training dataset, we found an interaction between age and group for the reactivity to eye opening (p = .042 uncorrected), and a significant but weak multivariate ASD vs. NT classification performance for PS and FC (sensitivity 0.52–0.62, specificity 0.59–0.73). None of these findings replicated significantly in the validation dataset, although the effect size in the validation dataset overlapped with the prediction interval from the training dataset. Limitations The statistical power to detect weak effects—of the magnitude of those found in the training dataset—in the validation dataset is small, and we cannot fully conclude on the reproducibility of the training dataset’s effects. Conclusions This suggests that PS and FC values in ASD and NT have a strong overlap, and that differences between both groups (in both mean and variance) have, at best, a small effect size. Larger studies would be needed to investigate and replicate such potential effects., Molecular Autism, 13

Published
2022

27. Psycho-social factors associated with mental resilience in the Corona lockdown

Author

Veer, Ilya M., Riepenhausen, Antje, Zerban, Matthias, Wackerhagen, Carolin, Puhlmann, Lara M. C., Engen, Haakon, Köber, Göran, Bögemann, Sophie A., Weermeijer, Jeroen, Uściłko, Aleksandra, Mor, Netali, Marciniak, Marta A., Askelund, Adrian Dahl, Al-Kamel, Abbas, Ayash, Sarah, Barsuola, Giulia, Bartkute-Norkuniene, Vaida, Battaglia, Simone, Bobko, Yaryna, Bölte, Sven, Cardone, Paolo, Chvojková, Edita, Damnjanović, Kaja, De Calheiros Velozo, Joana, de Thurah, Lena, Deza-Araujo, Yacila I., Dimitrov, Annika, Farkas, Kinga, Feller, Clémence, Gazea, Mary, Gilan, Donya, Gnjidić, Vedrana, Hajduk, Michal, Hiekkaranta, Anu P., Hofgaard, Live S., Ilen, Laura, Kasanova, Zuzana, Khanpour, Mohsen, Lau, Bobo Hi Po, Lenferink, Dionne B., Lindhardt, Thomas B., Magas, Dávid Á., Mituniewicz, Julian, Moreno-López, Laura, Muzychka, Sofiia, Ntafouli, Maria, O’Leary, Aet, Paparella, Ilenia, Põldver, Nele, Rintala, Aki, Robak, Natalia, Rosická, Anna M., Røysamb, Espen, Sadeghi, Siavash, Schneider, Maude, Siugzdaite, Roma, Stantić, Mirta, Teixeira, Ana, Todorovic, Ana, Wan, Wendy W. N., van Dick, Rolf, Lieb, Klaus, Kleim, Birgit, Hermans, Erno J., Kobylińska, Dorota, Hendler, Talma, Binder, Harald, Myin-Germeys, Inez, van Leeuwen, Judith M. C., Tüscher, Oliver, Yuen, Kenneth S. L., Walter, Henrik, Kalisch, Raffael, Riepenhausen, Antje [0000-0001-8749-5349], Wackerhagen, Carolin [0000-0002-5689-3472], Puhlmann, Lara MC [0000-0002-0870-8770], Marciniak, Marta A [0000-0003-4301-3269], Al-Kamel, Abbas [0000-0002-7941-0381], Ayash, Sarah [0000-0001-5146-1040], Bölte, Sven [0000-0002-4579-4970], Farkas, Kinga [0000-0002-1125-3957], Gnjidić, Vedrana [0000-0002-4036-4525], Hajduk, Michal [0000-0002-7073-7564], Põldver, Nele [0000-0001-7307-544X], van Dick, Rolf [0000-0002-6308-9466], Myin-Germeys, Inez [0000-0002-3731-4930], Tüscher, Oliver [0000-0002-4023-5301], Walter, Henrik [0000-0002-9403-6121], Kalisch, Raffael [0000-0002-9503-7601], Apollo - University of Cambridge Repository, Puhlmann, Lara M. C. [0000-0002-0870-8770], Marciniak, Marta A. [0000-0003-4301-3269], Veer I.M., Riepenhausen A., Zerban M., Wackerhagen C., Puhlmann L.M.C., Engen H., Kober G., Bogemann S.A., Weermeijer J., Uscilko A., Mor N., Marciniak M.A., Askelund A.D., Al-Kamel A., Ayash S., Barsuola G., Bartkute-Norkuniene V., Battaglia S., Bobko Y., Bolte S., Cardone P., Chvojkova E., Damnjanovic K., De Calheiros Velozo J., de Thurah L., Deza-Araujo Y.I., Dimitrov A., Farkas K., Feller C., Gazea M., Gilan D., Gnjidic V., Hajduk M., Hiekkaranta A.P., Hofgaard L.S., Ilen L., Kasanova Z., Khanpour M., Lau B.H.P., Lenferink D.B., Lindhardt T.B., Magas D.A., Mituniewicz J., Moreno-Lopez L., Muzychka S., Ntafouli M., O'Leary A., Paparella I., Poldver N., Rintala A., Robak N., Rosicka A.M., Roysamb E., Sadeghi S., Schneider M., Siugzdaite R., Stantic M., Teixeira A., Todorovic A., Wan W.W.N., van Dick R., Lieb K., Kleim B., Hermans E.J., Kobylinska D., Hendler T., Binder H., Myin-Germeys I., van Leeuwen J.M.C., Tuscher O., Yuen K.S.L., Walter H., Kalisch R., Ontwikkelingspsychologie (Psychologie, FMG), and Psychology Other Research (FMG)

Subjects
Adult, Male, OUTBREAK, Social Sciences, mental health, resilience, pandemic, coronavirus, positive appraisal style, international collaboration, Regression Analysi, lcsh:RC321-571, Cellular and Molecular Neuroscience, Young Adult, 631/477/2811, ddc:150, Human behaviour, 692/53/2421, Disease Transmission, Infectious, Humans, Social Factors, Multivariate Analysi, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Protective Factor, Biological Psychiatry, Cross-Sectional Studie, article, COVID-19, Social Support, Diagnostic markers, Middle Aged, Protective Factors, Resilience, Psychological, ddc:616.8, Europe, Psychiatry and Mental health, Cross-Sectional Studies, Mental Health, Disease Transmission, Infectiou, HEALTH-CARE, Multivariate Analysis, Regression Analysis, Female, Stress, Psychological, Human
Abstract

The SARS-CoV-2 pandemic is not only a threat to physical health but is also having severe impacts on mental health. Although increases in stress-related symptomatology and other adverse psycho-social outcomes, as well as their most important risk factors have been described, hardly anything is known about potential protective factors. Resilience refers to the maintenance of mental health despite adversity. To gain mechanistic insights about the relationship between described psycho-social resilience factors and resilience specifically in the current crisis, we assessed resilience factors, exposure to Corona crisis-specific and general stressors, as well as internalizing symptoms in a cross-sectional online survey conducted in 24 languages during the most intense phase of the lockdown in Europe (22 March to 19 April) in a convenience sample of N = 15,970 adults. Resilience, as an outcome, was conceptualized as good mental health despite stressor exposure and measured as the inverse residual between actual and predicted symptom total score. Preregistered hypotheses (osf.io/r6btn) were tested with multiple regression models and mediation analyses. Results confirmed our primary hypothesis that positive appraisal style (PAS) is positively associated with resilience (p

Published
2021

30. Preventing suicide in post-secondary students: a scoping review of suicide prevention programs

Author

Black, Melissa H., primary, Scott, Melissa, additional, Baker-Young, Elliot, additional, Thompson, Craig, additional, McGarry, Sarah, additional, Hayden-Evans, Maya, additional, Snyman, Zelma, additional, Zimmermann, Frank, additional, Kacic, Viktor, additional, Falkmer, Torbjorn, additional, Romanos, Marcel, additional, Bölte, Sven, additional, Girdler, Sonya, additional, and Milbourn, Benjamin, additional

Published
2021
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33. Novel AI driven approach to classify infant motor functions

Author

Reich, Simon, primary, Zhang, Dajie, additional, Kulvicius, Tomas, additional, Bölte, Sven, additional, Nielsen-Saines, Karin, additional, Pokorny, Florian B., additional, Peharz, Robert, additional, Poustka, Luise, additional, Wörgötter, Florentin, additional, Einspieler, Christa, additional, and Marschik, Peter B., additional

Published
2021
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41. Presynaptic dysfunction in CASK-related neurodevelopmental disorders

Author

Becker, Martin, primary, Mastropasqua, Francesca, additional, Reising, Jan Philipp, additional, Maier, Simon, additional, Ho, Mai-Lan, additional, Rabkina, Ielyzaveta, additional, Li, Danyang, additional, Neufeld, Janina, additional, Ballenberger, Lea, additional, Myers, Lynnea, additional, Moritz, Viveka, additional, Kele, Malin, additional, Wincent, Josephine, additional, Willfors, Charlotte, additional, Sitnikov, Rouslan, additional, Herlenius, Eric, additional, Anderlid, Britt-Marie, additional, Falk, Anna, additional, Bölte, Sven, additional, and Tammimies, Kristiina, additional

Published
2020
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45. Cross-Cultural Adaptation to Australia of the KONTAKT© Social Skills Group Training Program for Youth with Autism Spectrum Disorder: A Feasibility Study

Author

Afsharnejad, Bahareh, primary, Falkmer, Marita, additional, Black, Melissa H., additional, Alach, Tasha, additional, Lenhard, Fabian, additional, Fridell, Anna, additional, Coco, Christina, additional, Milne, Kelly, additional, Chen, Nigel T. M., additional, Bölte, Sven, additional, and Girdler, Sonya, additional

Published
2020
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