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12. Dissecting the phenotypic heterogeneity in sensory features in autism spectrum disorder: a factor mixture modelling approach

Author

Tillmann, J., Uljarevic, M., Crawley, D., Dumas, G., Loth, E., Murphy, D., Buitelaar, J., Charman, T., Ahmad, J., Ambrosino, S., Auyeung, B., Baumeister, S., Beckmann, C., Bourgeron, T., Bours, C., Brammer, M., Brandeis, D., Brogna, C., De Bruijn, Y., Chakrabarti, B., Cornelissen, I., Acqua, F. D., Ecker, C., Faulkner, J., Frouin, V., Garces, P., Goyard, D., Hayward, H., Hipp, J., Johnson, M. H., Jones, E. J. H., Kundu, P., Lai, M. -C., D'Ardhuy, X. L., Lombardo, M., Lythgoe, D. J., Mandl, R., Mason, L., Meyer-Lindenberg, A., Moessnang, C., Mueller, N., O'Dwyer, L., Oldehinkel, M., Oranje, B., Pandina, G., Persico, A. M., Ruggeri, B., Ruigrok, A., Sabet, J., Sacco, R., Toro, R., Tost, H., Waldman, J., Williams, S. C. R., Wooldridge, C., Zwiers, M. P., Tillmann, J [0000-0001-9574-9855], Apollo - University of Cambridge Repository, and University of Zurich

Subjects
Male, Neurology, medicine.medical_treatment, Audiology, Anxiety, lcsh:RC346-429, 1309 Developmental Biology, 2738 Psychiatry and Mental Health, 0302 clinical medicine, Autism spectrum disorder, Child, Uncategorized, 0303 health sciences, Confounding, Neuropsychology, 10058 Department of Child and Adolescent Psychiatry, communication symptoms, Psychiatry and Mental health, Phenotype, Regression Analysis, Female, medicine.symptom, Psychology, Adult, medicine.medical_specialty, Sensory processing, Adolescent, Sensation, 610 Medicine & health, Sensory system, Models, Biological, Sensory features, 2806 Developmental Neuroscience, 03 medical and health sciences, Young Adult, Social, Developmental Neuroscience, Heterogeneity, Social-communication symptoms, 1312 Molecular Biology, medicine, Humans, Molecular Biology, lcsh:Neurology. Diseases of the nervous system, 030304 developmental biology, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Genetic heterogeneity, Research, medicine.disease, Multivariate Analysis, 030217 neurology & neurosurgery, Developmental Biology
Abstract

Background Heterogeneity in the phenotypic presentation of autism spectrum disorder (ASD) is apparent in the profile and the severity of sensory features. Here, we applied factor mixture modelling (FMM) to test a multidimensional factor model of sensory processing in ASD. We aimed to identify homogeneous sensory subgroups in ASD that differ intrinsically in their severity along continuous factor scores. We also investigated sensory subgroups in relation to clinical variables: sex, age, IQ, social-communication symptoms, restricted and repetitive behaviours, adaptive functioning and symptoms of anxiety and attention-deficit/hyperactivity disorder. Methods Three hundred thirty-two children and adults with ASD between the ages of 6 and 30 years with IQs varying between 40 and 148 were included. First, three different confirmatory factor models were fit to the 38 items of the Short Sensory Profile (SSP). Then, latent class models (with two-to-six subgroups) were evaluated. The best performing factor model, the 7-factor structure, was subsequently used in two FMMs that varied in the number of subgroups: a two-subgroup, seven-factor model and a three-subgroup and seven-factor model. Results The ‘three-subgroup/seven-factor’ FMM was superior to all other models based on different fit criteria. Identified subgroups differed in sensory severity from severe, moderate to low. Accounting for the potential confounding effects of age and IQ, participants in these sensory subgroups had different levels of social-communicative symptoms, restricted and repetitive behaviours, adaptive functioning skills and symptoms of inattention and anxiety. Limitations Results were derived using a single parent-report measure of sensory features, the SSP, which limits the generalisability of findings. Conclusion Sensory features can be best described by three homogeneous sensory subgroups that differ in sensory severity gradients along seven continuous factor scores. Identified sensory subgroups were further differentiated by the severity of core and co-occurring symptoms, and level of adaptive functioning, providing novel evidence on the associated clinical correlates of sensory subgroups. These sensory subgroups provide a platform to further interrogate the neurobiological and genetic correlates of altered sensory processing in ASD.

Published
2020
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13. Genetic architecture of subcortical brain structures in 38,854 individuals worldwide

Author

Satizabal, C., Adams, H., Hibar, D., White, C., Knol, M., Stein, J., Scholz, M., Sargurupremraj, M., Jahanshad, N., Roshchupkin, G., Smith, A., Bis, J., Jian, X., Luciano, M., Hofer, E., Teumer, A., Van der Lee, S., Yang, J., Yanek, L., Lee, T., Li, S., Hu, Y., Koh, J., Eicher, J., Desrivières, S., Arias-Vasquez, A., Chauhan, G., Athanasiu, L., Renteria, M., Kim, S., Höhn, D., Armstrong, N., Chen, Q., Holmes, A., Den Braber, A., Kloszewska, I., Andersson, M., Espeseth, T., Grimm, O., Abramovic, L., Alhusaini, S., Milaneschi, Y., Papmeyer, M., Axelsson, T., Ehrlich, S., Roiz-Santiañez, R., Kraemer, B., Håberg, A., Jones, H., Pike, G., Stein, D., Stevens, A., Bralten, J., Vernooij, M., Harris, T., Filippi, I., Witte, A., Guadalupe, T., Wittfeld, K., Mosley, T., Becker, J., Doan, N., Hagenaars, S., Saba, Y., Cuellar-Partida, G., Amin, N., Hilal, S., Nho, K., Karbalai, N., Arfanakis, K., Becker, D., Ames, D., Goldman, A., Lee, P., Boomsma, D., Lovestone, S., Giddaluru, S., Le Hellard, S., Mattheisen, M., Bohlken, M., Kasperaviciute, D., Schmaal, L., Lawrie, S., Agartz, I., Walton, E., Tordesillas-Gutierrez, D., Davies, G., Shin, J., Ipser, J., Vinke, L., Hoogman, M., Jia, T., Burkhardt, R., Klein, M., Crivello, F., Janowitz, D., Carmichael, O., Haukvik, U., Aribisala, B., Schmidt, H., Strike, L., Cheng, C., Risacher, S., Pütz, B., Fleischman, D., Assareh, A., Mattay, V., Buckner, R., Mecocci, P., Dale, A., Cichon, S., Boks, M., Matarin, M., Penninx, B., Calhoun, V., Chakravarty, M., Marquand, A., Macare, C., Masouleh, S., Oosterlaan, J., Amouyel, P., Hegenscheid, K., Rotter, J., Schork, A., Liewald, D., De Zubicaray, G., Wong, T., Shen, L., Sämann, P., Brodaty, H., Roffman, J., De Geus, E., Tsolaki, M., Erk, S., Van Eijk, K., Cavalleri, G., Van der Wee, N., McIntosh, A., Gollub, R., Bulayeva, K., Bernard, M., Richards, J., Himali, J., Loeffler, M., Rommelse, N., Hoffmann, W., Westlye, L., Valdés Hernández, M., Hansell, N., Van Erp, T., Wolf, C., Kwok, J., Vellas, B., Heinz, A., Olde Loohuis, L., Delanty, N., Ho, B., Ching, C., Shumskaya, E., Singh, B., Hofman, A., Van der Meer, D., Homuth, G., Psaty, B., Bastin, M., Montgomery, G., Foroud, T., Reppermund, S., Hottenga, J., Simmons, A., Meyer-Lindenberg, A., Cahn, W., Whelan, C., Van Donkelaar, M., Yang, Q., Hosten, N., Green, R., Thalamuthu, A., Mohnke, S., Hulshoff Pol, H., Lin, H., Jack Jr., C., Schofield, P., Mühleisen, T., Maillard, P., Potkin, S., Wen, W., Fletcher, E., Toga, A., Gruber, O., Huentelman, M., Smith, G., Launer, L., Nyberg, L., Jönsson, E., Crespo-Facorro, B., Koen, N., Greve, D., Uitterlinden, A., Weinberger, D., Steen, V., Fedko, I., Groenewold, N., Niessen, W., Toro, R., Tzourio, C., Longstreth Jr., W., Ikram, M., Smoller, J., Van Tol, M., Sussmann, J., Paus, T., Lemaître, H., Schroeter, M., Mazoyer, B., Andreassen, O., Holsboer, F., Depondt, C., Veltman, D., Turner, J., Pausova, Z., Schumann, G., Van Rooij, D., Djurovic, S., Deary, I., McMahon, K., Müller-Myhsok, B., Brouwer, R., Soininen, H., Pandolfo, M., Wassink, T., Cheung, J., Wolfers, T., Martinot, J., Zwiers, M., Nauck, M., Melle, I., Martin, N., Kanai, R., Westman, E., Kahn, R., Sisodiya, S., White, T., Saremi, A., Van Bokhoven, H., Brunner, H., Völzke, H., Wright, M., Van 't Ent, D., Nöthen, M., Ophoff, R., Buitelaar, J., Fernández, G., Sachdev, P., Rietschel, M., Van Haren, N., Fisher, S., Beiser, A., Francks, C., Saykin, A., Mather, K., Romanczuk-Seiferth, N., Hartman, C., DeStefano, A., Heslenfeld, D., Weiner, M., Walter, H., Hoekstra, P., Nyquist, P., Franke, B., Bennett, D., Grabe, H., Johnson, A., Chen, C., Van Duijn, C., Lopez, O., Fornage, M., Wardlaw, J., Schmidt, R., DeCarli, C., De Jager, P., Villringer, A., Debette, S., Gudnason, V., Medland, S., Shulman, J., Thompson, P., and Seshadri, S.

Subjects
nervous system
Abstract

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.

Published
2019

14. Genetic architecture of subcortical brain structures in 38,851 individuals

Author

SATIZABAL, C. L., ADAMS, H. H. H., HIBAR, D. P., WHITE, C. C., KNOL, M. J., STEIN, J. L., Scholz, M., Sargurupremraj, Muralidharan, JAHANSHAD, N., ROSHCHUPKIN, G. V., SMITH, A. V., BIS, J. C., JIAN, X., LUCIANO, M., Hofer, E., TEUMER, A., VAN DER LEE, S. J., Yang, J., YANEK, L. R., LEE, T. V., Li, S., Hu, Y., KOH, J. Y., EICHER, J. D., DESRIVIERES, S., ARIAS-VASQUEZ, A., Chauhan, G., ATHANASIU, L., RENTERIA, M. E., Kim, S., HOEHN, D., ARMSTRONG, N. J., Chen, Q., HOLMES, A. J., DEN BRABER, A., KLOSZEWSKA, I., Andersson, M., ESPESETH, T., Grimm, O., ABRAMOVIC, L., ALHUSAINI, S., MILANESCHI, Y., PAPMEYER, M., AXELSSON, T., Ehrlich, S., ROIZ-SANTIANEZ, R., KRAEMER, B., HABERG, A. K., JONES, H. J., Pike, G. B., STEIN, D. J., Stevens, A., BRALTEN, J., VERNOOIJ, M. W., HARRIS, T. B., FILIPPI, I., WITTE, A. V., Guadalupe, T., WITTFELD, K., MOSLEY, T. H., BECKER, J. T., DOAN, N. T., HAGENAARS, S. P., SABA, Y., CUELLAR-PARTIDA, G., Amin, N., HILAL, S., NHO, K., MIRZA-SCHREIBER, N., ARFANAKIS, K., BECKER, D. M., Ames, D., GOLDMAN, A. L., LEE, P. H., Boomsma, D. I., LOVESTONE, S., GIDDALURU, S., LE HELLARD, S., Mattheisen, M., BOHLKEN, M. M., KASPERAVICIUTE, D., SCHMAAL, L., LAWRIE, S. M., Agartz, I., Walton, E., TORDESILLAS-GUTIERREZ, D., DAVIES, G. E., Shin, J., IPSER, J. C., VINKE, L. N., HOOGMAN, M., Jia, T., BURKHARDT, R., Klein, M., Crivello, Fabrice, JANOWITZ, D., CARMICHAEL, O., HAUKVIK, U. K., ARIBISALA, B. S., Schmidt, H., STRIKE, L. T., CHENG, C. Y., RISACHER, S. L., PUTZ, B., FLEISCHMAN, D. A., ASSAREH, A. A., MATTAY, V. S., BUCKNER, R. L., MECOCCI, P., DALE, A. M., Cichon, S., BOKS, M. P., MATARIN, M., PENNINX, Bwjh, CALHOUN, V. D., CHAKRAVARTY, M. M., MARQUAND, A. F., MACARE, C., KHARABIAN MASOULEH, S., OOSTERLAAN, J., Amouyel, P., HEGENSCHEID, K., ROTTER, J. I., SCHORK, A. J., LIEWALD, D. C. M., DE ZUBICARAY, G. I., WONG, T. Y., Shen, L., SAMANN, P. G., BRODATY, H., ROFFMAN, J. L., DE GEUS, E. J. C., TSOLAKI, M., ERK, S., VAN EIJK, K. R., CAVALLERI, G. L., VAN DER WEE, N. J. A., MCINTOSH, A. M., GOLLUB, R. L., BULAYEVA, K. B., Bernard, M., RICHARDS, J. S., HIMALI, J. J., Loeffler, M., ROMMELSE, N., Hoffmann, W., WESTLYE, L. T., VALDES HERNANDEZ, M. C., HANSELL, N. K., VAN ERP, T. G. M., Wolf, C., KWOK, J. B. J., Vellas, B., Heinz, A., OLDE LOOHUIS, L. M., DELANTY, N., HO, B. C., CHING, C. R. K., SHUMSKAYA, E., Singh, B., Hofman, A., VAN DER MEER, D., Homuth, G., PSATY, B. M., BASTIN, M. E., MONTGOMERY, G. W., FOROUD, T. M., REPPERMUND, S., HOTTENGA, J. J., Simmons, A., Meyer-Lindenberg, A., Cahn, W., WHELAN, C. D., VAN DONKELAAR, M. M. J., Yang, Q., HOSTEN, N., GREEN, R. C., THALAMUTHU, A., MOHNKE, S., HULSHOFF POL, H. E., Lin, H., JACK, C. R., Jr., SCHOFIELD, P. R., MUHLEISEN, T. W., MAILLARD, P., POTKIN, S. G., Wen, W., FLETCHER, E., TOGA, A. W., Gruber, O., HUENTELMAN, M., DAVEY SMITH, G., LAUNER, L. J., Nyberg, L., JONSSON, E. G., CRESPO-FACORRO, B., KOEN, N., GREVE, D. N., UITTERLINDEN, A. G., WEINBERGER, D. R., STEEN, V. M., FEDKO, I. O., GROENEWOLD, N. A., Niessen, W. J., TORO, R., Tzourio, Christophe, LONGSTRETH, W. T., Jr., SMOLLER, J. W., VAN TOL, M. J., SUSSMANN, J. E., PAUS, T., Lemaitre, H., SCHROETER, M. L., Mazoyer, B., ANDREASSEN, O. A., Holsboer, F., DEPONDT, C., VELTMAN, D. J., Turner, J. A., PAUSOVA, Z., Schumann, G., Van Rooij, D., Djurovic, S., DEARY, I. J., MCMAHON, K. L., MULLER-MYHSOK, B., BROUWER, R. M., Soininen, H., Pandolfo, M., WASSINK, T. H., CHEUNG, J. W., WOLFERS, T., MARTINOT, J. L., ZWIERS, M. P., Nauck, M., Melle, I., Martin, N. G., Kanai, R., WESTMAN, E., KAHN, R. S., Sisodiya, S. M., White, T., SAREMI, A., van Bokhoven, H., Brunner, H. G., VOLZKE, H., WRIGHT, M. J., VAN 'T ENT, D., NOTHEN, M. M., OPHOFF, R. A., BUITELAAR, J. K., Fernandez, G., SACHDEV, P. S., Rietschel, M., VAN HAREN, N. E. M., Fisher, S. E., BEISER, A. S., Francks, C., SAYKIN, A. J., MATHER, K. A., ROMANCZUK-SEIFERTH, N., HARTMAN, C. A., DeStefano, A. L., HESLENFELD, D. J., WEINER, M. W., Walter, H., HOEKSTRA, P. J., NYQUIST, P. A., Franke, B., BENNETT, D. A., Grabe, H. J., JOHNSON, A. D., Chen, C., VAN DUIJN, C. M., LOPEZ, O. L., FORNAGE, M., WARDLAW, J. M., Schmidt, R., DeCarli, C., DE JAGER, P. L., VILLRINGER, A., Debette, Stephanie, GUDNASON, V., Medland, S. E., SHULMAN, J. M., THOMPSON, P. M., SESHADRI, S., IKRAM, M. K., Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS)

Subjects
nervous system, VINTAGE, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, HEALTHY
Abstract

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.

Published
2019
Full Text
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16. The EU-AIMS Longitudinal European Autism Project (LEAP): Design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders

Author

Loth, E., Charman, T., Mason, L., Tillmann, J., Jones, E., Wooldridge, C., Ahmad, J., Auyeung, B., Brogna, C., Ambrosino, S., Banaschewski, T., Baron-Cohen, S., Baumeister, S., Beckmann, C., Brammer, M., Brandeis, D., Bolte, Sven, Bourgeron, T., Bours, C., De Bruijn, Y., Chakrabarti, B., Crawley, D., Cornelissen, I., Acqua, F., Dumas, G., Durston, S., Ecker, C., Faulkner, J., Frouin, V., Garces, P., Goyard, D., Hayward, H., Ham, L., Hipp, J., Holt, R., Johnson, M., Isaksson, J., Kundu, P., Lai, M., D'Ardhuy, X., Lombardo, M., Lythgoe, D., Mandl, R., Meyer-Lindenberg, A., Moessnang, C., Mueller, N., O'Dwyer, L., Oldehinkel, M., Oranje, B., Pandina, G., Persico, A., Ruigrok, A., Ruggeri, B., Sabet, J., Sacco, R., Cáceres, A., Simonoff, E., Toro, R., Tost, H., Waldman, J., Williams, S., Zwiers, M., Spooren, W., Murphy, D., Buitelaar, J., Loth, E., Charman, T., Mason, L., Tillmann, J., Jones, E., Wooldridge, C., Ahmad, J., Auyeung, B., Brogna, C., Ambrosino, S., Banaschewski, T., Baron-Cohen, S., Baumeister, S., Beckmann, C., Brammer, M., Brandeis, D., Bolte, Sven, Bourgeron, T., Bours, C., De Bruijn, Y., Chakrabarti, B., Crawley, D., Cornelissen, I., Acqua, F., Dumas, G., Durston, S., Ecker, C., Faulkner, J., Frouin, V., Garces, P., Goyard, D., Hayward, H., Ham, L., Hipp, J., Holt, R., Johnson, M., Isaksson, J., Kundu, P., Lai, M., D'Ardhuy, X., Lombardo, M., Lythgoe, D., Mandl, R., Meyer-Lindenberg, A., Moessnang, C., Mueller, N., O'Dwyer, L., Oldehinkel, M., Oranje, B., Pandina, G., Persico, A., Ruigrok, A., Ruggeri, B., Sabet, J., Sacco, R., Cáceres, A., Simonoff, E., Toro, R., Tost, H., Waldman, J., Williams, S., Zwiers, M., Spooren, W., Murphy, D., and Buitelaar, J.

Abstract

© 2017 The Author(s). Background: The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD. Methods: LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability. Results: Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some 'lessons learnt'. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted). Conclusi on

Published
2017

17. The EU-AIMS Longitudinal European Autism Project (LEAP): Clinical characterisation

Author

Charman, T., Loth, E., Tillmann, J., Crawley, D., Wooldridge, C., Goyard, D., Ahmad, J., Auyeung, B., Ambrosino, S., Banaschewski, T., Baron-Cohen, S., Baumeister, S., Beckmann, C., Bolte, Sven, Bourgeron, T., Bours, C., Brammer, M., Brandeis, D., Brogna, C., De Bruijn, Y., Chakrabarti, B., Cornelissen, I., Acqua, F., Dumas, G., Durston, S., Ecker, C., Faulkner, J., Frouin, V., Garcés, P., Ham, L., Hayward, H., Hipp, J., Holt, R., Isaksson, J., Johnson, M., Jones, E., Kundu, P., Lai, M., D'Ardhuy, X., Lombardo, M., Lythgoe, D., Mandl, R., Mason, L., Meyer-Lindenberg, A., Moessnang, C., Mueller, N., O'Dwyer, L., Oldehinkel, M., Oranje, B., Pandina, G., Persico, A., Ruggeri, B., Ruigrok, A., Sabet, J., Sacco, R., Cáceres, A., Simonoff, E., Toro, R., Tost, H., Waldman, J., Williams, S., Zwiers, M., Spooren, W., Murphy, D., Buitelaar, J., Charman, T., Loth, E., Tillmann, J., Crawley, D., Wooldridge, C., Goyard, D., Ahmad, J., Auyeung, B., Ambrosino, S., Banaschewski, T., Baron-Cohen, S., Baumeister, S., Beckmann, C., Bolte, Sven, Bourgeron, T., Bours, C., Brammer, M., Brandeis, D., Brogna, C., De Bruijn, Y., Chakrabarti, B., Cornelissen, I., Acqua, F., Dumas, G., Durston, S., Ecker, C., Faulkner, J., Frouin, V., Garcés, P., Ham, L., Hayward, H., Hipp, J., Holt, R., Isaksson, J., Johnson, M., Jones, E., Kundu, P., Lai, M., D'Ardhuy, X., Lombardo, M., Lythgoe, D., Mandl, R., Mason, L., Meyer-Lindenberg, A., Moessnang, C., Mueller, N., O'Dwyer, L., Oldehinkel, M., Oranje, B., Pandina, G., Persico, A., Ruggeri, B., Ruigrok, A., Sabet, J., Sacco, R., Cáceres, A., Simonoff, E., Toro, R., Tost, H., Waldman, J., Williams, S., Zwiers, M., Spooren, W., Murphy, D., and Buitelaar, J.

Abstract

© 2017 The Author(s). Background: The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study on biomarkers for autism spectrum disorder (ASD). The current paper describes the clinical characteristics of the LEAP cohort and examines age, sex and IQ differences in ASD core symptoms and common co-occurring psychiatric symptoms. A companion paper describes the overall design and experimental protocol and outlines the strategy to identify stratification biomarkers. Methods: From six research centres in four European countries, we recruited 437 children and adults with ASD and 300 controls between the ages of 6 and 30 years with IQs varying between 50 and 148. We conducted in-depth clinical characterisation including a wide range of observational, interview and questionnaire measures of the ASD phenotype, as well as co-occurring psychiatric symptoms. Results: The cohort showed heterogeneity in ASD symptom presentation, with only minimal to moderate site differences on core clinical and cognitive measures. On both parent-report interview and questionnaire measures, ASD symptom severity was lower in adults compared to children and adolescents. The precise pattern of differences varied across measures, but there was some evidence of both lower social symptoms and lower repetitive behaviour severity in adults. Males had higher ASD symptom scores than females on clinician-rated and parent interview diagnostic measures but not on parent-reported dimensional measures of ASD symptoms. In contrast, self-reported ASD symptom severity was higher in adults compared to adolescents, and in adult females compared to males. Higher scores on ASD symptom measures were moderately associated with lower IQ. Both inattentive and hyperactive/impulsive ADHD symptoms were lower in adults than in children and adolescents, and males with ASD had higher levels of inattentive and hyperactive/impulsive ADHD symptoms than females

Published
2017

20. Voting Rights

Author

Zwiers, M., Griffin, Larry, Hargis, Peggy, and Reagan Wilson, Charles

Published
2012

25. The effect of haemophilia and von Willebrand disease on arterial thrombosis: a systematic review

Author

Biere-Rafi, S., Zwiers, M., Peters, M., Meer, J., Rosendaal, F. R., Büller, H. R., and Pieter Kamphuisen

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, hemic and lymphatic diseases, Atherosclerosis arterial thrombosis flow mediated dilatation haemophilia intima media thickness von Willebrand disease ischemic-heart-disease cardiovascular-disease myocardial-infarction endothelial dysfunction risk-factors factor-viii mortality atherosclerosis death epidemiology
Abstract

Background: Patients with haemophilia and von Willebrand disease (VWD) may have a reduced cardiovascular mortality, due to a hypocoagulable state or decreased atherogenesis. We performed a systematic review to assess the association between haemophilia and VWD, and fatal and nonfatal arterial thrombosis and asymptomatic atherosclerosis. Methods: Medline and PubMed were searched to identify studies that assessed the incidence of cardiovascular mortality and morbidity in haemophilia and VWD, and that measured asymptomatic atherosclerosis with intima media thickness (IMT) of the carotid and femoral arteries, or flow-mediated dilatation (FMD) of the brachial artery. Weighted standardised mortality ratios (SMR) and mean differences (WMD) were calculated and pooled using a random effects model. Results: 15 longitudinal and cross-sectional studies consisting of 19,242 patients were included. Mortality due to arterial thrombosis was nonsignificantly reduced in patients with haemophilia compared with healthy controls (SMR 0.50, 95% CI 0.24 to 1.09). Haemophilia reduced nonfatal coronary events, and severe haemophilia offered better protection, but these results were based on a single study. No results were available for VWD. Although IMT of the carotid and femoral arteries was similar between VWD and haemophilia patients and healthy controls, atherosclerotic plaques of the large arteries were less prevalent in haemophilia patients. Only two studies assessed FMD and the results were inconsistent. Conclusion: Haemophilia may reduce arterial thrombosis, but this association should be further studied in haemophilia patients with a higher prevalence of cardiovascular risk factors.

Published
2010

27. Lynyrd Skynyrd

Author

Zwiers, M., Reagan Wilson, Charles, and Malone, Bill

Published
2009

28. Jimmy Reed

Author

Zwiers, M., Reagan Wilson, Charles, and Malone, Bill

Published
2009

29. Bo Diddley

Author

Zwiers, M., Reagan Wilson, Charles, and Malone, Bill

Published
2009

31. Kosten voor onkruidbestrijding op verhardingen: eindrapport

Author

Spijker, J.H., van der Straaten-Zwiers, M., Hekman, J., van Dijk, C.J., and Kempenaar, C.

Subjects
weed control, bestrating, urban areas, onkruidbestrijding, Alterra - Centrum Landschap, costs, pesticides, PRI Agrosysteemkunde, Landscape Centre, herbicides, pavements, stedelijke gebieden, pesticiden, kosten, Agrosystems, Wageningen Environmental Research, herbiciden
Abstract

Het doel van dit onderzoek is een beeld te krijgen van de gemiddelde jaarkosten van onkruidbeheer bij vergelijkbare beheerresultaten. Hierin moeten eventuele investeringskosten en terugverdienkosten kwalitatief en waar mogelijk kwantitatief worden meegenomen.

Published
2005

32. The ENIGMA Consortium: Large-scale collaborative analyses of neuroimaging and genetic data

Author

Thompson, P., Stein, J., Medland, S., Hibar, D., Vasquez, A., Renteria, M., Toro, R., Jahanshad, N., Schumann, G., Franke, B., Wright, M., Martin, N., Agartz, I., Alda, M., Alhusaini, S., Almasy, L., Almeida, J., Alpert, K., Andreasen, N., Andreassen, O., Apostolova, L., Appel, K., Armstrong, N., Aribisala, B., Bastin, M., Bauer, M., Bearden, C., Bergmann, O., Binder, E., Blangero, J., Bockholt, H., Boen, E., Bois, C., Boomsma, D., Booth, T., Bowman, I., Bralten, J., Brouwer, R., Brunner, H., Brohawn, D., Buckner, R., Buitelaar, J., Bulayeva, K., Bustillo, J., Calhoun, V., Cannon, D., Cantor, R., Carless, M., Caseras, X., Cavalleri, G., Chakravarty, M., Chang, K., Ching, C., Christoforou, A., Cichon, S., Clark, V., Conrod, P., Coppola, G., Crespo-Facorro, B., Curran, J., Czisch, M., Deary, I., de Geus, E., den Braber, A., Delvecchio, G., Depondt, C., de Haan, L., de Zubicaray, G., Dima, D., Dimitrova, R., Djurovic, S., Dong, H., Donohoe, G., Duggirala, R., Dyer, T., Ehrlich, S., Ekman, C., Elvsashagen, T., Emsell, L., Erk, S., Espeseth, T., Fagerness, J., Fears, S., Fedko, I., Fernandez, G., Fisher, S., Foroud, T., Fox, P., Francks, C., Frangou, S., Frey, E., Frodl, T., Frouin, V., Garavan, H., Giddaluru, S., Glahn, D., Godlewska, B., Goldstein, R., Gollub, R., Grabe, H., Grimm, O., Gruber, O., Guadalupe, T., Gur, R., Goering, H., Hagenaars, S., Hajek, T., Hall, G., Hall, J., Hardy, J., Hartman, C., Hass, J., Hatton, S., Haukvik, U., Hegenscheid, K., Heinz, A., Hickie, I., Ho, B., Hoehn, D., Hoekstra, P., Hollinshead, M., Holmes, A., Homuth, G., Hoogman, M., Hong, L., Hosten, N., Hottenga, J., Pol, H., Hwang, K., Jack, C., Jenkinson, M., Johnston, C., Joensson, E., Kahn, R., Kasperaviciute, D., Kelly, S., Kim, S., Kochunov, P., Koenders, L., Kraemer, B., Kwok, J., Lagopoulos, J., Laje, G., Landen, M., Landman, B., Lauriello, J., Lawrie, S., Lee, P., Le Hellard, S., Lemaitre, H., Leonardo, C., Li, C., Liberg, B., Liewald, D., Liu, X., Lopez, L., Loth, E., Lourdusamy, A., Luciano, M., Macciardi, F., Machielsen, M., MacQueen, G., Malt, U., Mandl, R., Manoach, D., Martinot, J., Matarin, M., Mather, K., Mattheisen, M., Mattingsdal, M., Meyer-Lindenberg, A., McDonald, C., McIntosh, A., McMahon, F., McMahon, K., Meisenzahl, E., Melle, I., Milaneschi, Y., Mohnke, S., Montgomery, G., Morris, D., Moses, Eric, Mueller, B., Munoz Maniega, S., Muehleisen, T., Mueller-Myhsok, B., Mwangi, B., Nauck, M., Nho, K., Nichols, T., Nilsson, L., Nugent, A., Nyberg, L., Olvera, R., Oosterlaan, J., Ophoff, R., Pandolfo, M., Papalampropoulou-Tsiridou, M., Papmeyer, M., Paus, T., Pausova, Z., Pearlson, G., Penninx, B., Peterson, C., Pfennig, A., Phillips, M., Pike, G., Poline, J., Potkin, S., Puetz, B., Ramasamy, A., Rasmussen, J., Rietschel, M., Rijpkema, M., Risacher, S., Roffman, J., Roiz-Santianez, R., Romanczuk-Seiferth, N., Rose, E., Royle, N., Rujescu, D., Ryten, M., Sachdev, P., Salami, A., Satterthwaite, T., Savitz, J., Saykin, A., Scanlon, C., Schmaal, L., Schnack, H., Schork, A., Schulz, S., Schuer, R., Seidman, L., Shen, L., Shoemaker, J., Simmons, A., Sisodiya, S., Smith, C., Smoller, J., Soares, J., Sponheim, S., Sprooten, E., Starr, J., Steen, V., Strakowski, S., Strike, L., Sussmann, J., Saemann, P., Teumer, A., Toga, A., Tordesillas-Gutierrez, D., Trabzuni, D., Trost, S., Turner, J., Van den Heuvel, M., van der Wee, N., van Eijk, K., van Erp, T., van Haren, N., van 't Ent, D., van Tol, M., Hernandez, M., Veltman, D., Versace, A., Voelzke, H., Walker, R., Walter, H., Wang, L., Wardlaw, J., Weale, M., Weiner, M., Wen, W., Westlye, L., Whalley, H., Whelan, C., White, T., Winkler, A., Wittfeld, K., Woldehawariat, G., Wolf, C., Zilles, D., Zwiers, M., Thalamuthu, A., Schofield, P., Freimer, N., Lawrence, N., Drevets, W., Thompson, P., Stein, J., Medland, S., Hibar, D., Vasquez, A., Renteria, M., Toro, R., Jahanshad, N., Schumann, G., Franke, B., Wright, M., Martin, N., Agartz, I., Alda, M., Alhusaini, S., Almasy, L., Almeida, J., Alpert, K., Andreasen, N., Andreassen, O., Apostolova, L., Appel, K., Armstrong, N., Aribisala, B., Bastin, M., Bauer, M., Bearden, C., Bergmann, O., Binder, E., Blangero, J., Bockholt, H., Boen, E., Bois, C., Boomsma, D., Booth, T., Bowman, I., Bralten, J., Brouwer, R., Brunner, H., Brohawn, D., Buckner, R., Buitelaar, J., Bulayeva, K., Bustillo, J., Calhoun, V., Cannon, D., Cantor, R., Carless, M., Caseras, X., Cavalleri, G., Chakravarty, M., Chang, K., Ching, C., Christoforou, A., Cichon, S., Clark, V., Conrod, P., Coppola, G., Crespo-Facorro, B., Curran, J., Czisch, M., Deary, I., de Geus, E., den Braber, A., Delvecchio, G., Depondt, C., de Haan, L., de Zubicaray, G., Dima, D., Dimitrova, R., Djurovic, S., Dong, H., Donohoe, G., Duggirala, R., Dyer, T., Ehrlich, S., Ekman, C., Elvsashagen, T., Emsell, L., Erk, S., Espeseth, T., Fagerness, J., Fears, S., Fedko, I., Fernandez, G., Fisher, S., Foroud, T., Fox, P., Francks, C., Frangou, S., Frey, E., Frodl, T., Frouin, V., Garavan, H., Giddaluru, S., Glahn, D., Godlewska, B., Goldstein, R., Gollub, R., Grabe, H., Grimm, O., Gruber, O., Guadalupe, T., Gur, R., Goering, H., Hagenaars, S., Hajek, T., Hall, G., Hall, J., Hardy, J., Hartman, C., Hass, J., Hatton, S., Haukvik, U., Hegenscheid, K., Heinz, A., Hickie, I., Ho, B., Hoehn, D., Hoekstra, P., Hollinshead, M., Holmes, A., Homuth, G., Hoogman, M., Hong, L., Hosten, N., Hottenga, J., Pol, H., Hwang, K., Jack, C., Jenkinson, M., Johnston, C., Joensson, E., Kahn, R., Kasperaviciute, D., Kelly, S., Kim, S., Kochunov, P., Koenders, L., Kraemer, B., Kwok, J., Lagopoulos, J., Laje, G., Landen, M., Landman, B., Lauriello, J., Lawrie, S., Lee, P., Le Hellard, S., Lemaitre, H., Leonardo, C., Li, C., Liberg, B., Liewald, D., Liu, X., Lopez, L., Loth, E., Lourdusamy, A., Luciano, M., Macciardi, F., Machielsen, M., MacQueen, G., Malt, U., Mandl, R., Manoach, D., Martinot, J., Matarin, M., Mather, K., Mattheisen, M., Mattingsdal, M., Meyer-Lindenberg, A., McDonald, C., McIntosh, A., McMahon, F., McMahon, K., Meisenzahl, E., Melle, I., Milaneschi, Y., Mohnke, S., Montgomery, G., Morris, D., Moses, Eric, Mueller, B., Munoz Maniega, S., Muehleisen, T., Mueller-Myhsok, B., Mwangi, B., Nauck, M., Nho, K., Nichols, T., Nilsson, L., Nugent, A., Nyberg, L., Olvera, R., Oosterlaan, J., Ophoff, R., Pandolfo, M., Papalampropoulou-Tsiridou, M., Papmeyer, M., Paus, T., Pausova, Z., Pearlson, G., Penninx, B., Peterson, C., Pfennig, A., Phillips, M., Pike, G., Poline, J., Potkin, S., Puetz, B., Ramasamy, A., Rasmussen, J., Rietschel, M., Rijpkema, M., Risacher, S., Roffman, J., Roiz-Santianez, R., Romanczuk-Seiferth, N., Rose, E., Royle, N., Rujescu, D., Ryten, M., Sachdev, P., Salami, A., Satterthwaite, T., Savitz, J., Saykin, A., Scanlon, C., Schmaal, L., Schnack, H., Schork, A., Schulz, S., Schuer, R., Seidman, L., Shen, L., Shoemaker, J., Simmons, A., Sisodiya, S., Smith, C., Smoller, J., Soares, J., Sponheim, S., Sprooten, E., Starr, J., Steen, V., Strakowski, S., Strike, L., Sussmann, J., Saemann, P., Teumer, A., Toga, A., Tordesillas-Gutierrez, D., Trabzuni, D., Trost, S., Turner, J., Van den Heuvel, M., van der Wee, N., van Eijk, K., van Erp, T., van Haren, N., van 't Ent, D., van Tol, M., Hernandez, M., Veltman, D., Versace, A., Voelzke, H., Walker, R., Walter, H., Wang, L., Wardlaw, J., Weale, M., Weiner, M., Wen, W., Westlye, L., Whalley, H., Whelan, C., White, T., Winkler, A., Wittfeld, K., Woldehawariat, G., Wolf, C., Zilles, D., Zwiers, M., Thalamuthu, A., Schofield, P., Freimer, N., Lawrence, N., and Drevets, W.

Abstract

The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way. © 2014 The Author(s).

Published
2014

41. Toxiciteit onder de loep : een speurtocht naar de oorzaken

Author

Berbee, R., Kate, E. ten, Zwiers, M., Berbee, R., Kate, E. ten, and Zwiers, M.

Abstract

Basisprincipes van de TIE-methode (toxicity-identification-evaluation). Deze toxiciteit identificatiemethode maakt onderdeel uit van totaal-effluentbeoordeling (TEB)

Published
2001

44. Bacterial Population Analysis of Human Colon and Terminal Ileum Biopsies with 16S rRNA-based Fluorescent Probes: Commensal Bacteria Live in Suspension and Have No Direct Contact with Epithelial Cells

Author

van der Waaij, Laurens A, primary, Harmsen, H J. M., additional, Madjipour, M, additional, Kroese, F G. M., additional, Zwiers, M, additional, van Dullemen, H M, additional, de Boer, N K, additional, Welling, G W, additional, and Jansen, P L. M., additional

Published
2005
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46. Kustdynamiek van vooroeversuppleties

Author

Zwiers, M. (author) and Zwiers, M. (author)

Abstract

Bij het verdedigen van een zandige kust wordt in toenemende mate gebruik gemaakt van zandsuppleties. Grote voordelen van zandsuppleties t.o.v. een verdediging met harde constructies (bv. strandhoofden) zijn de relatief lage aanlegkosten, de flexibiliteit en het feit dat het uiterlijk van de bestaande kust gehandhaafd blijft. Een nadeel is de beperkte levensduur van een suppletie doordat erosie ongehinderd voort kan gaan. Bij vooroeversuppleties wordt het zand onder water aangebracht. Doordat het zand minder ver getransporteerd hoeft te worden en niet door de brandingszone hoeft te worden gevoerd, kunnen de kosten per kubieke meter aanzienlijk lager zijn in vergelijking met een strandsuppletie. Door grotere verliezen naar dieper gelegen kustgedeelten kan het uiteindelijke effect echter sterk verminderd worden. In deze studie zijn de enige in Nederland uitgevoerde vooroeversuppleties onderzocht, te weten de suppleties uitgevoerd op het badstrand van Vlissingen in 1952 en 1966. Omtrent het zandtransportmechanisme op het badstrand dringt zich het volgende beeld op: - het langstransport betreft hoofdzakelijk brandingsstroomtransport; de invloed van het getij is verwaarloosbaar (in appendix 11 wordt dit m.b.v. de Bijkerformule gecontroleerd) - na een suppletie treedt dwarstransport naar hoger gelegen gedeelten van het profiel op om het door de suppletie verstoorde evenwichtsprofiel te herstellen - het dwarstransport naar dieper gelegen kustgedeelten kan verwaarloosd worden Aan de hand van dit scenario is getracht het gedrag van de kust na de suppleties m.b.v. één- en tweelijnmodellen te simuleren., Hydraulic Engineering, Civil Engineering and Geosciences

Published
1990

47. Subjective cognitive failures and hippocampal volume in elderly with white matter lesions

Author

Norden, A G.W. van, Fick, W F., Laat, K F. de, Uden, I W.M. van, Oudheusden, L J.B. van, Tendolkar, I, Zwiers, M P., and Leeuw, F E. de

Abstract

Subjective cognitive failures (SCF) and subjective memory failures (SMF) have been reported to be an early predictor of Alzheimer disease (AD) and have been attributed to white matter lesions (WML). Since AD is characterized by hippocampal degeneration, it is surprising that its relation with hippocampal atrophy has been investigated only sparsely. Previous studies on this are rare, limited in sample size, and did not adjust for WML.

Published
2008
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48. Saccade dysmetria indicates attenuated visual exploration in autism spectrum disorder

Author

Bast, N., Mason, L., Freitag, C. M., Smith, T., Portugal, A. M., Poustka, L., Banaschewski, T., Johnson, M., Ahmad, J., Ambrosino, S., Auyeung, B., Baron-Cohen, S., Baumeister, S., Beckmann, C. F., Bolte, S., Bourgeron, T., Bours, C., Brammer, M., Brandeis, D., Brogna, C., Bruijn, Y. d., Buitelaar, J. K., Chakrabarti, B., Charman, T., Cornelissen, I., Crawley, D., Dell'Acqua, F., Dumas, G., Durston, S., Ecker, C., Faulkner, J., Frouin, V., Garces, P., Goyard, D., Ham, L., Hayward, H., Hipp, J., Holt, R., Jones, E. J. H., Kundu, P., Lai, M. -C., D'Ardhuy, X. L., Lombardo, M. V., Loth, E., Lythgoe, D. J., Mandl, R., Marquand, A., Mennes, M., Meyer-Lindenberg, A., Moessnang, C., Murphy, D. G. M., Oakley, B., O'Dwyer, L., Oldehinkel, M., Oranje, B., Pandina, G., Persico, A., Ruggeri, B., Ruigrok, A., Sabet, J., Sacco, R., San Jose Caceres, A., Simonoff, E., Spooren, W., Tillmann, J., Toro, R., Tost, H., Waldman, J., Williams, S. C. R., Wooldridge, C., Zwiers, M. P., and The EU-AIMS LEAP Group

Subjects
Male, medicine.medical_specialty, cerebellum, Cerebellar Ataxia, Eye Movements, genetic structures, Autism Spectrum Disorder, Audiology, eye tracking, brainstem, 03 medical and health sciences, 0302 clinical medicine, ddc:150, Dysmetria, biomarker, Eye tracking, locus coeruleus, pupillometry, visual attention, Saccades, Developmental and Educational Psychology, medicine, Humans, Attention, 0501 psychology and cognitive sciences, ddc:610, 05 social sciences, Infant, Newborn, Cognition, Fixation (psychology), medicine.disease, Motor coordination, Psychiatry and Mental health, Autism spectrum disorder, Pediatrics, Perinatology and Child Health, Saccade, Female, Psychology, 030217 neurology & neurosurgery, Pupillometry, Neurotypical, 050104 developmental & child psychology
Abstract

Background: Visual exploration in autism spectrum disorder (ASD) is characterized by attenuated social attention. The underlying oculomotor function during visual exploration is understudied, whereas oculomotor function during restricted viewing suggested saccade dysmetria in ASD by altered pontocerebellar motor modulation. Methods: Oculomotor function was recorded using remote eye tracking in 142 ASD participants and 142 matched neurotypical controls during free viewing of naturalistic videos with and without human content. The sample was heterogenous concerning age (6–30 years), cognitive ability (60–140 IQ), and male/female ratio (3:1). Oculomotor function was defined as saccade, fixation, and pupil‐dilation features that were compared between groups in linear mixed models. Oculomotor function was investigated as ASD classifier and features were correlated with clinical measures. Results: We observed decreased saccade duration (∆M = −0.50, CI [−0.21, −0.78]) and amplitude (∆M = −0.42, CI [−0.12, −0.72]), which was independent of human video content. We observed null findings concerning fixation and pupil‐dilation features (POWER = .81). Oculomotor function is a valid ASD classifier comparable to social attention concerning discriminative power. Within ASD, saccade features correlated with measures of restricted and repetitive behavior. Conclusions: We conclude saccade dysmetria as ASD oculomotor phenotype relevant to visual exploration. Decreased saccade amplitude and duration indicate spatially clustered fixations that attenuate visual exploration and emphasize endogenous over exogenous attention. We propose altered pontocerebellar motor modulation as underlying mechanism that contributes to atypical (oculo‐)motor coordination and attention function in ASD.

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49. A real time information system in a steel plant

Author

Broekhuis, Ir. H., Mink, P., and Zwiers, M.

Abstract

Turing the past six years a network of computers has been built for the automatic handling of information regarding a production section reaching from blast furnaces to slabbing mills. In this section liquid pig iron produced by the blast furnaces is converted to ingots (blocks of steel) ready for rolling in the mills.

Published
1977
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50. Influence of candidate ADHD genes on reward processing and working memory in adult ADHD patients and healthy subjects.

Author

Hoogman, M., Aarts, E., Zwiers, M., Slaats-Willemse, D., Cools, R., Kan, C., Buitelaar, J., and Franke, B.

Abstract

Introduction and objectives: ADHD is a highly heritable disorder, which is attributable to multiple genes of small effect size. Understanding the modes of action of those genes already known can aid in unraveling biological mechanisms underlying ADHD. For that goal we built a large database of adult ADHD patients and controls extensively characterized using cognitive testing and functional imaging. Methods: We are currently focusing on functional genetic variants in two ADHD genes, NOS1 and DRD4, and their effects on cognitive and motivational functioning in ADHD. Results: Reward-related impulsivity and striatal activity are influenced by the NOS1 gene in ADHD patients (n = 69) and controls (n = 29). Working memory performance was not affected by DRD4 genotype, but prefrontal cortex activity was. Discussion: Our findings fit into a model in which ADHD genes act via glutamatergic and dopaminergic/serotonergic systems (NOS1) and signaling downstream of dopamine (DRD4) to affect brain function in subcortical and cortical areas. Conclusion: Functional effects of ADHD genes were more readily observed when analyzing the activity of relevant brain structures than at a behavioral level. We think this approach is an efficient way to elucidate ADHDs biological mechanisms. [ABSTRACT FROM AUTHOR]

Published
2010
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