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2. Rewiring the transcriptome of castration-resistant prostate cancer via cyclin-dependent kinase 9 inhibition

Author

Federici, E., primary, Civenni, G., additional, Storelli, E., additional, Sandrini, G., additional, Guarrera, L., additional, Bolis, M., additional, Kokanovic, A., additional, Mosole, S., additional, Rinaldi, A., additional, Scherle, P., additional, Chang, Y., additional, Ruggeri, B., additional, Carbone, G.M., additional, and Catapano, C.V., additional

Published
2023
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4. Subthreshold Depression and Regional Brain Volumes in Young Community Adolescents

Author

Dalley, J., Subramaniam, N., Theobald, D., Bach, C., Fauth-Bühler, M., Millenet, S., Spanagel, R., Albrecht, L., Ivanov, N., Rapp, M., Reuter, J., Strache, N., Ströhle, A., Lalanne, C., Poline, J.B., Schwartz, Y., Thyreau, B., Lathrop, M., Ireland, J., Rogers, J., Bordas, N., Bricaud, Z., Filippi, I., Galinowski, A., Gollier-Briant, F., Massicotte, J., Andrew, C., Cattrell, A., Desrivieres, S., Hall, D., Havatzias, S., Jia, T., Mallik, C., Nymberg, C., Reed, L., Ruggeri, B., Smith, L., Stueber, K., Topper, L., Werts, H., Brühl, R., Ihlenfeld, A., Walaszek, B., Hübner, T., Müller, K., Ripke, S., Rodehacke, S., Mennigen, E., Schmidt, D., Vetter, N., Ziesch, V., Carter, D., Connolly, C., Nugent, S., Jones, J., Whelan, R., Yacubian, J., Schneider, S., Head, K., Heym, N., Newman, C., Tahmasebi, A., Stephens, D., Vulser, Hélène, Lemaitre, Hervé, Artiges, Eric, Miranda, Ruben, Penttilä, Jani, Struve, Maren, Fadai, Tahmine, Kappel, Viola, Grimmer, Yvonne, Goodman, Robert, Stringaris, Argyris, Poustka, Luise, Conrod, Patricia, Frouin, Vincent, Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L.W., Bromberg, Uli, Büchel, Christian, Flor, Herta, Gallinat, Juergen, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Lawrence, Claire, Loth, Eva, Mann, Karl, Nees, Frauke, Paus, Tomas, Pausova, Zdenka, Rietschel, Marcella, Robbins, Trevor W., Smolka, Michael N., Schumann, Gunter, Martinot, Jean-Luc, and Paillère-Martinot, Marie-Laure

Published
2015
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9. A novel patient-derived tumorgraft model with TRAF1-ALK anaplastic large-cell lymphoma translocation

Author

Abate, F, Todaro, M, van der Krogt, J-A, Boi, M, Landra, I, Machiorlatti, R, Tabbò, F, Messana, K, Abele, C, Barreca, A, Novero, D, Gaudiano, M, Aliberti, S, Di Giacomo, F, Tousseyn, T, Lasorsa, E, Crescenzo, R, Bessone, L, Ficarra, E, Acquaviva, A, Rinaldi, A, Ponzoni, M, Longo, D L, Aime, S, Cheng, M, Ruggeri, B, Piccaluga, P P, Pileri, S, Tiacci, E, Falini, B, Pera-Gresely, B, Cerchietti, L, Iqbal, J, Chan, W C, Shultz, L D, Kwee, I, Piva, R, Wlodarska, I, Rabadan, R, Bertoni, F, and Inghirami, G

Published
2015
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10. Cellular and Molecular Changes During Mouse Skin Tumor Progression

Author

Klein-Szanto, A. J. P., Ruggeri, B., Bianchi, A., Conti, C. J., Herfarth, Ch., editor, Senn, H.-J., editor, Baum, M., editor, Diehl, V., editor, Gutzwiller, F., editor, Rajewsky, M. F., editor, Wannenmacher, M., editor, Hecker, Erich, editor, Jung, E. G., editor, Marks, F., editor, and Tilgen, W., editor

Published
1993
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11. The impact of synchronous liver resection on the risk of anastomotic leakage following elective colorectal resection. A propensity score match analysis on behalf of the iCral study group

Author

Guerra, Francesco, primary, Petrelli, Filippo, additional, Greco, Paola Antonella, additional, Sisti, Valerio, additional, Catarci, Marco, additional, Montalti, Roberto, additional, Patriti, Alberto, additional, Alagna, V., additional, Amodio, P., additional, Anania, G., additional, Angeloni, R., additional, Arici, E., additional, Baiocchi, G., additional, Baraghini, M., additional, Benedetti, M., additional, Bertocchi, E., additional, Borghi, F., additional, Brisinda, G., additional, Campagnacci, R., additional, Capolupo, G.T., additional, Caricato, M., additional, Carrara, A., additional, Ceccaroni, M., additional, Chiarello, M.M., additional, Cianflocca, D., additional, Ciano, P., additional, Cicconi, S., additional, Clementi, M., additional, Delrio, P., additional, Di Cesare, T., additional, Di Marco, C., additional, Falsetto, A., additional, Garulli, G., additional, Guadagni, S., additional, Guercioni, G., additional, Lambertini, M., additional, Liverani, A., additional, Longo, G., additional, Lucchi, A., additional, Luzzi, A.P., additional, Macarone Palmieri, R., additional, Mancini, S., additional, Marini, P., additional, Marsanic, P., additional, Martino, A., additional, Martorelli, G., additional, Marziali, I., additional, Maurizi, A., additional, Migliore, M., additional, Molfino, S., additional, Motter, M., additional, Muratore, A., additional, Pace, U., additional, Pandolfini, L., additional, Pavanello, M., additional, Pirozzi, F., additional, Ruffo, G., additional, Ruggeri, B., additional, Sagnotta, A., additional, Santoni, S., additional, Scabini, S., additional, Scatizzi, M., additional, Sciuto, A., additional, Sica, G., additional, Tirone, G., additional, Tomassini, F., additional, Vettoretto, N., additional, and Zigiotto, D., additional

Published
2021
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14. Single nucleotide polymorphism in the neuroplastin locus associates with cortical thickness and intellectual ability in adolescents

Author

Desrivières, S, Lourdusamy, A, Tao, C, Toro, R, Jia, T, Loth, E, Medina, L M, Kepa, A, Fernandes, A, Ruggeri, B, Carvalho, F M, Cocks, G, Banaschewski, T, Barker, G J, Bokde, A LW, Büchel, C, Conrod, P J, Flor, H, Heinz, A, Gallinat, J, Garavan, H, Gowland, P, Brühl, R, Lawrence, C, Mann, K, Martinot, M LP, Nees, F, Lathrop, M, Poline, J-B, Rietschel, M, Thompson, P, Fauth-Bühler, M, Smolka, M N, Pausova, Z, Paus, T, Feng, J, and Schumann, G

Published
2015
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16. Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group

Author

Jia, T, Chu, C, Liu, Y, van Dongen, J, Papastergios, E, Armstrong, NJ, Bastin, ME, Carrillo-Roa, T, den Braber, A, Harris, M, Jansen, R, Liu, J, Luciano, M, Ori, APS, Santianez, RR, Ruggeri, B, Sarkisyan, D, Shin, J, Sungeun, K, Gutierrez, DT, van't Ent, D, Ames, D, Artiges, E, Bakalkin, G, Banaschewski, T, Bokde, ALW, Brodaty, H, Bromberg, U, Brouwer, R, Buchel, C, Quinlan, EB, Cahn, W, de Zubicaray, G, Ehrlich, S, Ekstrom, TJ, Flor, H, Frohner, JH, Frouin, V, Garavan, H, Gowland, P, Heinz, A, Hoare, J, Ittermann, B, Jahanshad, N, Jiang, J, Kwok, JB, Martin, NG, Martinot, J-L, Mather, KA, McMahon, KL, McRae, AF, Nees, F, Orfanos, DP, Paus, T, Poustka, L, Samann, PG, Schofield, PR, Smolka, MN, Stein, DJ, Strike, LT, Teeuw, J, Thalamuthu, A, Trollor, J, Walter, H, Wardlaw, JM, Wen, W, Whelan, R, Apostolova, LG, Binder, EB, Boomsma, D, Calhoun, V, Crespo-Facorro, B, Deary, IJ, Pol, HH, Ophoff, RA, Pausova, Z, Sachdev, PS, Saykin, A, Wright, MJ, Thompson, PM, Schumann, G, Desrivieres, S, Jia, T, Chu, C, Liu, Y, van Dongen, J, Papastergios, E, Armstrong, NJ, Bastin, ME, Carrillo-Roa, T, den Braber, A, Harris, M, Jansen, R, Liu, J, Luciano, M, Ori, APS, Santianez, RR, Ruggeri, B, Sarkisyan, D, Shin, J, Sungeun, K, Gutierrez, DT, van't Ent, D, Ames, D, Artiges, E, Bakalkin, G, Banaschewski, T, Bokde, ALW, Brodaty, H, Bromberg, U, Brouwer, R, Buchel, C, Quinlan, EB, Cahn, W, de Zubicaray, G, Ehrlich, S, Ekstrom, TJ, Flor, H, Frohner, JH, Frouin, V, Garavan, H, Gowland, P, Heinz, A, Hoare, J, Ittermann, B, Jahanshad, N, Jiang, J, Kwok, JB, Martin, NG, Martinot, J-L, Mather, KA, McMahon, KL, McRae, AF, Nees, F, Orfanos, DP, Paus, T, Poustka, L, Samann, PG, Schofield, PR, Smolka, MN, Stein, DJ, Strike, LT, Teeuw, J, Thalamuthu, A, Trollor, J, Walter, H, Wardlaw, JM, Wen, W, Whelan, R, Apostolova, LG, Binder, EB, Boomsma, D, Calhoun, V, Crespo-Facorro, B, Deary, IJ, Pol, HH, Ophoff, RA, Pausova, Z, Sachdev, PS, Saykin, A, Wright, MJ, Thompson, PM, Schumann, G, and Desrivieres, S

Abstract

DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)-three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.

Published
2021

17. The impact of synchronous liver resection on the risk of anastomotic leakage following elective colorectal resection. A propensity score match analysis on behalf of the iCral study group

Author

Guerra, Paola Ofelia Francesca, Petrelli, F., Greco, P. A., Sisti, V., Catarci, Marco, Montalti, R., Patriti, A., Alagna, V., Amodio, P., Anania, G., Angeloni, Riccardo, Arici, E., Baiocchi, G., Baraghini, M., Benedetti, Marta, Bertocchi, E., Borghi, F., Brisinda, Giuseppe, Campagnacci, R., Capolupo, G. T., Caricato, M., Carrara, A., Ceccaroni, Marcello, Chiarello, M. M., Cianflocca, D., Ciano, P., Cicconi, S., Clementi, Maria Elisabetta, Delrio, P., Di Cesare, Tiziana, Di Marco, C., Falsetto, A., Garulli, G., Guadagni, S., Guercioni, G., Lambertini, M., Liverani, Antonio Maria Nicola, Longo, G., Lucchi, A., Luzzi, A. P., Macarone Palmieri, Raffaele, Mancini, S., Marini, P., Marsanic, P., Martino, A., Martorelli, G., Marziali, I., Maurizi, A., Migliore, M., Molfino, S., Motter, M., Muratore, A., Pace, U., Pandolfini, L., Pavanello, M., Pirozzi, F., Ruffo, G., Ruggeri, B., Sagnotta, A., Santoni, S., Scabini, S., Scatizzi, M., Sciuto, A., Sica, Gigliola, Tirone, G., Tomassini, F., Vettoretto, N., Zigiotto, D., Guerra F., Catarci M., Angeloni R., Benedetti M., Brisinda G. (ORCID:0000-0001-8820-9471), Ceccaroni M., Clementi M., Di Cesare T., Liverani A., Macarone Palmieri R., Sica G. (ORCID:0000-0002-7231-9139), Guerra, Paola Ofelia Francesca, Petrelli, F., Greco, P. A., Sisti, V., Catarci, Marco, Montalti, R., Patriti, A., Alagna, V., Amodio, P., Anania, G., Angeloni, Riccardo, Arici, E., Baiocchi, G., Baraghini, M., Benedetti, Marta, Bertocchi, E., Borghi, F., Brisinda, Giuseppe, Campagnacci, R., Capolupo, G. T., Caricato, M., Carrara, A., Ceccaroni, Marcello, Chiarello, M. M., Cianflocca, D., Ciano, P., Cicconi, S., Clementi, Maria Elisabetta, Delrio, P., Di Cesare, Tiziana, Di Marco, C., Falsetto, A., Garulli, G., Guadagni, S., Guercioni, G., Lambertini, M., Liverani, Antonio Maria Nicola, Longo, G., Lucchi, A., Luzzi, A. P., Macarone Palmieri, Raffaele, Mancini, S., Marini, P., Marsanic, P., Martino, A., Martorelli, G., Marziali, I., Maurizi, A., Migliore, M., Molfino, S., Motter, M., Muratore, A., Pace, U., Pandolfini, L., Pavanello, M., Pirozzi, F., Ruffo, G., Ruggeri, B., Sagnotta, A., Santoni, S., Scabini, S., Scatizzi, M., Sciuto, A., Sica, Gigliola, Tirone, G., Tomassini, F., Vettoretto, N., Zigiotto, D., Guerra F., Catarci M., Angeloni R., Benedetti M., Brisinda G. (ORCID:0000-0001-8820-9471), Ceccaroni M., Clementi M., Di Cesare T., Liverani A., Macarone Palmieri R., and Sica G. (ORCID:0000-0002-7231-9139)

Abstract

Introduction: how best to manage patients with colorectal cancer and synchronous liver metastasis is still controversial, with specific concerns of increased risk of postoperative complications following combined resection. We aimed at analyzing the influence of combined liver resection on the risk of anastomotic leak (AL) following colorectal resection. Methods: we reviewed the iCral prospectively maintained database to compare the relative risk of AL of patients undergoing colorectal resection for cancer to that of patients receiving simultaneous liver and colorectal resection for cancer with isolated hepatic metastases. The incidence of AL was the primary outcome of the analysis. Perioperative details and postoperative complications were also appraised. Results: out of a total of 996 patients who underwent colorectal resection for cancer, 206 receiving isolated colorectal resection were compared with a matched group of 53 patients undergoing simultaneous liver and colorectal resection. Combined surgery had greater operative time and resulted in longer postoperative hospitalization compared to colorectal resection alone. The proportion of overall morbidity following combined resection was significantly higher than after isolated colorectal resection (56.6% vs. 37.9%, p = 0.021). Overall, the two groups of patients did not differ neither on the rate of major postoperative complications, nor in terms of AL (9.4% vs. 6.3%, p = 0.381). At specific multivariate analysis, the duration of surgery was the only risk factor independently associated with the likelihood of AL. Conclusions: combining hepatic with colorectal resection for the treatment of synchronous liver metastasis from colorectal cancer does not increase significantly the incidence of AL.

Published
2021

18. Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group

Author

Jia, T., Chu, C., Liu, Y., van Dongen, J., Papastergios, E., Armstrong, Nicola, Bastin, M.E., Carrillo-Roa, T., den Braber, A., Harris, M., Jansen, R., Liu, J., Luciano, M., Ori, A.P.S., Roiz Santiañez, R., Ruggeri, B., Sarkisyan, D., Shin, J., Sungeun, K., Tordesillas Gutiérrez, D., van’t Ent, D., Ames, D., Artiges, E., Bakalkin, G., Banaschewski, T., Bokde, A.L.W., Brodaty, H., Bromberg, U., Brouwer, R., Büchel, C., Burke Quinlan, E., Cahn, W., de Zubicaray, G.I., Ehrlich, S., Ekström, T.J., Flor, H., Fröhner, J.H., Frouin, V., Garavan, H., Gowland, P., Heinz, A., Hoare, J., Ittermann, B., Jahanshad, N., Jiang, J., Kwok, J.B., Martin, N.G., Martinot, J.L., Mather, K.A., McMahon, K.L., McRae, A.F., Nees, F., Papadopoulos Orfanos, D., Paus, T., Poustka, L., Sämann, P.G., Schofield, P.R., Smolka, M.N., Stein, D.J., Strike, L.T., Teeuw, J., Thalamuthu, A., Trollor, J., Walter, H., Wardlaw, J.M., Wen, W., Whelan, R., Apostolova, L.G., Binder, E.B., Boomsma, D.I., Calhoun, V., Crespo-Facorro, B., Deary, I.J., Hulshoff Pol, H., Ophoff, R.A., Pausova, Z., Sachdev, P.S., Saykin, A., Wright, M.J., Thompson, P.M., Schumann, G., Desrivières, S., Jia, T., Chu, C., Liu, Y., van Dongen, J., Papastergios, E., Armstrong, Nicola, Bastin, M.E., Carrillo-Roa, T., den Braber, A., Harris, M., Jansen, R., Liu, J., Luciano, M., Ori, A.P.S., Roiz Santiañez, R., Ruggeri, B., Sarkisyan, D., Shin, J., Sungeun, K., Tordesillas Gutiérrez, D., van’t Ent, D., Ames, D., Artiges, E., Bakalkin, G., Banaschewski, T., Bokde, A.L.W., Brodaty, H., Bromberg, U., Brouwer, R., Büchel, C., Burke Quinlan, E., Cahn, W., de Zubicaray, G.I., Ehrlich, S., Ekström, T.J., Flor, H., Fröhner, J.H., Frouin, V., Garavan, H., Gowland, P., Heinz, A., Hoare, J., Ittermann, B., Jahanshad, N., Jiang, J., Kwok, J.B., Martin, N.G., Martinot, J.L., Mather, K.A., McMahon, K.L., McRae, A.F., Nees, F., Papadopoulos Orfanos, D., Paus, T., Poustka, L., Sämann, P.G., Schofield, P.R., Smolka, M.N., Stein, D.J., Strike, L.T., Teeuw, J., Thalamuthu, A., Trollor, J., Walter, H., Wardlaw, J.M., Wen, W., Whelan, R., Apostolova, L.G., Binder, E.B., Boomsma, D.I., Calhoun, V., Crespo-Facorro, B., Deary, I.J., Hulshoff Pol, H., Ophoff, R.A., Pausova, Z., Sachdev, P.S., Saykin, A., Wright, M.J., Thompson, P.M., Schumann, G., and Desrivières, S.

Abstract

DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)—three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.

Published
2021

20. Contributor contact details

Author

Basile, A., primary, Iulianeli, A., additional, Kim, J.W., additional, Boo, K.J., additional, Cho, J.H., additional, Moon, I., additional, Ota, K., additional, Mitsushima, S., additional, Matsuzawa, K., additional, Ishihara, A., additional, Twigg, M.V., additional, Dupont, V., additional, Fino, D., additional, Zanfir, M., additional, Kelly, N.A., additional, Bensaid, S., additional, Ruggeri, B., additional, Saracco, G., additional, Chiarello, G.L., additional, Selli, E., additional, Anisha, G.S., additional, John, R.P., additional, Giaconia, A., additional, Piemonte, V., additional, Di Paola, L., additional, De Falco, M., additional, Basile, A., additional, Matsumoto, Y., additional, Yukawa, H., additional, Nambu, T., additional, Millet, P., additional, Broom, D.P., additional, Book, D., additional, Squadrito, G., additional, Andaloro, L., additional, Ferraro, M., additional, Antonucci, V., additional, and Anstrom, J.R., additional

Published
2014
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29. 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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30. Investigational strategies for detection and intervention in early-stage pancreatic cancer: A meeting organized by national cancer institute, organ systems program, division of cancer biology, diagnosis, and centers, April 24–27, Annapolis, MD

Author

Longnecker, Daniel S., Pour, Parviz M., Scarpelli, Dante G., Caldas, Carlos, Redston, Mark S., Hahn, Stephan A., Seymour, Albert B., Hruban, Ralph H., Yeo, Charles J., Kern, Scott E., Ruggeri, B. A., Klein-Szanto, A. J. P., Huang, L. -Y., Lang, D., Andr’en-Sandberg, Åke, Johansson, Bertil, Sandgren, Eric P., Klöppel, Günter, Longnecker, Daniel S., Ghadirian, P., Howe, G. R., Howard, John M., Lynch, Henry T., Fusaro, LaVonne, Fusaro, Ramon, Lynch, Jane, Smyrk, Thomas, Andr’en-Sandberg, Åke, Fusaro, Ramon M., Lynch, Henry T., Günter Klöppel, Rao, M. Sambasiva, Reddy, Janardan K., Albores-Saavedra, Jorge, Milchgrub, Sara, Donald E. Henson, Klimstra, David S., Hameed, Meera R., Marrero, Arturo M., Conlon, Kevin C., Brennan, Murray F., Warshaw, Andrew L., Adrian, Thomas E., Herrnanek, P., Wittekind, Ch., Altendorf-Hofmann, A., Reber, Howard A., Korc, Murray, Vezeridis, Michael P., Bold, Richard J., Evers, B. Mark, Sperling, Howard E., Gomez, Guillermo, Ishizuka, Jin, Townsend, Courtney M., Thompson, James C., Kalthoff, H., Röder, C., Henne-Bruns, D., Kremer, B., Schmiegel, W., Smith, Jill Palmer, Zagon, Ian S., Schally, A. V., Szepeshazi, K., Qin, Y., Halmos, G., Ertl, T., Groot, K., Cai, R. -Z., Liebow, C., Poston, G. J., Lemoine, Nick, Beauchamp, Dan, Warshaw, Andrew L., Kim, Young S., Ho, Jenny J. L., Hollingsworth, Michael A., Juhl, Hartmut, Schott, Astrid, Krüger, Uwe, Henne-Bruns, Doris, Kremer, Bernd, Kalthoff, Holger, Lightdale, Charles J., Korc, Murray, Liebow, Charles, Adrian, Thomas E., Permert, Johan, Westermark, Gunilla T., Lehman, Glen A., Schally, A. V., Nagy, A., Cai, R. -Z., Reile, H., Radulovic, S., Qin, Y., Szepeshazi, K., Halmos, G., Comaru-Schally, Ana Maria, Sorenson, G. D., Pribish, D. M., Valone, F. H., Memoli, V. A., Bzik, D. J., Yao, S.-L, Scarpelli, Dante G., Mangold, K. A., Chang, K-W, Laconi, S., Hubchak, S., Szepeshazi, Karoly, Schally, Andrew V., Halmos, G., Longnecker, Daniel S., Pour, Parviz M., Frazier, Marsha L., Fernandez, Ester, de Llorens, Rafael, Löhr, Matthias, Trautmann, Birgit, Heller, Thomas, Peters, Stefanie, Maier, Anja, Schutt, Hans J., Zauner, Ira, Liebe, Stefan, Tsuei, B. J., Povoski, S. P., Zhou, W., Bell, R. H., Dobelbower, Ralph R., Casper, Ephraim S., Smith, Jill P., Liu, Guozhen, Stock, Elizabeth, Orenberg, Elaine K., Yu, Ning Y., Brown, Dennis M., Tempero, Margaret, Colcher, David, Hermanek, P., Gall, F. P., Wittekind, Ch., Altendorf-Hofmann, A., Charks Liebow, Bell, Richard H., Frazier, Marsha L., Hollingsworth, Michael A., Tempero, Margaret, and Comaru-Schally, Ana Maria

Published
1994
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31. 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, FD, Ecker, C, Faulkner, J, Frouin, V, Garces, P, Goyard, D, Hayward, H, Hipp, J, Johnson, MH, Jones, EJH, Kundu, P, Lai, M-C, D'ardhuy, XL, Lombardo, M, Lythgoe, DJ, Mandl, R, Mason, L, Meyer-Lindenberg, A, Moessnang, C, Mueller, N, O'Dwyer, L, Oldehinkel, M, Oranje, B, Pandina, G, Persico, AM, Ruggeri, B, Ruigrok, A, Sabet, J, Sacco, R, Toro, R, Tost, H, Waldman, J, Williams, SCR, Wooldridge, C, Zwiers, MP, 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, FD, Ecker, C, Faulkner, J, Frouin, V, Garces, P, Goyard, D, Hayward, H, Hipp, J, Johnson, MH, Jones, EJH, Kundu, P, Lai, M-C, D'ardhuy, XL, Lombardo, M, Lythgoe, DJ, Mandl, R, Mason, L, Meyer-Lindenberg, A, Moessnang, C, Mueller, N, O'Dwyer, L, Oldehinkel, M, Oranje, B, Pandina, G, Persico, AM, Ruggeri, B, Ruigrok, A, Sabet, J, Sacco, R, Toro, R, Tost, H, Waldman, J, Williams, SCR, Wooldridge, C, and Zwiers, MP

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 subgro

Published
2020

34. Benzo(a)pyrene-induced murine skin tumors exhibit frequent and characteristic G to T mutations in the p53 gene

Author

Ruggeri, B., DiRado, M., Zhang, S.Y., Bauer, B., Goodrow, T., and Klein-Szanto, A.J.P.

Subjects
Benzopyrene -- Genetic aspects, Skin cancer -- Research, Mutation (Biology) -- Analysis, Science and technology
Abstract

The frequency and pattern of p53 mutations in murine skin tumors induced by benzo(a)pyrene were investigated. The p53 mutations in B(a)P-induced skin tumors reveal a 33% frequency of missense mutations predominantly G to T transversions in exons 7 and 8 of the p53 gene and a 62% frequency of immunohistochemically positive carcinomas. In contrast, sequence analysis of 36 skin tumors induced by 7,12-dimethylbenz(a)anthracene reveal similar mutation frequencies but different mutation spectra. The resultssuggest that the p53 tumor suppressor gene is a selective target of metabolically activated B(a)P associated with human tobacco-related cancers.

Published
1993

38. Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: Findings from the ENIGMA Epigenetics Working Group

Author

Jia, T., Chu, C., Liu, Y., van Dongen, J., Papastergios, E., Armstrong, N.J., Bastin, M.E., Carrillo-Roa, T., den Braber, A., Harris, M., Jansen, R., Liu, J., Luciano, M., Ori, A.P.S., Roiz Santiañez, R., Ruggeri, B., Sarkisyan, D., Shin, J., Sungeun, K., Tordesillas Gutiérrez, D., van’t Ent, D., Ames, D., Artiges, E., Bakalkin, G., Banaschewski, T., Bokde, A.L.W., Brodaty, H., Bromberg, U., Brouwer, R., Büchel, C., Burke Quinlan, E., Cahn, W., de Zubicaray, G.I., Ehrlich, S., Ekström, T.J., Flor, H., Fröhner, J.H., Frouin, V., Garavan, H., Gowland, P., Heinz, A., Hoare, J., Ittermann, B., Jahanshad, N., Jiang, J., Kwok, J.B., Martin, N.G., Martinot, J-L, Mather, K.A., McMahon, K.L., McRae, A.F., Nees, F., Papadopoulos Orfanos, D., Paus, T., Poustka, L., Sämann, P.G., Schofield, P.R., Smolka, M.N., Stein, D.J., Strike, L.T., Teeuw, J., Thalamuthu, A., Trollor, J., Walter, H., Wardlaw, J.M., Wen, W., Whelan, R., Apostolova, L.G., Binder, E.B., Boomsma, D.I., Calhoun, V., Crespo-Facorro, B., Deary, I.J., Hulshoff Pol, H.E., Ophoff, R.A., Pausova, Z., Sachdev, P.S., Saykin, A., Wright, M.J., Thompson, P.M., Schumann, G., Desrivières, S., Jia, T., Chu, C., Liu, Y., van Dongen, J., Papastergios, E., Armstrong, N.J., Bastin, M.E., Carrillo-Roa, T., den Braber, A., Harris, M., Jansen, R., Liu, J., Luciano, M., Ori, A.P.S., Roiz Santiañez, R., Ruggeri, B., Sarkisyan, D., Shin, J., Sungeun, K., Tordesillas Gutiérrez, D., van’t Ent, D., Ames, D., Artiges, E., Bakalkin, G., Banaschewski, T., Bokde, A.L.W., Brodaty, H., Bromberg, U., Brouwer, R., Büchel, C., Burke Quinlan, E., Cahn, W., de Zubicaray, G.I., Ehrlich, S., Ekström, T.J., Flor, H., Fröhner, J.H., Frouin, V., Garavan, H., Gowland, P., Heinz, A., Hoare, J., Ittermann, B., Jahanshad, N., Jiang, J., Kwok, J.B., Martin, N.G., Martinot, J-L, Mather, K.A., McMahon, K.L., McRae, A.F., Nees, F., Papadopoulos Orfanos, D., Paus, T., Poustka, L., Sämann, P.G., Schofield, P.R., Smolka, M.N., Stein, D.J., Strike, L.T., Teeuw, J., Thalamuthu, A., Trollor, J., Walter, H., Wardlaw, J.M., Wen, W., Whelan, R., Apostolova, L.G., Binder, E.B., Boomsma, D.I., Calhoun, V., Crespo-Facorro, B., Deary, I.J., Hulshoff Pol, H.E., Ophoff, R.A., Pausova, Z., Sachdev, P.S., Saykin, A., Wright, M.J., Thompson, P.M., Schumann, G., and Desrivières, S.

Abstract

DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)—three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.

Published
2019

39. Epigenetic variance in dopamine D2 receptor: a marker of IQ malleability?

Author

Kaminski, J., Schlagenhauf, F., Rapp, M., Awasthi, S., Ruggeri, B., Deserno, L., Banaschewski, T., Bokde, A., Bromberg, U., Büchel , C., Quinlan, E., Desrivières, S., Flor, H., Frouin, V., Garavan, H., Gowland , P., Ittermann, B., Martinot, J., Paillère Martinot, M., Nees, F., Orfanos, D., Paus, T., Poustka, L., Smolka, M., Fröhner, J., Walter, H., Whelan, R., Ripke, S., Schumann, G., Heinz, A., and The IMAGEN Consortium

Subjects
Intelligence Tests, Male, Adolescent, Receptors, Dopamine D2, Dopamine, striatum, Intelligence, human intelligence, reward anticipation, prediction, psychopathology, Corpus Striatum, Article, Epigenesis, Genetic, stress, genome-wide association, Humans, Female, human brain, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit, metaanalysis
Abstract

Genetic and environmental factors both contribute to cognitive test performance. A substantial increase in average intelligence test results in the second half of the previous century within one generation is unlikely to be explained by genetic changes. One possible explanation for the strong malleability of cognitive performance measure is that environmental factors modify gene expression via epigenetic mechanisms. Epigenetic factors may help to understand the recent observations of an association between dopamine-dependent encoding of reward prediction errors and cognitive capacity, which was modulated by adverse life events. The possible manifestation of malleable biomarkers contributing to variance in cognitive test performance, and thus possibly contributing to the “missing heritability” between estimates from twin studies and variance explained by genetic markers, is still unclear. Here we show in 1475 healthy adolescents from the IMaging and GENetics (IMAGEN) sample that general IQ (gIQ) is associated with (1) polygenic scores for intelligence, (2) epigenetic modification of DRD2 gene, (3) gray matter density in striatum, and (4) functional striatal activation elicited by temporarily surprising reward-predicting cues. Comparing the relative importance for the prediction of gIQ in an overlapping subsample, our results demonstrate neurobiological correlates of the malleability of gIQ and point to equal importance of genetic variance, epigenetic modification of DRD2 receptor gene, as well as functional striatal activation, known to influence dopamine neurotransmission. Peripheral epigenetic markers are in need of confirmation in the central nervous system and should be tested in longitudinal settings specifically assessing individual and environmental factors that modify epigenetic structure.

Published
2018
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40. The EU-AIMS Longitudinal European Autism Project (LEAP): clinical characterisation

Author

Charman, T., Loth, Eva, Tillmann, Julian, Crawley, Daisy, Wooldridge, C., Goyard, David, Ahmad, Jumana, Auyeung, Bonnie, Ambrosino, Sara, Banaschewski, Tobias, Baron-Cohen,Simon, Baumeister, Sarah, Beckmann, Christian, Bölte, Sven, Bourgeron, Thomas, Bours, Carsten, Brammer, Michael, Brandeis, Daniel, Brogna, Claudia, De Bruijn, Y., Chakrabarti,B., Cornelissen, Ineke, Acqua, Flavio Dell, Dumas, G., Durston, Sarah, Ecker,C., Faulkner, J., Frouin, Vincent, Garces, Pilar, Ham, Lindsay M., Hayward, Hannah, Hipp, Joerg, Holt, R. J., Isaksson, Johan, Johnson, Mark H., Jones, Emily J. H., Kundu, Prantik, Lai,Meng-Chuan, D'Ardhuy, X. L., Lombardo, Michael V., Lythgoe, David J., Mandl, Rene, Mason, Luke, Meyer-Lindenberg, Andreas, Moessnang, Carolin, Mueller, Nico, O'Dwyer, Laurence, Oldehinkel, Marianne, Oranje, Bob, Pandina, Gahan J., Persico, Antonio M., Ruggeri, B., Ruigrok,Amber N. V., Sabet, Jessica, Sacco, Roberto, Caceres, Antonia San Jose, Simonoff, Emily, Toro, Roberto, Tost, Heike, Waldman, Jack, Williams,Steven C. R., Zwiers, Marcel P., Spooren, Will, Murphy,Declan G. M., Buitelaar, Jan K., Lombardo,Michael V., Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Service NEUROSPIN ( NEUROSPIN ), Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, University of Edinburgh, Autism Research Centre and Section of Developmental Psychiatry, University of Cambridge [UK] ( CAM ), University Medical Center [Utrecht], Universität Heidelberg [Heidelberg], Medizinische Fakultät Mannheim, Radboud University Medical Center [Nijmegen], Karolinska Institutet [Stockholm], Génétique humaine et Fonctions cognitives - Human Genetics and Cognitive Functions, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Università Campus Bio-Medico di Roma / University Campus Bio-Medico of Rome ( UCBM ), University of Reading ( UOR ), Goethe-University Frankfurt am Main, Roche Pharma Research and Early Development [Basel] ( pRED ), F. Hoffmann-La Roche [Basel], Uppsala University, Centre for Brain and Cognitive Development [Birkbeck College], Birkbeck College [University of London], Icahn School of Medicine at Mount Sinai [New York], University of Toronto, University of Cyprus [Nicosia], Janssen Research & Development, University of Messina, 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’ inkind contributions, and from Autism Speaks., European Project : 115300,EC:FP7:SP1-JTI,IMI-JU-03-2010,EU-AIMS ( 2012 ), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of Cambridge [UK] (CAM), Department of Child and Adolescent Psychiatry and Psychotherapy [Mannheim], Universität Heidelberg [Heidelberg] = Heidelberg University, Stockholm County Council, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Università Campus Bio-Medico di Roma / University Campus Bio-Medico of Rome ( UCBM), University of Reading (UOR), Universitätsklinikum Frankfurt, Roche Pharma Research and Early Development [Basel] (pRED), University of London [London], Icahn School of Medicine at Mount Sinai [New York] (MSSM), University of Cyprus [Nicosia] (UCY), Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], 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., European Project: 115300,EC:FP7:SP1-JTI,IMI-JU-03-2010,EU-AIMS(2012), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Radboud university [Nijmegen], Lombardo, Michael V. [0000-0001-6780-8619], Charman, Tony [0000-0003-1993-6549], Loth, Eva [0000-0001-9458-9167], Tillmann, Julian [0000-0001-9574-9855], Crawley, Daisy [0000-0001-9901-1110], Ahmad, Jumana [0000-0001-5271-0731], Banaschewski, Tobias [0000-0003-4595-1144], Baron-Cohen, Simon [0000-0001-9217-2544], Brogna, Claudia [0000-0002-9526-6367], Dumas, Guillaume [0000-0002-2253-1844], Hayward, Hannah [0000-0001-5552-2146], Hipp, Joerg [0000-0002-7875-2988], Isaksson, Johan [0000-0003-1033-2618], Johnson, Mark [0000-0003-4229-2585], Jones, Emily JH [0000-0001-5747-9540], Lai, Meng-Chuan [0000-0002-9593-5508], Lythgoe, David J [0000-0002-5078-9025], Moessnang, Carolin [0000-0003-4357-2706], Ruggeri, Barbara [0000-0002-6231-8829], Ruigrok, Amber [0000-0001-7711-8056], Simonoff, Emily [0000-0002-5450-0823], Toro, Roberto [0000-0002-6671-858X], Williams, Steve CR [0000-0003-4299-1941], Murphy, Declan GM [0000-0002-6664-7451], and Apollo - University of Cambridge Repository

Subjects
Parents, Male, [SDV]Life Sciences [q-bio], Autism, [ SDV.MHEP.PSM ] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], Individuality, Behaviours, Severity of Illness Index, lcsh:RC346-429, psyc, 0302 clinical medicine, Age, autism, autism spectrum disorder, behaviours, heterogeneity, IQ, phenotype, sex, molecular biology, developmental neuroscience, developmental biology, psychiatry and mental health, Surveys and Questionnaires, Longitudinal Studies, Autism spectrum disorder, Child, Psychiatry, Age, autism, autism spectrum disorder, behaviours, heterogeneity, IQ, phenotype, sex, molecular biology, developmental neuroscience, developmental biology, psychiatry and mental health, 05 social sciences, Neuropsychology, Age Factors, 220 Statistical Imaging Neuroscience, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Cognition, Psychiatry and Mental health, Phenotype, Cohort, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Sex, Psychology, 050104 developmental & child psychology, Adult, medicine.medical_specialty, Adolescent, BF, behavioral disciplines and activities, 150 000 MR Techniques in Brain Function, Psykiatri, 03 medical and health sciences, Genetic Heterogeneity, [ SHS.PSY ] Humanities and Social Sciences/Psychology, Sex Factors, Developmental Neuroscience, Severity of illness, mental disorders, medicine, Journal Article, Humans, 0501 psychology and cognitive sciences, Molecular Biology, lcsh:Neurology. Diseases of the nervous system, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Research, medicine.disease, R1, Clinical trial, Impulsive Behavior, Observational study, Self Report, Heterogeneity, 030217 neurology & neurosurgery, Biomarkers, Developmental Biology
Abstract

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. Conclusions The established phenotypic heterogeneity in ASD is well captured in the LEAP cohort. Variation both in core ASD symptom severity and in commonly co-occurring psychiatric symptoms were systematically associated with sex, age and IQ. The pattern of ASD symptom differences with age and sex also varied by whether these were clinician ratings or parent- or self-reported which has important implications for establishing stratification biomarkers and for their potential use as outcome measures in clinical trials. Electronic supplementary material The online version of this article (doi:10.1186/s13229-017-0145-9) contains supplementary material, which is available to authorized users.

Published
2017
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42. Recovery of D-limonene through moderate temperature extraction and pyrolytic products from orange peels

Author

Negro, V, Ruggeri, B, Mancini, Giuseppe, and Fino, D.

Subjects
Accelerated extraction, D-limonene, Orange peels, Pyrolysis, Biotechnology, Chemical Engineering (all), Renewable Energy, Sustainability and the Environment, Fuel Technology, Waste Management and Disposal, Pollution, Organic Chemistry, Inorganic Chemistry, Sustainability and the Environment, Accelerated extraction, D-limonene, Orange peels, Pyrolysis, Renewable Energy
Published
2017

43. KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference

Author

Schumann, G, Liu, C, O'Reilly, P, Gao, H, Song, P, Xu, B, Ruggeri, B, Amin, N, Jia, T, Preis, S, Lepe, MS, Akira, S, Barbieri, C, Baumeister, S, Cauchi, S, Clarke, TK, Enroth, S, Fischer, K, Hällfors, J, Harris, SE, Hieber, S, Hofer, E, Hottenga, JJ, Johansson, Å, Joshi, PK, Kaartinen, N, Laitinen, J, Lemaitre, R, Loukola, A, Luan, J, Lyytikäinen, LP, Mangino, M, Manichaikul, A, Mbarek, H, Milaneschi, Y, Moayyeri, A, Mukamal, K, Nelson, C, Nettleton, J, Partinen, E, Rawal, R, Robino, A, Rose, L, Sala, C, Satoh, T, Schmidt, R, Schraut, K, Scott, R, Smith, AV, Starr, JM, Teumer, A, Trompet, S, Uitterlinden, AG, Venturini, C, Vergnaud, AC, Verweij, N, Vitart, V, Vuckovic, D, Wedenoja, J, Yengo, L, Yu, B, Zhang, W, Zhao, JH, Boomsma, DI, Chambers, J, Chasman, DI, Daniela, T, De Geus, E, Deary, I, Eriksson, JG, Esko, T, and Eulenburg, V

Abstract

Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among > 105,000 individuals of European ancestry and identified β-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 × 10-12). β-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific β-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver-brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.

Published
2016
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46. Correlated gene expression supports synchronous activity in brain networks

Author

Richiardi, J., Altmann, A., Milazzo, A.-C., Chang, C., Chakravarty, M. M., Banaschewski, T., Barker, G. J., Bokde, A. L. W., Bromberg, U., Buchel, C., Conrod, P., Fauth-Buhler, M., Flor, H., Frouin, V., Gallinat, J., Garavan, H., Gowland, P., Heinz, A., Lemaitre, H., Mann, K. F., Martinot, J.-L., Nees, F., Paus, T., Pausova, Z., Rietschel, M., Robbins, T. W., Smolka, M. N., Spanagel, R., Strohle, A., Schumann, G., Hawrylycz, M., Poline, J.-B., Greicius, M. D., Albrecht, L., Andrew, C., Arroyo, M., Artiges, E., Aydin, S., Bach, C., Barbot, A., Barker, Gareth, Boddaert, N., Bokde, A., Bricaud, Z., Bruehl, R., Cachia, A., Cattrell, A., Constant, P., Dalley, J., Decideur, B., Desrivieres, S., Fadai, T., Briand, F. G., Heinrichs, B., Heym, N., Hubner, T., Ireland, J., Ittermann, B., Jia, T., Lathrop, M., Lanzerath, D., Lawrence, C., Ludemann, K., Macare, C., Mallik, C., Mangin, J.-F., Mann, K., Martinot, J.- L., Mennigen, E., Mesquita de Carvahlo, F., Mignon, X., Miranda, Ruben, Muller, K., Nymberg, C., Paillere, M.-L., Poustka, L., Rapp, M., Robert, G., Reuter, J., Ripke, S., Robbins, Trevor, Rodehacke, S., Rogers, J., Romanowski, A., Ruggeri, B., Schmal, C., Schmidt, D., Schneider, S., Schumann, M., Schubert, F., Schwartz, Y., Smolka, M., Sommer, W., Speiser, C., Spranger, T., Stedman, A., Steiner, S., Stephens, D., Strache, N., Struve, M., Subramaniam, N., Topper, L., Whelan, R., Williams, S., Yacubian, J., Zilbovicius, M., Wong, C. P., Lubbe, S., Martinez-Medina, L., Fernandes, A., Tahmasebi, A., and IMAGEN consortium

Subjects
Multidisciplinary
Published
2015

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

Abstract

Contains fulltext : 177208.pdf (publisher's version ) (Open Access), 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). CONCLUSION: We expect that LEAP wil

Published
2017

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