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1. Bright light therapy versus physical exercise to prevent co-occurring depression in adolescents and young adults with attention-deficit/hyperactivity disorder: a multicentre, three-arm, randomised controlled, pilot phase-IIa trial

Author

Mayer, Jutta S., Kohlhas, Laura, Stermann, Jacek, Medda, Juliane, Brandt, Geva A., Grimm, Oliver, Pawley, Adam D., Asherson, Philip, Sanchez, Judit Palacio, Richarte, Vanesa, Bergsma, Douwe, Koch, Elena D., Muntaner-Mas, Adrià, Ebner-Priemer, Ulrich W., Kieser, Meinhard, Retz, Wolfgang, Ortega, Francisco B., Colla, Michael, Buitelaar, Jan K., Kuntsi, Jonna, Ramos-Quiroga, Josep A., Reif, Andreas, and Freitag, Christine M.

Published
2024
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2. Polygenic association between attention-deficit/hyperactivity disorder liability and cognitive impairments

Author

Vainieri, Isabella, Martin, Joanna, Rommel, Anna-Sophie, Asherson, Philip, Banaschewski, Tobias, Buitelaar, Jan, Cormand, Bru, Crosbie, Jennifer, Faraone, Stephen V, Franke, Barbara, Loo, Sandra K, Miranda, Ana, Manor, Iris, Oades, Robert D, Purves, Kirstin L, Ramos-Quiroga, J Antoni, Ribasés, Marta, Roeyers, Herbert, Rothenberger, Aribert, Schachar, Russell, Sergeant, Joseph, Steinhausen, Hans-Christoph, Vuijk, Pieter J, Doyle, Alysa E, and Kuntsi, Jonna

Subjects
Attention Deficit Hyperactivity Disorder (ADHD), Genetics, Prevention, Human Genome, Mental Health, 2.1 Biological and endogenous factors, Aetiology, Adolescent, Adult, Child, Humans, Young Adult, Attention Deficit Disorder with Hyperactivity, Cognitive Dysfunction, Genome-Wide Association Study, Phenotype, Reaction Time, Case-Control Studies, ADHD, attention, cognition, inhibition, polygenic risk scores, reaction time variability, Neurosciences, Public Health and Health Services, Psychology, Psychiatry
Abstract

BackgroundA recent genome-wide association study (GWAS) identified 12 independent loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). Polygenic risk scores (PRS), derived from the GWAS, can be used to assess genetic overlap between ADHD and other traits. Using ADHD samples from several international sites, we derived PRS for ADHD from the recent GWAS to test whether genetic variants that contribute to ADHD also influence two cognitive functions that show strong association with ADHD: attention regulation and response inhibition, captured by reaction time variability (RTV) and commission errors (CE).MethodsThe discovery GWAS included 19 099 ADHD cases and 34 194 control participants. The combined target sample included 845 people with ADHD (age: 8-40 years). RTV and CE were available from reaction time and response inhibition tasks. ADHD PRS were calculated from the GWAS using a leave-one-study-out approach. Regression analyses were run to investigate whether ADHD PRS were associated with CE and RTV. Results across sites were combined via random effect meta-analyses.ResultsWhen combining the studies in meta-analyses, results were significant for RTV (R2 = 0.011, β = 0.088, p = 0.02) but not for CE (R2 = 0.011, β = 0.013, p = 0.732). No significant association was found between ADHD PRS and RTV or CE in any sample individually (p > 0.10).ConclusionsWe detected a significant association between PRS for ADHD and RTV (but not CE) in individuals with ADHD, suggesting that common genetic risk variants for ADHD influence attention regulation.

Published
2022

4. The management of ADHD in children and adolescents: bringing evidence to the clinic: perspective from the European ADHD Guidelines Group (EAGG)

Author

Coghill, David, Banaschewski, Tobias, Cortese, Samuele, Asherson, Philip, Brandeis, Daniel, Buitelaar, Jan, Daley, David, Danckaerts, Marina, Dittmann, Ralf W., Doepfner, Manfred, Ferrin, Maite, Hollis, Chris, Holtmann, Martin, Paramala, Santosh, Sonuga-Barke, Edmund, Soutullo, César, Steinhausen, Hans-Christoph, Van der Oord, Saskia, Wong, Ian C K, Zuddas, Alessandro, and Simonoff, Emily

Published
2023
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5. Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years.

Author

Dima, Danai, Modabbernia, Amirhossein, Papachristou, Efstathios, Doucet, Gaelle E, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N, Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn I, Andersson, Micael, Andreasen, Nancy C, Andreassen, Ole A, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret I, Borgwardt, Stefan, Bourque, Josiane, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M, Buitelaar, Jan K, Busatto, Geraldo F, Buckner, Randy L, Calhoun, Vincent, Canales-Rodríguez, Erick J, Cannon, Dara M, Caseras, Xavier, Castellanos, Francisco X, Cervenka, Simon, Chaim-Avancini, Tiffany M, Ching, Christopher RK, Chubar, Victoria, Clark, Vincent P, Conrod, Patricia, Conzelmann, Annette, Crespo-Facorro, Benedicto, Crivello, Fabrice, Crone, Eveline A, Dannlowski, Udo, Dale, Anders M, Davey, Christopher, de Geus, Eco JC, de Haan, Lieuwe, de Zubicaray, Greig I, den Braber, Anouk, Dickie, Erin W, Di Giorgio, Annabella, Doan, Nhat Trung, Dørum, Erlend S, Ehrlich, Stefan, Erk, Susanne, Espeseth, Thomas, Fatouros-Bergman, Helena, Fisher, Simon E, Fouche, Jean-Paul, Franke, Barbara, Frodl, Thomas, Fuentes-Claramonte, Paola, Glahn, David C, Gotlib, Ian H, Grabe, Hans-Jörgen, Grimm, Oliver, Groenewold, Nynke A, Grotegerd, Dominik, Gruber, Oliver, Gruner, Patricia, Gur, Rachel E, Gur, Ruben C, Hahn, Tim, Harrison, Ben J, Hartman, Catharine A, Hatton, Sean N, Heinz, Andreas, Heslenfeld, Dirk J, Hibar, Derrek P, Hickie, Ian B, Ho, Beng-Choon, Hoekstra, Pieter J, Hohmann, Sarah, Holmes, Avram J, Hoogman, Martine, Hosten, Norbert, Howells, Fleur M, Hulshoff Pol, Hilleke E, Huyser, Chaim, Jahanshad, Neda, James, Anthony, Jernigan, Terry L, Jiang, Jiyang, Jönsson, Erik G, Joska, John A, Kahn, Rene, and Kalnin, Andrew

Subjects
Karolinska Schizophrenia Project, Amygdala, Hippocampus, Thalamus, Corpus Striatum, Humans, Human Development, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Child, Child, Preschool, Female, Male, Young Adult, Neuroimaging, ENIGMA, brain morphometry, longitudinal trajectories, multisite, Neurosciences, Aging, Aetiology, 2.1 Biological and endogenous factors, Mental health, Cognitive Sciences, Experimental Psychology
Abstract

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.

Published
2022

6. Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3–90 years

Author

Frangou, Sophia, Modabbernia, Amirhossein, Williams, Steven CR, Papachristou, Efstathios, Doucet, Gaelle E, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N, Albajes‐Eizagirre, Anton, Alnæs, Dag, Alpert, Kathryn I, Andersson, Micael, Andreasen, Nancy C, Andreassen, Ole A, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur‐Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret I, Borgwardt, Stefan, Bourque, Josiane, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M, Buitelaar, Jan K, Busatto, Geraldo F, Buckner, Randy L, Calhoun, Vincent, Canales‐Rodríguez, Erick J, Cannon, Dara M, Caseras, Xavier, Castellanos, Francisco X, Cervenka, Simon, Chaim‐Avancini, Tiffany M, Ching, Christopher RK, Chubar, Victoria, Clark, Vincent P, Conrod, Patricia, Conzelmann, Annette, Crespo‐Facorro, Benedicto, Crivello, Fabrice, Crone, Eveline A, Dale, Anders M, Dannlowski, Udo, Davey, Christopher, Geus, Eco JC, Haan, Lieuwe, Zubicaray, Greig I, Braber, Anouk, Dickie, Erin W, Di Giorgio, Annabella, Doan, Nhat Trung, Dørum, Erlend S, Ehrlich, Stefan, Erk, Susanne, Espeseth, Thomas, Fatouros‐Bergman, Helena, Fisher, Simon E, Fouche, Jean‐Paul, Franke, Barbara, Frodl, Thomas, Fuentes‐Claramonte, Paola, Glahn, David C, Gotlib, Ian H, Grabe, Hans‐Jörgen, Grimm, Oliver, Groenewold, Nynke A, Grotegerd, Dominik, Gruber, Oliver, Gruner, Patricia, Gur, Rachel E, Gur, Ruben C, Hahn, Tim, Harrison, Ben J, Hartman, Catharine A, Hatton, Sean N, Heinz, Andreas, Heslenfeld, Dirk J, Hibar, Derrek P, Hickie, Ian B, Ho, Beng‐Choon, Hoekstra, Pieter J, Hohmann, Sarah, Holmes, Avram J, Hoogman, Martine, Hosten, Norbert, Howells, Fleur M, Pol, Hilleke E Hulshoff, Huyser, Chaim, Jahanshad, Neda, James, Anthony, Jernigan, Terry L, Jiang, Jiyang, Jönsson, Erik G, Joska, John A, and Kahn, Rene

Subjects
Behavioral and Social Science, Neurosciences, Aging, Adolescent, Adult, Aged, Aged, 80 and over, Cerebral Cortex, Child, Child, Preschool, Cross-Sectional Studies, Female, Human Development, Humans, Male, Middle Aged, Neuroimaging, Young Adult, aging, cortical thickness, development, trajectories, Karolinska Schizophrenia Project, Cognitive Sciences, Experimental Psychology
Abstract

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.

Published
2022

7. Analysis of structural brain asymmetries in attention‐deficit/hyperactivity disorder in 39 datasets

Author

Postema, Merel C, Hoogman, Martine, Ambrosino, Sara, Asherson, Philip, Banaschewski, Tobias, Bandeira, Cibele E, Baranov, Alexandr, Bau, Claiton HD, Baumeister, Sarah, Baur‐Streubel, Ramona, Bellgrove, Mark A, Biederman, Joseph, Bralten, Janita, Brandeis, Daniel, Brem, Silvia, Buitelaar, Jan K, Busatto, Geraldo F, Castellanos, Francisco X, Cercignani, Mara, Chaim‐Avancini, Tiffany M, Chantiluke, Kaylita C, Christakou, Anastasia, Coghill, David, Conzelmann, Annette, Cubillo, Ana I, Cupertino, Renata B, de Zeeuw, Patrick, Doyle, Alysa E, Durston, Sarah, Earl, Eric A, Epstein, Jeffery N, Ethofer, Thomas, Fair, Damien A, Fallgatter, Andreas J, Faraone, Stephen V, Frodl, Thomas, Gabel, Matt C, Gogberashvili, Tinatin, Grevet, Eugenio H, Haavik, Jan, Harrison, Neil A, Hartman, Catharina A, Heslenfeld, Dirk J, Hoekstra, Pieter J, Hohmann, Sarah, Høvik, Marie F, Jernigan, Terry L, Kardatzki, Bernd, Karkashadze, Georgii, Kelly, Clare, Kohls, Gregor, Konrad, Kerstin, Kuntsi, Jonna, Lazaro, Luisa, Lera‐Miguel, Sara, Lesch, Klaus‐Peter, Louza, Mario R, Lundervold, Astri J, Malpas, Charles B, Mattos, Paulo, McCarthy, Hazel, Namazova‐Baranova, Leyla, Nicolau, Rosa, Nigg, Joel T, Novotny, Stephanie E, Weiss, Eileen Oberwelland, Tuura, Ruth L O'Gorman, Oosterlaan, Jaap, Oranje, Bob, Paloyelis, Yannis, Pauli, Paul, Picon, Felipe A, Plessen, Kerstin J, Ramos‐Quiroga, J Antoni, Reif, Andreas, Reneman, Liesbeth, Rosa, Pedro GP, Rubia, Katya, Schrantee, Anouk, Schweren, Lizanne JS, Seitz, Jochen, Shaw, Philip, Silk, Tim J, Skokauskas, Norbert, Vila, Juan C Soliva, Stevens, Michael C, Sudre, Gustavo, Tamm, Leanne, Tovar‐Moll, Fernanda, van Erp, Theo GM, Vance, Alasdair, Vilarroya, Oscar, Vives‐Gilabert, Yolanda, von Polier, Georg G, Walitza, Susanne, Yoncheva, Yuliya N, Zanetti, Marcus V, Ziegler, Georg C, Glahn, David C, and Jahanshad, Neda

Subjects
Biological Psychology, Psychology, Pediatric, Brain Disorders, Mental Health, Neurosciences, Attention Deficit Hyperactivity Disorder (ADHD), Pediatric Research Initiative, Aetiology, 2.1 Biological and endogenous factors, Mental health, Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Autism Spectrum Disorder, Brain, Caudate Nucleus, Child, Humans, Magnetic Resonance Imaging, Attention&#8208, deficit, hyperactivity disorder, brain asymmetry, brain laterality, structural MRI, large&#8208, scale data, ENIGMA ADHD Working Group, Attention-deficit, large-scale data, Clinical Sciences, Cognitive Sciences, Developmental & Child Psychology, Clinical sciences, Applied and developmental psychology, Clinical and health psychology
Abstract

ObjectiveSome studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium.MethodsWe analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries.ResultsThere was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen's d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing.ConclusionPrior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.

Published
2021

8. The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder

Author

Faraone, Stephen V, Banaschewski, Tobias, Coghill, David, Zheng, Yi, Biederman, Joseph, Bellgrove, Mark A, Newcorn, Jeffrey H, Gignac, Martin, Al Saud, Nouf M, Manor, Iris, Rohde, Luis Augusto, Yang, Li, Cortese, Samuele, Almagor, Doron, Stein, Mark A, Albatti, Turki H, Aljoudi, Haya F, Alqahtani, Mohammed MJ, Asherson, Philip, Atwoli, Lukoye, Bölte, Sven, Buitelaar, Jan K, Crunelle, Cleo L, Daley, David, Dalsgaard, Søren, Döpfner, Manfred, Espinet, Stacey, Fitzgerald, Michael, Franke, Barbara, Gerlach, Manfred, Haavik, Jan, Hartman, Catharina A, Hartung, Cynthia M, Hinshaw, Stephen P, Hoekstra, Pieter J, Hollis, Chris, Kollins, Scott H, Kooij, JJ Sandra, Kuntsi, Jonna, Larsson, Henrik, Li, Tingyu, Liu, Jing, Merzon, Eugene, Mattingly, Gregory, Mattos, Paulo, McCarthy, Suzanne, Mikami, Amori Yee, Molina, Brooke SG, Nigg, Joel T, Purper-Ouakil, Diane, Omigbodun, Olayinka O, Polanczyk, Guilherme V, Pollak, Yehuda, Poulton, Alison S, Rajkumar, Ravi Philip, Reding, Andrew, Reif, Andreas, Rubia, Katya, Rucklidge, Julia, Romanos, Marcel, Ramos-Quiroga, J Antoni, Schellekens, Arnt, Scheres, Anouk, Schoeman, Renata, Schweitzer, Julie B, Shah, Henal, Solanto, Mary V, Sonuga-Barke, Edmund, Soutullo, César, Steinhausen, Hans-Christoph, Swanson, James M, Thapar, Anita, Tripp, Gail, van de Glind, Geurt, van den Brink, Wim, Van der Oord, Saskia, Venter, Andre, Vitiello, Benedetto, Walitza, Susanne, and Wang, Yufeng

Subjects
Epidemiology, Health Sciences, Behavioral and Social Science, Mental Illness, Brain Disorders, Clinical Research, Attention Deficit Hyperactivity Disorder (ADHD), Mental Health, Comparative Effectiveness Research, Pediatric, Mental health, Attention Deficit Disorder with Hyperactivity, Humans, Network Meta-Analysis, Publication Bias, ADHD, Diagnosis, Treatment, Course, Outcome, Genetics, Brain, Medical and Health Sciences, Psychology and Cognitive Sciences, Behavioral Science & Comparative Psychology, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundMisconceptions about ADHD stigmatize affected people, reduce credibility of providers, and prevent/delay treatment. To challenge misconceptions, we curated findings with strong evidence base.MethodsWe reviewed studies with more than 2000 participants or meta-analyses from five or more studies or 2000 or more participants. We excluded meta-analyses that did not assess publication bias, except for meta-analyses of prevalence. For network meta-analyses we required comparison adjusted funnel plots. We excluded treatment studies with waiting-list or treatment as usual controls. From this literature, we extracted evidence-based assertions about the disorder.ResultsWe generated 208 empirically supported statements about ADHD. The status of the included statements as empirically supported is approved by 80 authors from 27 countries and 6 continents. The contents of the manuscript are endorsed by 366 people who have read this document and agree with its contents.ConclusionsMany findings in ADHD are supported by meta-analysis. These allow for firm statements about the nature, course, outcome causes, and treatments for disorders that are useful for reducing misconceptions and stigma.

Published
2021

9. Characterizing neuroanatomic heterogeneity in people with and without ADHD based on subcortical brain volumes

Author

Li, Ting, van Rooij, Daan, Mota, Nina Roth, Buitelaar, Jan K, Ambrosino, Sara, Banaschewski, Tobias, Bandeira, Cibele E, Bau, Claiton HD, Baumeister, Sarah, Baur‐Streubel, Ramona, Bellgrove, Mark A, Biederman, Joseph, Bralten, Janita, Bramati, Ivanei E, Brandeis, Daniel, Berm, Silvia, Busatto, Geraldo F, Calvo, Anna, Castellanos, Francisco X, Cercignani, Mara, Chantiluke, Kaylita C, Christakou, Anastasia, Coghill, David, Conzelmann, Annette, Cubillo, Ana I, Cupertino, Renata B, de Zeeuw, Parick, Durston, Sarah, Earl, Eric A, Epstein, Jeffery N, Ethofer, Thomas, Fallgatter, Andreas J, Fair, Damien A, Faraone, Stephen V, Frodl, Thomas, Gabel, Matt C, Gogberashvili, Tinatin, Grevet, Eugenio H, Haavik, Jan, Harrison, Neil A, Hartman, Catharina A, Heslenfeld, Dirk J, Hoekstra, Pieter J, Høvik, Marie F, Jahanshad, Neda, Kardatzki, Bernd, Karkashadze, Georgii, Kelly, Clare, Kohls, Gregor, Konrad, Kerstin, Kuntsi, Jonna, Lazaro, Luisa, Lera‐Miguel, Sara, Lesch, Klaus‐Peter, Louza, Mario R, Lundervold, Astri J, Malpas, Charles B, Mattos, Paulo, McCarthy, Hazel, Nicolau, Rosa, Nigg, Joel T, Tuura, Ruth L O'Gorman, Oosterlaan, Jaap, Oranje, Bob, Paloyelis, Yannis, Pauli, Paul, Picon, Felipe A, Plessen, Kerstin J, Ramos‐Quiroga, J Antoni, Reif, Andreas, Reneman, Liesbeth, Rosa, Pedro GP, Rubia, Katya, Schrantee, Anouk, Schweren, Lizanne JS, Seitz, Jochen, Shaw, Philip, Silk, Tim J, Skokauskas, Norbert, Vila, Juan Carlos Soliva, Soloveva, Anastasiia, Stevens, Michael C, Sudre, Gustavo, Tamm, Leanne, Thompson, Paul M, Tovar‐Moll, Fernanda, van Erp, Theo GM, Vance, Alasdair, Vilarroya, Oscar, Vives‐Gilabert, Yolanda, von Polier, Georg G, Walitza, Susanne, Yoncheva, Yuliya N, Zanetti, Marcus V, Ziegler, Georg C, Anikin, Anatoly, Asherson, Philip, Baranov, Alexandr, Chaim‐Avanicini, Tiffany, and Dale, Anders M

Subjects
Biological Psychology, Psychology, Mental Health, Pediatric, Brain Disorders, Attention Deficit Hyperactivity Disorder (ADHD), Clinical Research, Neurosciences, Adult, Attention Deficit Disorder with Hyperactivity, Brain, Case-Control Studies, Female, Humans, Magnetic Resonance Imaging, Male, Thalamus, ADHD, subcortical volume, neuroanatomic heterogeneity, community detection, effect sizes, ENIGMA ADHD Working Group, Clinical Sciences, Cognitive Sciences, Developmental & Child Psychology, Clinical sciences, Applied and developmental psychology, Clinical and health psychology
Abstract

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder. Neuroanatomic heterogeneity limits our understanding of ADHD's etiology. This study aimed to parse heterogeneity of ADHD and to determine whether patient subgroups could be discerned based on subcortical brain volumes.MethodsUsing the large ENIGMA-ADHD Working Group dataset, four subsamples of 993 boys with and without ADHD and to subsamples of 653 adult men, 400 girls, and 447 women were included in analyses. We applied exploratory factor analysis (EFA) to seven subcortical volumes in order to constrain the complexity of the input variables and ensure more stable clustering results. Factor scores derived from the EFA were used to build networks. A community detection (CD) algorithm clustered participants into subgroups based on the networks.ResultsExploratory factor analysis revealed three factors (basal ganglia, limbic system, and thalamus) in boys and men with and without ADHD. Factor structures for girls and women differed from those in males. Given sample size considerations, we concentrated subsequent analyses on males. Male participants could be separated into four communities, of which one was absent in healthy men. Significant case-control differences of subcortical volumes were observed within communities in boys, often with stronger effect sizes compared to the entire sample. As in the entire sample, none were observed in men. Affected men in two of the communities presented comorbidities more frequently than those in other communities. There were no significant differences in ADHD symptom severity, IQ, and medication use between communities in either boys or men.ConclusionsOur results indicate that neuroanatomic heterogeneity in subcortical volumes exists, irrespective of ADHD diagnosis. Effect sizes of case-control differences appear more pronounced at least in some of the subgroups.

Published
2021

10. Association between relative age at school and persistence of ADHD in prospective studies: an individual participant data meta-analysis

Author

Gosling, Corentin J, Caparos, Serge, Pinabiaux, Charlotte, Schwarzer, Guido, Rücker, Gerta, Agha, Sharifah S, Alrouh, Hekmat, Ambler, Antony, Anderson, Peter, Andiarena, Ainara, Arnold, L Eugene, Arseneault, Louise, Asherson, Philip, Babinski, Leslie, Barbati, Vittoria, Barkley, Russel, Barros, Aluisio J D, Barros, Fernando, Bates, John E, Bell, Laura J, Berenguer, Carmen, van Bergen, Elsje, Biederman, Joseph, Birmaher, Boris, B⊘e, Tormod, Boomsma, Dorret I, Brandt, Valerie C, Bressan, Rodrigo A, Brocki, Karin, Broughton, Thomas R, Bufferd, Sara J, Bussing, Regina, Cao, Meng, Cartigny, Ariane, Casas, Ana Miranda, Caspi, Avshalom, Castellanos, F Xavier, Caye, Arthur, Cederkvist, Luise, Collishaw, Stephan, Copeland, William E, Cote, Sylvana M, Coventry, William L, Debes, Nanette M.M. Mol, Denyer, Hayley, Dodge, Kenneth A, Dogru, Hicran, Efron, Daryl, Eller, Jami, Abd Elmaksoud, Marwa, Ercan, Eyup Sabri, Faraone, Stephen V, Fenesy, Michelle, Fernández, Mariana F, Fernández-Somoano, Ana, Findling, Robert, Fombonne, Eric, Fossum, Ingrid N, Freire, Carmen, Friedman, Naomi P, Fristad, Mary A, Galera, Cedric, Garcia-Argibay, Miguel, Garvan, Cynthia S, González-Safont, Llúcia, Groenman, Annabeth P, Guxens, Mònica, Halperin, Jeffrey M, Hamadeh, Randah R, Hartman, Catharina A, Hill, Shirley Y, Hinshaw, Stephen P, Hipwell, Alison, Hokkanen, Laura, Holz, Nathalie, Íñiguez, Carmen, Jahrami, Haitham A, Jansen, Pauline W, Jónsdóttir, Lilja K, Julvez, Jordi, Kaiser, Anna, Keenan, Kate, Klein, Daniel N, Klein, Rachel G, Kuntsi, Jonna, Langfus, Joshua, Langley, Kate, Lansford, Jennifer E, Larsen, Sally A, Larsson, Henrik, Law, Evelyn, Lee, Steve S, Lertxundi, Nerea, Li, Xiaobo, Li, Yueling, Lichtenstein, Paul, Liu, Jianghong, Lundervold, Astri J, Lundström, Sebastian, Marks, David J, Martin, Joanna, Masi, Gabriele, Matijasevich, Alicia, Melchior, Maria, Moffitt, Terrie E, Monninger, Maximilian, Morrison, Claire L, Mulraney, Melissa, Muratori, Pietro, Nguyen, Phuc T, Nicholson, Jan M, Øie, Merete Glenne, O'Neill, Sarah, O'Connor, Cliodhna, Orri, Massimiliano, Pan, Pedro M, Pascoe, Leona, Pettit, Gregory S, Price, Jolie, Rebagliato, Marisa, Riaño-Galán, Isolina, Rohde, Luis A, Roisman, Glenn I, Rosa, Maria, Rosenbaum, Jerrold F, Salum, Giovanni A, Sammallahti, Sara, Santos, Ina S, Schiavone, Nella S, Schmid, Lorrie, Sciberras, Emma, Shaw, Philip, Silk, Tim J, Simpson, Jeffry A, Skogli, Erik W, Stepp, Stephanie, Strandberg-Larsen, Katrine, Sudre, Gustavo, Sunyer, Jordi, Tandon, Mini, Thapar, Anita, Thomson, Phoebe, Thorell, Lisa B, Tinchant, Hannah, Torrent, Maties, Tovo-Rodrigues, Luciana, Tripp, Gail, Ukoumunne, Obioha, Van Goozen, Stephanie HM, Vos, Melissa, Wallez, Solène, Wang, Yufeng, Westermaier, Franz G, Whalen, Diana J, Yoncheva, Yuliya, Youngstrom, Eric A, Sayal, Kapil, Solmi, Marco, Delorme, Richard, and Cortese, Samuele

Published
2023
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11. Subcortical Brain Volume, Regional Cortical Thickness, and Cortical Surface Area Across Disorders: Findings From the ENIGMA ADHD, ASD, and OCD Working Groups

Author

Boedhoe, Premika SW, van Rooij, Daan, Hoogman, Martine, Twisk, Jos WR, Schmaal, Lianne, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H, Anikin, Anatoly, Anticevic, Alan, Arango, Celso, Arnold, Paul D, Asherson, Philip, Assogna, Francesca, Auzias, Guillaume, Banaschewski, Tobias, Baranov, Alexander, Batistuzzo, Marcelo C, Baumeister, Sarah, Baur-Streubel, Ramona, Behrmann, Marlene, Bellgrove, Mark A, Benedetti, Francesco, Beucke, Jan C, Biederman, Joseph, Bollettini, Irene, Bose, Anushree, Bralten, Janita, Bramati, Ivanei E, Brandeis, Daniel, Brem, Silvia, Brennan, Brian P, Busatto, Geraldo F, Calderoni, Sara, Calvo, Anna, Calvo, Rosa, Castellanos, Francisco X, Cercignani, Mara, Chaim-Avancini, Tiffany M, Chantiluke, Kaylita C, Cheng, Yuqi, Cho, Kang Ik K, Christakou, Anastasia, Coghill, David, Conzelmann, Annette, Cubillo, Ana I, Dale, Anders M, Dallaspezia, Sara, Daly, Eileen, Denys, Damiaan, Deruelle, Christine, Di Martino, Adriana, Dinstein, Ilan, Doyle, Alysa E, Durston, Sarah, Earl, Eric A, Ecker, Christine, Ehrlich, Stefan, Ely, Benjamin A, Epstein, Jeffrey N, Ethofer, Thomas, Fair, Damien A, Fallgatter, Andreas J, Faraone, Stephen V, Fedor, Jennifer, Feng, Xin, Feusner, Jamie D, Fitzgerald, Jackie, Fitzgerald, Kate D, Fouche, Jean-Paul, Freitag, Christine M, Fridgeirsson, Egill A, Frodl, Thomas, Gabel, Matt C, Gallagher, Louise, Gogberashvili, Tinatin, Gori, Ilaria, Gruner, Patricia, Gürsel, Deniz A, Haar, Shlomi, Haavik, Jan, Hall, Geoffrey B, Harrison, Neil A, Hartman, Catharina A, Heslenfeld, Dirk J, Hirano, Yoshiyuki, Hoekstra, Pieter J, Hoexter, Marcelo Q, Hohmann, Sarah, Høvik, Marie F, Hu, Hao, Huyser, Chaim, Jahanshad, Neda, Jalbrzikowski, Maria, James, Anthony, Janssen, Joost, Jaspers-Fayer, Fern, Jernigan, Terry L, Kapilushniy, Dmitry, and Kardatzki, Bernd

Subjects
Attention Deficit Hyperactivity Disorder (ADHD), Behavioral and Social Science, Clinical Research, Mental Health, Neurosciences, Pediatric, Autism, Intellectual and Developmental Disabilities (IDD), Brain Disorders, 2.1 Biological and endogenous factors, 2.3 Psychological, social and economic factors, Aetiology, Mental health, Neurological, Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Autism Spectrum Disorder, Cerebrum, Child, Female, Human Development, Humans, Male, Neuroimaging, Obsessive-Compulsive Disorder, Organ Size, Psychopathology, Research Report, Systems Analysis, ENIGMA ADHD working group, ENIGMA ASD working group, ENIGMA OCD working group, Attention Deficit Hyperactivity Disorder, ENIGMA, Structural MRI, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

ObjectiveAttention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data.MethodsStructural T1-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures).ResultsNo shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood.ConclusionsThe study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.

Published
2020

12. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Author

Consortium, Cross-Disorder Group of the Psychiatric Genomics, Lee, Phil H, Anttila, Verneri, Won, Hyejung, Feng, Yen-Chen A, Rosenthal, Jacob, Zhu, Zhaozhong, Tucker-Drob, Elliot M, Nivard, Michel G, Grotzinger, Andrew D, Posthuma, Danielle, Wang, Meg M-J, Yu, Dongmei, Stahl, Eli A, Walters, Raymond K, Anney, Richard JL, Duncan, Laramie E, Ge, Tian, Adolfsson, Rolf, Banaschewski, Tobias, Belangero, Sintia, Cook, Edwin H, Coppola, Giovanni, Derks, Eske M, Hoekstra, Pieter J, Kaprio, Jaakko, Keski-Rahkonen, Anna, Kirov, George, Kranzler, Henry R, Luykx, Jurjen J, Rohde, Luis A, Zai, Clement C, Agerbo, Esben, Arranz, MJ, Asherson, Philip, Bækvad-Hansen, Marie, Baldursson, Gísli, Bellgrove, Mark, Belliveau, Richard A, Buitelaar, Jan, Burton, Christie L, Bybjerg-Grauholm, Jonas, Casas, Miquel, Cerrato, Felecia, Chambert, Kimberly, Churchhouse, Claire, Cormand, Bru, Crosbie, Jennifer, Dalsgaard, Søren, Demontis, Ditte, Doyle, Alysa E, Dumont, Ashley, Elia, Josephine, Grove, Jakob, Gudmundsson, Olafur O, Haavik, Jan, Hakonarson, Hakon, Hansen, Christine S, Hartman, Catharina A, Hawi, Ziarih, Hervás, Amaia, Hougaard, David M, Howrigan, Daniel P, Huang, Hailiang, Kuntsi, Jonna, Langley, Kate, Lesch, Klaus-Peter, Leung, Patrick WL, Loo, Sandra K, Martin, Joanna, Martin, Alicia R, McGough, James J, Medland, Sarah E, Moran, Jennifer L, Mors, Ole, Mortensen, Preben B, Oades, Robert D, Palmer, Duncan S, Pedersen, Carsten B, Pedersen, Marianne G, Peters, Triinu, Poterba, Timothy, Poulsen, Jesper B, Ramos-Quiroga, Josep Antoni, Reif, Andreas, Ribasés, Marta, Rothenberger, Aribert, Rovira, Paula, Sánchez-Mora, Cristina, Satterstrom, F Kyle, Schachar, Russell, Artigas, Maria Soler, Steinberg, Stacy, Stefansson, Hreinn, Turley, Patrick, Walters, G Bragi, Team, 23andMe Research, Werge, Thomas, Zayats, Tetyana, and Arking, Dan E

Subjects
Neurosciences, Serious Mental Illness, Human Genome, Schizophrenia, Intellectual and Developmental Disabilities (IDD), Brain Disorders, Genetics, Pediatric, Mental Health, Aetiology, 2.1 Biological and endogenous factors, Mental health, Genetic Pleiotropy, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Mental Disorders, Neurogenesis, Quantitative Trait Loci, Cross-Disorder Group of the Psychiatric Genomics Consortium. Electronic address: plee0@mgh.harvard.edu, Cross-Disorder Group of the Psychiatric Genomics Consortium, GWAS, Psychiatric genetics, cross-disorder genetics, functional genomics, gene expression, genetic architecture, genetic correlation, neurodevelopment, pleiotropy, psychiatric disorders, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.

Published
2019

14. Brain Imaging of the Cortex in ADHD: A Coordinated Analysis of Large-Scale Clinical and Population-Based Samples

Author

Hoogman, Martine, Muetzel, Ryan, Guimaraes, Joao P, Shumskaya, Elena, Mennes, Maarten, Zwiers, Marcel P, Jahanshad, Neda, Sudre, Gustavo, Wolfers, Thomas, Earl, Eric A, Soliva Vila, Juan Carlos, Vives-Gilabert, Yolanda, Khadka, Sabin, Novotny, Stephanie E, Hartman, Catharina A, Heslenfeld, Dirk J, Schweren, Lizanne JS, Ambrosino, Sara, Oranje, Bob, de Zeeuw, Patrick, Chaim-Avancini, Tiffany M, Rosa, Pedro GP, Zanetti, Marcus V, Malpas, Charles B, Kohls, Gregor, von Polier, Georg G, Seitz, Jochen, Biederman, Joseph, Doyle, Alysa E, Dale, Anders M, van Erp, Theo GM, Epstein, Jeffery N, Jernigan, Terry L, Baur-Streubel, Ramona, Ziegler, Georg C, Zierhut, Kathrin C, Schrantee, Anouk, Høvik, Marie F, Lundervold, Astri J, Kelly, Clare, McCarthy, Hazel, Skokauskas, Norbert, O’Gorman Tuura, Ruth L, Calvo, Anna, Lera-Miguel, Sara, Nicolau, Rosa, Chantiluke, Kaylita C, Christakou, Anastasia, Vance, Alasdair, Cercignani, Mara, Gabel, Matt C, Asherson, Philip, Baumeister, Sarah, Brandeis, Daniel, Hohmann, Sarah, Bramati, Ivanei E, Tovar-Moll, Fernanda, Fallgatter, Andreas J, Kardatzki, Bernd, Schwarz, Lena, Anikin, Anatoly, Baranov, Alexandr, Gogberashvili, Tinatin, Kapilushniy, Dmitry, Solovieva, Anastasia, El Marroun, Hanan, White, Tonya, Karkashadze, Georgii, Namazova-Baranova, Leyla, Ethofer, Thomas, Mattos, Paulo, Banaschewski, Tobias, Coghill, David, Plessen, Kerstin J, Kuntsi, Jonna, Mehta, Mitul A, Paloyelis, Yannis, Harrison, Neil A, Bellgrove, Mark A, Silk, Tim J, Cubillo, Ana I, Rubia, Katya, Lazaro, Luisa, Brem, Silvia, Walitza, Susanne, Frodl, Thomas, Zentis, Mariam, Castellanos, Francisco X, Yoncheva, Yuliya N, Haavik, Jan, Reneman, Liesbeth, Conzelmann, Annette, Lesch, Klaus-Peter, Pauli, Paul, Reif, Andreas, Tamm, Leanne, Konrad, Kerstin, Oberwelland Weiss, Eileen, Busatto, Geraldo F, and Louza, Mario R

Subjects
Pediatric, Neurosciences, Mental Health, Attention Deficit Hyperactivity Disorder (ADHD), Behavioral and Social Science, Clinical Research, Brain Disorders, Pediatric Research Initiative, Aetiology, 2.1 Biological and endogenous factors, Mental health, Adolescent, Adult, Age Factors, Attention Deficit Disorder with Hyperactivity, Case-Control Studies, Cerebral Cortex, Child, Child, Preschool, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, Psychiatric Status Rating Scales, Sex Factors, Young Adult, Attention Deficit Hyperactivity Disorder, Cortical Surface Area, Cortical Thickness, Imaging, Meta-Analysis, Neuroanatomy, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

ObjectiveNeuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonreplications are frequent. The authors sought to identify cortical characteristics related to ADHD using large-scale studies.MethodsCortical thickness and surface area (based on the Desikan-Killiany atlas) were compared between case subjects with ADHD (N=2,246) and control subjects (N=1,934) for children, adolescents, and adults separately in ENIGMA-ADHD, a consortium of 36 centers. To assess familial effects on cortical measures, case subjects, unaffected siblings, and control subjects in the NeuroIMAGE study (N=506) were compared. Associations of the attention scale from the Child Behavior Checklist with cortical measures were determined in a pediatric population sample (Generation-R, N=2,707).ResultsIn the ENIGMA-ADHD sample, lower surface area values were found in children with ADHD, mainly in frontal, cingulate, and temporal regions; the largest significant effect was for total surface area (Cohen's d=-0.21). Fusiform gyrus and temporal pole cortical thickness was also lower in children with ADHD. Neither surface area nor thickness differences were found in the adolescent or adult groups. Familial effects were seen for surface area in several regions. In an overlapping set of regions, surface area, but not thickness, was associated with attention problems in the Generation-R sample.ConclusionsSubtle differences in cortical surface area are widespread in children but not adolescents and adults with ADHD, confirming involvement of the frontal cortex and highlighting regions deserving further attention. Notably, the alterations behave like endophenotypes in families and are linked to ADHD symptoms in the population, extending evidence that ADHD behaves as a continuous trait in the population. Future longitudinal studies should clarify individual lifespan trajectories that lead to nonsignificant findings in adolescent and adult groups despite the presence of an ADHD diagnosis.

Published
2019

15. Atypical functional connectivity in adolescents and adults with persistent and remitted ADHD during a cognitive control task.

Author

Michelini, Giorgia, Jurgiel, Joseph, Bakolis, Ioannis, Cheung, Celeste HM, Asherson, Philip, Loo, Sandra K, Kuntsi, Jonna, and Mohammad-Rezazadeh, Iman

Subjects
Brain, Neural Pathways, Humans, Magnetic Resonance Imaging, Cognition, Psychomotor Performance, Attention Deficit Disorder with Hyperactivity, Evoked Potentials, Adolescent, Female, Male, Young Adult, Mental Health, Clinical Research, Attention Deficit Disorder (ADD), Brain Disorders, Behavioral and Social Science, Neurosciences, Pediatric, 2.1 Biological and endogenous factors, Psychology, Clinical Sciences, Public Health and Health Services
Abstract

We previously provided initial evidence for cognitive and event-related potential markers of persistence/remission of attention-deficit/hyperactivity disorder (ADHD) from childhood to adolescence and adulthood. Here, using a novel brain-network connectivity approach, we aimed to examine whether task-based functional connectivity reflects a marker of ADHD remission or an enduring deficit unrelated to ADHD outcome. High-density EEG was recorded in a follow-up of 110 adolescents and young adults with childhood ADHD (87 persisters, 23 remitters) and 169 typically developing individuals during an arrow-flanker task, eliciting cognitive control. Functional connectivity was quantified with network-based graph-theory metrics before incongruent (high-conflict) target onset (pre-stimulus), during target processing (post-stimulus) and in the degree of change between pre-stimulus/post-stimulus. ADHD outcome was examined with parent-reported symptoms and impairment using both a categorical (DSM-IV) and a dimensional approach. Graph-theory measures converged in indicating that, compared to controls, ADHD persisters showed increased connectivity in pre-stimulus theta, alpha, and beta and in post-stimulus beta (all p

Published
2019

16. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder.

Author

Demontis, Ditte, Walters, Raymond K, Martin, Joanna, Mattheisen, Manuel, Als, Thomas D, Agerbo, Esben, Baldursson, Gísli, Belliveau, Rich, Bybjerg-Grauholm, Jonas, Bækvad-Hansen, Marie, Cerrato, Felecia, Chambert, Kimberly, Churchhouse, Claire, Dumont, Ashley, Eriksson, Nicholas, Gandal, Michael, Goldstein, Jacqueline I, Grasby, Katrina L, Grove, Jakob, Gudmundsson, Olafur O, Hansen, Christine S, Hauberg, Mads Engel, Hollegaard, Mads V, Howrigan, Daniel P, Huang, Hailiang, Maller, Julian B, Martin, Alicia R, Martin, Nicholas G, Moran, Jennifer, Pallesen, Jonatan, Palmer, Duncan S, Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Poterba, Timothy, Poulsen, Jesper Buchhave, Ripke, Stephan, Robinson, Elise B, Satterstrom, F Kyle, Stefansson, Hreinn, Stevens, Christine, Turley, Patrick, Walters, G Bragi, Won, Hyejung, Wright, Margaret J, ADHD Working Group of the Psychiatric Genomics Consortium (PGC), Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium, 23andMe Research Team, Andreassen, Ole A, Asherson, Philip, Burton, Christie L, Boomsma, Dorret I, Cormand, Bru, Dalsgaard, Søren, Franke, Barbara, Gelernter, Joel, Geschwind, Daniel, Hakonarson, Hakon, Haavik, Jan, Kranzler, Henry R, Kuntsi, Jonna, Langley, Kate, Lesch, Klaus-Peter, Middeldorp, Christel, Reif, Andreas, Rohde, Luis Augusto, Roussos, Panos, Schachar, Russell, Sklar, Pamela, Sonuga-Barke, Edmund JS, Sullivan, Patrick F, Thapar, Anita, Tung, Joyce Y, Waldman, Irwin D, Medland, Sarah E, Stefansson, Kari, Nordentoft, Merete, Hougaard, David M, Werge, Thomas, Mors, Ole, Mortensen, Preben Bo, Daly, Mark J, Faraone, Stephen V, Børglum, Anders D, and Neale, Benjamin M

Subjects
ADHD Working Group of the Psychiatric Genomics Consortium, Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium, 23andMe Research Team, Brain, Humans, Genetic Predisposition to Disease, Risk, Cohort Studies, Attention Deficit Disorder with Hyperactivity, Gene Expression Regulation, Polymorphism, Single Nucleotide, Adolescent, Child, Child, Preschool, Female, Male, Genome-Wide Association Study, Genetic Loci, Clinical Research, Mental Health, Human Genome, Pediatric, Prevention, Genetics, Brain Disorders, Attention Deficit Hyperactivity Disorder (ADHD), Behavioral and Social Science, Aetiology, 2.1 Biological and endogenous factors, Mental health, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Attention deficit/hyperactivity disorder (ADHD) is a highly heritable childhood behavioral disorder affecting 5% of children and 2.5% of adults. Common genetic variants contribute substantially to ADHD susceptibility, but no variants have been robustly associated with ADHD. We report a genome-wide association meta-analysis of 20,183 individuals diagnosed with ADHD and 35,191 controls that identifies variants surpassing genome-wide significance in 12 independent loci, finding important new information about the underlying biology of ADHD. Associations are enriched in evolutionarily constrained genomic regions and loss-of-function intolerant genes and around brain-expressed regulatory marks. Analyses of three replication studies: a cohort of individuals diagnosed with ADHD, a self-reported ADHD sample and a meta-analysis of quantitative measures of ADHD symptoms in the population, support these findings while highlighting study-specific differences on genetic overlap with educational attainment. Strong concordance with GWAS of quantitative population measures of ADHD symptoms supports that clinical diagnosis of ADHD is an extreme expression of continuous heritable traits.

Published
2019

19. The adult ADHD assessment quality assurance standard.

Author

Adamou, Marios, Arif, Muhammad, Asherson, Philip, Cubbin, Sally, Leaver, Laurence, Sedgwick-Müller, Jane, Müller-Sedgwick, Ulrich, van Rensburg, Kobus, and Kustow, James

Subjects
ATTENTION-deficit hyperactivity disorder, CORE competencies, ADULTS, SEMI-structured interviews, QUALITY standards
Abstract

Background: Attention Deficit Hyperactivity Disorder (ADHD) frequently persists into adulthood. There are practice guidelines that outline the requirements for the assessment and treatment of adults. Nevertheless, guidelines specifying what constitutes a good quality diagnostic assessment and report and the competencies required to be a specialist assessor are lacking. This can lead to variation in the quality and reliability of adult ADHD assessments. Poor quality assessments may not be accepted as valid indicators of the presence of ADHD by other clinicians or services, resulting in wasteful re-assessments and delays in providing treatment. To address this issue the UK Adult ADHD Network (UKAAN) proposes a quality framework for adult ADHD assessments - the Adult ADHD Assessment Quality Assurance Standard (AQAS). Methods: The co-authors agreed on five questions or themes that then guided the development of a set of consensus statements. An initial draft was reviewed and amended in an iterative process to reach a final consensus. Results: What constitutes a high-quality diagnostic assessment and report was agreed by consensus of the co-authors. The resulting guideline emphasises the need to evaluate impairment, describes core competencies required by the assessor and highlights the importance of linking the diagnosis to an appropriate post-diagnostic discussion. Assessments should be completed in the context of a full psychiatric and neurodevelopmental review, and need good interview skills, using a semi-structured interview with open questioning and probing to elicit real life examples of symptoms and impairments. It is recommended that 2 hours or more is required for an adequate assessment including both the diagnostic assessment and initial post-assessment discussions. Conclusion: The AQAS has been developed as a practical resource to support reliable and valid diagnostic assessments of adult ADHD. It is intended to complement formal training. A secondary objective is to empower patients by providing them with evidence-based information on what to expect from an assessment and assessment report. [ABSTRACT FROM AUTHOR]

Published
2024
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21. Normative modelling of brain morphometry across the lifespan with CentileBrain: algorithm benchmarking and model optimisation

Author

Ge, Ruiyang, primary, Yu, Yuetong, additional, Qi, Yi Xuan, additional, Fan, Yu-nan, additional, Chen, Shiyu, additional, Gao, Chuntong, additional, Haas, Shalaila S, additional, New, Faye, additional, Boomsma, Dorret I, additional, Brodaty, Henry, additional, Brouwer, Rachel M, additional, Buckner, Randy, additional, Caseras, Xavier, additional, Crivello, Fabrice, additional, Crone, Eveline A, additional, Erk, Susanne, additional, Fisher, Simon E, additional, Franke, Barbara, additional, Glahn, David C, additional, Dannlowski, Udo, additional, Grotegerd, Dominik, additional, Gruber, Oliver, additional, Hulshoff Pol, Hilleke E, additional, Schumann, Gunter, additional, Tamnes, Christian K, additional, Walter, Henrik, additional, Wierenga, Lara M, additional, Jahanshad, Neda, additional, Thompson, Paul M, additional, Frangou, Sophia, additional, Agartz, Ingrid, additional, Asherson, Philip, additional, Ayesa-Arriola, Rosa, additional, Banaj, Nerisa, additional, Banaschewski, Tobias, additional, Baumeister, Sarah, additional, Bertolino, Alessandro, additional, Borgwardt, Stefan, additional, Bourque, Josiane, additional, Brandeis, Daniel, additional, Breier, Alan, additional, Buitelaar, Jan K, additional, Cannon, Dara M, additional, Cervenka, Simon, additional, Conrod, Patricia J, additional, Crespo-Facorro, Benedicto, additional, Davey, Christopher G, additional, de Haan, Lieuwe, additional, de Zubicaray, Greig I, additional, Di Giorgio, Annabella, additional, Frodl, Thomas, additional, Gruner, Patricia, additional, Gur, Raquel E, additional, Gur, Ruben C, additional, Harrison, Ben J, additional, Hatton, Sean N, additional, Hickie, Ian, additional, Howells, Fleur M, additional, Huyser, Chaim, additional, Jernigan, Terry L, additional, Jiang, Jiyang, additional, Joska, John A, additional, Kahn, René S, additional, Kalnin, Andrew J, additional, Kochan, Nicole A, additional, Koops, Sanne, additional, Kuntsi, Jonna, additional, Lagopoulos, Jim, additional, Lazaro, Luisa, additional, Lebedeva, Irina S, additional, Lochner, Christine, additional, Martin, Nicholas G, additional, Mazoyer, Bernard, additional, McDonald, Brenna C, additional, McDonald, Colm, additional, McMahon, Katie L, additional, Medland, Sarah, additional, Modabbernia, Amirhossein, additional, Mwangi, Benson, additional, Nakao, Tomohiro, additional, Nyberg, Lars, additional, Piras, Fabrizio, additional, Portella, Maria J, additional, Qiu, Jiang, additional, Roffman, Joshua L, additional, Sachdev, Perminder S, additional, Sanford, Nicole, additional, Satterthwaite, Theodore D, additional, Saykin, Andrew J, additional, Sellgren, Carl M, additional, Sim, Kang, additional, Smoller, Jordan W, additional, Soares, Jair C, additional, Sommer, Iris E, additional, Spalletta, Gianfranco, additional, Stein, Dan J, additional, Thomopoulos, Sophia I, additional, Tomyshev, Alexander S, additional, Tordesillas-Gutiérrez, Diana, additional, Trollor, Julian N, additional, van 't Ent, Dennis, additional, van den Heuvel, Odile A, additional, van Erp, Theo GM, additional, van Haren, Neeltje EM, additional, Vecchio, Daniela, additional, Veltman, Dick J, additional, Wang, Yang, additional, Weber, Bernd, additional, Wei, Dongtao, additional, Wen, Wei, additional, Westlye, Lars T, additional, Williams, Steven CR, additional, Wright, Margaret J, additional, Wu, Mon-Ju, additional, and Yu, Kevin, additional

Published
2024
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22. The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder

Author

Faraone, Stephen V., Banaschewski, Tobias, Coghill, David, Zheng, Yi, Biederman, Joseph, Bellgrove, Mark A., Newcorn, Jeffrey H., Gignac, Martin, Al Saud, Nouf M., Manor, Iris, Rohde, Luis Augusto, Yang, Li, Cortese, Samuele, Almagor, Doron, Stein, Mark A., Albatti, Turki H., Aljoudi, Haya F., Alqahtani, Mohammed M.J., Asherson, Philip, Atwoli, Lukoye, Bölte, Sven, Buitelaar, Jan K., Crunelle, Cleo L., Daley, David, Dalsgaard, Søren, Döpfner, Manfred, Espinet (on behalf of CADDRA), Stacey, Fitzgerald, Michael, Franke, Barbara, Gerlach, Manfred, Haavik, Jan, Hartman, Catharina A., Hartung, Cynthia M., Hinshaw, Stephen P., Hoekstra, Pieter J., Hollis, Chris, Kollins, Scott H., Sandra Kooij, J.J., Kuntsi, Jonna, Larsson, Henrik, Li, Tingyu, Liu, Jing, Merzon, Eugene, Mattingly, Gregory, Mattos, Paulo, McCarthy, Suzanne, Mikami, Amori Yee, Molina, Brooke S.G., Nigg, Joel T., Purper-Ouakil, Diane, Omigbodun, Olayinka O., Polanczyk, Guilherme V., Pollak, Yehuda, Poulton, Alison S., Rajkumar, Ravi Philip, Reding, Andrew, Reif, Andreas, Rubia, Katya, Rucklidge, Julia, Romanos, Marcel, Ramos-Quiroga, J. Antoni, Schellekens, Arnt, Scheres, Anouk, Schoeman, Renata, Schweitzer, Julie B., Shah, Henal, Solanto, Mary V., Sonuga-Barke, Edmund, Soutullo, César, Steinhausen, Hans-Christoph, Swanson, James M., Thapar, Anita, Tripp, Gail, van de Glind, Geurt, van den Brink, Wim, Van der Oord, Saskia, Venter, Andre, Vitiello, Benedetto, Walitza, Susanne, and Wang, Yufeng

Published
2021
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27. Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults: a cross-sectional mega-analysis

Author

Hoogman, Martine, Bralten, Janita, Hibar, Derrek P, Mennes, Maarten, Zwiers, Marcel P, Schweren, Lizanne SJ, van Hulzen, Kimm JE, Medland, Sarah E, Shumskaya, Elena, Jahanshad, Neda, de Zeeuw, Patrick, Szekely, Eszter, Sudre, Gustavo, Wolfers, Thomas, Onnink, Alberdingk MH, Dammers, Janneke T, Mostert, Jeanette C, Vives-Gilabert, Yolanda, Kohls, Gregor, Oberwelland, Eileen, Seitz, Jochen, Schulte-Rüther, Martin, Ambrosino, Sara, Doyle, Alysa E, Høvik, Marie F, Dramsdahl, Margaretha, Tamm, Leanne, van Erp, Theo GM, Dale, Anders, Schork, Andrew, Conzelmann, Annette, Zierhut, Kathrin, Baur, Ramona, McCarthy, Hazel, Yoncheva, Yuliya N, Cubillo, Ana, Chantiluke, Kaylita, Mehta, Mitul A, Paloyelis, Yannis, Hohmann, Sarah, Baumeister, Sarah, Bramati, Ivanei, Mattos, Paulo, Tovar-Moll, Fernanda, Douglas, Pamela, Banaschewski, Tobias, Brandeis, Daniel, Kuntsi, Jonna, Asherson, Philip, Rubia, Katya, Kelly, Clare, Di Martino, Adriana, Milham, Michael P, Castellanos, Francisco X, Frodl, Thomas, Zentis, Mariam, Lesch, Klaus-Peter, Reif, Andreas, Pauli, Paul, Jernigan, Terry L, Haavik, Jan, Plessen, Kerstin J, Lundervold, Astri J, Hugdahl, Kenneth, Seidman, Larry J, Biederman, Joseph, Rommelse, Nanda, Heslenfeld, Dirk J, Hartman, Catharina A, Hoekstra, Pieter J, Oosterlaan, Jaap, von Polier, Georg, Konrad, Kerstin, Vilarroya, Oscar, Ramos-Quiroga, Josep Antoni, Soliva, Joan Carles, Durston, Sarah, Buitelaar, Jan K, Faraone, Stephen V, Shaw, Philip, Thompson, Paul M, and Franke, Barbara

Subjects
Brain Disorders, Neurosciences, Attention Deficit Hyperactivity Disorder (ADHD), Clinical Research, Mental Health, Pediatric, Biomedical Imaging, 2.1 Biological and endogenous factors, Aetiology, Mental health, Good Health and Well Being, Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Brain, Case-Control Studies, Child, Child, Preschool, Cross-Sectional Studies, Female, Humans, Linear Models, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, Young Adult, Clinical Sciences, Public Health and Health Services, Psychology
Abstract

BackgroundNeuroimaging studies have shown structural alterations in several brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). Through the formation of the international ENIGMA ADHD Working Group, we aimed to address weaknesses of previous imaging studies and meta-analyses, namely inadequate sample size and methodological heterogeneity. We aimed to investigate whether there are structural differences in children and adults with ADHD compared with those without this diagnosis.MethodsIn this cross-sectional mega-analysis, we used the data from the international ENIGMA Working Group collaboration, which in the present analysis was frozen at Feb 8, 2015. Individual sites analysed structural T1-weighted MRI brain scans with harmonised protocols of individuals with ADHD compared with those who do not have this diagnosis. Our primary outcome was to assess case-control differences in subcortical structures and intracranial volume through pooling of all individual data from all cohorts in this collaboration. For this analysis, p values were significant at the false discovery rate corrected threshold of p=0·0156.FindingsOur sample comprised 1713 participants with ADHD and 1529 controls from 23 sites with a median age of 14 years (range 4-63 years). The volumes of the accumbens (Cohen's d=-0·15), amygdala (d=-0·19), caudate (d=-0·11), hippocampus (d=-0·11), putamen (d=-0·14), and intracranial volume (d=-0·10) were smaller in individuals with ADHD compared with controls in the mega-analysis. There was no difference in volume size in the pallidum (p=0·95) and thalamus (p=0·39) between people with ADHD and controls. Exploratory lifespan modelling suggested a delay of maturation and a delay of degeneration, as effect sizes were highest in most subgroups of children (21 years): in the accumbens (Cohen's d=-0·19 vs -0·10), amygdala (d=-0·18 vs -0·14), caudate (d=-0·13 vs -0·07), hippocampus (d=-0·12 vs -0·06), putamen (d=-0·18 vs -0·08), and intracranial volume (d=-0·14 vs 0·01). There was no difference between children and adults for the pallidum (p=0·79) or thalamus (p=0·89). Case-control differences in adults were non-significant (all p>0·03). Psychostimulant medication use (all p>0·15) or symptom scores (all p>0·02) did not influence results, nor did the presence of comorbid psychiatric disorders (all p>0·5).InterpretationWith the largest dataset to date, we add new knowledge about bilateral amygdala, accumbens, and hippocampus reductions in ADHD. We extend the brain maturation delay theory for ADHD to include subcortical structures and refute medication effects on brain volume suggested by earlier meta-analyses. Lifespan analyses suggest that, in the absence of well powered longitudinal studies, the ENIGMA cross-sectional sample across six decades of ages provides a means to generate hypotheses about lifespan trajectories in brain phenotypes.FundingNational Institutes of Health.

Published
2017

28. Normative modelling of brain morphometry across the lifespan with CentileBrain:algorithm benchmarking and model optimisation

Author

Ge, Ruiyang, Yu, Yuetong, Qi, Yi Xuan, Fan, Yu nan, Chen, Shiyu, Gao, Chuntong, Haas, Shalaila S., New, Faye, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Buckner, Randy, Caseras, Xavier, Crivello, Fabrice, Crone, Eveline A., Erk, Susanne, Fisher, Simon E., Franke, Barbara, Glahn, David C., Dannlowski, Udo, Grotegerd, Dominik, Gruber, Oliver, Hulshoff Pol, Hilleke E., Schumann, Gunter, Tamnes, Christian K., Walter, Henrik, Wierenga, Lara M., Jahanshad, Neda, Thompson, Paul M., Frangou, Sophia, Agartz, Ingrid, Asherson, Philip, Ayesa-Arriola, Rosa, Banaj, Nerisa, Banaschewski, Tobias, Baumeister, Sarah, Bertolino, Alessandro, Borgwardt, Stefan, Bourque, Josiane, Brandeis, Daniel, Breier, Alan, Buitelaar, Jan K., Cannon, Dara M., Cervenka, Simon, Conrod, Patricia J., Crespo-Facorro, Benedicto, Davey, Christopher G., de Haan, Lieuwe, de Zubicaray, Greig I., van Haren, Neeltje EM, Ge, Ruiyang, Yu, Yuetong, Qi, Yi Xuan, Fan, Yu nan, Chen, Shiyu, Gao, Chuntong, Haas, Shalaila S., New, Faye, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Buckner, Randy, Caseras, Xavier, Crivello, Fabrice, Crone, Eveline A., Erk, Susanne, Fisher, Simon E., Franke, Barbara, Glahn, David C., Dannlowski, Udo, Grotegerd, Dominik, Gruber, Oliver, Hulshoff Pol, Hilleke E., Schumann, Gunter, Tamnes, Christian K., Walter, Henrik, Wierenga, Lara M., Jahanshad, Neda, Thompson, Paul M., Frangou, Sophia, Agartz, Ingrid, Asherson, Philip, Ayesa-Arriola, Rosa, Banaj, Nerisa, Banaschewski, Tobias, Baumeister, Sarah, Bertolino, Alessandro, Borgwardt, Stefan, Bourque, Josiane, Brandeis, Daniel, Breier, Alan, Buitelaar, Jan K., Cannon, Dara M., Cervenka, Simon, Conrod, Patricia J., Crespo-Facorro, Benedicto, Davey, Christopher G., de Haan, Lieuwe, de Zubicaray, Greig I., and van Haren, Neeltje EM

Abstract

The value of normative models in research and clinical practice relies on their robustness and a systematic comparison of different modelling algorithms and parameters; however, this has not been done to date. We aimed to identify the optimal approach for normative modelling of brain morphometric data through systematic empirical benchmarking, by quantifying the accuracy of different algorithms and identifying parameters that optimised model performance. We developed this framework with regional morphometric data from 37 407 healthy individuals (53% female and 47% male; aged 3–90 years) from 87 datasets from Europe, Australia, the USA, South Africa, and east Asia following a comparative evaluation of eight algorithms and multiple covariate combinations pertaining to image acquisition and quality, parcellation software versions, global neuroimaging measures, and longitudinal stability. The multivariate fractional polynomial regression (MFPR) emerged as the preferred algorithm, optimised with non-linear polynomials for age and linear effects of global measures as covariates. The MFPR models showed excellent accuracy across the lifespan and within distinct age-bins and longitudinal stability over a 2-year period. The performance of all MFPR models plateaued at sample sizes exceeding 3000 study participants. This model can inform about the biological and behavioural implications of deviations from typical age-related neuroanatomical changes and support future study designs. The model and scripts described here are freely available through CentileBrain.

Published
2024

29. Verbal memory performance in adolescents and adults with ADHD

Author

Pawley, Adam D., Mayer, Jutta, Medda, Juliane, Brandt, Geva A., Agnew-Blais, Jessica C., Asherson, Philip, Rommel, Anna-Sophie, Ramos-Quiroga, J. Antoni, Palacio Sanchez, Judit, Bergsma, Douwe, Buitelaar, Jan K., Ortega, Francisco B., Muntaner-Mas, Adrià, Grimm, Oliver, Reif, Andreas, Freitag, Christine M., Kuntsi, Jonna, Pawley, Adam D., Mayer, Jutta, Medda, Juliane, Brandt, Geva A., Agnew-Blais, Jessica C., Asherson, Philip, Rommel, Anna-Sophie, Ramos-Quiroga, J. Antoni, Palacio Sanchez, Judit, Bergsma, Douwe, Buitelaar, Jan K., Ortega, Francisco B., Muntaner-Mas, Adrià, Grimm, Oliver, Reif, Andreas, Freitag, Christine M., and Kuntsi, Jonna

Abstract

Beyond well-established difficulties with working memory in individuals with attention deficit hyperactivity disorder (ADHD), evidence is emerging that other memory processes may also be affected. We investigated, first, which memory processes show differences in adults and adolescents with ADHD in comparison to control participants, focusing on working and short-term memory, initial learning, interference, delayed and recognition memory. Second, we investigated whether ADHD severity, co-occurring depressive symptoms, IQ and physical fitness are associated with the memory performance in the individuals with ADHD. We assessed 205 participants with ADHD (mean age 25.8 years, SD 7.99) and 50 control participants (mean age 21.1 years, SD 5.07) on cognitive tasks including the digit span forward (DSF) and backward (DSB), the Rey Auditory Verbal Learning Test (RAVLT), and the vocabulary and matrix reasoning subtests of the Wechsler Abbreviated Scale of Intelligence. Participants with ADHD were additionally assessed on ADHD severity, depression symptoms and cardiorespiratory fitness. A series of regressions were run, with sensitivity analyses performed when variables were skewed. ADHD-control comparisons were significant for DSF, DSB, delayed and recognition memory, with people with ADHD performing less well than the control participants. The result for recognition memory was no longer significant in sensitivity analysis. Memory performance was not associated with greater ADHD or depression symptoms severity. IQ was positively associated with all memory variables except DSF. Cardiorespiratory fitness was negatively associated with the majority of RAVLT variables. Individuals with ADHD showed difficulties with working memory, short-term memory and delayed memory, as well as a potential difficulty with recognition memory, despite preserved initial learning.

Published
2024

34. Editorial Perspective: How should child psychologists and psychiatrists interpret FDA device approval? Caveat emptor

Author

Arns, Martijn, Loo, Sandra K, Sterman, M Barry, Heinrich, Hartmut, Kuntsi, Jonna, Asherson, Philip, Banaschewski, Tobias, and Brandeis, Daniel

Subjects
Clinical and Health Psychology, Psychology, Attention Deficit Hyperactivity Disorder (ADHD), Brain Disorders, Mental Health, Pediatric, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Good Health and Well Being, Attention Deficit Disorder with Hyperactivity, Child Psychiatry, Device Approval, Electroencephalography, Humans, Psychology, Child, Attention deficit hyperactivity disorder, electroencephalogram, Electroencephalogram-Based Attention Deficit Hyperactivity Disorder Assessment Aid, theta-to-beta ratio, Federal Drug Administration, diagnostic test, Clinical Sciences, Cognitive Sciences, Developmental & Child Psychology, Clinical sciences, Applied and developmental psychology, Clinical and health psychology
Abstract

Recently several new tests have received US Federal Drug Administration (FDA) marketing approval as aids in the diagnostic process for attention deficit hyperactivity disorder (ADHD), including the Neuropsychiatric electroencephalogram (EEG)-Based ADHD Assessment Aid (NEBA) Health test. The NEBA test relies upon an EEG-based measure, called the theta to beta ratio (TBR). Although this measure has yielded large differences between ADHD and non-ADHD groups in studies prior to 2009, recent studies and a meta-analysis could not replicate these findings. In this article, we have used the NEBA device as an exemplar for a discussion that distinguishes between FDA de novo marketing approval for a device and any claims that that device is empirically supported, scientifically validated with replicated findings. It is understood that the aims of each differ; however, for many, including the lay public as well as some mental health professionals, these terms may be confused and treated as though they are synonymous. With regard to the TBR measure, there is no reliable association or replication for its clinical usage in the ADHD diagnostic process. The recommendation for potential consumers of the NEBA Health test (as well as perhaps for other existing FDA-approved diagnostic tests) is caveat emptor (let the buyer beware!).

Published
2016

36. Recommendations for occupational therapy interventions for adults with ADHD: a consensus statement from the UK adult ADHD network

Author

Adamou, Marios, Asherson, Philip, Arif, Muhammad, Buckenham, Louise, Cubbin, Sally, Dancza, Karina, Gorman, Kirstie, Gudjonsson, Gísli, Gutman, Sharon, Kustow, James, Mabbott, Kerry, May-Benson, Teresa, Muller-Sedgwick, Ulrich, Pell, Emma, Pitts, Mark, Rastrick, Suzanne, Sedgwick, Jane, Smith, Kath, Taylor, Clare, Thompson, Lucy, van Rensburg, Kobus, and Young, Susan

Published
2021
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38. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

Author

O'Dushlaine, Colm, Rossin, Lizzy, Lee, Phil H, Duncan, Laramie, Parikshak, Neelroop N, Newhouse, Stephen, Ripke, Stephan, Neale, Benjamin M, Purcell, Shaun M, Posthuma, Danielle, Nurnberger, John I, Lee, S Hong, Faraone, Stephen V, Perlis, Roy H, Mowry, Bryan J, Thapar, Anita, Goddard, Michael E, Witte, John S, Absher, Devin, Agartz, Ingrid, Akil, Huda, Amin, Farooq, Andreassen, Ole A, Anjorin, Adebayo, Anney, Richard, Anttila, Verneri, Arking, Dan E, Asherson, Philip, Azevedo, Maria H, Backlund, Lena, Badner, Judith A, Bailey, Anthony J, Banaschewski, Tobias, Barchas, Jack D, Barnes, Michael R, Barrett, Thomas B, Bass, Nicholas, Battaglia, Agatino, Bauer, Michael, Bayes, Monica, Bellivier, Frank, Bergen, Sarah E, Berrettini, Wade, Betancur, Catalina, Bettecken, Thomas, Biederman, Joseph, Binder, Elisabeth B, Black, Donald W, Blackwood, Douglas HR, Bloss, Cinnamon S, Boehnke, Michael, Boomsma, Dorret I, Breuer, Rene, Bruggeman, Richard, Cormican, Paul, Buccola, Nancy G, Buitelaar, Jan K, Bunney, William E, Buxbaum, Joseph D, Byerley, William F, Byrne, Enda M, Caesar, Sian, Cahn, Wiepke, Cantor, Rita M, Casas, Miguel, Chakravarti, Aravinda, Chambert, Kimberly, Choudhury, Khalid, Cichon, Sven, Mattheisen, Manuel, Cloninger, C Robert, Collier, David A, Cook, Edwin H, Coon, Hilary, Cormand, Bru, Corvin, Aiden, Coryell, William H, Craig, David W, Craig, Ian W, Crosbie, Jennifer, Cuccaro, Michael L, Curtis, David, Czamara, Darina, Datta, Susmita, Dawson, Geraldine, Day, Richard, De Geus, Eco J, Degenhardt, Franziska, Djurovic, Srdjan, Donohoe, Gary J, Doyle, Alysa E, Duan, Jubao, Dudbridge, Frank, Duketis, Eftichia, Ebstein, Richard P, Edenberg, Howard J, Elia, Josephine, Ennis, Sean, Etain, Bruno, and Fanous, Ayman

Subjects
Human Genome, Brain Disorders, Serious Mental Illness, Schizophrenia, Genetics, Depression, Mental Health, Aetiology, 2.1 Biological and endogenous factors, Mental health, Good Health and Well Being, Brain, Databases, Genetic, Genetic Predisposition to Disease, Genome-Wide Association Study, Histones, Humans, Mental Disorders, Signal Transduction, Network and Pathway Analysis Subgroup of Psychiatric Genomics Consortium, Neurosciences, Psychology, Cognitive Sciences, Neurology & Neurosurgery
Abstract

Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.

Published
2015

39. Resting-State Neurophysiological Activity Patterns in Young People with ASD, ADHD, and ASD + ADHD

Author

Shephard, Elizabeth, Tye, Charlotte, Ashwood, Karen L., Azadi, Bahar, Asherson, Philip, Bolton, Patrick F., and McLoughlin, Grainne

Abstract

Altered power of resting-state neurophysiological activity has been associated with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), which commonly co-occur. We compared resting-state neurophysiological power in children with ASD, ADHD, co-occurring ASD + ADHD, and typically developing controls. Children with ASD (ASD/ASD + ADHD) showed reduced theta and alpha power compared to children without ASD (controls/ADHD). Children with ADHD (ADHD/ASD + ADHD) displayed decreased delta power compared to children without ADHD (ASD/controls). Children with ASD + ADHD largely presented as an additive co-occurrence with deficits of both disorders, although reduced theta compared to ADHD-only and reduced delta compared to controls suggested some unique markers. Identifying specific neurophysiological profiles in ASD and ADHD may assist in characterising more homogeneous subgroups to inform treatment approaches and aetiological investigations.

Published
2018
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40. Needs of Adolescents and Young Adults with Neurodevelopmental Disorders: Comparisons of Young People and Parent Perspectives

Author

Eklund, Hanna, Findon, James, Cadman, Tim, Hayward, Hannah, Murphy, Declan, Asherson, Philip, Glaser, Karen, and Xenitidis, Kiriakos

Abstract

This study used the Camberwell Assessment of Need for adults with Developmental and Intellectual Disabilities (CANDID) to examine the social, physical health and mental health needs of 168 young people (aged 14-24 years) with neurodevelopmental disorders and compared young person and parent ratings of need. Agreement was poor in 21 out of 25 domains. Parents consistently reported higher levels of need than young people in the majority of domains although young people with ADHD reported significantly more needs in "physical health," "eyesight/hearing," "seizures," "other mental health problems" and "safety of others than their parents." Both parent and young person perspectives of needs are necessary to ensure that needs that are predictive of current or future poor outcomes are not missed.

Published
2018
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45. Assessments for adult ADHD: what makes them good enough?

Author

Leaver, Laurence, primary, van Rensburg, Kobus, additional, Adamou, Marios, additional, Arif, Muhammad, additional, Asherson, Philip, additional, Cubbin, Sally, additional, Kustow, James, additional, Müller-Sedgwick, Ulrich, additional, and Sedgwick-Müller, Jane, additional

Published
2023
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46. ADHD in adults

Author

Maltezos, Stefanos, additional, Whitwell, Susannah, additional, and Asherson, Philip, additional

Published
2020
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49. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs.

Author

Absher, Devin, Agartz, Ingrid, Akil, Huda, Amin, Farooq, Andreassen, Ole, Anjorin, Adebayo, Anney, Richard, Anttila, Verneri, Arking, Dan, Asherson, Philip, Azevedo, Maria, Backlund, Lena, Badner, Judith, Bailey, Anthony, Banaschewski, Tobias, Barchas, Jack, Barnes, Michael, Barrett, Thomas, Bass, Nicholas, Battaglia, Agatino, Bauer, Michael, Bayés, Mònica, Bellivier, Frank, Bergen, Sarah, Berrettini, Wade, Betancur, Catalina, Bettecken, Thomas, Biederman, Joseph, Binder, Elisabeth, Black, Donald, Blackwood, Douglas, Boehnke, Michael, Boomsma, Dorret, Breen, Gerome, Breuer, René, Bruggeman, Richard, Cormican, Paul, Buccola, Nancy, Buitelaar, Jan, Bunney, William, Buxbaum, Joseph, Byerley, William, Byrne, Enda, Caesar, Sian, Cahn, Wiepke, Cantor, Rita, Casas, Miguel, Chakravarti, Aravinda, Chambert, Kimberly, Choudhury, Khalid, Cichon, Sven, Cloninger, C, Collier, David, Cook, Edwin, Coon, Hilary, Cormand, Bru, Corvin, Aiden, Coryell, William, Craig, David, Craig, Ian, Crosbie, Jennifer, Cuccaro, Michael, Curtis, David, Czamara, Darina, Datta, Susmita, Dawson, Geraldine, Day, Richard, De Geus, Eco, Degenhardt, Franziska, Djurovic, Srdjan, Donohoe, Gary, Doyle, Alysa, Duan, Jubao, Dudbridge, Frank, Duketis, Eftichia, Ebstein, Richard, Edenberg, Howard, Elia, Josephine, Ennis, Sean, Etain, Bruno, Fanous, Ayman, Farmer, Anne, Ferrier, I, Flickinger, Matthew, Fombonne, Eric, Foroud, Tatiana, Frank, Josef, Franke, Barbara, Fraser, Christine, Freedman, Robert, Giegling, Ina, Gill, Michael, Gordon, Scott, Gordon-Smith, Katherine, Green, Elaine, Greenwood, Tiffany, Grice, Dorothy, Gross, Magdalena, Grozeva, Detelina, and Guan, Weihua

Subjects
Adult, Attention Deficit Disorder with Hyperactivity, Bipolar Disorder, Child, Child Development Disorders, Pervasive, Crohn Disease, Depressive Disorder, Major, Genetic Heterogeneity, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Humans, Inheritance Patterns, Mental Disorders, Polymorphism, Single Nucleotide, Schizophrenia
Abstract

Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohns disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

Published
2013

50. High Loading of Polygenic Risk for ADHD in Children With Comorbid Aggression

Author

Hamshere, Marian L, Langley, Kate, Martin, Joanna, Agha, Sharifah Shameem, Stergiakouli, Evangelia, Anney, Richard JL, Buitelaar, Jan, Faraone, Stephen V, Lesch, Klaus-Peter, Neale, Benjamin M, Franke, Barbara, Sonuga-Barke, Edmund, Asherson, Philip, Merwood, Andrew, Kuntsi, Jonna, Medland, Sarah E, Ripke, Stephan, Steinhausen, Hans-Christoph, Freitag, Christine, Reif, Andreas, Renner, Tobias J, Romanos, Marcel, Romanos, Jasmin, Warnke, Andreas, Meyer, Jobst, Palmason, Haukur, Vasquez, Alejandro Arias, Lambregts-Rommelse, Nanda, Roeyers, Herbert, Biederman, Joseph, Doyle, Alysa E, Hakonarson, Hakon, Rothenberger, Aribert, Banaschewski, Tobias, Oades, Robert D, McGough, James J, Kent, Lindsey, Williams, Nigel, Owen, Michael J, Holmans, Peter, O’Donovan, Michael C, and Thapar, Anita

Subjects
Prevention, Behavioral and Social Science, Human Genome, Genetics, Mental Health, Attention Deficit Hyperactivity Disorder (ADHD), Clinical Research, Brain Disorders, Pediatric, Aetiology, 2.1 Biological and endogenous factors, Mental health, Aggression, Anxiety Disorders, Attention Deficit Disorder with Hyperactivity, Child, Child, Preschool, Comorbidity, Conduct Disorder, Depressive Disorder, Female, Genetic Predisposition to Disease, Genetic Variation, Humans, Male, Multifactorial Inheritance, United Kingdom, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

OBJECTIVE Although attention deficit hyperactivity disorder (ADHD) is highly heritable, genome-wide association studies (GWAS) have not yet identified any common genetic variants that contribute to risk. There is evidence that aggression or conduct disorder in children with ADHD indexes higher genetic loading and clinical severity. The authors examine whether common genetic variants considered en masse as polygenic scores for ADHD are especially enriched in children with comorbid conduct disorder. METHOD Polygenic scores derived from an ADHD GWAS meta-analysis were calculated in an independent ADHD sample (452 case subjects, 5,081 comparison subjects). Multivariate logistic regression analyses were employed to compare polygenic scores in the ADHD and comparison groups and test for higher scores in ADHD case subjects with comorbid conduct disorder relative to comparison subjects and relative to those without comorbid conduct disorder. Association with symptom scores was tested using linear regression. RESULTS Polygenic risk for ADHD, derived from the meta-analysis, was higher in the independent ADHD group than in the comparison group. Polygenic score was significantly higher in ADHD case subjects with conduct disorder relative to ADHD case subjects without conduct disorder. ADHD polygenic score showed significant association with comorbid conduct disorder symptoms. This relationship was explained by the aggression items. CONCLUSIONS Common genetic variation is relevant to ADHD, especially in individuals with comorbid aggression. The findings suggest that the previously published ADHD GWAS meta-analysis contains weak but true associations with common variants, support for which falls below genome-wide significance levels. The findings also highlight the fact that aggression in ADHD indexes genetic as well as clinical severity.

Published
2013

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