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1. Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets.

Author

Postema MC, Hoogman M, Ambrosino S, Asherson P, Banaschewski T, Bandeira CE, Baranov A, Bau CHD, Baumeister S, Baur-Streubel R, Bellgrove MA, Biederman J, Bralten J, Brandeis D, Brem S, Buitelaar JK, Busatto GF, Castellanos FX, Cercignani M, Chaim-Avancini TM, Chantiluke KC, Christakou A, Coghill D, Conzelmann A, Cubillo AI, Cupertino RB, de Zeeuw P, Doyle AE, Durston S, Earl EA, Epstein JN, Ethofer T, Fair DA, Fallgatter AJ, Faraone SV, Frodl T, Gabel MC, Gogberashvili T, Grevet EH, Haavik J, Harrison NA, Hartman CA, Heslenfeld DJ, Hoekstra PJ, Hohmann S, Høvik MF, Jernigan TL, Kardatzki B, Karkashadze G, Kelly C, Kohls G, Konrad K, Kuntsi J, Lazaro L, Lera-Miguel S, Lesch KP, Louza MR, Lundervold AJ, Malpas CB, Mattos P, McCarthy H, Namazova-Baranova L, Nicolau R, Nigg JT, Novotny SE, Oberwelland Weiss E, O'Gorman Tuura RL, Oosterlaan J, Oranje B, Paloyelis Y, Pauli P, Picon FA, Plessen KJ, Ramos-Quiroga JA, Reif A, Reneman L, Rosa PGP, Rubia K, Schrantee A, Schweren LJS, Seitz J, Shaw P, Silk TJ, Skokauskas N, Soliva Vila JC, Stevens MC, Sudre G, Tamm L, Tovar-Moll F, van Erp TGM, Vance A, Vilarroya O, Vives-Gilabert Y, von Polier GG, Walitza S, Yoncheva YN, Zanetti MV, Ziegler GC, Glahn DC, Jahanshad N, Medland SE, Thompson PM, Fisher SE, Franke B, and Francks C

Subjects
Adolescent, Adult, Brain diagnostic imaging, Caudate Nucleus, Child, Humans, Magnetic Resonance Imaging, Attention Deficit Disorder with Hyperactivity, Autism Spectrum Disorder
Abstract

Objective: Some 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., Methods: We 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., Results: There 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., Conclusion: Prior 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., (© 2021 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Published
2021
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2. Subcortical Brain Volume, Regional Cortical Thickness, and Cortical Surface Area Across Disorders: Findings From the ENIGMA ADHD, ASD, and OCD Working Groups.

Author

Boedhoe PSW, van Rooij D, Hoogman M, Twisk JWR, Schmaal L, Abe Y, Alonso P, Ameis SH, Anikin A, Anticevic A, Arango C, Arnold PD, Asherson P, Assogna F, Auzias G, Banaschewski T, Baranov A, Batistuzzo MC, Baumeister S, Baur-Streubel R, Behrmann M, Bellgrove MA, Benedetti F, Beucke JC, Biederman J, Bollettini I, Bose A, Bralten J, Bramati IE, Brandeis D, Brem S, Brennan BP, Busatto GF, Calderoni S, Calvo A, Calvo R, Castellanos FX, Cercignani M, Chaim-Avancini TM, Chantiluke KC, Cheng Y, Cho KIK, Christakou A, Coghill D, Conzelmann A, Cubillo AI, Dale AM, Dallaspezia S, Daly E, Denys D, Deruelle C, Di Martino A, Dinstein I, Doyle AE, Durston S, Earl EA, Ecker C, Ehrlich S, Ely BA, Epstein JN, Ethofer T, Fair DA, Fallgatter AJ, Faraone SV, Fedor J, Feng X, Feusner JD, Fitzgerald J, Fitzgerald KD, Fouche JP, Freitag CM, Fridgeirsson EA, Frodl T, Gabel MC, Gallagher L, Gogberashvili T, Gori I, Gruner P, Gürsel DA, Haar S, Haavik J, Hall GB, Harrison NA, Hartman CA, Heslenfeld DJ, Hirano Y, Hoekstra PJ, Hoexter MQ, Hohmann S, Høvik MF, Hu H, Huyser C, Jahanshad N, Jalbrzikowski M, James A, Janssen J, Jaspers-Fayer F, Jernigan TL, Kapilushniy D, Kardatzki B, Karkashadze G, Kathmann N, Kaufmann C, Kelly C, Khadka S, King JA, Koch K, Kohls G, Konrad K, Kuno M, Kuntsi J, Kvale G, Kwon JS, Lázaro L, Lera-Miguel S, Lesch KP, Hoekstra L, Liu Y, Lochner C, Louza MR, Luna B, Lundervold AJ, Malpas CB, Marques P, Marsh R, Martínez-Zalacaín I, Mataix-Cols D, Mattos P, McCarthy H, McGrath J, Mehta MA, Menchón JM, Mennes M, Martinho MM, Moreira PS, Morer A, Morgado P, Muratori F, Murphy CM, Murphy DGM, Nakagawa A, Nakamae T, Nakao T, Namazova-Baranova L, Narayanaswamy JC, Nicolau R, Nigg JT, Novotny SE, Nurmi EL, Weiss EO, O'Gorman Tuura RL, O'Hearn K, O'Neill J, Oosterlaan J, Oranje B, Paloyelis Y, Parellada M, Pauli P, Perriello C, Piacentini J, Piras F, Piras F, Plessen KJ, Puig O, Ramos-Quiroga JA, Reddy YCJ, Reif A, Reneman L, Retico A, Rosa PGP, Rubia K, Rus OG, Sakai Y, Schrantee A, Schwarz L, Schweren LJS, Seitz J, Shaw P, Shook D, Silk TJ, Simpson HB, Skokauskas N, Soliva Vila JC, Solovieva A, Soreni N, Soriano-Mas C, Spalletta G, Stern ER, Stevens MC, Stewart SE, Sudre G, Szeszko PR, Tamm L, Taylor MJ, Tolin DF, Tosetti M, Tovar-Moll F, Tsuchiyagaito A, van Erp TGM, van Wingen GA, Vance A, Venkatasubramanian G, Vilarroya O, Vives-Gilabert Y, von Polier GG, Walitza S, Wallace GL, Wang Z, Wolfers T, Yoncheva YN, Yun JY, Zanetti MV, Zhou F, Ziegler GC, Zierhut KC, Zwiers MP, Thompson PM, Stein DJ, Buitelaar J, Franke B, and van den Heuvel OA

Subjects
Adolescent, Adult, Child, Female, Human Development physiology, Humans, Male, Organ Size, Psychopathology, Research Report, Systems Analysis, Attention Deficit Disorder with Hyperactivity diagnosis, Attention Deficit Disorder with Hyperactivity physiopathology, Attention Deficit Disorder with Hyperactivity psychology, Autism Spectrum Disorder diagnosis, Autism Spectrum Disorder physiopathology, Autism Spectrum Disorder psychology, Cerebrum diagnostic imaging, Cerebrum pathology, Cerebrum physiopathology, Neuroimaging methods, Obsessive-Compulsive Disorder diagnosis, Obsessive-Compulsive Disorder physiopathology, Obsessive-Compulsive Disorder psychology
Abstract

Objective: Attention 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., Methods: Structural T 1 -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)., Results: No 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., Conclusions: The 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
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3. Association of White Matter Structure With Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder.

Author

Aoki Y, Yoncheva YN, Chen B, Nath T, Sharp D, Lazar M, Velasco P, Milham MP, and Di Martino A

Subjects
Anisotropy, Case-Control Studies, Child, Cross-Sectional Studies, Diffusion Tensor Imaging, Female, Humans, Male, Neuroimaging, Attention Deficit Disorder with Hyperactivity pathology, Autism Spectrum Disorder pathology, Corpus Callosum pathology, White Matter pathology
Abstract

Importance: Clinical overlap between autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) is increasingly appreciated, but the underlying brain mechanisms remain unknown to date., Objective: To examine associations between white matter organization and 2 commonly co-occurring neurodevelopmental conditions, ASD and ADHD, through both categorical and dimensional approaches., Design, Setting, and Participants: This investigation was a cross-sectional diffusion tensor imaging (DTI) study at an outpatient academic clinical and research center, the Department of Child and Adolescent Psychiatry at New York University Langone Medical Center. Participants were children with ASD, children with ADHD, or typically developing children. Data collection was ongoing from December 2008 to October 2015., Main Outcomes and Measures: The primary measure was voxelwise fractional anisotropy (FA) analyzed via tract-based spatial statistics. Additional voxelwise DTI metrics included radial diffusivity (RD), mean diffusivity (MD), axial diffusivity (AD), and mode of anisotropy (MA)., Results: This cross-sectional DTI study analyzed data from 174 children (age range, 6.0-12.9 years), selected from a larger sample after quality assurance to be group matched on age and sex. After quality control, the study analyzed data from 69 children with ASD (mean [SD] age, 8.9 [1.7] years; 62 male), 55 children with ADHD (mean [SD] age, 9.5 [1.5] years; 41 male), and 50 typically developing children (mean [SD] age, 9.4 [1.5] years; 38 male). Categorical analyses revealed a significant influence of ASD diagnosis on several DTI metrics (FA, MD, RD, and AD), primarily in the corpus callosum. For example, FA analyses identified a cluster of 4179 voxels (TFCE FEW corrected P < .05) in posterior portions of the corpus callosum. Dimensional analyses revealed associations between ASD severity and FA, RD, and MD in more extended portions of the corpus callosum and beyond (eg, corona radiata and inferior longitudinal fasciculus) across all individuals, regardless of diagnosis. For example, FA analyses revealed clusters overall encompassing 12121 voxels (TFCE FWE corrected P < .05) with a significant association with parent ratings in the social responsiveness scale. Similar results were evident using an independent measure of ASD traits (ie, children communication checklist, second edition). Total severity of ADHD-traits was not significantly related to DTI metrics but inattention scores were related to AD in corpus callosum in a cluster sized 716 voxels. All these findings were robust to algorithmic correction of motion artifacts with the DTIPrep software., Conclusions and Relevance: Dimensional analyses provided a more complete picture of associations between ASD traits and inattention and indexes of white matter organization, particularly in the corpus callosum. This transdiagnostic approach can reveal dimensional relationships linking white matter structure to neurodevelopmental symptoms.

Published
2017
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4. Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults: a cross-sectional mega-analysis.

Author

Hoogman M, Bralten J, Hibar DP, Mennes M, Zwiers MP, Schweren LSJ, van Hulzen KJE, Medland SE, Shumskaya E, Jahanshad N, Zeeuw P, Szekely E, Sudre G, Wolfers T, Onnink AMH, Dammers JT, Mostert JC, Vives-Gilabert Y, Kohls G, Oberwelland E, Seitz J, Schulte-Rüther M, Ambrosino S, Doyle AE, Høvik MF, Dramsdahl M, Tamm L, van Erp TGM, Dale A, Schork A, Conzelmann A, Zierhut K, Baur R, McCarthy H, Yoncheva YN, Cubillo A, Chantiluke K, Mehta MA, Paloyelis Y, Hohmann S, Baumeister S, Bramati I, Mattos P, Tovar-Moll F, Douglas P, Banaschewski T, Brandeis D, Kuntsi J, Asherson P, Rubia K, Kelly C, Martino AD, Milham MP, Castellanos FX, Frodl T, Zentis M, Lesch KP, Reif A, Pauli P, Jernigan TL, Haavik J, Plessen KJ, Lundervold AJ, Hugdahl K, Seidman LJ, Biederman J, Rommelse N, Heslenfeld DJ, Hartman CA, Hoekstra PJ, Oosterlaan J, Polier GV, Konrad K, Vilarroya O, Ramos-Quiroga JA, Soliva JC, Durston S, Buitelaar JK, Faraone SV, Shaw P, Thompson PM, and Franke B

Subjects
Adolescent, Adult, Attention Deficit Disorder with Hyperactivity physiopathology, Brain physiopathology, Case-Control Studies, Child, Child, Preschool, Cross-Sectional Studies, Female, Humans, Linear Models, Longitudinal Studies, Male, Middle Aged, Neuroimaging, Young Adult, Attention Deficit Disorder with Hyperactivity pathology, Brain pathology, Magnetic Resonance Imaging
Abstract

Background: Neuroimaging 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., Methods: In 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., Findings: Our 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 (<15 years) versus adults (>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)., Interpretation: With 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., Funding: National Institutes of Health., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Published
2017
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5. Mode of Anisotropy Reveals Global Diffusion Alterations in Attention-Deficit/Hyperactivity Disorder.

Author

Yoncheva YN, Somandepalli K, Reiss PT, Kelly C, Di Martino A, Lazar M, Zhou J, Milham MP, and Castellanos FX

Subjects
Adolescent, Adult, Anisotropy, Attention Deficit Disorder with Hyperactivity diagnostic imaging, Attention Deficit Disorder with Hyperactivity psychology, Brain diagnostic imaging, Brain physiopathology, Case-Control Studies, Child, Diffusion Tensor Imaging psychology, Female, Humans, Male, White Matter diagnostic imaging, White Matter physiology, White Matter physiopathology, Attention Deficit Disorder with Hyperactivity physiopathology, Diffusion Tensor Imaging methods
Abstract

Objective: Diffusion tensor imaging (DTI) can identify structural connectivity alterations in attention-deficit/hyperactivity disorder (ADHD). Most ADHD DTI studies have concentrated on regional differences in fractional anisotropy (FA) despite its limited sensitivity to complex white matter architecture and increasing evidence of global brain differences in ADHD. Here, we examine multiple DTI metrics in separate samples of children and adults with and without ADHD with a principal focus on global between-group differences., Method: Two samples: adults with ADHD (n = 42) and without (n = 65) and children with ADHD (n = 82) and without (n = 80) were separately group matched for age, sex, and head motion. Five DTI metrics (FA, axial diffusivity, radial diffusivity, mean diffusivity, and mode of anisotropy) were analyzed via tract-based spatial statistics. Group analyses tested for diagnostic differences at the global (averaged across the entire white matter skeleton) and regional level for each metric., Results: Robust global group differences in diffusion indices were found in adults, with the largest effect size for mode of anisotropy (MA; Cohen's d = 1.45). Global MA also differed significantly between groups in the pediatric sample (d = 0.68). In both samples, global MA increased classification accuracy compared to the model with clinical Conners' ADHD ratings alone. Regional diagnostic differences did not survive familywise correction for multiple comparisons., Conclusion: Global DTI metrics, particularly the mode of anisotropy, which is sensitive to crossing fibers, capture connectivity abnormalities in ADHD across both pediatric and adult samples. These findings highlight potential diffuse white matter microarchitecture differences in ADHD., (Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Published
2016
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6. 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

7. 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

8. 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, Oberwelland Weiss, Eileen, O'Gorman Tuura, Ruth L, 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, Soliva Vila, Juan C, 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
Adult, Pediatric Research Initiative, Adolescent, Autism Spectrum Disorder, Clinical Sciences, Attention-deficit, deficit, Developmental & Child Psychology, ENIGMA ADHD Working Group, Humans, 2.1 Biological and endogenous factors, Psychology, Aetiology, Child, large&#8208, structural MRI, large-scale data, Pediatric, brain laterality, Neurosciences, scale data, Brain, Magnetic Resonance Imaging, Attention Deficit Hyperactivity Disorder (ADHD), Brain Disorders, Mental Health, Attention&#8208, Attention Deficit Disorder with Hyperactivity, brain asymmetry, hyperactivity disorder, Cognitive Sciences, Caudate Nucleus
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

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

Author

Li, Ting, Rooij, Daan, Roth Mota, Nina, Buitelaar, Jan K., Hoogman, Martine, Arias Vasquez, Alejandro, Franke, Barbara, Ambrosino, Sara, Banaschewski, Tobias, Bandeira, Cibele E., Bau, Claiton H.D., 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., 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., O'Gorman Tuura, Ruth L., Oosterlaan, Jaap, Oranje, Bob, Paloyelis, Yannis, Pauli, Paul, Picon, Felipe A., Plessen, Kerstin J., Ramos‐Quiroga, J. Antoni, Reif, Andreas, Reneman, Liesbeth, Rosa, Pedro G.P., Rubia, Katya, Schrantee, Anouk, Schweren, Lizanne J.S., Seitz, Jochen, Shaw, Philip, Silk, Tim J., Skokauskas, Norbert, Carlos Soliva Vila, Juan, Soloveva, Anastasiia, Stevens, Michael C., Sudre, Gustavo, Tamm, Leanne, Thompson, Paul M., Tovar‐Moll, Fernanda, Erp, Theo GM, Vance, Alasdair, Vilarroya, Oscar, Vives‐Gilabert, Yolanda, Polier, Georg G., Walitza, Susanne, Yoncheva, Yuliya N., Zanetti, Marcus V., Ziegler, Georg C., Anikin, Anatoly, Asherson, Philip, Baranov, Alexandr, Chaim‐Avanicini, Tiffany, Dale, Anders M., Doyle, Alysa E., Jernigan, Terry, Hohmann, Sarah, Kapilushniy, Dmitry, Mehta, Mitul, Namazova‐Baranova, Leyla, Novotny, Stephanie E., Oberwelland Weiss, Eileen, Schwarz, Lena, General Paediatrics, ARD - Amsterdam Reproduction and Development, Radiology and Nuclear Medicine, APH - Mental Health, APH - Personalized Medicine, ANS - Brain Imaging, ANS - Compulsivity, Impulsivity & Attention, ENIGMA ADHD Working Group, Ambrosino, S., Banaschewski, T., Bandeira, C.E., Bau, CHD, Baumeister, S., Baur-Streubel, R., Bellgrove, M.A., Biederman, J., Bralten, J., Bramati, I.E., Brandeis, D., Berm, S., Busatto, G.F., Calvo, A., Castellanos, F.X., Cercignani, M., Chantiluke, K.C., Christakou, A., Coghill, D., Conzelmann, A., Cubillo, A.I., Cupertino, R.B., de Zeeuw, P., Durston, S., Earl, E.A., Epstein, J.N., Ethofer, T., Fallgatter, A.J., Fair, D.A., Faraone, S.V., Frodl, T., Gabel, M.C., Gogberashvili, T., Grevet, E.H., Haavik, J., Harrison, N.A., Hartman, C.A., Heslenfeld, D.J., Hoekstra, P.J., Høvik, M.F., Jahanshad, N., Kardatzki, B., Karkashadze, G., Kelly, C., Kohls, G., Konrad, K., Kuntsi, J., Lazaro, L., Lera-Miguel, S., Lesch, K.P., Louza, M.R., Lundervold, A.J., Malpas, C.B., Mattos, P., McCarthy, H., Nicolau, R., Nigg, J.T., O'Gorman Tuura, R.L., Oosterlaan, J., Oranje, B., Paloyelis, Y., Pauli, P., Picon, F.A., Plessen, K.J., Ramos-Quiroga, J.A., Reif, A., Reneman, L., Rosa, PGP, Rubia, K., Schrantee, A., Schweren, LJS, Seitz, J., Shaw, P., Silk, T.J., Skokauskas, N., Carlos Soliva Vila, J., Soloveva, A., Stevens, M.C., Sudre, G., Tamm, L., Thompson, P.M., Tovar-Moll, F., van Erp, T.G., Vance, A., Vilarroya, O., Vives-Gilabert, Y., von Polier, G.G., Walitza, S., Yoncheva, Y.N., Zanetti, M.V., Ziegler, G.C., Anikin, A., Asherson, P., Baranov, A., Chaim-Avanicini, T., Dale, A.M., Doyle, A.E., L Jernigan, T., Hohmann, S., Kapilushniy, D., Mehta, M., Namazova-Baranova, L., Novotny, S.E., Oberwelland Weiss, E., and Schwarz, L.

Subjects
Adult, Attention Deficit Disorder with Hyperactivity/diagnostic imaging, Attention Deficit Disorder with Hyperactivity/epidemiology, Brain/diagnostic imaging, Case-Control Studies, Female, Humans, Magnetic Resonance Imaging, Male, Thalamus/diagnostic imaging, ADHD, community detection, effect sizes, neuroanatomic heterogeneity, subcortical volume, INCREASED EFFECT, 0302 clinical medicine, Limbic system, Neurodevelopmental disorder, Thalamus, 130 000 Cognitive Neurology & Memory, Basal ganglia, Developmental and Educational Psychology, Psychology, Pediatric, 0303 health sciences, 05 social sciences, Brain, Exploratory factor analysis, Psychiatry and Mental health, Mental Health, medicine.anatomical_structure, Attention Deficit Disorder (ADD), Cognitive Sciences, Original Article, 050104 developmental & child psychology, Clinical psychology, Clinical Sciences, Patient subgroups, Developmental & Child Psychology, 03 medical and health sciences, ENIGMA ADHD Working Group, Clinical Research, mental disorders, medicine, In patient, 0501 psychology and cognitive sciences, ddc:610, 030304 developmental biology, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, Neurosciences, Case-control study, Original Articles, medicine.disease, Attention Deficit Hyperactivity Disorder (ADHD), Brain Disorders, Attention Deficit Disorder with Hyperactivity, Sample size determination, Pediatrics, Perinatology and Child Health, Etiology, business, 030217 neurology & neurosurgery
Abstract

The journal of child psychology and psychiatry 62(9), 1140-1149 (2021). doi:10.1111/jcpp.13384, Published by Wiley-Blackwell, Oxford

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10. Subcortical brain volume, regional cortical thickness, and cortical surface area across disorders:Findings from the ENIGMA ADHD, ASD, and OCD working groups

Author

Pedro Moreira, Ruth O'Gorman Tuura, Mara Cercignani, Philip Aherson, Maria Jalbrzikowski, Kate D. Fitzgerald, Declan G. Murphy, Bernd Kardatzki, Christine Ecker, David F. Tolin, Fern Jaspers-Fayer, Pedro Morgado, Juan Carlos Soliva Vila, Kang Ik K. Cho, Kathrin Koch, Timothy J. Silk, Philip R. Szeszko, Thomas Frodl, Mara Parellada, Shlomi Haar, Eileen Daly, Bob Oranje, Anouk Schrantee, Leyla Namazova-Baranova, Joseph A. King, Beatriz Luna, Silvia Brem, Eric Earl, Alasdair Vance, Michela Tosetti, Christine Deruelle, Ramona Baur-Streubel, Jackie Fitzgerald, Kirsten O'Hearn, Michael C. Stevens, Yoshiyuki Hirano, J. Antoni Ramos-Quiroga, Erika L. Nurmi, Kaylita Chantiluke, Joseph O'Neill, Kerstin Kohls, Olga Puig, Devon Shook, Clodagh M. Murphy, Gustavo Sudre, Marlene Behrmann, Jaap Oosterlaan, Tinatin Gogberashvili, Lianne Schmaal, Carles Soriano-Mas, Liesbeth Hoekstra, Ignacio Martínez-Zalacaín, Noam Soreni, Marcel P. Zwiers, Paulo Mattos, Gregor Kohls, Andreas J. Fallgatter, Tiffany M. Chaim-Avancini, Alexander Baranov, S. Evelyn Stewart, Sara Dallaspezia, Gianfranco Spalletta, Jonna Kuntsi, Lizanne J. S. Schweren, Joel T. Nigg, Leanne Tamm, Premika S.W. Boedhoe, Adriana Di Martino, Jane McGrath, Marcelo C. Batistuzzo, Norbert Skokauskas, Filippo Muratori, John Piacentini, Jean-Paul Fouche, Sarah Baumeister, Alan Anticevic, Neil A. Harrison, Christine M. Freitag, Pedro G.P. Rosa, Stephen V. Faraone, Ana Cubillo, David Mataix-Cols, Yuki Sakai, Stefan Ehrlich, Eileen Oberwelland Weiss, Fabrizio Piras, Dirk J. Heslenfeld, Je-Yeon Yun, Paul Pauli, Catharina A. Hartman, Ganesan Venkatasubramanian, Janardhanan C. Narayanaswamy, Charles B Malpas, Jan C. Beucke, José M. Menchón, Egill A. Fridgeirsson, Margot J. Taylor, Mauricio Moller Martinho, H. Blair Simpson, Jan K. Buitelaar, Gerd Kvale, Ivanei E. Bramati, Aki Tsuchiyagaito, Susanne Walitza, Irene Bollettini, Jeffery N. Epstein, Anders M. Dale, Thomas Ethofer, Terry L. Jernigan, David Coghill, Rachel Marsh, Andreas Reif, Astri J. Lundervold, Pieter J. Hoekstra, Oana Georgiana Rus, Damiaan Denys, Gregory L. Wallace, Matt C. Gabel, Hazel McCarthy, Sarah Hohmann, Rosa Nicolau, Stephanie H. Ameis, Neda Jahanshad, Takashi Nakamae, Xin Feng, Emily R. Stern, Georg G. von Polier, Yanni Liu, Paulo Marques, Anushree Bose, Hao Hu, Sara Lera-Miguel, Deniz A. Gürsel, Jochen Seitz, Jos W. R. Twisk, Mario Rodrigues Louzã, Clare Kelly, Annette Conzelmann, Alysa E. Doyle, Odile A. van den Heuvel, Anthony A. James, Chris Perriello, Joost Janssen, Damien A. Fair, Norbert Kathmann, Francisco X. Castellanos, Paul D. Arnold, Oscar Vilarroya, Geraldo F. Busatto, Federica Piras, Pino Alonso, Akiko Nakagawa, Sarah Durston, Lena Schwarz, Mitul A. Mehta, Dan J. Stein, Celso Arango, Daan van Rooij, Ilan Dinstein, Anastasia Christakou, Klaus-Peter Lesch, Kerstin J. Plessen, Jennifer Fedor, Yolanda Vives-Gilabert, Ilaria Gori, Louise Gallagher, Brian P. Brennan, Yuqi Cheng, Barbara Franke, Sabin Khadka, Stephanie E. Novotny, Martine Hoogman, Georgii Karkashadze, Georg C. Ziegler, Yuliya N. Yoncheva, Rosa Calvo, Thomas Wolfers, Marcelo Q. Hoexter, Benjamin A. Ely, Masaru Kuno, Alessandra Retico, Yoshinari Abe, Geoffrey B. Hall, Tobias Banaschewski, Anatoly Anikin, Christine Lochner, Astrid Morer, Guido van Wingen, Jan Haavik, Joseph Biederman, Luisa Lázaro, Francesco Benedetti, Fengfeng Zhou, Guillaume Auzias, Daniel Brandeis, Dmitry Kapilushniy, Katya Rubia, Philip Shaw, Christian Kaufmann, Sara Calderoni, Marcus V. Zanetti, Anastasia Solovieva, Zhen Wang, Francesca Assogna, Jamie D. Feusner, Chaim Huyser, Fernanda Tovar-Moll, Theo G.M. van Erp, Y.C. Janardhan Reddy, Jun Soo Kwon, Yannis Paloyelis, Anna Calvo, Patricia Gruner, Kathrin C. Zierhut, Liesbeth Reneman, Tomohiro Nakao, Janita Bralten, Marie F. Høvik, Mark A. Bellgrove, Maarten Mennes, Paul M. Thompson, Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Epidemiology and Data Science, Pediatric surgery, Radiology and nuclear medicine, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Psychiatry, APH - Methodology, APH - Health Behaviors & Chronic Diseases, Boedhoe, Premika S W, van Rooij, Daan, Hoogman, Martine, Twisk, Jos W R, 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, Tobia, 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, Thoma, 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, Thoma, 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, Kardatzki, Bernd, Karkashadze, Georgii, Kathmann, Norbert, Kaufmann, Christian, Kelly, Clare, Khadka, Sabin, King, Joseph A, Koch, Kathrin, Kohls, Gregor, Konrad, Kerstin, Kuno, Masaru, Kuntsi, Jonna, Kvale, Gerd, Kwon, Jun Soo, Lázaro, Luisa, Lera-Miguel, Sara, Lesch, Klaus-Peter, Hoekstra, Liesbeth, Liu, Yanni, Lochner, Christine, Louza, Mario R, Luna, Beatriz, Lundervold, Astri J, Malpas, Charles B, Marques, Paulo, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Mattos, Paulo, Mccarthy, Hazel, Mcgrath, Jane, Mehta, Mitul A, Menchón, José M, Mennes, Maarten, Martinho, Mauricio Moller, Moreira, Pedro S, Morer, Astrid, Morgado, Pedro, Muratori, Filippo, Murphy, Clodagh M, Murphy, Declan G M, Nakagawa, Akiko, Nakamae, Takashi, Nakao, Tomohiro, Namazova-Baranova, Leyla, Narayanaswamy, Janardhanan C, Nicolau, Rosa, Nigg, Joel T, Novotny, Stephanie E, Nurmi, Erika L, Weiss, Eileen Oberwelland, O'Gorman Tuura, Ruth L, O'Hearn, Kirsten, O'Neill, Joseph, Oosterlaan, Jaap, Oranje, Bob, Paloyelis, Yanni, Parellada, Mara, Pauli, Paul, Perriello, Chri, Piacentini, John, Piras, Fabrizio, Piras, Federica, Plessen, Kerstin J, Puig, Olga, Ramos-Quiroga, J Antoni, Reddy, Y C Janardhan, Reif, Andrea, Reneman, Liesbeth, Retico, Alessandra, Rosa, Pedro G P, Rubia, Katya, Rus, Oana Georgiana, Sakai, Yuki, Schrantee, Anouk, Schwarz, Lena, Schweren, Lizanne J S, Seitz, Jochen, Shaw, Philip, Shook, Devon, Silk, Tim J, Simpson, H Blair, Skokauskas, Norbert, Soliva Vila, Juan Carlo, Solovieva, Anastasia, Soreni, Noam, Soriano-Mas, Carle, Spalletta, Gianfranco, Stern, Emily R, Stevens, Michael C, Stewart, S Evelyn, Sudre, Gustavo, Szeszko, Philip R, Tamm, Leanne, Taylor, Margot J, Tolin, David F, Tosetti, Michela, Tovar-Moll, Fernanda, Tsuchiyagaito, Aki, van Erp, Theo G M, van Wingen, Guido A, Vance, Alasdair, Venkatasubramanian, Ganesan, Vilarroya, Oscar, Vives-Gilabert, Yolanda, von Polier, Georg G, Walitza, Susanne, Wallace, Gregory L, Wang, Zhen, Wolfers, Thoma, Yoncheva, Yuliya N, Yun, Je-Yeon, Zanetti, Marcus V, Zhou, Fengfeng, Ziegler, Georg C, Zierhut, Kathrin C, Zwiers, Marcel P, Thompson, Paul M, Stein, Dan J, Buitelaar, Jan, Franke, Barbara, van den Heuvel, Odile A, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Adult Psychiatry, ANS - Compulsivity, Impulsivity & Attention, Graduate School, Child Psychiatry, General Paediatrics, ARD - Amsterdam Reproduction and Development, Radiology and Nuclear Medicine, APH - Personalized Medicine, and APH - Mental Health

Subjects
Male, Research Report, Obsessive-Compulsive Disorder, Frontal cortex, Systems Analysis, Attention Deficit Hyperactivity Disorder, Autism Spectrum Disorder, [SDV]Life Sciences [q-bio], Hippocampal formation, Audiology, 0302 clinical medicine, 130 000 Cognitive Neurology & Memory, Child, Obsessive-compulsive disorder (OCD), ComputingMilieux_MISCELLANEOUS, Intelligence quotient, Psychopathology, ATTENTION-DEFICIT/HYPERACTIVITY DISORDER, ABNORMALITIES, ENIGMA, Organ Size, 3. Good health, Psychiatry and Mental health, Autism spectrum disorder, Brain size, Cohort, Female, MRI, Adult, medicine.medical_specialty, CORTEX, Adolescent, DEFICIT HYPERACTIVITY DISORDER, Human Development, Neuroimaging, behavioral disciplines and activities, Article, 03 medical and health sciences, FIELD-STRENGTH, mental disorders, medicine, MEGA-ANALYSIS, Attention deficit hyperactivity disorder, Humans, Cortical surface, Structural MRI, Attention Deficit Disorder with Hyperactivity, Cerebrum, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, medicine.disease, 030227 psychiatry, VOXEL, Autism, business, 030217 neurology & neurosurgery
Abstract

ObjectiveAttention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. We aimed to directly compare all three disorders. The ENIGMA consortium is ideally positioned to investigate structural brain alterations across these disorders.MethodsStructural T1-weighted whole-brain MRI of controls (n=5,827) and 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. We examined subcortical volume, cortical thickness and 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 ICV for subcortical and surface area measures).ResultsWe found no shared alterations among all three disorders, while shared alterations between any two disorders did not survive multiple comparisons correction. Children with ADHD compared to those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller ICV than controls and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared to adult controls and other clinical groups. No OCD-specific alterations across different age-groups and surface area alterations among all disorders in childhood and adulthood were observed.ConclusionOur findings suggest robust but subtle alterations across different age-groups among ADHD, ASD, and OCD. ADHD-specific ICV and hippocampal alterations in children and adolescents, and ASD-specific cortical thickness alterations in the frontal cortex in adults support previous work emphasizing neurodevelopmental alterations in these disorders.

Published
2020

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