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1. Mapping Cortical and Subcortical Asymmetry in Obsessive-Compulsive Disorder: Findings From the ENIGMA Consortium

Author

Kong, X-Z, Boedhoe, PSW, Abe, Y, Alonso, P, Ameis, SH, Arnold, PD, Assogna, F, Baker, JT, Batistuzzo, MC, Benedetti, F, Beucke, JC, Bollettini, I, Bose, A, Brem, S, Brennan, BP, Buitelaar, J, Calvo, R, Cheng, Y, Cho, KIK, Dallaspezia, S, Denys, D, Ely, BA, Feusner, J, Fitzgerald, KD, Fouche, J-P, Fridgeirsson, EA, Glahn, DC, Gruner, P, Gursel, DA, Hauser, TU, Hirano, Y, Hoexter, MQ, Hu, H, Huyser, C, James, A, Jaspers-Fayer, F, Kathmann, N, Kaufmann, C, Koch, K, Kuno, M, Kvale, G, Kwon, JS, Lazaro, L, Liu, Y, Lochner, C, Marques, P, Marsh, R, Martinez-Zalacain, I, Mataix-Cols, D, Medland, SE, Menchon, JM, Minuzzi, L, Moreira, PS, Morer, A, Morgado, P, Nakagawa, A, Nakamae, T, Nakao, T, Narayanaswamy, JC, Nurmi, EL, O'Neill, J, Pariente, JC, Perriello, C, Piacentini, J, Piras, F, Pittenger, C, Reddy, YCJ, Rus-Oswald, OG, Sakai, Y, Sato, JR, Schmaal, L, Simpson, HB, Soreni, N, Soriano-Mas, C, Spalletta, G, Stern, ER, Stevens, MC, Stewart, SE, Szeszko, PR, Tolin, DF, Tsuchiyagaito, A, van Rooij, D, van Wingen, GA, Venkatasubramanian, G, Wang, Z, Yun, J-Y, Thompson, PM, Stein, DJ, van den Heuvel, OA, Francks, C, Kong, X-Z, Boedhoe, PSW, Abe, Y, Alonso, P, Ameis, SH, Arnold, PD, Assogna, F, Baker, JT, Batistuzzo, MC, Benedetti, F, Beucke, JC, Bollettini, I, Bose, A, Brem, S, Brennan, BP, Buitelaar, J, Calvo, R, Cheng, Y, Cho, KIK, Dallaspezia, S, Denys, D, Ely, BA, Feusner, J, Fitzgerald, KD, Fouche, J-P, Fridgeirsson, EA, Glahn, DC, Gruner, P, Gursel, DA, Hauser, TU, Hirano, Y, Hoexter, MQ, Hu, H, Huyser, C, James, A, Jaspers-Fayer, F, Kathmann, N, Kaufmann, C, Koch, K, Kuno, M, Kvale, G, Kwon, JS, Lazaro, L, Liu, Y, Lochner, C, Marques, P, Marsh, R, Martinez-Zalacain, I, Mataix-Cols, D, Medland, SE, Menchon, JM, Minuzzi, L, Moreira, PS, Morer, A, Morgado, P, Nakagawa, A, Nakamae, T, Nakao, T, Narayanaswamy, JC, Nurmi, EL, O'Neill, J, Pariente, JC, Perriello, C, Piacentini, J, Piras, F, Pittenger, C, Reddy, YCJ, Rus-Oswald, OG, Sakai, Y, Sato, JR, Schmaal, L, Simpson, HB, Soreni, N, Soriano-Mas, C, Spalletta, G, Stern, ER, Stevens, MC, Stewart, SE, Szeszko, PR, Tolin, DF, Tsuchiyagaito, A, van Rooij, D, van Wingen, GA, Venkatasubramanian, G, Wang, Z, Yun, J-Y, Thompson, PM, Stein, DJ, van den Heuvel, OA, and Francks, C

Abstract

BACKGROUND: Lateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. Here we carried out what is by far the largest study of brain structural asymmetry in OCD. METHODS: We studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status. RESULTS: In the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen's d = 0.19) and the pallidum (less leftward; d = -0.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets. CONCLUSIONS: The results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD.

Published
2020

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, A, 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, S, Fedor, J, Feng, X, Feusner, JD, Fitzgerald, J, Fitzgerald, KD, Fouche, J-P, Freitag, CM, Fridgeirsson, EA, Frodl, T, Gabel, MC, Gallagher, L, Gogberashvili, T, Gori, I, Gruner, P, Gursel, DA, Haar, S, Haavik, J, Hall, GB, Harrison, NA, Hartman, CA, Heslenfeld, DJ, Hirano, Y, Hoekstra, PJ, Hoexter, MQ, Hohmann, S, Hovik, 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, Lazaro, L, Lera-Miguel, S, Lesch, K-P, Hoekstra, L, Liu, Y, Lochner, C, Louza, MR, Luna, B, Lundervold, AJ, Malpas, CB, Marques, P, Marsh, R, Martinez-Zalacain, I, Mataix-Cols, D, Mattos, P, McCarthy, H, McGrath, J, Mehta, MA, Menchon, 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, Tuura, RLO, O'Hearn, K, O'Neill, J, Oosterlaan, J, Oranje, B, Paloyelis, Y, Parellada, M, Pauli, P, Perriello, C, Piacentini, J, 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, Vila, JCS, 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, J-Y, Zanetti, M, Zhou, F, Ziegler, GC, Zierhut, KC, Zwiers, MP, Thompson, PM, Stein, DJ, Buitelaar, J, Franke, B, van den Heuvel, OA, 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, A, 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, S, Fedor, J, Feng, X, Feusner, JD, Fitzgerald, J, Fitzgerald, KD, Fouche, J-P, Freitag, CM, Fridgeirsson, EA, Frodl, T, Gabel, MC, Gallagher, L, Gogberashvili, T, Gori, I, Gruner, P, Gursel, DA, Haar, S, Haavik, J, Hall, GB, Harrison, NA, Hartman, CA, Heslenfeld, DJ, Hirano, Y, Hoekstra, PJ, Hoexter, MQ, Hohmann, S, Hovik, 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, Lazaro, L, Lera-Miguel, S, Lesch, K-P, Hoekstra, L, Liu, Y, Lochner, C, Louza, MR, Luna, B, Lundervold, AJ, Malpas, CB, Marques, P, Marsh, R, Martinez-Zalacain, I, Mataix-Cols, D, Mattos, P, McCarthy, H, McGrath, J, Mehta, MA, Menchon, 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, Tuura, RLO, O'Hearn, K, O'Neill, J, Oosterlaan, J, Oranje, B, Paloyelis, Y, Parellada, M, Pauli, P, Perriello, C, Piacentini, J, 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, Vila, JCS, 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, J-Y, Zanetti, M, Zhou, F, Ziegler, GC, Zierhut, KC, Zwiers, MP, Thompson, PM, Stein, DJ, Buitelaar, J, Franke, B, and van den Heuvel, OA

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 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). 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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