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1. ADGRL3 (LPHN3) variants predict substance use disorder.

Author

Arcos-Burgos, Mauricio, Vélez, Jorge I, Martinez, Ariel F, Ribasés, Marta, Ramos-Quiroga, Josep A, Sánchez-Mora, Cristina, Richarte, Vanesa, Roncero, Carlos, Cormand, Bru, Fernández-Castillo, Noelia, Casas, Miguel, Lopera, Francisco, Pineda, David A, Palacio, Juan D, Acosta-López, Johan E, Cervantes-Henriquez, Martha L, Sánchez-Rojas, Manuel G, Puentes-Rozo, Pedro J, Molina, Brooke SG, MTA Cooperative Group, Boden, Margaret T, Wallis, Deeann, Lidbury, Brett, Newman, Saul, Easteal, Simon, Swanson, James, Patel, Hardip, Volkow, Nora, Acosta, Maria T, Castellanos, Francisco X, de Leon, Jose, Mastronardi, Claudio A, and Muenke, Maximilian

Subjects
MTA Cooperative Group, Humans, Substance-Related Disorders, Genetic Predisposition to Disease, Receptors, G-Protein-Coupled, Receptors, Peptide, Risk Factors, Case-Control Studies, Longitudinal Studies, Polymorphism, Single Nucleotide, Adult, Female, Male, Young Adult, Pediatric, Clinical Research, Human Genome, Patient Safety, Attention Deficit Disorder (ADD), Mental Health, Brain Disorders, Genetic Testing, Substance Abuse, Drug Abuse (NIDA only), Genetics, 2.1 Biological and endogenous factors, Receptors, G-Protein-Coupled, Peptide, Polymorphism, Single Nucleotide, Psychology, Clinical Sciences, Public Health and Health Services
Abstract

Genetic factors are strongly implicated in the susceptibility to develop externalizing syndromes such as attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder, conduct disorder, and substance use disorder (SUD). Variants in the ADGRL3 (LPHN3) gene predispose to ADHD and predict ADHD severity, disruptive behaviors comorbidity, long-term outcome, and response to treatment. In this study, we investigated whether variants within ADGRL3 are associated with SUD, a disorder that is frequently co-morbid with ADHD. Using family-based, case-control, and longitudinal samples from disparate regions of the world (n = 2698), recruited either for clinical, genetic epidemiological or pharmacogenomic studies of ADHD, we assembled recursive-partitioning frameworks (classification tree analyses) with clinical, demographic, and ADGRL3 genetic information to predict SUD susceptibility. Our results indicate that SUD can be efficiently and robustly predicted in ADHD participants. The genetic models used remained highly efficient in predicting SUD in a large sample of individuals with severe SUD from a psychiatric institution that were not ascertained on the basis of ADHD diagnosis, thus identifying ADGRL3 as a risk gene for SUD. Recursive-partitioning analyses revealed that rs4860437 was the predominant predictive variant. This new methodological approach offers novel insights into higher order predictive interactions and offers a unique opportunity for translational application in the clinical assessment of patients at high risk for SUD.

Published
2019

2. Genome‐wide association meta‐analysis of age at first cannabis use

Author

Minică, Camelia C, Verweij, Karin JH, van der Most, Peter J, Mbarek, Hamdi, Bernard, Manon, van Eijk, Kristel R, Lind, Penelope A, Liu, Meng Zhen, Maciejewski, Dominique F, Palviainen, Teemu, Sánchez‐Mora, Cristina, Sherva, Richard, Taylor, Michelle, Walters, Raymond K, Abdellaoui, Abdel, Bigdeli, Timothy B, Branje, Susan JT, Brown, Sandra A, Casas, Miguel, Corley, Robin P, Davey‐Smith, George, Davies, Gareth E, Ehli, Erik A, Farrer, Lindsay, Fedko, Iryna O, Garcia‐Martínez, Iris, Gordon, Scott D, Hartman, Catharina A, Heath, Andrew C, Hickie, Ian B, Hickman, Matthew, Hopfer, Christian J, Hottenga, Jouke Jan, Kahn, René S, Kaprio, Jaakko, Korhonen, Tellervo, Kranzler, Henry R, Krauter, Ken, van Lier, Pol AC, Madden, Pamela AF, Medland, Sarah E, Neale, Michael C, Meeus, Wim HJ, Montgomery, Grant W, Nolte, Ilja M, Oldehinkel, Albertine J, Pausova, Zdenka, Ramos‐Quiroga, Josep A, Richarte, Vanesa, Rose, Richard J, Shin, Jean, Stallings, Michael C, Wall, Tamara L, Ware, Jennifer J, Wright, Margaret J, Zhao, Hongyu, Koot, Hans M, Paus, Tomas, Hewitt, John K, Ribasés, Marta, Loukola, Anu, Boks, Marco P, Snieder, Harold, Munafò, Marcus R, Gelernter, Joel, Boomsma, Dorret I, Martin, Nicholas G, Gillespie, Nathan A, Vink, Jacqueline M, and Derks, Eske M

Subjects
Biological Psychology, Epidemiology, Health Sciences, Psychology, Cannabinoid Research, Substance Misuse, Brain Disorders, Human Genome, Clinical Research, Prevention, Drug Abuse (NIDA only), Pediatric, Genetics, 2.1 Biological and endogenous factors, Mental health, Good Health and Well Being, Adolescent, Adult, Age of Onset, Calcium-Transporting ATPases, Female, Genome-Wide Association Study, Humans, Male, Marijuana Use, Middle Aged, Polymorphism, Single Nucleotide, Twins, Young Adult, Age at first use, ATP2C2, cannabis initiation, genome-wide association, heritability, substance use, Medical and Health Sciences, Psychology and Cognitive Sciences, Substance Abuse, Public health, Clinical and health psychology
Abstract

Background and aimsCannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes, including multi-substance use and dependence. This study estimated the heritability of age at first cannabis use and identified associations with genetic variants.MethodsA twin-based heritability analysis using 8055 twins from three cohorts was performed. We then carried out a genome-wide association meta-analysis of age at first cannabis use in a discovery sample of 24 953 individuals from nine European, North American and Australian cohorts, and a replication sample of 3735 individuals.ResultsThe twin-based heritability for age at first cannabis use was 38% [95% confidence interval (CI) = 19-60%]. Shared and unique environmental factors explained 39% (95% CI = 20-56%) and 22% (95% CI = 16-29%). The genome-wide association meta-analysis identified five single nucleotide polymorphisms (SNPs) on chromosome 16 within the calcium-transporting ATPase gene (ATP2C2) at P  0.8), with the strongest association at the intronic variant rs1574587 (P = 4.09E-09). Gene-based tests of association identified the ATP2C2 gene on 16q24.1 (P = 1.33e-06). Although the five SNPs and ATP2C2 did not replicate, ATP2C2 has been associated with cocaine dependence in a previous study. ATP2B2, which is a member of the same calcium signalling pathway, has been associated previously with opioid dependence. SNP-based heritability for age at first cannabis use was non-significant.ConclusionAge at cannabis initiation appears to be moderately heritable in western countries, and individual differences in onset can be explained by separate but correlated genetic liabilities. The significant association between age of initiation and ATP2C2 is consistent with the role of calcium signalling mechanisms in substance use disorders.

Published
2018

3. The Prevalence and Treatment of ADHD in Spain: A Retrospective Cohort Analysis.

Author

Ramos-Quiroga, Jose Antonio, Richarte, Vanesa, Soto, Isabel, Targhetta, Maria, Ward, John, and Perulero, Núria

Subjects
COHORT analysis, ATTENTION-deficit hyperactivity disorder, ELECTRONIC health records
Abstract

Objective: Estimate the prevalence and incidence of Attention Deficit Hyperactivity Disorder (ADHD) and analyze variations in its treatment across Spain. Method: Analyses were performed using IQVIA's clinical practice RealWorld Database, the electronic medical records of some 1 million patients from 2013 to 2018. MPH treatment was assessed using the Defined Daily Dose (DDD), MPH sales were extracted from IQVIA's Sell-Out database and the number of active psychiatrists from IQVIA's OneKey Database. Results: Significantly higher ADHD prevalence and incidence (1) in children than in adults and (2) in males compared to females. 91% of patients take MPH. Regional variations in MPH consumption range from 247 Daily Dose per Inhabitant (DDI) per 100,000 inhabitants to 414. Conclusion: ADHD continues to be underdiagnosed and undertreated, particularly in adults, and more so in females. The lack of diagnostic tools for adults and the variations in treatment across the country need to be addressed. [ABSTRACT FROM AUTHOR]

Published
2023
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4. Caracterització de la microbiota intestinal en el trastorn per dèficit d'atenció i hiperactivitat en l'edat adulta

Author

Richarte, Vanesa, Ramos-Quiroga, Josep Antoni, and Ribasés Haro, Marta

Subjects
Adult, Adulto, ADHD, TDAH, Microbiome, Ciències de la Salut, Microbioma
Abstract

El trastorn per dèficit d'atenció amb hiperactivitat (TDAH) és un trastorn del neurodesenvolupament que presenta una etiologia complexa i és causat per la contribució de múltiples gens de susceptibilitat i factors ambientals. Recentment, diferents estudis han revelat alteracions en la composició de la microbiota intestinal en pacients amb trastorns del neurodesenvolupament. En aquest sentit, hi ha evidències de l'existència d'una diversitat microbiana intestinal diferencial, tant pel que fa a la composició bacteriana com en l'abundància relativa d'aquesta, en pacients TDAH comparat amb individus control. No obstant, els resultats fins ara han estat discordants. Aquesta heterogeneïtat podria explicar-se per diferents factors, com serien la mida reduïda de les mostres estudiades i que es centren principalment en població infantil i adolescent. L'objectiu global del present treball de tesi doctoral ha estat el d'ampliar el coneixement sobre el TDAH en població adulta. En aquest sentit, els resultats dels estudis que conformen aquesta tesi doctoral aporten informació rellevant que permet, en primer lloc, avançar en el diagnòstic de l'adult amb TDAH i en segon lloc, estudiar nous biomarcadors, com és el cas de la microbiota intestinal en el TDAH. El primer estudi determina que l'adaptació a l'espanyol de l'ADHD-RS en població adulta presenta unes adequades propietats psicomètriques, que justifiquen el seu ús com instrument diagnòstic del TDAH en l'adult. A la vegada, la nova proposta de puntuació en funció de la presentació clínica del TDAH ens permet detectar els pacients que presenten un TDAH amb una presentació predominantment de manca d'atenció, que podrien no ser detectats amb altres instruments diagnòstics o amb punts de tall diferents. La segona part d'aquest treball de tesi doctoral s'ha centrat en l'estudi de la relació existent entre la microbiota intestinal i el TDAH en població adulta. En aquest context, tres dels estudis que conformen la present tesi doctoral han pretès aportar nou coneixement sobre aquesta relació. El nostre estudi, realitza la major caracterització de la microbiota intestinal en 100 adults amb TDAH i 100 individus control, observant diferències en l'abundància relativa de diversos taxons microbians en comparació amb individus control. Aquests resultats estan amb consonància amb estudis realitzats amb població infantil, on també s'ha observat una correlació entre el TDAH i la composició bacteriana i/o abundància relativa de diferents taxons bacterians en comparació a individus control. Per altra banda, no s'ha detectat una correlació entre els gèneres que difereixen en abundància relativa entre els adults amb TDAH i els individus controls (Anaerotaenia, Dialister, Gracilibacter i Megamonas) i les puntuacions de les subescales de l'ADHD-RS. Per últim, tenint en compte que els probiòtics poden revertir la composició de la microbiota intestinal, i modular la conducta a través de l'eix intestí-cervell; el quart treball realitza un disseny d'un assaig clínic amb un suplement probiòtic per a reduir els comportaments impulsius en pacients adults amb TDAH . Aquests treballs en el seu conjunt, estimulen la línia de recerca sobre l'impacte de la microbiota intestinal en el desenvolupament del TDAH, així com sobre futurs tractaments. El trastorno por déficit de atención con hiperactividad (TDAH) es un trastorno del neurodesarrollo que presenta una etiología compleja y es causado por la contribución de múltiples genes de susceptibilidad y factores ambientales. Recientemente, diferentes estudios han revelado alteraciones en la composición de la microbiota intestinal en pacientes con trastornos del neurodesarrollo. En este sentido, hay evidencias de la existencia de una diversidad microbiana intestinal diferencial, tanto en cuanto a la composición bacteriana como en la abundancia relativa, en pacientes TDAH comparado con individuos control. No obstante, los resultados hasta ahora han sido discordantes. Esta heterogeneidad podría explicarse por diferentes factores, como serían el tamaño reducido de las muestras estudiadas y que se centran principalmente en población infantil y adolescente. El objetivo global del presente trabajo de tesis doctoral ha sido el de ampliar el conocimiento sobre el TDAH en población adulta. En este sentido, los resultados de los estudios que conforman esta tesis doctoral aportan información relevante que permite, en primer lugar, avanzar en el diagnóstico del adulto con TDAH y en segundo lugar, estudiar nuevos biomarcadores, como es el caso de la microbiota intestinal en el TDAH. El primer estudio determina que la adaptación al español de la ADHD-RS en población adulta presenta unas adecuadas propiedades psicométricas, que justifican su uso como instrumento diagnóstico del TDAH en el adulto. A su vez, la nueva propuesta de puntuación en función de la presentación clínica del TDAH nos permite detectar los pacientes que presentan un TDAH con una presentación predominantemente de déficit de atención, que podrían no ser detectados con otros instrumentos diagnósticos o con puntos de corte diferentes. La segunda parte de este trabajo de tesis doctoral se ha centrado en el estudio de la relación existente entre la microbiota intestinal y el TDAH en población adulta. En este contexto, tres de los estudios que conforman la presente tesis doctoral han pretendido aportar un nuevo conocimiento sobre esta relación. Nuestro estudio realiza la mayor caracterización de la microbiota intestinal en 100 adultos con TDAH y 100 individuos control, observando diferencias en la abundancia relativa de varios taxones microbianos en comparación con individuos control. Estos resultados están en consonancia con estudios realizados en población infantil, donde también se ha observado una correlación entre el TDAH y la composición bacteriana y/o abundancia relativa de diferentes taxones bacterianos en comparación con individuos control. Por otro lado, no se ha detectado una correlación entre los géneros que difieren en abundancia relativa entre los adultos con TDAH y los individuos control (Anaerotaenia, Dialister, Gracilibacter y Megamonas) y las puntuaciones de las subescalas de la ADHD-RS. Por último, teniendo en cuenta que los probióticos pueden revertir la composición de la microbiota intestinal, y modular la conducta a través del eje intestino-cerebro; el cuarto trabajo realiza un diseño de un ensayo clínico con un suplemento probiótico para reducir los comportamientos impulsivos en pacientes adultos con TDAH . Estos trabajos en su conjunto, estimulan la línea de investigación sobre el impacto de la microbiota intestinal en el desarrollo del TDAH, así como sobre futuros tratamientos. Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a complex aetiology caused by the contribution of multiple susceptibility genes and environmental factors. Recently, different studies have revealed alterations in the composition of the gut microbiota in patients with neurodevelopmental disorders. In this regard, there is evidence of differential gut microbial diversity, both in terms of bacterial composition and relative abundance, in ADHD patients compared to control individuals. However, the results so far have been discordant. This heterogeneity could be explained by different factors, such as the small size of the samples studied and the fact that they are mainly focused on children and adolescents. The overall aim of the present doctoral thesis work has been to increase knowledge about ADHD in the adult population. In this sense, the results of the studies that make up this doctoral thesis provide relevant information that allows, firstly, to advance in the diagnosis of adults with ADHD and secondly, to study new biomarkers, as is the case of the intestinal microbiota in ADHD. The first study determines that the Spanish adaptation of the ADHD-RS in the adult population has adequate psychometric properties, which justify its use as a diagnostic instrument for ADHD in adults. In turn, the new scoring proposal according to the clinical presentation of ADHD allows us to detect patients with ADHD with a predominantly attention deficit presentation, who might not be detected with other diagnostic instruments or with different cut-off points. The second part of this doctoral thesis work has focused on the study of the relationship between gut microbiota and ADHD in the adult population. In this context, three of the studies that make up this doctoral thesis have sought to provide new knowledge about this relationship. The study on the increased characterisation of the gut microbiota in 100 adults with ADHD and 100 control individuals has observed differences in the relative abundance of several microbial taxa compared to control individuals. These results are in line with studies in children, where a correlation has also been observed between ADHD and the bacterial composition and/or relative abundance of different bacterial taxa compared to control individuals. On the other hand, no correlation has been detected between genera that differ in relative abundance between adults with ADHD and control individuals (Anaerotaenia, Dialister, Gracilibacter and Megamonas) and ADHD-RS subscale scores. Finally, considering that probiotics can reverse the composition of the gut microbiota, and modulate behaviour through the gut-brain axis, the fourth paper designs a clinical trial with a probiotic supplement to reduce impulsive behaviours in adult ADHD patients. Together, these papers stimulate research into the impact of gut microbiota on the development of ADHD, as well as future treatments.

Published
2021

5. Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders

Author

Committee, Writing, Disorder, Autism Spectrum, French, Leon, Grevet, Eugenio H, Groenewold, Nynke A, Grotegerd, Dominik, Gruber, Oliver, Gruner, Patricia, Guerrero-Pedraza, Amalia, Gur, Raquel E, Gur, Ruben C, Haar, Shlomi, Haarman, Bartholomeus C M, Thomopoulos, Sophia I, Haavik, Jan, Hahn, Tim, Hajek, Tomas, Harrison, Benjamin J, Harrison, Neil A, Hartman, Catharina A, Whalley, Heather C, Heslenfeld, Dirk J, Hibar, Derrek P, Hilland, Eva, Pozzi, Elena, Hirano, Yoshiyuki, Ho, Tiffany C, Hoekstra, Pieter J, Hoekstra, Liesbeth, Hohmann, Sarah, Hong, L. E., Höschl, Cyril, Høvik, Marie F, Howells, Fleur M, Nenadic, Igor, Abe, Yoshinari, Jalbrzikowski, Maria, James, Anthony C, Janssen, Joost, Jaspers-Fayer, Fern, Xu, Jian, Jonassen, Rune, Karkashadze, Georgii, King, Joseph A, Kircher, Tilo, Kirschner, Matthias, Abé, Christoph, Koch, Kathrin, Kochunov, Peter, Kohls, Gregor, Konrad, Kerstin, Krämer, Bernd, Krug, Axel, Kuntsi, Jonna, Kwon, Jun Soo, Landén, Mikael, Landrø, Nils I, Anticevic, Alan, Lazaro, Luisa, Lebedeva, Irina S, Leehr, Elisabeth J, Lera-Miguel, Sara, Lesch, Klaus-Peter, Lochner, Christine, Louza, Mario R, Luna, Beatriz, Lundervold, Astri J, MacMaster, Frank P, Alda, Martin, Maglanoc, Luigi A, Malpas, Charles B, Portella, Maria J, Marsh, Rachel, Martyn, Fiona M, Mataix-Cols, David, Mathalon, Daniel H, McCarthy, Hazel, McDonald, Colm, McPhilemy, Genevieve, Aleman, Andre, Meinert, Susanne, Menchón, José M, Minuzzi, Luciano, Mitchell, Philip B, Moreno, Carmen, Morgado, Pedro, Muratori, Filippo, Murphy, Clodagh M, Murphy, Declan, Mwangi, Benson, Alloza, Clara, Nabulsi, Leila, Nakagawa, Akiko, Nakamae, Takashi, Namazova, Leyla, Narayanaswamy, Janardhanan, Jahanshad, Neda, Nguyen, Danai D, Nicolau, Rosa, O'Gorman Tuura, Ruth L, O'Hearn, Kirsten, Alonso-Lana, Silvia, Oosterlaan, Jaap, Opel, Nils, Ophoff, Roel A, Oranje, Bob, García de la Foz, Victor Ortiz, Overs, Bronwyn J, Paloyelis, Yannis, Pantelis, Christos, Parellada, Mara, Pauli, Paul, Disorder, Bipolar, Ameis, Stephanie H, Picó-Pérez, Maria, Picon, Felipe A, Piras, Fabrizio, Piras, Federica, Plessen, Kerstin J, Pomarol-Clotet, Edith, Preda, Adrian, Puig, Olga, Quidé, Yann, Radua, Joaquim, Anagnostou, Evdokia, Ramos-Quiroga, J Antoni, Rasser, Paul E, Rauer, Lisa, Reddy, Janardhan, Redlich, Ronny, Reif, Andreas, Reneman, Liesbeth, Repple, Jonathan, Retico, Alessandra, Richarte, Vanesa, McIntosh, Andrew A, Richter, Anja, Rosa, Pedro G P, Rubia, Katya K, Hashimoto, Ryota, Sacchet, Matthew D, Salvador, Raymond, Santonja, Javier, Sarink, Kelvin, Sarró, Salvador, Satterthwaite, Theodore D, Arango, Celso, Sawa, Akira, Schall, Ulrich, Schofield, Peter R, Schrantee, Anouk, Seitz, Jochen, Serpa, Mauricio H, Setién-Suero, Esther, Shaw, Philip, Shook, Devon, Silk, Tim J, Arnold, Paul D, Sim, Kang, Simon, Schmitt, Simpson, Helen Blair, Singh, Aditya, Skoch, Antonin, Skokauskas, Norbert, Soares, Jair C, Soreni, Noam, Soriano-Mas, Carles, Spalletta, Gianfranco, Asherson, Philip, Spaniel, Filip, Lawrie, Stephen M, Stern, Emily R, Stewart, S Evelyn, Takayanagi, Yoichiro, Temmingh, Henk S, Tolin, David F, Tomecek, David, Tordesillas-Gutiérrez, Diana, Tosetti, Michela, Assogna, Francesca, Uhlmann, Anne, van Amelsvoort, Therese, van der Wee, Nic J A, van der Werff, Steven J A, van Haren, Neeltje E M, van Wingen, Guido A, Vance, Alasdair, Vázquez-Bourgon, Javier, Vecchio, Daniela, Venkatasubramanian, Ganesan, Auzias, Guillaume, Vieta, Eduard, Vilarroya, Oscar, Vives-Gilabert, Yolanda, Voineskos, Aristotle N, Völzke, Henry, von Polier, Georg G, Walton, Esther, Weickert, Thomas W, Weickert, Cynthia Shannon, Weideman, Andrea S, Ayesa-Arriola, Rosa, Wittfeld, Katharina, Wolf, Daniel H, Wu, Mon-Ju, Yang, T. T., Yang, Sikun, Yoncheva, Yuliya, Yun, Je-Yeon, Cheng, Yuqi, Zanetti, Marcus V, Ziegler, Georg C, Bakker, Geor, Franke, Barbara, Hoogman, Martine, Buitelaar, Jan K, van Rooij, Daan, Andreassen, Ole A, Ching, Christopher R K, Veltman, Dick J, Schmaal, Lianne, Stein, Dan J, van den Heuvel, Odile A, Disorder, Major Depressive, Banaj, Nerisa, Turner, Jessica A, van Erp, Theo G M, Pausova, Zdenka, Thompson, Paul M, Paus, Tomáš, Attention-Deficit/Hyperactivity Disorder, Banaschewski, Tobias, Bandeira, Cibele E, Baranov, Alexandr, Bargalló, Núria, Bau, Claiton H D, Baumeister, Sarah, Baune, Bernhard T, Bellgrove, Mark A, Benedetti, Francesco, Disorder, Obsessive-Compulsive, Bertolino, Alessandro, Boedhoe, Premika S W, Boks, Marco, Bollettini, Irene, Del Mar Bonnin, Caterina, Borgers, Tiana, Borgwardt, Stefan, Brandeis, Daniel, Brennan, Brian P, Bruggemann, Jason M, Groups, Schizophrenia ENIGMA Working, Bülow, Robin, Busatto, Geraldo F, Calderoni, Sara, Calhoun, Vince D, Calvo, Rosa, Canales-Rodríguez, Erick J, Cannon, Dara M, Carr, Vaughan J, Cascella, Nicola, Cercignani, Mara, Patel, Yash, Chaim-Avancini, Tiffany M, Christakou, Anastasia, Coghill, David, Conzelmann, Annette, Crespo-Facorro, Benedicto, Cubillo, Ana I, Cullen, Kathryn R, Cupertino, Renata B, Daly, Eileen, Dannlowski, Udo, Parker, Nadine, Davey, Christopher G, Denys, Damiaan, Deruelle, Christine, Di Giorgio, Annabella, Dickie, Erin W, Dima, Danai, Dohm, Katharina, Ehrlich, Stefan, Ely, Benjamin A, Erwin-Grabner, Tracy, Shin, Jean, Ethofer, Thomas, Fair, Damien A, Fallgatter, Andreas, Faraone, Stephen V, Fatjó-Vilas, Mar, Fedor, Jennifer M, Fitzgerald, Kate D, Ford, Judith M, Frodl, Thomas, Fu, Cynthia H Y, Howard, Derek, Fullerton, Janice M, Gabel, Matt C, Glahn, David C, Roberts, Gloria, Gogberashvili, Tinatin, Goikolea, Jose M, Gotlib, Ian H, Goya-Maldonado, Roberto, Grabe, Hans, Green, Melissa J, Patel, Y., Parker, N., Shin, J., Howard, D., French, L., Thomopoulos, S. I., Pozzi, E., Abe, Y., Abe, C., Anticevic, A., Alda, M., Aleman, A., Alloza, C., Alonso-Lana, S., Ameis, S. H., Anagnostou, E., Mcintosh, A. A., Arango, C., Arnold, P. D., Asherson, P., Assogna, F., Auzias, G., Ayesa-Arriola, R., Bakker, G., Banaj, N., Banaschewski, T., Bandeira, C. E., Baranov, A., Bargallo, N., Bau, C. H. D., Baumeister, S., Baune, B. T., Bellgrove, M. A., Benedetti, F., Bertolino, A., Boedhoe, P. S. W., Boks, M., Bollettini, I., Del Mar Bonnin, C., Borgers, T., Borgwardt, S., Brandeis, D., Brennan, B. P., Bruggemann, J. M., Bulow, R., Busatto, G. F., Calderoni, S., Calhoun, V. D., Calvo, R., Canales-Rodriguez, E. J., Cannon, D. M., Carr, V. J., Cascella, N., Cercignani, M., Chaim-Avancini, T. M., Christakou, A., Coghill, D., Conzelmann, A., Crespo-Facorro, B., Cubillo, A. I., Cullen, K. R., Cupertino, R. B., Daly, E., Dannlowski, U., Davey, C. G., Denys, D., Deruelle, C., Di Giorgio, A., Dickie, E. W., Dima, D., Dohm, K., Ehrlich, S., Ely, B. A., Erwin-Grabner, T., Ethofer, T., Fair, D. A., Fallgatter, A. J., Faraone, S. V., Fatjo-Vilas, M., Fedor, J. M., Fitzgerald, K. D., Ford, J. M., Frodl, T., Fu, C. H. Y., Fullerton, J. M., Gabel, M. C., Glahn, D. C., Roberts, G., Gogberashvili, T., Goikolea, J. M., Gotlib, I. H., Goya-Maldonado, R., Grabe, H. J., Green, M. J., Grevet, E. H., Groenewold, N. A., Grotegerd, D., Gruber, O., Gruner, P., Guerrero-Pedraza, A., Gur, R. E., Gur, R. C., Haar, S., Haarman, B. C. M., Haavik, J., Hahn, T., Hajek, T., Harrison, B. J., Harrison, N. A., Hartman, C. A., Whalley, H. C., Heslenfeld, D. J., Hibar, D. P., Hilland, E., Hirano, Y., Ho, T. C., Hoekstra, P. J., Hoekstra, L., Hohmann, S., Hong, L. E., Hoschl, C., Hovik, M. F., Howells, F. M., Nenadic, I., Jalbrzikowski, M., James, A. C., Janssen, J., Jaspers-Fayer, F., Xu, J., Jonassen, R., Karkashadze, G., King, J. A., Kircher, T., Kirschner, M., Koch, K., Kochunov, P., Kohls, G., Konrad, K., Kramer, B., Krug, A., Kuntsi, J., Kwon, J. S., Landen, M., Landro, N. I., Lazaro, L., Lebedeva, I. S., Leehr, E. J., Lera-Miguel, S., Lesch, K. -P., Lochner, C., Louza, M. R., Luna, B., Lundervold, A. J., Macmaster, F. P., Maglanoc, L. A., Malpas, C. B., Portella, M. J., Marsh, R., Martyn, F. M., Mataix-Cols, D., Mathalon, D. H., Mccarthy, H., Mcdonald, C., Mcphilemy, G., Meinert, S., Menchon, J. M., Minuzzi, L., Mitchell, P. B., Moreno, C., Morgado, P., Muratori, F., Murphy, C. M., Murphy, D., Mwangi, B., Nabulsi, L., Nakagawa, A., Nakamae, T., Namazova, L., Narayanaswamy, J., Jahanshad, N., Nguyen, D. D., Nicolau, R., O'Gorman Tuura, R. L., O'Hearn, K., Oosterlaan, J., Opel, N., Ophoff, R. A., Oranje, B., Garcia De La Foz, V. O., Overs, B. J., Paloyelis, Y., Pantelis, C., Parellada, M., Pauli, P., Pico-Perez, M., Picon, F. A., Piras, F., Plessen, K. J., Pomarol-Clotet, E., Preda, A., Puig, O., Quide, Y., Radua, J., Ramos-Quiroga, J. A., Rasser, P. E., Rauer, L., Reddy, J., Redlich, R., Reif, A., Reneman, L., Repple, J., Retico, A., Richarte, V., Richter, A., Rosa, P. G. P., Rubia, K. K., Hashimoto, R., Sacchet, M. D., Salvador, R., Santonja, J., Sarink, K., Sarro, S., Satterthwaite, T. D., Sawa, A., Schall, U., Schofield, P. R., Schrantee, A., Seitz, J., Serpa, M. H., Setien-Suero, E., Shaw, P., Shook, D., Silk, T. J., Sim, K., Simon, S., Simpson, H. B., Singh, A., Skoch, A., Skokauskas, N., Soares, J. C., Soreni, N., Soriano-Mas, C., Spalletta, G., Spaniel, F., Lawrie, S. M., Stern, E. R., Stewart, S. E., Takayanagi, Y., Temmingh, H. S., Tolin, D. F., Tomecek, D., Tordesillas-Gutierrez, D., Tosetti, M., Uhlmann, A., Van Amelsvoort, T., Van Der Wee, N. J. A., Van Der Werff, S. J. A., Van Haren, N. E. M., Van Wingen, G. A., Vance, A., Vazquez-Bourgon, J., Vecchio, D., Venkatasubramanian, G., Vieta, E., Vilarroya, O., Vives-Gilabert, Y., Voineskos, A. N., Volzke, H., Von Polier, G. G., Walton, E., Weickert, T. W., Weickert, C. S., Weideman, A. S., Wittfeld, K., Wolf, D. H., Wu, M. -J., Yang, T. T., Yang, K., Yoncheva, Y., Yun, J. -Y., Cheng, Y., Zanetti, M. V., Ziegler, G. C., Franke, B., Hoogman, M., Buitelaar, J. K., Van Rooij, D., Andreassen, O. A., Ching, C. R. K., Veltman, D. J., Schmaal, L., Stein, D. J., Van Den Heuvel, O. A., Turner, J. A., Van Erp, T. G. M., Pausova, Z., Thompson, P. M., Paus, T., Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Pediatric surgery, Radiology and nuclear medicine, Anatomy and neurosciences, Psychiatry, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Neurodegeneration, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, MUMC+: MA Med Staf Spec Psychiatrie (9), Adult Psychiatry, ANS - Compulsivity, Impulsivity & Attention, General Paediatrics, ARD - Amsterdam Reproduction and Development, Radiology and Nuclear Medicine, APH - Personalized Medicine, ANS - Brain Imaging, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, University of Zurich, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Clinical Neuropsychology, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Child and Adolescent Psychiatry / Psychology, IBBA, and Cognitive Psychology

Subjects
Male, Obsessive-Compulsive Disorder, Bipolar Disorder, Autism Spectrum Disorder, Autism, [SDV]Life Sciences [q-bio], Gene Expression, cytology [Cerebral Cortex], Cohort Studies, Fetal Development, physiology [Gene Expression], 2738 Psychiatry and Mental Health, 0302 clinical medicine, diagnostic imaging [Cerebral Cortex], SCHIZOPHRENIA, BRAIN, Child, Obsessive-compulsive disorder (OCD), Original Investigation, Aged, 80 and over, Cerebral Cortex, 0303 health sciences, pathology [Depressive Disorder, Major], Principal Component Analysis, Adolescent psychiatry, 10058 Department of Child and Adolescent Psychiatry, Middle Aged, diagnostic imaging [Obsessive-Compulsive Disorder], REGIONS, Magnetic Resonance Imaging, 3. Good health, FALSE DISCOVERY RATE, Psychiatry and Mental health, Autism spectrum disorder, Schizophrenia, growth & development [Cerebral Cortex], Child, Preschool, Major depressive disorder, diagnostic imaging [Schizophrenia], Esquizofrènia, Female, Psiquiatria infantil, Psiquiatria de l'adolescència, diagnostic imaging [Autism Spectrum Disorder], Adult, medicine.medical_specialty, Adolescent, Human Development, 610 Medicine & health, diagnostic imaging [Bipolar Disorder], pathology [Autism Spectrum Disorder], diagnostic imaging [Depressive Disorder, Major], 03 medical and health sciences, Young Adult, All institutes and research themes of the Radboud University Medical Center, Neuroimaging, SDG 3 - Good Health and Well-being, CEREBRAL-CORTEX, Child psychiatry, medicine, Attention deficit hyperactivity disorder, Humans, Bipolar disorder, ddc:610, Psychiatry, pathology [Schizophrenia], 030304 developmental biology, Aged, Depressive Disorder, Major, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, DENDRITE, Computational Biology, Correction, pathology [Attention Deficit Disorder with Hyperactivity], physiology [Fetal Development], medicine.disease, PATHOLOGY, pathology [Bipolar Disorder], pathology [Obsessive-Compulsive Disorder], 10036 Medical Clinic, Attention Deficit Disorder with Hyperactivity, 10054 Clinic for Psychiatry, Psychotherapy, and Psychosomatics, Case-Control Studies, DENSITY, ORIGINS, HIPPOCAMPUS, diagnostic imaging [Attention Deficit Disorder with Hyperactivity], pathology [Cerebral Cortex], Autisme, business, Neuroscience, 030217 neurology & neurosurgery, physiology [Human Development]
Abstract

[Importance] Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood., [Objective] To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia., [Design, Setting, and Participants] Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244., [Main Outcomes and Measures] Interregional profiles of group difference in cortical thickness between cases and controls., [Results] A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders., [Conclusions and Relevance] In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.

Published
2021
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6. The Relationship Between Neuropsychological Deficits and Emotional Lability in Adults With ADHD.

Author

Gisbert, Laura, Richarte, Vanesa, Corrales, Montserrat, Ibáñez, Pol, Bosch, Rosa, Bellina, Mariano, Fadeuilhe, Christian, Casas, Miquel, and Ramos-Quiroga, Josep Antoni

Subjects
ATTENTION-deficit disorder in adults, NEUROPSYCHOLOGY, EXECUTIVE function, NEUROPSYCHOLOGICAL tests, SYMPTOMS, AFFECTIVE disorders, ALEXITHYMIA, ATTENTION-deficit hyperactivity disorder, COMPARATIVE studies, RESEARCH methodology, MEDICAL cooperation, PERSONALITY disorders, PSYCHOLOGICAL tests, RESEARCH, EVALUATION research, PSYCHOLOGICAL factors
Abstract

Objective: The objective of this study was to investigate the extent to which neuropsychological performance parameters implicated in ADHD might mediate the relationship between emotional lability (EL) and this disorder. Method: Eight hundred twelve adult patients with ADHD were examined. EL was assessed using the EL subscale of Conners' Adult ADHD Rating Scales (CAARS). To assess cognitive and executive functions, a battery of neuropsychological tests was performed in 262 patients with ADHD and high EL symptomatology and 550 patients with ADHD and low EL symptomatology. Results: Several differences between groups were found regarding neuropsychological performance; however, nearly all significant differences disappeared when the effect of gender, inattention, and hyperactive symptoms and psychiatric comorbidities were taken into account. Conclusion: Our results do not support the hypothesis that neuropsychological deficits are associated with EL in adults with ADHD. [ABSTRACT FROM AUTHOR]

Published
2019
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7. Genome-wide analysis of emotional lability in adult attention deficit hyperactivity disorder (ADHD).

Author

Gisbert, Laura, Vilar, Laura, Rovira, Paula, Sánchez-Mora, Cristina, Pagerols, Mireia, Garcia-Martínez, Iris, Richarte, Vanesa, Corrales, Montserrat, Casas, Miguel, Ramos-Quiroga, Josep Antoni, Soler Artigas, María, and Ribasés, Marta

Subjects
*ATTENTION-deficit hyperactivity disorder, *22Q11 deletion syndrome, *EMOTIONAL conditioning, *MENTAL illness
Abstract

Emotional lability is strongly associated with Attention Deficit Hyperactivity Disorder (ADHD), represents a major source of impairment and predicts poor clinical outcome in ADHD. Given that no specific genes with a role in the co-occurrence of both conditions have been described, we conducted a GWAS of emotional lability in 563 adults with ADHD. Despite not reaching genome-wide significance, the results highlighted genes related with neurotransmission, cognitive function and a wide range of psychiatric disorders that have emotional lability as common clinical feature. By constructing polygenic risk scores on mood instability in the UK Biobank sample and assessing their association with emotional lability in our clinical dataset, we found suggestive evidence of common genetic variation contributing to emotional lability in general population and in clinically diagnosed ADHD. Although not conclusive, these tentative results are in agreement with previous studies that suggest emotion dysregulation as a transdiagnostic construct and highlight the need for further investigation to disentangle the genetic basis of mood instability in ADHD and co-occurring psychiatric disorders. [ABSTRACT FROM AUTHOR]

Published
2019
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