Obsessive-Compulsive Disorder (OCD); Attention Deficit-Hyperactivity Disorder (ADHD); children; action monitoring; inhibition; cognitive flexibility; orbito-fronto-striatal circuit; anterior cingulate cortex; functional magnetic resonance imaging (fMRI); event related potentials (ERP); Child and Adolescent Psychiatry; EEG; FMRI; ERP; neuroimaging; genetics
Guadalupe Tulio, Mathias Samuel R, vanErp Theo G M, Whelan Christopher D, Zwiers Marcel P, Abe Yoshinari, Abramovic Lucija, Agartz Ingrid, Andreassen Ole A, Arias-Vásquez Alejandro, Aribisala Benjamin S, Armstrong Nicola J, Arolt Volker, Artiges Eric, Ayesa-Arriola Rosa, Baboyan Vatche G, Banaschewski Tobias, Barker Gareth, Bastin Mark E, Baune Bernhard T, Blangero John, Bokde Arun L W, Boedhoe Premika S W, Bose Anushree, Brem Silvia, Brodaty Henry, Bromberg Uli, Brooks Samantha, Büchel Christian, Buitelaar Jan, Calhoun Vince D, Cannon Dara M, Cattrell Anna, Cheng Yuqi, Conrod Patricia J, Conzelmann Annette, Corvin Aiden, Crespo-Facorro Benedicto, Crivello Fabrice, Dannlowski Udo, de Zubicaray Greig I, de Zwarte Sonja M C, Deary Ian J, Desrivières Sylvane, Doan Nhat Trung, Donohoe Gary, Dørum Erlend S, Ehrlich Stefan, Espeseth Thomas, Fernández Guillén, Flor Herta, Fouche Jean-Paul, Frouin Vincent, Fukunaga Masaki, Gallinat Jürgen, Garavan Hugh, Gill Michael, Suarez Andrea Gonzalez, Gowland Penny, Grabe Hans J, Grotegerd Dominik, Gruber Oliver, Hagenaars Saskia, Hashimoto Ryota, Hauser Tobias U, Heinz Andreas, Hibar Derrek P, Hoekstra Pieter J, Hoogman Martine, Howells Fleur M, Hu Hao, Hulshoff Pol Hilleke E, Huyser Chaim, Ittermann Bernd, Jahanshad Neda, Jönsson Erik G, Jurk Sarah, Kahn Rene S, Kelly Sinead, Kraemer Bernd, Kugel Harald, Kwon Jun Soo, Lemaitre Herve, Lesch Klaus-Peter, Lochner Christine, Luciano Michelle, Marquand Andre F, Martin Nicholas G, Martínez-Zalacaín Ignacio, Martinot Jean-Luc, Mataix-Cols David, Mather Karen, McDonald Colm, McMahon Katie L, Medland Sarah E, Menchón José M, Morris Derek W, Mothersill Omar, Maniega Susana Munoz, Mwangi Benson (2017), Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex., in Brain imaging and behavior
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Hauser T U, Iannaccone R, Dolan R J, Ball J, Hättenschwiler J, Drechsler R, Rufer M, Brandeis D, Walitza S, Brem S (2017), Increased fronto-striatal reward prediction errors moderate decision making in obsessive-compulsive disorder., in Psychological medicine
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Hauser Tobias U, Moutoussis Michael, Iannaccone Reto, Brem Silvia, Walitza Susanne, Drechsler Renate, Dayan Peter, Dolan Raymond J (2017), Increased decision thresholds enhance information gathering performance in juvenile Obsessive-Compulsive Disorder (OCD)., in PLoS computational biology
, 13(4), 1005440-1005440.
Boedhoe Premika S W, Schmaal Lianne, Abe Yoshinari, Ameis Stephanie H, Arnold Paul D, Batistuzzo Marcelo C, Benedetti Francesco, Beucke Jan C, Bollettini Irene, Bose Anushree, Brem Silvia, Calvo Anna, Cheng Yuqi, Cho Kang Ik K, Dallaspezia Sara, Denys Damiaan, Fitzgerald Kate D, Fouche Jean-Paul, Giménez Mònica, Gruner Patricia, Hanna Gregory L, Hibar Derrek P, Hoexter Marcelo Q, Hu Hao, Huyser Chaim, Ikari Keisuke, Jahanshad Neda, Kathmann Norbert, Kaufmann Christian, Koch Kathrin, Kwon Jun Soo, Lazaro Luisa, Liu Yanni, Lochner Christine, Marsh Rachel, Martínez-Zalacaín Ignacio, Mataix-Cols David, Menchón José M, Minuzzi Luciano, Nakamae Takashi, Nakao Tomohiro, Narayanaswamy Janardhanan C, Piras Fabrizio, Piras Federica, Pittenger Christopher, Reddy Y C Janardhan, Sato Joao R, Simpson H Blair, Soreni Noam, Soriano-Mas Carles, Spalletta Gianfranco, Stevens Michael C, Szeszko Philip R, Tolin David F, Venkatasubramanian Ganesan, Walitza Susanne, Wang Zhen, van Wingen Guido A, Xu Jian, Xu Xiufeng, Yun Je-Yeon, Zhao Qing, Zhao Qing, Thompson Paul M, Stein Dan J, van den Heuvel Odile A (2017), Distinct Subcortical Volume Alterations in Pediatric and Adult OCD: A Worldwide Meta- and Mega-Analysis., in The American journal of psychiatry
, 174(1), 60-69.
Iannaccone Reto, Hauser Tobias U, Ball Juliane, Brandeis Daniel, Walitza Susanne, Brem Silvia (2015), Classifying adolescent attention-deficit/hyperactivity disorder (ADHD) based on functional and structural imaging., in European child & adolescent psychiatry
, 24(10), 1279-89.
Hauser Tobias U, Hunt Laurence T, Iannaccone Reto, Walitza Susanne, Brandeis Daniel, Brem Silvia, Dolan Raymond J (2015), Temporally Dissociable Contributions of Human Medial Prefrontal Subregions to Reward-Guided Learning., in The Journal of neuroscience : the official journal of the Society for Neuroscience
, 35(32), 11209-20.
Iannaccone Reto, Hauser Tobias U, Staempfli Philipp, Walitza Susanne, Brandeis Daniel, Brem Silvia (2015), Conflict monitoring and error processing: new insights from simultaneous EEG-fMRI., in NeuroImage
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Hauser Tobias U, Iannaccone Reto, Walitza Susanne, Brandeis Daniel, Brem Silvia (2015), Cognitive flexibility in adolescence: neural and behavioral mechanisms of reward prediction error processing in adaptive decision making during development., in NeuroImage
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Grünblatt Edna, Hauser Tobias U, Walitza Susanne (2014), Imaging genetics in obsessive-compulsive disorder: linking genetic variations to alterations in neuroimaging., in Progress in neurobiology
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Hauser Tobias U, Iannaccone Reto, Ball Juliane, Mathys Christoph, Brandeis Daniel, Walitza Susanne, Brem Silvia (2014), Role of the medial prefrontal cortex in impaired decision making in juvenile attention-deficit/hyperactivity disorder., in JAMA psychiatry
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Brem Silvia, Grünblatt Edna, Drechsler Renate, Riederer Peter, Walitza Susanne (2014), The neurobiological link between OCD and ADHD., in Attention deficit and hyperactivity disorders
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Walitza Susanne, Marinova Zoya, Grünblatt Edna, Lazic Stanley E, Remschmidt Helmut, Vloet Timo D, Wendland Jens R (2014), Trio study and meta-analysis support the association of genetic variation at the serotonin transporter with early-onset obsessive-compulsive disorder., in Neuroscience letters
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Walitza Susanne (2014), [Obsessive-compulsive disorders in DSM-5 – what is new?]., in Zeitschrift fur Kinder- und Jugendpsychiatrie und Psychotherapie
, 42(2), 121-127.
Grünblatt Edna, Tschakarjan Senop, Brezinka Veronika, Walitza Susanne (2014), Extraordinarily fast response to low-dose sertraline in a child with severe obsessive-compulsive disorder and high functioning serotonin transporter genotype., in Journal of child and adolescent psychopharmacology
, 24(2), 102-4.
Werling Anna, Drechsler Renate, Walitza Susanne (2014), Klinische Praxis der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörungen und hyperkinetischen Störungen, in PSYCH up2date
, 8(4), 257-272.
Hauser Tobias U., Iannaccone Reto, Stämpfli Philipp, Drechsler Renate, Brandeis Daniel, Walitza Susanne, Brem Silvia (2014), The feedback-related negativity (FRN) revisited: New insights into the localization, meaning and network organization, in NeuroImage
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Walitza Susanne, Brem Silvia, Hauser Tobias, Gruenblatt Edna (2014), Wie biologisch sind Zwangsstörungen? Genetische Befunde und Bildgebung bei Zwangsstörungen, in Kindheit und Entwicklung
Grünblatt Edna, Bartl Jasmin, Marinova Zoya, Walitza Susanne (2013), In vitro study methodologies to investigate genetic aspects and effects of drugs used in attention-deficit hyperactivity disorder., in Journal of neural transmission (Vienna, Austria : 1996)
, 120(1), 131-9.
Keck Martin E, Ropohl Axel, Bondolfi Guido, Brenni Corinna Constantin, Hättenschwiler Josef, Hatzinger Martin, Hemmeter Ulrich Michael, Holsboer-Trachsler Edith, Kawohl Wolfram, Poppe Christine, Preisig Martin, Rennhard Stefan, Seifritz Erich, Weidt Steffi, Walitza Susanne, Rufer Michael (2013), Die Behandlung der Angsterkrankungen. Teil 2: Zwangsstörungen und posttraumatische Belastungsstörung, in Swiss Medical Forum
, 13(17), 337-344.
Brem Silvia, Hauser Tobias U., Iannaccone Reto, Brandeis Daniel, Drechsler Renate, Walitza Susanne (2012), Neuroimaging of cognitive brain function in paediatric obsessive compulsive disorder: A review of literature and preliminary meta-analysis, in Journal of Neural Transmission
, 119(11), 1425-1448.
Background: Obsessive-compulsive disorder (OCD) is the world’s fourth most common psychiatric disorder. An early age of symptom onset has been observed in over 50% of the patients and early onset OCD has a poor long-term prognosis. Children and adults with OCD suffer from unrealistic and excessive recurrent and intrusive thoughts (obsessions) which are usually accompanied by stereotypic repetitive behaviours (compulsions). The present knowledge about the etiology of OCD is limited despite its high prevalence of 1-3% especially because only few studies have addressed OCD in children and adolescents and due to the highly variable nature of the phenotype. Genetic studies have demonstrated high familiality of the disorder, especially in early onset OCD. Attention-deficit/hyperactivity disorder (ADHD) is the most frequent psychiatric disorder in children and adolescents. It affects up to 6-12% according to DSM-IV criteria and is characterized by inappropriate levels of inattention, hyperactivity and/or impulsivity. The causes and pathophysiology of ADHD are still unknown, but considerable evidence suggests that this heterogeneous, highly heritable disorder results from complex gene-gene and gene-environment interactions. Multimodal neuroimaging studies with functional magnetic resonance imaging (fMRI) and event related potentials (ERP) are essential to test and refine neurobiological and neuropsychological models of the disorder, as they provide direct insight into deviant information processing in the critical brain circuits regarding spatial distribution, timing and connectivity. Convergent evidence points to the importance of the orbitofronto-striatal (OFS) circuit in the pathophysiology of OCD. Hyperactivation of specific structures of the OFS loop during resting state, symptom provocation and cognitive task performance has been related to an overactive monitoring system since brain structures such as the anterior cingulated cortex (ACC) or the orbitofrontal cortex (OFC) are involved in response monitoring and decision making processes. The ACC overactivation in OCD contrasts with hypoactivation of the ACC in patients with ADHD during monitoring, which correlates with their constantly interruptive behaviour. Contrasting ACC monitoring deficits in these disorders thus provides a unique opportunity to understand the full normal and clinical range of ACC function in adolescence, and avoids a simplistic localisation of functional deficits. Failures in inhibition processes which in turn facilitate the characteristic repetitive behaviour of OCD patients may be reflected by hypoactivation of the lateral OFC during challenging cognitive tasks. Despite an increasing number of functional neuroimaging studies the direction of causality linking hypo- and hyperactivation to OCD still remains unknown and demands further research. Aims & Hypotheses: The focus of this project is to clarify the role of the corticostriatal loops in the pathophysiology of paediatric OCD and ADHD patients by using fMRI and ERPs. Cognitive tasks probing response inhibition, error monitoring or cognitive flexibility will yield information on OFS and ACC (dys)function in OCD and ADHD as compared to controls. Gene-fMRI and gene-ERP analyses will provide a multi-level perspective on the question whether brain hyper- or hypoactivation in patients with OCD and/or ADHD is modulated by genetic variants during task performance. Finally, characteristic neuropsychological patterns of performance in the domain of cognitive flexibility (neuroanatomically related to ACC or dlPFC networks), decision-making (related to OFC networks) and self evaluation of performance will be determined and related to abnormal activity in functional networks.Experimental Design and Methods: A group of non-medicated children with OCD will be compared to patients with ADHD and a healthy age, gender and IQ matched control group. All three groups will include 16 children aged between 12 and 16 years. An additional group of 16 healthy adult controls will serve to clarify developmental aspects in error monitoring, inhibition and reversal learning. All participants will take part in neuropsychological testings and separate electroencephalography (EEG) and functional/structural magnetic resonance (MRI) sessions. The same two cognitive tasks, testing cognitive flexibility, error processing and inhibition will be used in EEG and fMRI sessions, so that information about spatial and temporal processing can be combined. Expected Value: To summarize, the present study represents a unique interdisciplinary approach, which will integrate findings from two complementary approaches of functional imaging sensitive to either spatial (fMRI) or temporal processing (EEG). Neuropsychology, genetics and biochemical studies will complement the neuroimaging investigations to determine sensitive biomarkers for improving diagnostics and treatment especially in juvenile OCD. Since confounding factors that emerge through the chronicity of the disease, medication and past treatments are minimized in our paediatric sample this study crucially contributes to unveil the causes and dysfunctions underlying the disorder.