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3. A cooperative interaction between LPHN3 and 11q doubles the risk for ADHD

Author

Jain, M, Vélez, JI, Acosta, MT, Palacio, LG, Balog, J, Roessler, E, Pineda, D, Londoño, AC, Palacio, JD, Arbelaez, A, Lopera, F, Elia, J, Hakonarson, H, Seitz, C, Freitag, CM, Palmason, H, Meyer, J, Romanos, M, Walitza, S, Hemminger, U, Warnke, A, Romanos, J, Renner, T, Jacob, C, Lesch, K-P, Swanson, J, Castellanos, FX, Bailey-Wilson, JE, Arcos-Burgos, M, and Muenke, M

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Clinical and Health Psychology, Clinical Sciences, Psychology, Neurosciences, Genetics, Attention Deficit Hyperactivity Disorder (ADHD), Mental Health, 2.1 Biological and endogenous factors, Aetiology, Aspartic Acid, Attention Deficit Disorder with Hyperactivity, Brain, Case-Control Studies, Choline, Chromosomes, Human, Pair 11, Genetic Linkage, Genetic Predisposition to Disease, Glutamine, Humans, Inositol, Magnetic Resonance Spectroscopy, Methylphenidate, Polymorphism, Single Nucleotide, Protons, Receptors, G-Protein-Coupled, Receptors, Peptide, ADHD, genetic interaction, LPHN3, NCAM1, DRD2, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract

In previous studies of a genetic isolate, we identified significant linkage of attention deficit hyperactivity disorder (ADHD) to 4q, 5q, 8q, 11q and 17p. The existence of unique large size families linked to multiple regions, and the fact that these families came from an isolated population, we hypothesized that two-locus interaction contributions to ADHD were plausible. Several analytical models converged to show significant interaction between 4q and 11q (P

Published
2012

5. Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome

Author

Jain, P., Miller-Fleming, T., Topaloudi, A., Yu, D., Drineas, P., Georgitsi, M., Yang, Z, Rizzo, R., Müller-Vahl, K.R., Tumer, Z., Debes, N. Mol, Hartmann, A., Depienne, C., Worbe, Y., Mir, P., Cath, D.C., Boomsma, D.I., Roessner, V., Wolanczyk, T., Janik, P., Szejko, N., Zekanowski, C., Barta, C., Nemoda, Z., Tarnok, Z., Buxbaum, J.D., Grice, D., Glennon, J., Stefansson, H., Hengerer, B., Benaroya-Milshtein, N., Cardona, F., Hedderly, T., Heyman, I., Huyser, C., Morer, A., Mueller, N., Munchau, A., Plessen, K.J., Porcelli, C., Walitza, S., Schrag, A., Martino, D. de, Dietrich, A., Mathews, Carol A., Scharf, J.M., Hoekstra, P.J., Buitelaar, J.K., Davis, L.K., Paschou, P., Jain, P., Miller-Fleming, T., Topaloudi, A., Yu, D., Drineas, P., Georgitsi, M., Yang, Z, Rizzo, R., Müller-Vahl, K.R., Tumer, Z., Debes, N. Mol, Hartmann, A., Depienne, C., Worbe, Y., Mir, P., Cath, D.C., Boomsma, D.I., Roessner, V., Wolanczyk, T., Janik, P., Szejko, N., Zekanowski, C., Barta, C., Nemoda, Z., Tarnok, Z., Buxbaum, J.D., Grice, D., Glennon, J., Stefansson, H., Hengerer, B., Benaroya-Milshtein, N., Cardona, F., Hedderly, T., Heyman, I., Huyser, C., Morer, A., Mueller, N., Munchau, A., Plessen, K.J., Porcelli, C., Walitza, S., Schrag, A., Martino, D. de, Dietrich, A., Mathews, Carol A., Scharf, J.M., Hoekstra, P.J., Buitelaar, J.K., Davis, L.K., and Paschou, P.

Abstract

Contains fulltext : 291641.pdf (Publisher’s version ) (Open Access), Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders.

Published
2023

6. Empathy deficits, callous-unemotional traits and structural underpinnings in autism spectrum disorder and conduct disorder youth

Author

Tkalcec, A., Bierlein, M., Seeger-Schneider, G., Walitza, S., Jenny, B., Menks, W.M., Fehlbaum, L.V., Borbás, R., Cole, D.M., Raschle, N.M., Herbrecht, E., Stadler, C., Cubillo, A., Tkalcec, A., Bierlein, M., Seeger-Schneider, G., Walitza, S., Jenny, B., Menks, W.M., Fehlbaum, L.V., Borbás, R., Cole, D.M., Raschle, N.M., Herbrecht, E., Stadler, C., and Cubillo, A.

Abstract

07 augustus 2023, Item does not contain fulltext, Distinct empathy deficits are often described in patients with conduct disorder (CD) and autism spectrum disorder (ASD) yet their neural underpinnings and the influence of comorbid Callous-Unemotional (CU) traits are unclear. This study compares the cognitive (CE) and affective empathy (AE) abilities of youth with CD and ASD, their potential neuroanatomical correlates, and the influence of CU traits on empathy. Adolescents and parents/caregivers completed empathy questionnaires (N = 148 adolescents, mean age = 15.16 years) and T1 weighted images were obtained from a subsample (N = 130). Group differences in empathy and the influence of CU traits were investigated using Bayesian analyses and Voxel-Based Morphometry with Threshold-Free Cluster Enhancement focusing on regions involved in AE (insula, amygdala, inferior frontal gyrus and cingulate cortex) and CE processes (ventromedial prefrontal cortex, temporoparietal junction, superior temporal gyrus, and precuneus). The ASD group showed lower parent-reported AE and CE scores and lower self-reported CE scores while the CD group showed lower parent-reported CE scores than controls. When accounting for the influence of CU traits no AE deficits in ASD and CE deficits in CD were found, but CE deficits in ASD remained. Across all participants, CU traits were negatively associated with gray matter volumes in anterior cingulate which extends into the mid cingulate, ventromedial prefrontal cortex, and precuneus. Thus, although co-occurring CU traits have been linked to global empathy deficits in reports and underlying brain structures, its influence on empathy aspects might be disorder-specific. Investigating the subdimensions of empathy may therefore help to identify disorder-specific empathy deficits.

Published
2023

7. Age-related brain deviations and aggression.

Author

Holz, N.E., Floris, D.L., Llera, A., Aggensteiner, P.M., Kia, S.M., Wolfers, T., Baumeister, S., Böttinger, B., Glennon, J.C., Hoekstra, P.J., Dietrich, A., Saam, M.C., Schulze, U.M.E., Lythgoe, D.J., Williams, S.C.R., Santosh, P., Rosa-Justicia, M., Bargallo, N., Castro-Fornieles, J., Arango, C., Penzol, M.J., Walitza, S., Meyer-Lindenberg, A., Zwiers, M.P., Franke, B., Buitelaar, J.K., Naaijen, J., Brandeis, D., Beckmann, C.F., Banaschewski, T., Marquand, A.F., Holz, N.E., Floris, D.L., Llera, A., Aggensteiner, P.M., Kia, S.M., Wolfers, T., Baumeister, S., Böttinger, B., Glennon, J.C., Hoekstra, P.J., Dietrich, A., Saam, M.C., Schulze, U.M.E., Lythgoe, D.J., Williams, S.C.R., Santosh, P., Rosa-Justicia, M., Bargallo, N., Castro-Fornieles, J., Arango, C., Penzol, M.J., Walitza, S., Meyer-Lindenberg, A., Zwiers, M.P., Franke, B., Buitelaar, J.K., Naaijen, J., Brandeis, D., Beckmann, C.F., Banaschewski, T., and Marquand, A.F.

Abstract

01 juli 2023, Contains fulltext : 296661.pdf (Publisher’s version ) (Open Access), BACKGROUND: Disruptive behavior disorders (DBD) are heterogeneous at the clinical and the biological level. Therefore, the aims were to dissect the heterogeneous neurodevelopmental deviations of the affective brain circuitry and provide an integration of these differences across modalities. METHODS: We combined two novel approaches. First, normative modeling to map deviations from the typical age-related pattern at the level of the individual of (i) activity during emotion matching and (ii) of anatomical images derived from DBD cases (n = 77) and controls (n = 52) aged 8-18 years from the EU-funded Aggressotype and MATRICS consortia. Second, linked independent component analysis to integrate subject-specific deviations from both modalities. RESULTS: While cases exhibited on average a higher activity than would be expected for their age during face processing in regions such as the amygdala when compared to controls these positive deviations were widespread at the individual level. A multimodal integration of all functional and anatomical deviations explained 23% of the variance in the clinical DBD phenotype. Most notably, the top marker, encompassing the default mode network (DMN) and subcortical regions such as the amygdala and the striatum, was related to aggression across the whole sample. CONCLUSIONS: Overall increased age-related deviations in the amygdala in DBD suggest a maturational delay, which has to be further validated in future studies. Further, the integration of individual deviation patterns from multiple imaging modalities allowed to dissect some of the heterogeneity of DBD and identified the DMN, the striatum and the amygdala as neural signatures that were associated with aggression.

Published
2023

8. The future of child and adolescent clinical psychopharmacology: A systematic review of phase 2, 3, or 4 randomized controlled trials of pharmacologic agents without regulatory approval or for unapproved indications

Author

Cortese, S., McGinn, K., Højlund, M., Apter, A., Arango, C., Baeza, I., Banaschewski, T., Buitelaar, J.K., Castro-Fornieles, J., Coghill, D., Cohen, D., Grünblatt, E., Hoekstra, P.J., James, A., Jeppesen, P., Nagy, P., Pagsberg, A.K., Parellada, M., Persico, A.M., Purper-Ouakil, D., Roessner, V., Santosh, P., Simonoff, E., Stevanovic, D., Stringaris, A., Vitiello, B., Walitza, S., Weizman, A., Wohlfarth, T., Wong, I.C.K., Zalsman, G., Zuddas, A., Moreno, C., Solmi, M., Correll, C.U., Cortese, S., McGinn, K., Højlund, M., Apter, A., Arango, C., Baeza, I., Banaschewski, T., Buitelaar, J.K., Castro-Fornieles, J., Coghill, D., Cohen, D., Grünblatt, E., Hoekstra, P.J., James, A., Jeppesen, P., Nagy, P., Pagsberg, A.K., Parellada, M., Persico, A.M., Purper-Ouakil, D., Roessner, V., Santosh, P., Simonoff, E., Stevanovic, D., Stringaris, A., Vitiello, B., Walitza, S., Weizman, A., Wohlfarth, T., Wong, I.C.K., Zalsman, G., Zuddas, A., Moreno, C., Solmi, M., and Correll, C.U.

Abstract

Item does not contain fulltext, We aimed to identify promising novel medications for child and adolescent mental health problems. We systematically searched https://clinicaltrials.gov/ and https://www.clinicaltrialsregister.eu/ (from 01/01/2010-08/23/2022) for phase 2 or 3 randomized controlled trials (RCTs) of medications without regulatory approval in the US, Europe or Asia, including also RCTs of dietary interventions/probiotics. Additionally, we searched phase 4 RCTs of agents targeting unlicensed indications for children/adolescents with mental health disorders. We retrieved 234 ongoing or completed RCTs, including 26 (11%) with positive findings on ≥ 1 primary outcome, 43 (18%) with negative/unavailable results on every primary outcome, and 165 (70%) without publicly available statistical results. The only two compounds with evidence of significant effects that were replicated in ≥ 1 additional RCT without any negative RCTs were dasotraline for attention-deficit/hyperactivity disorder, and carbetocin for hyperphagia in Prader-Willi syndrome. Among other strategies, targeting specific symptom dimensions in samples stratified based on clinical characteristics or established biomarkers may increase chances of success in future development programmes.

Published
2023

9. Angststörungen und Phobien

Author

Gerlach, Manfred, Mehler-Wex, Claudia, Romanos, Marcel; https://orcid.org/0000-0001-7628-8299, Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Wewetzer, Christoph, Gerlach, M ( Manfred ), Mehler-Wex, C ( Claudia ), Romanos, M ( Marcel ), Walitza, S ( Susanne ), Wewetzer, C ( Christoph ), Renner, Tobias, Melfsen, Siebke; https://orcid.org/0000-0002-4189-2645, Gerlach, Manfred, Mehler-Wex, Claudia, Romanos, Marcel; https://orcid.org/0000-0001-7628-8299, Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Wewetzer, Christoph, Gerlach, M ( Manfred ), Mehler-Wex, C ( Claudia ), Romanos, M ( Marcel ), Walitza, S ( Susanne ), Wewetzer, C ( Christoph ), Renner, Tobias, and Melfsen, Siebke; https://orcid.org/0000-0002-4189-2645

Abstract

Unter Angststörungen und Phobien wird ein breites Spektrum von Erkrankungen verstanden, bei dem die Kernsymptomatik ein übermäßiges Angst- und Vermeidungsverhalten umfasst. Die Intensität der therapeutischen Behandlung richtet sich vor allem nach dem Grad der psychosozialen Beeinträchtigung. Sowohl kognitive Verhaltenstherapie (KVT) als auch Pharmakotherapie zeigen sich nach der aktuellen Evidenzlage als sicher und wirksam. Nach dem aktuellen Stand kann eine leichte bis moderat ausgeprägte Angststörung mit KVT behandelt werden, während bei schweren Angststörungen im Rahmen einer multimodalen Behandlung zusätzlich eine Medikation indiziert sein kann. Selektive Serotonin- Wiederaufnahmehemmer (SSRIs) sind dabei im Kindes- und Jugendalter die erste Wahl. Im Gegensatz zum Erwachsenenalter ist die Evidenz für andere Wirkstoffgruppen deutlich geringer, es liegen jedoch für Venlafaxin und Duloxetin positive Befunde vor, und diese können nach den internationalen Leitlinien für die Behandlung von Angststörungen im Kindesund Jugendalter als Medikation der zweiten Wahl angesehen werden. Kurzfristig angstlösende Wirkstoffe wie Benzodiazepine sind nur dann indiziert, wenn eine sofortige Angstreduktion erforderlich ist. Wegen des Risikos einer Abhängigkeit ist ihre Verschreibung nur für eine Akutbehandlung geeignet.

Published
2023

10. Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung

Author

Gerlach, Manfred, Mehler-Wex, Claudia, Romanos, Marcel, Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Wewetzer, Christoph, Gerlach, M ( Manfred ), Mehler-Wex, C ( Claudia ), Romanos, M ( Marcel ), Walitza, S ( Susanne ), Wewetzer, C ( Christoph ), Banaschewski, Tobias; https://orcid.org/0000-0003-4595-1144, Häge, Alexander; https://orcid.org/0000-0002-3434-2995, Gerlach, Manfred, Mehler-Wex, Claudia, Romanos, Marcel, Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Wewetzer, Christoph, Gerlach, M ( Manfred ), Mehler-Wex, C ( Claudia ), Romanos, M ( Marcel ), Walitza, S ( Susanne ), Wewetzer, C ( Christoph ), Banaschewski, Tobias; https://orcid.org/0000-0003-4595-1144, and Häge, Alexander; https://orcid.org/0000-0002-3434-2995

Abstract

In der spezifischen Behandlung der Aufmerksamkeitsdefizit‑/Hyperaktivitätsstörung (ADHS) findet die medikamentöse Therapie häufige Anwendung und zeigt eine sehr gute Wirksamkeit, Tolerabilität und Sicherheit. Dabei stehen im Kindes- und Jugendalter Psychostimulanzien (Methylphenidat und Amphetamin) in verschiedenen Applikationsformen als Medikation der ersten Wahl zur Verfügung. Nicht-Psychostimulanzien wie Atomoxetin und Guanfacin sind weitere Optionen in der medikamentösen Behandlung. Langwirksame Formulierungen von Psychostimulanzien bieten häufig Vorteile hinsichtlich Wirkung und Medikamentenadhärenz. Entscheidend für die Indikation zur Medikation einer ADHS sind die individuelle psychosoziale Beeinträchtigung, das Alter der Patienten und der Schweregrad der Störung. In der Wahl des geeigneten Medikamentes sind, eingebettet in ein multimodales Behandlungskonzept, individuelle Gegebenheiten wie Komorbiditäten zu berücksichtigen. Unter der Behandlung sind regelmäßige Kontrollen z. B. von Gewichtsentwicklung, Puls und Blutdruck zur Erfassung eventueller unerwünschter Arzneimittelwirkungen sowie Auslassversuche durchzuführen. Das folgende Kapitel gibt neben der Störungsdefinition einen Überblick über diagnostische Voraussetzungen, die individuelle Indikationsstellung und die Anwendung der Psychopharmakotherapie in der Behandlung der ADHS und einiger häufiger komorbider Störungen.

Published
2023

11. Zwangsstörungen im Kindes- und Jugendalter

Author

Gerlach, Manfred, Mehler-Wex, Claudia, Romanos, Marcel, Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Wewetzer, Christoph, Gerlach, M ( Manfred ), Mehler-Wex, C ( Claudia ), Romanos, M ( Marcel ), Walitza, S ( Susanne ), Wewetzer, C ( Christoph ), Gerlach, Manfred, Mehler-Wex, Claudia, Romanos, Marcel, Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Wewetzer, Christoph, Gerlach, M ( Manfred ), Mehler-Wex, C ( Claudia ), Romanos, M ( Marcel ), Walitza, S ( Susanne ), and Wewetzer, C ( Christoph )

Abstract

Die Zwangsstörungen zählen mit einer Prävalenz von 1–2 % zu den häufigsten Störungen im Kindes- und Jugendalter. Die Therapie orientiert sich am Schweregrad der Zwangsstörung und am Vorhandensein komorbider Störungen. Eine evidenzbasierte Therapie bei Kindern und Jugendlichen beinhaltet Elemente der Psychoedukation, der kognitiv-verhaltenstherapeutischen Psychotherapie (KVT) und einer pharmakologischen Behandlung. Die KVT und ihre Bausteine Exposition und Reaktionsverhinderung sind besonders wirksam. Je nach Alter der Patienten sollte die Familie in die Therapie einbezogen werden. Auch selektive Serotonin-Wiederaufnahmehemmer (SSRIs) zeigen sich in verschiedenen Metaanalysen, die randomisiert-placebokontrollierte Studien an Kindern und Jugendlichen eingeschlossen hatten, als sehr wirksam und sind Wirkstoffe der ersten Wahl. Um eine ausreichende Wirkung zu erzielen, bedarf es bei der Behandlung von Zwangsstörungen in der Regel mehr Zeit und oft höherer Dosen als bei anderen Indikationen. Die Kombination von KVT und einer Medikation zeigt nicht immer eine Überlegenheit, hat sich aber bei besonders schwierigen Konstellationen, z. B. bei komorbiden Depressionen, bewährt. Wirkstoff der zweiten Wahl ist das trizyklische Antidepressivum Clomipramin. Zugelassen in den meisten europäischen Ländern und in den USA für die Behandlung bei Kindern und Jugendlichen mit Zwängen sind Sertralin und Fluvoxamin. Fluoxetin hat zwar keine explizite Zulassung für Zwangsstörungen, aufgrund der positiven Studienlage nimmt die Bedeutung jedoch zu. Zur Augmentation mit Antipsychotika ist die Studienlage im Kindes- und Jugendalter gering.

Published
2023

12. Psychostimulanzien und andere Arzneistoffe, die zur Behandlung der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) angewendet werden

Author

Gerlach, Manfred, Mehler-Wex, Claudia, Romanos, Marcel; https://orcid.org/0000-0001-7628-8299, Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Wewetzer, Christoph, Gerlach, M ( Manfred ), Mehler-Wex, C ( Claudia ), Romanos, M ( Marcel ), Walitza, S ( Susanne ), Wewetzer, C ( Christoph ), Smigielski, Lukasz; https://orcid.org/0000-0002-7428-7644, Gerlach, Manfred, Mehler-Wex, Claudia, Romanos, Marcel; https://orcid.org/0000-0001-7628-8299, Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Wewetzer, Christoph, Gerlach, M ( Manfred ), Mehler-Wex, C ( Claudia ), Romanos, M ( Marcel ), Walitza, S ( Susanne ), Wewetzer, C ( Christoph ), and Smigielski, Lukasz; https://orcid.org/0000-0002-7428-7644

Abstract

Als Psychostimulanzien oder Stimulanzien wird die Gruppe von Neuro‑/Psychopharmaka bezeichnet, die vorwiegend eine erregende Wirkung auf das zentrale Nervensystem und die Psyche ausüben. Das Hauptanwendungsgebiet der Psychostimulanzien Methylphenidat und Amphetamin ist die Therapie der Aufmerksamkeitsdefizit‑/Hyperaktivitätsstörung (ADHS). Weitere Wirkstoffe zur Behandlung der ADHS sind Atomoxetin und Guanfacin, die als Nicht-Psychostimulanzien eingeordnet werden. In diesem Kapitel werden die Wirk(ungs)mechanismen dieser Wirkstoffe besprochen und schwerpunktmäßig diejenigen pharmakologischen Aspekte dargestellt, die für Kliniker für den therapeutischen Einsatz dieser Substanzen relevant sind. Dabei wird u. a. auf Anwendungsgebiete, die klinische Wirksamkeit und die Studienlage eingegangen. Es werden Dosierungsempfehlungen gegeben und mögliche unerwünschte Arzneimittelwirkungen und -wechselwirkungen behandelt. Das Kapitel schließt mit Empfehlungen zur Behandlungsdauer sowie zu notwendigen Kontrolluntersuchungen im Rahmen der ADHS-Pharmakotherapie.

Published
2023

18. Psychostimulanzien

Author

Walitza, S., Romanos, M., Seifert, J., Warnke, A., Gerlach, M., Gerlach, Manfred, editor, Warnke, Andreas, editor, Mehler-Wex, Claudia, editor, Walitza, Susanne, editor, and Wewetzer, Christoph, editor

Published
2009
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21. Psychostimulanzien

Author

Gerlach, M., Walitza, S., Seifert, J., Warnke, A., Trott, G. -E., Riederer, Peter, editor, and Laux, Gerd, editor

Published
2006
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23. Therapeutic drug monitoring of sertraline in pediatric population: A naturalistic study with insights into the clinical response of obsessive-compulsive disorder

Author

Tini, E., additional, Smigielski, L., additional, Romanos, M., additional, Wewetzer, C., additional, Karwautz, A., additional, Reitzle, K., additional, Correll, C.U., additional, Plener, P.L., additional, Malzahn, U., additional, Heuschmann, P., additional, Unterecker, S., additional, Scherf-Clavel, M., additional, Rock, H., additional, Antony, G., additional, Briegel, W., additional, Fleischhaker, C., additional, Banaschewski, T., additional, Hellenschmidt, T., additional, Imgart, H., additional, Kaess, M., additional, Kölch, M., additional, Renner, T., additional, Reuter-Dang, S.Y., additional, Rexroth, C., additional, Schulte-Körne, G., additional, Theisen, F., additional, Fekete, S., additional, Taurines, R., additional, Gerlach, M., additional, Egberts, K.M., additional, and Walitza, S., additional

Published
2022
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24. Zwangsstörungen

Author

Wewetzer, Ch., Walitza, S., Gerlach, Manfred, editor, Warnke, Andreas, editor, and Wewetzer, Christoph, editor

Published
2004
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26. Psychostimulanzien

Author

Walitza, S., Seifert, J., Warnke, A., Gerlach, M., Gerlach, Manfred, editor, Warnke, Andreas, editor, and Wewetzer, Christoph, editor

Published
2004
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27. Consortium neuroscience of attention deficit/hyperactivity disorder and autism spectrum disorder: The ENIGMA adventure

Author

Hoogman, M., Rooij, D. van, Klein, M., Boedhoe, P., Ilioska, I., Li, T., Patel, Y., Postema, M.C., Zhang-James, Y., Anagnostou, E., Arango, C., Auzias, G., Banaschewski, T., Bau, C.H.D., Behrmann, M., Bellgrove, Mark A., Brandeis, D., Brem, S., Busatto, G.F., Calderoni, S., Calvo, R., Castellanos, F.X., Coghill, D., Conzelmann, A., Daly, E., Deruelle, C., Dinstein, I., Durston, S., Ecker, C., Ehrlich, S., Epstein, J.N., Fair, D.A., Fitzgerald, J., Freitag, C.M., Frodl, T., Gallagher, L., Grevet, E.H., Haavik, J., Hoekstra, P.J., Janssen, J., Karkashadze, G., King, J.A., Konrad, K., Kuntsi, J., Lazaro, L., Lerch, J.P., Lesch, K.P., Louza, M.R., Luna, B., Mattos, P., McGrath, J., Muratori, F., Murphy, C., Nigg, J.T., Oberwelland-Weiss, E., Tuura, R.L. O'Gorman, O'Hearn, K., Oosterlaan, J., Parellada, M., Pauli, P., Plessen, K.J., Ramos-Quiroga, J.A., Reif, A., Reneman, L., Retico, A., Rosa, P.G., Rubia, K., Shaw, P., Silk, T.J., Tamm, L., Vilarroya, O., Walitza, S., Jahanshad, N., Faraone, S.V, Francks, C., Heuvel, O.A. van den, Paus, T., Thompson, P.M., Buitelaar, J.K., Franke, B., Hoogman, M., Rooij, D. van, Klein, M., Boedhoe, P., Ilioska, I., Li, T., Patel, Y., Postema, M.C., Zhang-James, Y., Anagnostou, E., Arango, C., Auzias, G., Banaschewski, T., Bau, C.H.D., Behrmann, M., Bellgrove, Mark A., Brandeis, D., Brem, S., Busatto, G.F., Calderoni, S., Calvo, R., Castellanos, F.X., Coghill, D., Conzelmann, A., Daly, E., Deruelle, C., Dinstein, I., Durston, S., Ecker, C., Ehrlich, S., Epstein, J.N., Fair, D.A., Fitzgerald, J., Freitag, C.M., Frodl, T., Gallagher, L., Grevet, E.H., Haavik, J., Hoekstra, P.J., Janssen, J., Karkashadze, G., King, J.A., Konrad, K., Kuntsi, J., Lazaro, L., Lerch, J.P., Lesch, K.P., Louza, M.R., Luna, B., Mattos, P., McGrath, J., Muratori, F., Murphy, C., Nigg, J.T., Oberwelland-Weiss, E., Tuura, R.L. O'Gorman, O'Hearn, K., Oosterlaan, J., Parellada, M., Pauli, P., Plessen, K.J., Ramos-Quiroga, J.A., Reif, A., Reneman, L., Retico, A., Rosa, P.G., Rubia, K., Shaw, P., Silk, T.J., Tamm, L., Vilarroya, O., Walitza, S., Jahanshad, N., Faraone, S.V, Francks, C., Heuvel, O.A. van den, Paus, T., Thompson, P.M., Buitelaar, J.K., and Franke, B.

Abstract

Contains fulltext : 248364.pdf (Publisher’s version ) (Open Access), Neuroimaging has been extensively used to study brain structure and function in individuals with attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) over the past decades. Two of the main shortcomings of the neuroimaging literature of these disorders are the small sample sizes employed and the heterogeneity of methods used. In 2013 and 2014, the ENIGMA-ADHD and ENIGMA-ASD working groups were respectively, founded with a common goal to address these limitations. Here, we provide a narrative review of the thus far completed and still ongoing projects of these working groups. Due to an implicitly hierarchical psychiatric diagnostic classification system, the fields of ADHD and ASD have developed largely in isolation, despite the considerable overlap in the occurrence of the disorders. The collaboration between the ENIGMA-ADHD and -ASD working groups seeks to bring the neuroimaging efforts of the two disorders closer together. The outcomes of case-control studies of subcortical and cortical structures showed that subcortical volumes are similarly affected in ASD and ADHD, albeit with small effect sizes. Cortical analyses identified unique differences in each disorder, but also considerable overlap between the two, specifically in cortical thickness. Ongoing work is examining alternative research questions, such as brain laterality, prediction of case-control status, and anatomical heterogeneity. In brief, great strides have been made toward fulfilling the aims of the ENIGMA collaborations, while new ideas and follow-up analyses continue that include more imaging modalities (diffusion MRI and resting-state functional MRI), collaborations with other large databases, and samples with dual diagnoses.

Published
2022

28. Vorwort

Author

Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), Steinhausen, H ( Hans-Christoph ), Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), and Steinhausen, H ( Hans-Christoph )

Published
2022

29. Die Fachstelle für Autismus

Author

Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), Steinhausen, H ( Hans-Christoph ), Gundelfinger, Ronnie, Seeger, Gudrun, Studer, Nadja, Jenny, Bettina, Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), Steinhausen, H ( Hans-Christoph ), Gundelfinger, Ronnie, Seeger, Gudrun, Studer, Nadja, and Jenny, Bettina

Published
2022

30. Das Zentrum für Jugendpsychiatrie

Author

Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), Steinhausen, H ( Hans-Christoph ), Prün, Hadmut, Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), Steinhausen, H ( Hans-Christoph ), and Prün, Hadmut

Published
2022

31. Computerbasierte Diagnostik und Therapie an der KJPP

Author

Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), Steinhausen, H ( Hans-Christoph ), Brezinka, Veronika; https://orcid.org/0000-0003-2192-3093, Franscini, Maurizia, Traber-Walker, Nina, Blumenthal, Yolanda, Brem, Silvia; https://orcid.org/0000-0002-8031-1305, Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), Steinhausen, H ( Hans-Christoph ), Brezinka, Veronika; https://orcid.org/0000-0003-2192-3093, Franscini, Maurizia, Traber-Walker, Nina, Blumenthal, Yolanda, and Brem, Silvia; https://orcid.org/0000-0002-8031-1305

Published
2022

32. Das Krisen-, Notfall-, Abklärungs- und Triagezentrum (KANT)

Author

Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), Steinhausen, H ( Hans-Christoph ), Berger, Gregor E; https://orcid.org/0000-0003-2030-141X, Garstick, Vesna, Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), Steinhausen, H ( Hans-Christoph ), Berger, Gregor E; https://orcid.org/0000-0003-2030-141X, and Garstick, Vesna

Published
2022

33. Die Entwicklung der Rolle der Psycholog:innen über die Jahrzehnte

Author

Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), Steinhausen, H ( Hans-Christoph ), Della Casa, André; https://orcid.org/0000-0002-2010-9359, Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), Steinhausen, H ( Hans-Christoph ), and Della Casa, André; https://orcid.org/0000-0002-2010-9359

Published
2022

34. Die Therapiekonzepte im Zentrum für Kinderpsychiatrie «Brüschhalde»

Author

Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), Steinhausen, H ( Hans-Christoph ), Mailänder, Veronika, Altenburg, Thomas, Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), Steinhausen, H ( Hans-Christoph ), Mailänder, Veronika, and Altenburg, Thomas

Published
2022

35. Bildgebende Forschung

Author

Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), Steinhausen, H ( Hans-Christoph ), Brandeis, Daniel, Brem, Silvia; https://orcid.org/0000-0002-8031-1305, Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), Steinhausen, H ( Hans-Christoph ), Brandeis, Daniel, and Brem, Silvia; https://orcid.org/0000-0002-8031-1305

Published
2022

36. Der schönste Beruf der Welt

Author

Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), Steinhausen, H ( Hans-Christoph ), Stokvis, Schmuel, Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), Steinhausen, H ( Hans-Christoph ), and Stokvis, Schmuel

Published
2022

37. Die Bedeutung der Klinikschule im interdisziplinären Kontext

Author

Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), Steinhausen, H ( Hans-Christoph ), Abeler, Kai, Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), Steinhausen, H ( Hans-Christoph ), and Abeler, Kai

Published
2022

38. Aufbau und Aktivitäten des molekulargenetischen translationalen Labor

Author

Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), Steinhausen, H ( Hans-Christoph ), Grünblatt, Edna; https://orcid.org/0000-0001-8505-7265, Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), Steinhausen, H ( Hans-Christoph ), and Grünblatt, Edna; https://orcid.org/0000-0001-8505-7265

Published
2022

39. Die Zürcher Kinder- und Jugendpsychiatrie 1919 - 2022

Author

Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), Steinhausen, H ( Hans-Christoph ), Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), and Steinhausen, H ( Hans-Christoph )

Published
2022

40. Die Entwicklung des klinischen Angebotes der KJPP Zürich

Author

Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), Steinhausen, H ( Hans-Christoph ), Pauli, Dagmar, Walitza, Susanne; https://orcid.org/0000-0002-8161-8683, Steinhausen, Hans-Christoph; https://orcid.org/0000-0002-6400-4436, Walitza, S ( Susanne ), Steinhausen, H ( Hans-Christoph ), and Pauli, Dagmar

Published
2022

41. European Multicentre Tics in Children Studies (EMTICS)

Author

Schrag, A, Martino, D, Apter, A, Ball, J, Bartolini, E, Benaroya-Milshtein, N, Buttiglione, M, Cardona, F, Creti, R, Efstratiou, A, Gariup, M, Georgitsi, M, Hedderly, T, Heyman, I, Margarit, I, Mir, P, Moll, N, Morer, A, Müller, N, Müller-Vahl, K, Münchau, A, Orefici, G, Plessen, Kj, Porcelli, C, Paschou, P, Rizzo, R, Roessner, V, Schwarz, Mj, Steinberg, T, Tagwerker Gloor, F, Tarnok, Z, Walitza, S, Dietrich, A, Hoekstra, Pj, Zacharias, Anastasiou, Isobel, Heyman, Chaim, Huyser, Marcos, Madruga, Pablo, Mir, Astrid, Morer, Nanette Mol Debes, Natalie, Moll, Norbert Mu ̈ller, Peter, Nagy, Kerstin Jessica Plessen, Cesare, Porcelli, Renata, Rizzo, Veit, Roessner, Jaana, Schnell, Liselotte, Skov, Zsanett, Tarnok, Susanne, Walitza, Andrea, Dietrich, Baglioni, Valentina, Juliane, Ball, Emese, Bognar, Bianka, Burger, Judith, Buse, Marta Correa Vela, Maria Cristina Ferro, Carolin, Fremer, Mariangela, Gulisano, Annelieke, Hagen, Julie, Hagstrøm, Anna, Marotta, Neri, Valeria, Thaïra J, C Openneer, Pellico, Alessandra, Kerstin, J Plessen, Daphna, Ruhrman, Jaana M, L Schnell, Silvestri, PAOLA ROSARIA, Tamar, Steinberg, Friederike Tagwerker Gloor, Elif, Weidinger, EMTICS Collaborative Group, Anastasiou, Z., Apter, A., Baglioni, V., Ball, J., Bartolini, E., Benaroya-Milshtein, N., Bodmer, B., Bognar, E., Burger, B., Buse, J., Buttiglione, M., Cardona, F., Correa Vela, M., Creti, R., Dietrich, A., Debes, N.M., Efstratiou, A., Ferro, M.C., Fremer, C., Garcia-Delgar, B., Gariup, M., Georgitsi, M., Gulisano, M., Hagen, A., Hagstrøm, J., Hedderly, T.J., Heyman, I., Hoekstra, P.J., Huyser, C., Imperi, M., Karagiannidis, I., Laviola, G., Macri, S., Madruga-Garrido, M., Margarit, I., Marotta, A., Martino, D., Meier, U.C., Mir, P., Moll, N., Morer, A., Müller, N., Müller-Vahl, K., Münchau, A., Nagy, P., Neri, V., Openneer, TJC, Orefici, G., Paschou, P., Pellico, A., Petruzzelli, O., Plessen, K.J., Porcelli, C., Redondo, M., Rizzo, R., Roazzi, P., Roessner, V., Ruhrman, D., Schnell, JML, Schrag, A., Schütze, G.A., Schwarz, M.J., Silvestri, P.R., Skov, L., Steinberg, T., Stöber, S., Gloor, F.T., Tallon, M., Tarnok, Z., Turner, V.L., Walitza, S., Weidinger, E., Woods, M.L., European Commission, National Institute for Health Research (UK), NIHR Biomedical Research Centre (UK), University College London, NHS Foundation Trust, GlaxoSmithKline, German Research Foundation, Instituto de Biomedicina de Sevilla (IBIS), and Clinical Cognitive Neuropsychiatry Research Program (CCNP)

Subjects
Male, Pediatrics, Tic disorder, BLOOD, Tourette syndrome, Obsessive–compulsive disorder, Cohort Studies, 0302 clinical medicine, Risk Factors, QUALITY-OF-LIFE, Obsessive-compulsive disorder, Developmental and Educational Psychology, Genetics, Longitudinal, Streptococcal infection, Stress, Prospective cohort study, Child, GENE-EXPRESSION, education.field_of_study, HAIR CORTISOL, 05 social sciences, A STREPTOCOCCAL INFECTIONS, Original Contribution, General Medicine, 3. Good health, Europe, Psychiatry and Mental health, LA-TOURETTE SYNDROME, Child, Preschool, NEUROPSYCHIATRIC DISORDERS, Cohort, Female, 050104 developmental & child psychology, Cohort study, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Tics, Adolescent, PSYCHOSOCIAL STRESS, Population, 03 medical and health sciences, mental disorders, medicine, Humans, 0501 psychology and cognitive sciences, Genetic Predisposition to Disease, education, Tic Disorders/complications, Tic Disorders/diagnosis, Tic Disorders/pathology, business.industry, OBSESSIVE-COMPULSIVE DISORDER, medicine.disease, 030227 psychiatry, nervous system diseases, body regions, PSYCHOMETRIC PROPERTIES, Tic Disorders, Pediatrics, Perinatology and Child Health, Chronic Tic Disorder, business, human activities
Abstract

EMTICS Collaborative Group., Genetic predisposition, autoimmunity and environmental factors [e.g. pre- and perinatal difficulties, Group A Streptococcal (GAS) and other infections, stress-inducing events] might interact to create a neurobiological vulnerability to the development of tics and associated behaviours. However, the existing evidence for this relies primarily on small prospective or larger retrospective population-based studies, and is therefore still inconclusive. This article describes the design and methodology of the EMTICS study, a longitudinal observational European multicentre study involving 16 clinical centres, with the following objectives: (1) to investigate the association of environmental factors (GAS exposure and psychosocial stress, primarily) with the onset and course of tics and/or obsessive–compulsive symptoms through the prospective observation of at-risk individuals (ONSET cohort: 260 children aged 3–10 years who are tic-free at study entry and have a first-degree relative with a chronic tic disorder) and affected individuals (COURSE cohort: 715 youth aged 3–16 years with a tic disorder); (2) to characterise the immune response to microbial antigens and the host’s immune response regulation in association with onset and exacerbations of tics; (3) to increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders; and (4) to develop prediction models for the risk of onset and exacerbations of tic disorders. The EMTICS study is, to our knowledge, the largest prospective cohort assessment of the contribution of different genetic and environmental factors to the risk of developing tics in putatively predisposed individuals and to the risk of exacerbating tics in young individuals with chronic tic disorders., This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under Grant agreement no. 278367. Schrag was supported by the National Institute for Health Research UCLH Biomedical Research Centre, and Müller, Burger, Schnell and Weidinger by Stiftung Immunität und Seele. This research was supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London (Heyman); partially sponsored by GSK Vaccines (Margarit, Bartolini); and Deutsche Forschungsgemeinschaft (DFG): projects 1692/3-1, 4-1 (Münchau).

Published
2019

44. White matter microstructure and its relation to clinical features of obsessive–compulsive disorder: findings from the ENIGMA OCD Working Group

Author

Piras F., Abe Y., Agarwal S. M., Anticevic A., Ameis S., Arnold P., Banaj N., Bargallo N., Batistuzzo M. C., Benedetti F., Beucke J. -C., Boedhoe P. S. W., Bollettini I., Brem S., Calvo A., Cho K. I. K., Ciullo V., Dallaspezia S., Dickie E., Ely B. A., Fan S., Fouche J. -P., Gruner P., Gursel D. A., Hauser T., Hirano Y., Hoexter M. Q., Iorio M., James A., Reddy Y. C. J., Kaufmann C., Koch K., Kochunov P., Kwon J. S., Lazaro L., Lochner C., Marsh R., Nakagawa A., Nakamae T., Narayanaswamy J. C., Sakai Y., Shimizu E., Simon D., Simpson H. B., Soreni N., Stampfli P., Stern E. R., Szeszko P., Takahashi J., Venkatasubramanian G., Wang Z., Yun J. -Y., Assogna F., Calvo R., Wit S. J., Hough M., Kuno M., Miguel E. C., Morer A., Pittenger C., Poletti S., Smeraldi E., Sato J. R., Tsuchiyagaito A., Walitza S., van der Werf Y. D., Vecchio D., Zarei M., Stein D. J., Jahanshad N., Thompson P. M., van den Heuvel O. A., Spalletta G., Piras, F., Abe, Y., Agarwal, S. M., Anticevic, A., Ameis, S., Arnold, P., Banaj, N., Bargallo, N., Batistuzzo, M. C., Benedetti, F., Beucke, J. -C., Boedhoe, P. S. W., Bollettini, I., Brem, S., Calvo, A., Cho, K. I. K., Ciullo, V., Dallaspezia, S., Dickie, E., Ely, B. A., Fan, S., Fouche, J. -P., Gruner, P., Gursel, D. A., Hauser, T., Hirano, Y., Hoexter, M. Q., Iorio, M., James, A., Reddy, Y. C. J., Kaufmann, C., Koch, K., Kochunov, P., Kwon, J. S., Lazaro, L., Lochner, C., Marsh, R., Nakagawa, A., Nakamae, T., Narayanaswamy, J. C., Sakai, Y., Shimizu, E., Simon, D., Simpson, H. B., Soreni, N., Stampfli, P., Stern, E. R., Szeszko, P., Takahashi, J., Venkatasubramanian, G., Wang, Z., Yun, J. -Y., Assogna, F., Calvo, R., Wit, S. J., Hough, M., Kuno, M., Miguel, E. C., Morer, A., Pittenger, C., Poletti, S., Smeraldi, E., Sato, J. R., Tsuchiyagaito, A., Walitza, S., van der Werf, Y. D., Vecchio, D., Zarei, M., Stein, D. J., Jahanshad, N., Thompson, P. M., van den Heuvel, O. A., Spalletta, G., Anatomy and neurosciences, Psychiatry, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, and Amsterdam Neuroscience - Neurodegeneration

Subjects
Adult, Obsessive-Compulsive Disorder, medicine.medical_specialty, Younger age, Cross-sectional study, Article, lcsh:RC321-571, White matter, neuroscience, Cellular and Molecular Neuroscience, Group differences, Obsessive compulsive, Internal medicine, Fractional anisotropy, medicine, Humans, 100 Philosophie und Psychologie::150 Psychologie::150 Psychologie, Child, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, business.industry, Brain, White Matter, White matter microstructure, obsessive-compulsive disorder, Psychiatry and Mental health, Cross-Sectional Studies, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging, medicine.anatomical_structure, psychiatric disorders, Anisotropy, business, Diffusion MRI
Abstract

Microstructural alterations in cortico-subcortical connections are thought to be present in obsessive–compulsive disorder (OCD). However, prior studies have yielded inconsistent findings, perhaps because small sample sizes provided insufficient power to detect subtle abnormalities. Here we investigated microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date. We analyzed diffusion tensor imaging metrics from 700 adult patients and 645 adult controls, as well as 174 pediatric patients and 144 pediatric controls across 19 sites participating in the ENIGMA OCD Working Group, in a cross-sectional case-control magnetic resonance study. We extracted measures of fractional anisotropy (FA) as main outcome, and mean diffusivity, radial diffusivity, and axial diffusivity as secondary outcomes for 25 white matter regions. We meta-analyzed patient-control group differences (Cohen’s d) across sites, after adjusting for age and sex, and investigated associations with clinical characteristics. Adult OCD patients showed significant FA reduction in the sagittal stratum (d = −0.21, z = −3.21, p = 0.001) and posterior thalamic radiation (d = −0.26, z = −4.57, p z = 2.71, p = 0.006), longer duration of illness (z = −2.086, p = 0.036), and a higher percentage of medicated patients in the cohorts studied (z = −1.98, p = 0.047). No significant association with symptom severity was found. Pediatric OCD patients did not show any detectable microstructural abnormalities compared to controls. Our findings of microstructural alterations in projection and association fibers to posterior brain regions in OCD are consistent with models emphasizing deficits in connectivity as an important feature of this disorder.

Published
2021

47. Exploring the genetic link between RLS and ADHD

Author

Schimmelmann, B.G., Friedel, S., Nguyen, T.T., Sauer, S., Vogel, C.I. Ganz, Konrad, K., Wilhelm, C., Sinzig, J., Renner, T.J., Romanos, M., Palmason, H., Dempfle, A., Walitza, S., Freitag, C., Meyer, J., Linder, M., Schäfer, H., Warnke, A., Lesch, K.P., Herpertz-Dahlman, B., Hinney, A., and Hebebrand, J.

Published
2009
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49. Genome-wide association study of obsessive-compulsive disorder

Author

Stewart, S E, Yu, D, Scharf, J M, Neale, B M, Fagerness, J A, Mathews, C A, Arnold, P D, Evans, P D, Gamazon, E R, Osiecki, L, McGrath, L, Haddad, S, Crane, J, Hezel, D, Illman, C, Mayerfeld, C, Konkashbaev, A, Liu, C, Pluzhnikov, A, Tikhomirov, A, Edlund, C K, Rauch, S L, Moessner, R, Falkai, P, Maier, W, Ruhrmann, S, Grabe, H-J, Lennertz, L, Wagner, M, Bellodi, L, Cavallini, M C, Richter, M A, Cook, Jr, E H, Kennedy, J L, Rosenberg, D, Stein, D J, Hemmings, S M J, Lochner, C, Azzam, A, Chavira, D A, Fournier, E, Garrido, H, Sheppard, B, Umaña, P, Murphy, D L, Wendland, J R, Veenstra-VanderWeele, J, Denys, D, Blom, R, Deforce, D, Van Nieuwerburgh, F, Westenberg, H G M, Walitza, S, Egberts, K, Renner, T, Miguel, E C, Cappi, C, Hounie, A G, Conceição do Rosário, M, Sampaio, A S, Vallada, H, Nicolini, H, Lanzagorta, N, Camarena, B, Delorme, R, Leboyer, M, Pato, C N, Pato, M T, Voyiaziakis, E, Heutink, P, Cath, D C, Posthuma, D, Smit, J H, Samuels, J, Bienvenu, O J, Cullen, B, Fyer, A J, Grados, M A, Greenberg, B D, McCracken, J T, Riddle, M A, Wang, Y, Coric, V, Leckman, J F, Bloch, M, Pittenger, C, Eapen, V, Black, D W, Ophoff, R A, Strengman, E, Cusi, D, Turiel, M, Frau, F, Macciardi, F, Gibbs, J R, Cookson, M R, Singleton, A, Hardy, J, Crenshaw, A T, Parkin, M A, Mirel, D B, Conti, D V, Purcell, S, Nestadt, G, Hanna, G L, Jenike, M A, Knowles, J A, Cox, N, and Pauls, D L

Published
2013
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50. Genome-wide association study of pediatric obsessive-compulsive traits: shared genetic risk between traits and disorder

Author

Burton, CL, Lemire, M, Xiao, B, Corfield, EC, Erdman, L, Bralten, J, Poelmans, G, Yu, D, Shaheen, SM, Goodale, T, Sinopoli, VM, Askland, KD, Barlassina, C, Bienvenu, OJ, Black, D, Bloch, M, Brentani, H, Camarena, B, Cappi, C, Cath, D, Cavallini, MC, Ciullo, V, Conti, D, Cook, EH, Coric, V, Cullen, BA, Cusi, D, Davis, LK, Delorme, R, Denys, D, Derks, E, Eapen, V, Edlund, C, Falkai, P, Fyer, AJ, Geller, DA, Goes, FS, Grabe, HJ, Grados, MA, Greenberg, BD, Grünblatt, E, Guo, W, Hounie, AG, Jenike, M, Keenan, CL, Kennedy, JL, Khramtsova, EA, Knowles, JA, Krasnow, J, Lange, C, Lanzagorta, N, Leboyer, M, Liang, KY, Lochner, C, Macciardi, F, Maher, B, Mathews, CA, Mattheisen, M, McCracken, JT, McGregor, N, McLaughlin, NCR, Miguel, EC, Neale, B, Nestadt, G, Nestadt, PS, Nicolini, H, Nurmi, EL, Osiecki, L, Piacentini, J, Pittenger, C, Posthuma, D, Pulver, AE, Rasmussen, SA, Rauch, S, Richter, MA, Riddle, MA, Ripke, S, Ruhrmann, S, Sampaio, AS, Samuels, JF, Scharf, JM, Shugart, YY, Smit, JH, Stein, DJ, Stewart, SE, Turiel, M, Vallada, H, Veenstra-VanderWeele, J, Vulink, N, Wagner, M, Walitza, S, Wang, Y, Wendland, J, Zai, G, Soreni, N, Hanna, GL, Fitzgerald, KD, Rosenberg, D, Paterson, AD, Burton, CL, Lemire, M, Xiao, B, Corfield, EC, Erdman, L, Bralten, J, Poelmans, G, Yu, D, Shaheen, SM, Goodale, T, Sinopoli, VM, Askland, KD, Barlassina, C, Bienvenu, OJ, Black, D, Bloch, M, Brentani, H, Camarena, B, Cappi, C, Cath, D, Cavallini, MC, Ciullo, V, Conti, D, Cook, EH, Coric, V, Cullen, BA, Cusi, D, Davis, LK, Delorme, R, Denys, D, Derks, E, Eapen, V, Edlund, C, Falkai, P, Fyer, AJ, Geller, DA, Goes, FS, Grabe, HJ, Grados, MA, Greenberg, BD, Grünblatt, E, Guo, W, Hounie, AG, Jenike, M, Keenan, CL, Kennedy, JL, Khramtsova, EA, Knowles, JA, Krasnow, J, Lange, C, Lanzagorta, N, Leboyer, M, Liang, KY, Lochner, C, Macciardi, F, Maher, B, Mathews, CA, Mattheisen, M, McCracken, JT, McGregor, N, McLaughlin, NCR, Miguel, EC, Neale, B, Nestadt, G, Nestadt, PS, Nicolini, H, Nurmi, EL, Osiecki, L, Piacentini, J, Pittenger, C, Posthuma, D, Pulver, AE, Rasmussen, SA, Rauch, S, Richter, MA, Riddle, MA, Ripke, S, Ruhrmann, S, Sampaio, AS, Samuels, JF, Scharf, JM, Shugart, YY, Smit, JH, Stein, DJ, Stewart, SE, Turiel, M, Vallada, H, Veenstra-VanderWeele, J, Vulink, N, Wagner, M, Walitza, S, Wang, Y, Wendland, J, Zai, G, Soreni, N, Hanna, GL, Fitzgerald, KD, Rosenberg, D, and Paterson, AD

Abstract

Using a novel trait-based measure, we examined genetic variants associated with obsessive-compulsive (OC) traits and tested whether OC traits and obsessive-compulsive disorder (OCD) shared genetic risk. We conducted a genome-wide association analysis (GWAS) of OC traits using the Toronto Obsessive-Compulsive Scale (TOCS) in 5018 unrelated Caucasian children and adolescents from the community (Spit for Science sample). We tested the hypothesis that genetic variants associated with OC traits from the community would be associated with clinical OCD using a meta-analysis of all currently available OCD cases. Shared genetic risk was examined between OC traits and OCD in the respective samples using polygenic risk score and genetic correlation analyses. A locus tagged by rs7856850 in an intron of PTPRD (protein tyrosine phosphatase δ) was significantly associated with OC traits at the genome-wide significance level (p = 2.48 × 10−8). rs7856850 was also associated with OCD in a meta-analysis of OCD case/control genome-wide datasets (p = 0.0069). The direction of effect was the same as in the community sample. Polygenic risk scores from OC traits were significantly associated with OCD in case/control datasets and vice versa (p’s < 0.01). OC traits were highly, but not significantly, genetically correlated with OCD (rg = 0.71, p = 0.062). We report the first validated genome-wide significant variant for OC traits in PTPRD, downstream of the most significant locus in a previous OCD GWAS. OC traits measured in the community sample shared genetic risk with OCD case/control status. Our results demonstrate the feasibility and power of using trait-based approaches in community samples for genetic discovery.

Published
2021

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