<span class="fett">Fragestellung:</span> Welche genetischen Faktoren sind relevant für die putative Komorbiditätsbeziehung zwischen Alkoholmissbrauch, -abhängigkeit und adulten Aufmerksamkeitsdefizit-/Hyperaktivitätssyndromen? </p><p> <span class="fett">Methodik:</span> Aktuelle Studien werden unter besonderer Berücksichtigung von Meta-Analysen dargestellt und bewertet. </p><p> <span class="fett">Ergebnisse:</span> Die Gene für Serotonintransporter und Dopamin-D4-Rezeptor sind als potenzielle Kandidaten zu diskutieren. Die Datenlage ist insgesamt jedoch inkonsistent, da die Geneffekte gering bis moderat sind und kategoriale Modelle sich nicht für komplexe Störungen eignen, die entsprechend dem »Quantitative Trait Loci«-Konzept vererbt werden. </p><p> <span class="fett">Schlussfolgerungen:</span> Weitere Studien unter der Einbeziehung von dimensionalen Modellen oder Endophänotypen sind notwendig.
AbstractGenetic variability is being discussed as a source of inter‐individual differences in Theory of Mind development. Previous studies documented an association between variations in DRD4 VNTR 48 bp, OXTR rs53576, COMT rs4680, and Theory of Mind task performance. As empirical evidence on these associations is sparse, we conducted a preregistered replication attempt of a study reporting a link between DRD4 VNTR 48 bp and false belief understanding in 50‐month‐old children [Lackner, C., Sabbagh, M. A., Hallinan, E., Liu, X., & Holden, J. J. (2012). Developmental Science, 15(2), 272–280.]. Additionally, we attempted a replication of studies on the role of OXTR rs53576 and COMT rs4680 in Theory of Mind. In both replication attempts, we did not find any evidence for associations between the sampled genetic markers and Theory of Mind ability in a series of analyses. Extending the replication attempt of Lackner et al., we employed longitudinal data from several tasks and measurement points, which allowed us to run follow‐up robustness checks with more reliable scores. These extensive analyses corroborated our null finding. This comprehensive non‐replication is important to balance current research on genetic markers of Theory of Mind. In a combined evaluation of our own and previous studies, we point to substantial methodological issues that research on the genetic basis of Theory of Mind development faces. We conclude that these limitations currently prevent firm conclusions on genetic influences on Theory of Mind development.
Attention-deficit hyperactivity disorder (ADHD) is a complex neurodevelopmental disorder characterized by hyperactivity, impulsivity, and/or inattention, which are symptoms also observed in many rare genetic disorders. We searched for genes involved in Mendelian disorders presenting with ADHD symptoms in the Online Mendelian Inheritance in Man (OMIM) database, to curate a list of new candidate risk genes for ADHD. We explored the enrichment of functions and pathways in this gene list, and tested whether rare or common variants in these genes are associated with ADHD or with its comorbidities. We identified 139 genes, causal for 137 rare disorders, mainly related to neurodevelopmental and brain function. Most of these Mendelian disorders also present with other psychiatric traits that are often comorbid with ADHD. Using whole exome sequencing (WES) data from 668 ADHD cases, we found rare variants associated with the dimension of the severity of inattention symptoms in three genes: KIF11, WAC, and CRBN. Then, we focused on common variants and identified six genes associated with ADHD (in 19,099 cases and 34,194 controls): MANBA, UQCC2, HIVEP2, FOPX1, KANSL1, and AUH. Furthermore, HIVEP2, FOXP1, and KANSL1 were nominally associated with autism spectrum disorder (ASD) (18,382 cases and 27,969 controls), as well as HIVEP2 with anxiety (7016 cases and 14,475 controls), and FOXP1 with aggression (18,988 individuals), which is in line with the symptomatology of the rare disorders they are responsible for. In conclusion, inspecting Mendelian disorders and the genes responsible for them constitutes a valuable approach for identifying new risk genes and the mechanisms of complex disorders. ; This work was supported mainly by funding from the European Union H2020 Program [H2020/2014–2020, grant agreements n° 667302, 643051 and 728018, corresponding to projects CoCA, coca-project.eu/; Eat2BeNice: newbrainnutrition.com/ (accessed on 16 December 2021); and MiND; www.mind-project.eu (accessed on 16 December 2021), respectively], and from the 'ECNP network on ADHD across the lifespan'. NC-F received funding from 'Plan Nacional Sobre Drogas of the Spanish Ministry of Health' [PNSD-2020I042] and was supported by a contract of the 'Centro de Investigación Biomédica en Red de Enfermedades Raras' (CIBERER). BC received funding from the Spanish 'Ministerio de Economía y Competitividad' [SAF2015-68341-R, RTI2018-100968-B-100 and PID2021-1277760B-I100], 'Plan Nacional sobre Drogas of the Spanish Ministry of Health' [PNSD-2017I050] and AGAUR, 'Generalitat de Catalunya' [2017-SGR-738]. JC-D and BT were supported by the H2020 CoCA (n° 667302) and Eat2beNICE (n° 728018) projects. DBK was supported by the European Union H2020 Program [H2020/2014-2020] under grant agreements n° 643051 (MiND) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq-148273/2016-5). OL acknowledges the support from Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa, CERCA Program/Generalitat de Catalunya, Spanish Ministry of Science and Innovation through the Instituto de Salud Carlos III, Generalitat de Catalunya through Departament de Salut and Departament d'Empresa i Coneixement, Co-financing with funds from the European Regional Development Fund by the Spanish Ministry of Science and Innovation corresponding to the Programa Operativo FEDER Plurirregional de España (POPE) 2014–2020 and by the Secretaria d'Universitats i Recerca, Departament d'Empresa i Coneixement of the Generalitat de Catalunya corresponding to the Programa Operatiu FEDER de Catalunya 2014–2020, Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness)—RYC-2013-14797, BFU2015-68759-P and PGC2018-098574-B-I00 and Generalitat de Catalunya (Government of Catalonia)—GRC 2017 SGR 937.
Altres ajuts: This work was partly carried out on the Dutch national e-infrastructure with the support of the SURF Foundation. Barbara Franke and her team are supported by funding from a personal Vici grant of the Netherlands Organisation for Scientific Research (NWO; grant 016-130-669, to BF), [.]. In addition, this work was supported by the European College of Neuropsychopharmacology (ECNP Network "ADHD across the Lifespan"). Klaus-Peter Lesch and his team are supported by the Deutsche Forschungsgemeinschaft (DFG: CRU 125, CRC TRR 58 A1/A5), [.], Fritz Thyssen Foundation (No. 10.13.1185), ERA-Net NEURON/RESPOND, No. 01EW1602B, and 5-100 Russian Academic Excellence Project. [.]. The NBS exome chip data were generated in a research project that was financially supported by BBMRI-NL, a Research Infrastructure financed by the Dutch government (NWO 184.021.007). The Heinz Nixdorf Recall (HNR) study is supported by the Heinz Nixdorf Foundation (Germany). Additionally, the study is funded by the German Ministry of Education and Science and the German Research Council (DFG; Project SI 236/8-1, SI236/9-1, ER 155/6-1). [.]. MR is a recipient of [.] and a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation. Jan Haavik and his team are supported by the K.G. Jebsen Foundation for Medical Research, University of Bergen, the Western Norwegian Health Authorities (Helse Vest). [.]. SC is supported by the German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders) under the auspices of the e:Med Program (grant 01ZX1314A). He also receives support by the Swiss National Science Foundation (project no. 310030_156791). This publication was funded by the German Research Foundation (DFG) and the University of Wuerzburg in the funding programme Open Access Publishing. ; Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with a complex genetic background, ...
The results leading to this publication have received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777394 for the project AIMS-2-TRIALS. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA and AUTISM SPEAKS, Autistica, SFARI. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Any views expressed are those of the author(s) and not necessarily those of the funders.
The results leading to this publication have received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777394 for the project AIMS-2-TRIALS. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA and AUTISM SPEAKS, Autistica, SFARI. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Any views expressed are those of the author(s) and not necessarily those of the funders.
Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3–96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders. ; The author list between I.A. and M.Z. is in alphabetic order. The authors were funded by the Research Council of Norway (276082 LifespanHealth (T.K.), 213837 (O.A.A), 223273 NORMENT (O.A.A.), 204966 (L.T.W.), 229129 (O.A.A.), 249795 (L.T.W.), 273345 (L.T.W.) and 283798 SYNSCHIZ (O.A.A.)), the South-Eastern Norway Regional Health Authority (2013-123 (O.A.A.), 2014-097 (L.T.W.), 2015-073 (L.T.W.) and 2016083 (L.T.W.)), Stiftelsen Kristian Gerhard Jebsen (SKGJ-MED-008), the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (ERC Starting Grant, Grant agreement No. 802998 BRAINMINT (L.T.W.)), NVIDIA Corporation GPU Grant (T.K.), and the European Commission 7th Framework Programme (602450, IMAGEMEND (A.M.-L.)). ; acceptedVersion
