A Common CDH13 Variant is Associated with Low Agreeableness and Neural Responses to Working Memory Tasks in ADHD

Please always quote using this URN: urn:nbn:de:bvb:20-opus-245220
  • The cell—cell signaling gene CDH13 is associated with a wide spectrum of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), autism, and major depression. CDH13 regulates axonal outgrowth and synapse formation, substantiating its relevance for neurodevelopmental processes. Several studies support the influence of CDH13 on personality traits, behavior, and executive functions. However, evidence for functional effects of common gene variation in the CDH13 gene in humans is sparse. Therefore, we tested forThe cell—cell signaling gene CDH13 is associated with a wide spectrum of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), autism, and major depression. CDH13 regulates axonal outgrowth and synapse formation, substantiating its relevance for neurodevelopmental processes. Several studies support the influence of CDH13 on personality traits, behavior, and executive functions. However, evidence for functional effects of common gene variation in the CDH13 gene in humans is sparse. Therefore, we tested for association of a functional intronic CDH13 SNP rs2199430 with ADHD in a sample of 998 adult patients and 884 healthy controls. The Big Five personality traits were assessed by the NEO-PI-R questionnaire. Assuming that altered neural correlates of working memory and cognitive response inhibition show genotype-dependent alterations, task performance and electroencephalographic event-related potentials were measured by n-back and continuous performance (Go/NoGo) tasks. The rs2199430 genotype was not associated with adult ADHD on the categorical diagnosis level. However, rs2199430 was significantly associated with agreeableness, with minor G allele homozygotes scoring lower than A allele carriers. Whereas task performance was not affected by genotype, a significant heterosis effect limited to the ADHD group was identified for the n-back task. Heterozygotes (AG) exhibited significantly higher N200 amplitudes during both the 1-back and 2-back condition in the central electrode position Cz. Consequently, the common genetic variation of CDH13 is associated with personality traits and impacts neural processing during working memory tasks. Thus, CDH13 might contribute to symptomatic core dysfunctions of social and cognitive impairment in ADHD.show moreshow less

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Author: Georg C. Ziegler, Ann-Christine Ehlis, Heike Weber, Maria Rosaria Vitale, Johanna E. M. Zöller, Hsing-Ping Ku, Miriam A. Schiele, Laura I. Kürbitz, Marcel Romanos, Paul Pauli, Raffael Kalisch, Peter Zwanzger, Katharina Domschke, Andreas J. Fallgatter, Andreas Reif, Klaus-Peter Lesch
URN:urn:nbn:de:bvb:20-opus-245220
Document Type:Journal article
Faculties:Medizinische Fakultät / Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie
Medizinische Fakultät / Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Medizinische Fakultät / Abteilung für Molekulare Innere Medizin (in der Medizinischen Klinik und Poliklinik II)
Fakultät für Humanwissenschaften (Philos., Psycho., Erziehungs- u. Gesell.-Wissensch.) / Institut für Psychologie
Language:English
Parent Title (English):Genes
ISSN:2073-4425
Year of Completion:2021
Volume:12
Issue:9
Article Number:1356
Source:Genes 2021, 12(9), 1356; https://doi.org/10.3390/genes12091356
DOI:https://doi.org/10.3390/genes12091356
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:ADHD; Big Five; CDH13; agreeableness; executive functions; neurodevelopment; working memory
Release Date:2022/01/11
Date of first Publication:2021/08/29
EU-Project number / Contract (GA) number:01EW1902
EU-Project number / Contract (GA) number:728018
OpenAIRE:OpenAIRE
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International