A common CDH13 variant is associated with low agreeableness and neural responses to working memory tasks in ADHD

  • 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 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.

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Author:Georg Christoph ZieglerORCiDGND, Ann-Christine EhlisORCiDGND, Heike WeberORCiDGND, Maria Rosaria VitaleORCiD, Johanna E. M. Zöller, Hsing-Ping Ku, Miriam A. Schiele, Laura I. Kürbitz, Marcel RomanosORCiDGND, Paul Pauli, Raffael Kalisch, Peter M. Zwanzger, Katharina Domschke, Andreas J. FallgatterORCiD, Andreas ReifORCiDGND, Klaus-Peter J. LeschORCiDGND
Parent Title (English):Genes
Place of publication:Basel
Document Type:Article
Date of Publication (online):2021/08/29
Date of first Publication:2021/08/29
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/05/09
Tag:ADHD; Big Five; CDH13; agreeableness; executive functions; neurodevelopment; working memory
Issue:9, art. 1356
Page Number:14
First Page:1
Last Page:14
This research was funded by the ERA-NET NEURON under Grant No. 01EW1902 (DECODE!), the Horizon 2020 Research and Innovation Programme under Grant No. 728018 (Eat2beNICE), the 5-100 Russian Academic Excellence Project, and the University of Würzburg in the funding program Open Access Publishing. G.C.Z is supported by a grant from the DFG (Project No. 413657723; Clinician Scientist-Program UNION CVD). This publication was supported by the Open Access Publication Fund of the University of Würzburg.
Dewey Decimal Classification:1 Philosophie und Psychologie / 15 Psychologie / 150 Psychologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0