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

Autor: Ziegler GC; Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University of Würzburg, 97080 Würzburg, Germany.; Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, 97080 Würzburg, Germany., Ehlis AC; Department of Psychiatry and Psychotherapy, Tübingen Center for Mental Health (TüCMH), University of Tübingen, 72076 Tübingen, Germany., Weber H; Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University of Würzburg, 97080 Würzburg, Germany., Vitale MR; Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, 97080 Würzburg, Germany.; Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine, Sechenov First Moscow State Medical University, 119991 Moscow, Russia., Zöller JEM; Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, 97080 Würzburg, Germany., Ku HP; Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, 97080 Würzburg, Germany., Schiele MA; Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany., Kürbitz LI; Center of Psychosocial Medicine, Institute for Sex Research, Sexual Medicine and Forensic Psychiatry, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Romanos M; Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, 97080 Würzburg, Germany., Pauli P; Department of Psychology I, University of Würzburg, 97070 Würzburg, Germany., Kalisch R; Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), Johannes Gutenberg University Medical Center, 55131 Mainz, Germany.; Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Zwanzger P; kbo-Inn-Salzach-Klinikum, 83512 Wasserburg am Inn, Germany.; Department of Psychiatry, Ludwig-Maximilian-University of Munich, 80336 Munich, Germany., Domschke K; Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany., Fallgatter AJ; Department of Psychiatry and Psychotherapy, Tübingen Center for Mental Health (TüCMH), University of Tübingen, 72076 Tübingen, Germany., Reif A; Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, 60528 Frankfurt am Main, Germany., Lesch KP; Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, 97080 Würzburg, Germany.; Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine, Sechenov First Moscow State Medical University, 119991 Moscow, Russia.; Department of Translational Neuroscience, School for Mental Health and Neuroscience (MHeNS), Maastricht University, 6229 ER Maastricht, The Netherlands.
Jazyk: angličtina
Zdroj: Genes [Genes (Basel)] 2021 Aug 29; Vol. 12 (9). Date of Electronic Publication: 2021 Aug 29.
DOI: 10.3390/genes12091356
Abstrakt: 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.
Databáze: MEDLINE