KCNJ6 variants modulate reward‐related brain processes and impact executive functions in attention‐deficit/hyperactivity disorder
Autor: | Christoph Röser, Georg C. Ziegler, Marcel Romanos, Susanne Walitza, Andreas J. Fallgatter, Christian Jacob, Astrid Dempfle, Klaus-Peter Lesch, Ann-Christine Ehlis, Andreas Reif, Tim Hahn, Tobias J. Renner, Heike Weber |
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Přispěvatelé: | University of Zurich, Ziegler, Georg C, Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience |
Rok vydání: | 2019 |
Předmět: |
Male
0301 basic medicine Brain activity and meditation Dopamine 2804 Cellular and Molecular Neuroscience HYPERACTIVITY 030105 genetics & heredity Electroencephalography RESPONSE CONTROL 2738 Psychiatry and Mental Health Executive Function VENTRAL STRIATUM ANTICIPATION Genetics (clinical) Brain Mapping SUBSTANTIA-NIGRA medicine.diagnostic_test Dopaminergic Brain ASSOCIATION 10058 Department of Child and Adolescent Psychiatry executive functions Executive functions Magnetic Resonance Imaging Anticipation Psychiatry and Mental health Phenotype Female Adult 2716 Genetics (clinical) 610 Medicine & health Biology Polymorphism Single Nucleotide Young Adult 03 medical and health sciences Cellular and Molecular Neuroscience Reward KCNJ6 medicine ADHD Humans Attention deficit hyperactivity disorder Family Health THETA OSCILLATIONS RECTIFYING K+ CHANNELS DOPAMINERGIC-NEURONS medicine.disease GENE 030104 developmental biology G Protein-Coupled Inwardly-Rectifying Potassium Channels Haplotypes Reward dependence Attention Deficit Disorder with Hyperactivity Mutagenesis Case-Control Studies 5' Untranslated Regions Functional magnetic resonance imaging Neuroscience |
Zdroj: | American Journal of Medical Genetics Part B-neuropsychiatric Genetics, 183(5), 247-257. Wiley |
ISSN: | 1552-485X 1552-4841 |
Popis: | KCNJ6, encoding a potassium channel subunit, regulates the excitability of dopaminergic neurons and is expressed in attention-deficit/hyperactivity disorder (ADHD)-relevant brain regions. As a potential ADHD risk gene, KCNJ6, therefore, may contribute to the endophenotypic variation of the disorder. The impact of two SNPs, rs7275707 and rs6517442, both located in the transcriptional control region of KCNJ6, on reporter gene expression was explored in cultured cells. The KCNJ6 variants were then tested for association with ADHD and personality traits in a family-based sample (165 affected children) and an adult case-control sample (450 patients, 426 controls). Furthermore, the genotypic influence on performance in an n-back task and a cued continuous performance test (cCPT) was investigated by electroencephalography recordings. Finally, rs6517442 function was assessed by a reward anticipation paradigm using functional magnetic resonance imaging. Different haplotypes of rs7275707 and rs6517442 significantly influenced KCNJ6 gene expression proving their functional relevance on the molecular level. In the family-based children sample rs7275707 was associated with ADHD (p = .038). Moreover, rs7275707 showed association with the personality trait of Reward Dependence (p = .031). In the ADHD group, both rs7275707 and rs6517442 influenced the Go-centroid location in the cCPT and the N200 amplitude in the n-back task. Furthermore, ventral striatal activation was impacted by rs6517442 during reward anticipation. Our data indicate that functional variants of KCNJ6 influence brain activity during reward-related and executive processes supporting the view of a differential, age-dependent modulatory impact of dopamine-related brain processes in ADHD risk. |
Databáze: | OpenAIRE |
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