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
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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