Anxiety risk SNPs on chromosome 2 modulate arousal in children in a fear generalization paradigm
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ORIGINAL CONTRIBUTION
Anxiety risk SNPs on chromosome 2 modulate arousal in children in a fear generalization paradigm Julia Reinhard1 · Carsten Drepper1 · Heike Weber2,3 · Miriam A. Schiele4 · Katharina Kneer1 · Anna Mittermeier1 · Lillien Frey1 · Andreas Reif3 · Paul Pauli5 · Katharina Domschke4 · Jürgen Deckert2 · Marcel Romanos1 Received: 22 September 2019 / Accepted: 11 December 2019 © The Author(s) 2019
Abstract Alterations in fear learning/generalization are considered to be relevant mechanisms engendering the development of anxiety disorders being the most prevalent mental disorders. Although anxiety disorders almost exclusively have their first onset in childhood and adolescence, etiological research focuses on adult individuals. In this study, we evaluated findings of a recent meta-analysis of genome-wide association studies in adult anxiety disorders with significant associations of four single nucleotide polymorphisms (SNPs) in a large cohort of 347 healthy children (8–12 years) characterized for dimensional anxiety. We investigated the modulation of anxiety parameters by these SNPs in a discriminative fear conditioning and generalization paradigm in the to-date largest sample of children. Results extended findings of the meta-analysis showing a genomic locus on 2p21 to modulate anxious personality traits and arousal ratings. These SNPs might, thus, serve as susceptibility markers for a shared risk across pathological anxiety, presumably mediated by alterations in arousal. Keywords Anxiety disorders · Childhood and adolescence · Anxious personality traits · Fear conditioning and generalization · Arousal · Anxiety risk genes
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00787-019-01458-7) contains supplementary material, which is available to authorized users. * Julia Reinhard [email protected] 1
Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany
2
Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany
3
Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital of Frankfurt, Frankfurt, Germany
4
Department of Psychiatry and Psychotherapy, Medical Center, Faculty of Medicine, University of Freiburg, University of Freiburg, Freiburg, Germany
5
Department of Psychology (Biological Psychology, Clinical Psychology and Psychotherapy), University of Würzburg, Würzburg, Germany
Anxiety disorders (AD) represent the most prevalent mental disorders [1] and are typically characterized by an early onset in childhood [2]. AD often persist from childhood into adulthood [3] and are the precursor to a range of other psychiatric disorders, e.g., depression [4]. Since pathological anxiety has long-term negative consequences for child development [5], advancing our understanding of the pathogenic, as well as risk fa
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