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.
Highlights
Anxiety disorders (AD) represent the most prevalent mental disorders [1] and are typically characterized by an early onset in childhood [2]
The present study investigated the impact of four genetic risk variants, recently identified as associated with pathological anxiety in adults in a meta-analysis of genome-wide association studies of anxiety disorders (AD) [23], on fearand anxiety-relevant personality traits in a large sample of typically developing children aged 8 to 12 years
Assuming that common variants play a crucial role in AD susceptibility, we analyzed those risk variants with genome-wide significance [23] in healthy children with respect to generalization gradients according to subjective and objective measures of arousal, since overgeneralization and heightened arousal are assumed risk factors in the pathogenesis of AD [12, 14, 15, 36]
Summary
Anxiety disorders (AD) represent the most prevalent mental disorders [1] and are typically characterized by an early onset in childhood [2]. Since pathological anxiety has long-term negative consequences for child development [5], advancing our understanding of the pathogenic, as well as risk factors and mechanisms of AD, has substantial societal impact by defining concrete points of intervention, and improving treatment efficiency, as well as in aiding preventative and treatment efforts. There are different diagnostic definitions relative to their clinical presentation, AD as a group is believed to have a common underlying diathesis relating to an abnormal threat-response regulation [6]. Unlike categorical definitions, which could be afflicted, e.g., with threshold problems, AD can be considered on a dimensional continuum with respect to symptom intensity,
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