Abstract
Past-oriented rumination and future-oriented worry are two aspects of perseverative negative thinking related to the neuroticism endophenotype and associated with depression and anxiety. Our present aim was to investigate the genomic background of these two aspects of perseverative negative thinking within separate groups of individuals with suboptimal versus optimal folate intake. We conducted a genome-wide association study in the UK Biobank database (n = 72,621) on the “rumination” and “worry” items of the Eysenck Personality Inventory Neuroticism scale in these separate groups. Optimal folate intake was related to lower worry, but unrelated to rumination. In contrast, genetic associations for worry did not implicate specific biological processes, while past-oriented rumination had a more specific genetic background, emphasizing its endophenotypic nature. Furthermore, biological pathways leading to rumination appeared to differ according to folate intake: purinergic signaling and circadian regulator gene ARNTL emerged in the whole sample, blastocyst development, DNA replication, and C-C chemokines in the suboptimal folate group, and prostaglandin response and K+ channel subunit gene KCNH3 in the optimal folate group. Our results point to possible benefits of folate in anxiety disorders, and to the importance of simultaneously taking into account genetic and environmental factors to determine personalized intervention in polygenic and multifactorial disorders.
Highlights
Neuroticism is a personality trait manifested as a tendency to experience negative, distressing emotions and cognitions [1,2]
Our study demonstrated that the past-focused rumination component of perseverative negative thinking has a more specific genetic background compared to general worry, which seems more heterogeneous
[55,56], may exert their effects on rumination through divergent biological pathw compensated by sufficientreceptors, folate intake, our results suggested that developmental receptors, implicated in our results and in animal studies of persev implicated inreceptors, our results and in animal of perseve implicated in our studies results and in ani Purinergic effects on eachof ofthese these narrower pathways pathways are hypothes timing is crucial in folate’s compensatory impact ineffects case biological and
Summary
Neuroticism is a personality trait manifested as a tendency to experience negative, distressing emotions and cognitions [1,2]. The association of neuroticism with depression or anxiety symptoms has been demonstrated to be either fully or partially mediated by rumination, worry, or both [2,3,4,5]. Rumination and worry represent two types of repetitive thought or perseverative cognition. They are negatively valenced, attentive and frequent thoughts about oneself and one’s world which dysfunctionally prolong mental representations of a stressor [6,7,8]. While rumination is considered a past-oriented form of repetitive thought concerning themes of loss and worry is future-oriented negative thinking [7], they share a common latent factor in their variance which predicts future depression and anxiety levels in case of stress [9].
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