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Biology of Perseverative Negative Thinking: The Role of Timing and Folate Intake.

Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University, Nagyvárad tér 4, H-1089 Budapest, Hungary. NAP-2-SE New Antidepressant Target Research Group, Hungarian Brain Research Program, Semmelweis University, Nagyvárad tér 4, H-1089 Budapest, Hungary. Department of Measurement and Information Systems, Budapest University of Technology and Economics, Magyar Tudósok krt. 2, H-1521 Budapest, Hungary. MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian Academy of Sciences, Semmelweis University, Nagyvárad tér 4, H-1089 Budapest, Hungary. Bioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan. Department of Psychiatry and Psychotherapy, Semmelweis University, Gyulai Pál utca 2, H-1085 Budapest, Hungary. Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Memory Lane, London SE5 8AF, UK. UK National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre (BRC), London SE5 8AF, UK. Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health, The University of Manchester, Oxford Road, Manchester M13 9PL, UK. SE-NAP 2 Genetic Brain Imaging Migraine Research Group, Hungarian Brain Research Program, Semmelweis University, Nagyvárad tér 4, H-1089 Budapest, Hungary.

Nutrients. 2021;(12)
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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.