Circadian Clock Model Supports Molecular Link Between PER3 and Human Anxiety
Open Access
- 31 August 2017
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 7 (1), 1-10
- https://doi.org/10.1038/s41598-017-07957-4
Abstract
Generalized anxiety and major depression have become increasingly common in the United States, affecting 18.6 percent of the adult population. Mood disorders can be debilitating, and are often correlated with poor general health, life dissatisfaction, and the need for disability benefits due to inability to work. Recent evidence suggests that some mood disorders have a circadian component, and disruptions in circadian rhythms may even trigger the development of these disorders. However, the molecular mechanisms of this interaction are not well understood. Polymorphisms in a circadian clock-related gene, PER3, are associated with behavioral phenotypes (extreme diurnal preference in arousal and activity) and sleep/mood disorders, including seasonal affective disorder (SAD). Here we show that two PER3 mutations, a variable number tandem repeat (VNTR) allele and a single-nucleotide polymorphism (SNP), are associated with diurnal preference and higher Trait-Anxiety scores, supporting a role for PER3 in mood modulation. In addition, we explore a potential mechanism for how PER3 influences mood by utilizing a comprehensive circadian clock model that accurately predicts the changes in circadian period evident in knock-out phenotypes and individuals with PER3-related clock disorders.This publication has 77 references indexed in Scilit:
- A mechanism for robust circadian timekeeping via stoichiometric balanceMolecular Systems Biology, 2012
- Cryptochromes mediate rhythmic repression of the glucocorticoid receptorNature, 2011
- Forebrain overexpression of CK1δ leads to down-regulation of dopamine receptors and altered locomotor activity reminiscent of ADHDProceedings of the National Academy of Sciences of the United States of America, 2010
- Deciphering a transcriptional regulatory code: modeling short‐range repression in the Drosophila embryoMolecular Systems Biology, 2010
- Differential Association of Circadian Genes with Mood Disorders: CRY1 and NPAS2 are Associated with Unipolar Major Depression and CLOCK and VIP with Bipolar DisorderNeuropsychopharmacology, 2010
- A Genome-wide RNAi Screen for Modifiers of the Circadian Clock in Human CellsCell, 2009
- A model of the cell-autonomous mammalian circadian clockProceedings of the National Academy of Sciences of the United States of America, 2009
- Molecular insights into human daily behaviorProceedings of the National Academy of Sciences of the United States of America, 2008
- microRNA Modulation of Circadian-Clock Period and EntrainmentNeuron, 2007
- Molecular Analysis of Mammalian Circadian RhythmsAnnual Review of Physiology, 2001