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Circadian Clock Model Supports Molecular Link Between PER3 and Human Anxiety

journal contribution
posted on 2023-05-19, 05:25 authored by Amanda R Liberman, Soo Bin Kwon, Ha VuHa Vu, Allan Filipowicz, Ahmet Ay, Krista K Ingram
AbstractGeneralized 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.

History

Journal

SCIENTIFIC REPORTS

Volume

7

Article number

ARTN 9893

Location

England

ISSN

2045-2322

eISSN

2045-2322

Language

English

Publication classification

C1.1 Refereed article in a scholarly journal

Issue

1

Publisher

NATURE RESEARCH