Biology Department, Colgate University, Hamilton, NY, 13346, USA.
Bioinformatics Program, University of California, Los Angeles, CA, 90024, USA.
Sci Rep. 2017 Aug 31;7(1):9893. doi: 10.1038/s41598-017-07957-4.
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.
广泛性焦虑和重度抑郁症在美国越来越常见，影响了 18.6%的成年人口。情绪障碍可能使人衰弱，并且通常与整体健康状况不佳、生活不满以及因无法工作而需要残疾福利相关。最近的证据表明，一些情绪障碍与昼夜节律有关，昼夜节律紊乱甚至可能引发这些障碍的发展。然而，这种相互作用的分子机制尚不清楚。与昼夜节律钟相关的基因 PER3 的多态性与行为表型（觉醒和活动中的极端日间偏好）和睡眠/情绪障碍有关，包括季节性情感障碍（SAD）。在这里，我们展示了两种 PER3 突变，一个可变数串联重复（VNTR）等位基因和一个单核苷酸多态性（SNP），与日间偏好和更高的特质焦虑评分有关，支持 PER3 在情绪调节中的作用。此外，我们通过利用一个全面的昼夜节律钟模型来探索 PER3 影响情绪的潜在机制，该模型可以准确预测敲除表型和具有 PER3 相关时钟障碍的个体中明显的昼夜节律周期变化。
