Journal of Affective Disorders Reports (Dec 2022)
Low circadian amplitude and delayed phase are linked to seasonal affective disorder (SAD)
Abstract
Background: Symptoms of seasonal affective disorder (SAD) can affect up to 10–20% of individuals in temperate populations and are more common in females. Depressive symptoms within SAD individuals provide a model for investigating how genetic, environmental, and physiological factors interact to influence mood. Winter-type SAD occurs during short photoperiod seasons, suggesting circadian physiology may influence susceptibility to SAD. Methods: Using a longitudinal cross-season design in a Northeastern US population (n = 213), we tested how SAD symptoms (SPAQ-GSS) were associated with gender, depression scores (BDI-II), chronotype (MCTQ-MSF), and in-vivo circadian phase and amplitude. In addition, we used computational modeling to simulate whether circadian gene variants reproduce SAD phenotypes across seasons. Results: We found that high seasonality scores are associated with lower circadian amplitude, delayed circadian phases in winter, and evening chronotypes. Our model reproduces seasonal decreases in amplitude and delayed phases for circadian gene variants associated with SAD. Modeling further suggests that transcriptional increases for variants in Cry1 and Cry2 genes and changes in transcription, phosphorylation and/or degradation rates of Per3 variants may be associated with these seasonal changes. Limitations: Our study examined clock gene expression from peripheral tissues which represent circadian rhythms influenced by both intrinsic, physiological and external, environmental factors. The mutant conditions for the modeling study are limited, and many biochemical reaction rates in humans are unknown. Conclusions: Our study validates previous results linking SAD symptoms with gender, chronotype, and depressive symptoms and provides evidence for potential genetic and physiological mechanisms of SAD—low circadian amplitude and seasonally delayed circadian phase.
