Sleep Quality, Sleep Structure, and PER3 Genotype Mediate Chronotype Effects on Depressive Symptoms in Young Adults

Abstract

Depression and its related mood disorders are a major global health issue that disproportionately affects young adults. A number of factors that influence depressive symptoms are particularly relevant to the young adult developmental stage, including sleep loss, poor sleep quality, and the tendency toward eveningness in circadian preferences. However, relatively few studies have examined the relationship between sleep and circadian phenotypes, and their respective influences on mood, or considered potential molecular mechanisms driving these associations. Here, we use a multi-year, cross-sectional study of 806 primarily undergraduates to examine the relationships between sleep-wake chronotype, sleep disturbance, depression and genotypes associated with the PER3 variable number of tandom repeats (VNTR) polymorphism-circadian gene variants associated with both chronotype and sleep homeostatic drive. In addition, we use objective, Fitbit-generated sleep structure data on a subset of these participants (n = 67) to examine the relationships between chronotype, depression scores, actual measures of sleep duration, social jetlag, and the percent of deep and rapid eye movement (REM) sleep per night. In this population, chronotype is weakly associated with depressive symptoms and moderately correlated with self-reported sleep disturbance. Sleep disturbance is significantly associated with depression scores, but objective sleep parameters are not directly correlated with Beck Depression Inventory (BDI-II) scores, with the exceptions of a moderate correlation between social jetlag and depression scores in females and a marginal correlation between sleep duration and depression scores. Multiple regression and path analyses reveal that chronotype effects on depressive symptoms in this population are mediated largely by sleep disturbance. The PER3 VNTR genotype significantly predicts depressive symptoms in a model with objective sleep parameters, but it does not significantly predict depressive symptoms in a model with chronotype or subjective sleep disturbance. Interestingly, PER3 5,5 genotypes, in males only, are independently related to chronotype and depression scores. Our results support hypotheses linking subjective sleep quality and chronotype and provide a first step in understanding how objective sleep structure may be linked to chronotype and depressive symptoms. Our results also suggest that circadian gene variants may show sex-specific effects linking sleep duration and sleep structure to depression.

Association of occupational stress, period circadian regulator 3 (PER3) gene polymorphism and their interaction with poor sleep quality

“…In other words, PER3 5/5 individuals tended to sleep late or be awake at night (nocturnal). This is inconsistent with previous studies, which suggested that PER3 5/5 carriers tend to go to bed earlier and wake earlier than those with PER3 4/4 (Hida et al, 2014;Pereira et al, 2005;Viola et al, 2012;Weiss et al, 2020). Unfortunately, our present data do not allow us to detect the reasons, there may be other unknown mechanisms or genes involved in sleep latency.…”

Chronotype, circadian rhythm, and psychiatric disorders: Recent evidence and potential mechanisms

“…Importantly, there is no association between chronotype and PER3 polymorphism ( Silva A. et al, 2020 ). This conclusion may arise because the gender-specific effects of chronotype and depression were overlooked ( Weiss et al, 2020 ). Other scholars also identified PER3 mutations associated with chronotype and anxiety ( Liberman et al, 2017 ).…”

“…A potential explanation is the gender difference in melatonin, sex hormones, and behavioral and psychological factors (sleep quality, alcohol intake) ( Kim et al, 2020 ). In addition, the circadian gene PER3 variable number of tandem repeats was independently related to chronotype only in males ( Weiss et al, 2020 ). Taken together, both the chronotype and psychiatric disorders showed significant sex-specific effects, although the causes and mechanisms are unclear.…”

Effects of Work Stress and Period3 Gene Polymorphism and Their Interaction on Sleep Quality of Non-Manual Workers in Xinjiang, China: A Cross-Sectional Study

“…Per3 VNTR variants are associated with circadian preferences, non-visual responses to light, and brain and cognitive responses to sleep deprivation/circadian rhythm dysregulation. Per3 5/5 carriers are more likely to go to bed early and wake up earlier than Per3 4/4 carriers [ 53 , 54 , 55 ]. Cheng et al [ 56 ] reported that the Per3 5/5 genotype was associated with an increased risk of daytime sleep disturbance in night shift workers.…”