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

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, PER35,5 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.

Circadian Effects on Performance and Effort in Collegiate Swimmers.

Although individual athletic performance generally tends to peak in the evening, individuals who exhibit a strong diurnal preference perform better closer to their circadian peak. Time-of-day performance effects are influenced by circadian phenotype (diurnal preference and chronotype-sleep-wake patterns), homeostatic energy reserves and, potentially, genotype, yet little is known about how these factors influence physiological effort. Here, we investigate the effects of time of day, diurnal preference, chronotype, and PER3 (a circadian clock gene) genotype on both effort and performance in a population of Division I collegiate swimmers (n = 27). Participants competed in 200m time trials at 7:00 and 19:00 and were sampled pre- and post-trial for salivary α-amylase levels (as a measure of physiological effort), allowing for per-individual measures of performance and physiological effort. Hair samples were collected for genotype analysis (a variable-number tandem-repeat (VNTR) and a single nucleotide polymorphism (SNP) in PER3). Our results indicate significant and parallel time-of-day by circadian phenotype effects on swim performance and effort; evening-type swimmers swam on average 6% slower with 50% greater α-amylase levels in the morning than they did in the evening, and morning types required 5-7 times more effort in the evening trial to achieve the same performance result as the morning trial. In addition, our results suggest that these performance effects may be influenced by gene (circadian clock gene PER3 variants) by environment (time of day) interactions. Participants homozygous for the PER34,4 length variant (rs57875989) or who possess a single G-allele at PER3 SNP rs228697 swam 3-6% slower in the morning. Overall, these results suggest that intra-individual variation in athletic performance and effort with time of day is associated with circadian phenotype and PER3 genotype.