Circadian Clock Model Supports Molecular Link Between PER3 and Human Anxiety

Liberman, Amanda R.; Kwon, Soo Bin; Vu, Ha; Filipowicz, Allan; Ay, Ahmet; Ingram, Krista K.

doi:10.1038/s41598-017-07957-4

Cited by 58 publications

(54 citation statements)

References 75 publications

(125 reference statements)

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“…The two specific polymorphisms examined in this study alter coding regions containing phosphorylation sites. Reduced phosphorylation of PER3 may be associated with a lengthening of period and a delay in the circadian phase, both of which are typically associated with an evening phenotype [14462524]. This delay in circadian phase exacerbates the social jetlag (or misalignment of internal rhythms with daily sleep patterns) [423043], and likely enhances the offset in the physiological peak of evening-types.…”

Section: Discussionmentioning

confidence: 99%

Circadian Effects on Performance and Effort in Collegiate Swimmers

Anderson¹,

Murray²,

Herlihy³

et al. 2018

Journal of Circadian Rhythms

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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.

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Section: Discussionmentioning

confidence: 99%

Circadian Effects on Performance and Effort in Collegiate Swimmers

Anderson¹,

Murray²,

Herlihy³

et al. 2018

Journal of Circadian Rhythms

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“…One candidate mechanism is the PER3 gene, a highly rhythmic, circadian-related gene with expression in both the central nervous system and peripheral tissues (Archer et al, 2018). In humans, variants of the PER3 gene are associated with chronotype, sleep homeostasis, and mental disorders (Archer et al, 2003;Johansson et al, 2003;Akashi et al, 2010;McClung, 2013;Hida et al, 2014;Zhang et al, 2016;Liberman et al, 2017Liberman et al, , 2018Nguyen et al, 2019). A well-studied PER3 polymorphism in exon 18, rs57875989, encodes a variable number tandem repeat region (VNTR) containing a motif of 54 base pairs or 18 amino acids.…”

Section: Introductionmentioning

confidence: 99%

“…Morning-types are more likely to be homozygous for the 5-repeat allele (PER3 5/5 ), and evening-types and individuals with delayed sleep phase disorder (DSPD) have greater frequencies of PER3 4/4 homozygotes (Ebisawa et al, 2001;Archer et al, 2003Archer et al, , 2010Pereira et al, 2005;Jones et al, 2007;Lázár et al, 2012;Liberman et al, 2017Liberman et al, , 2018. For sleep phenotypes, PER3 5/5 homozygotes show earlier sleep and wake times (Lázár et al, 2012) and multiple markers of greater homeostatic sleep pressure (reviewed in Dijk and Archer, 2010).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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“…Circadian rhythm is associated with mood regulation, and disturbances can be linked to the development of psychiatric symptoms [ 37 , 92 ]. There has been the suggestion that this may be related to clock genes, which regulate circadian entrainment.…”

Section: Crossover Pathophysiology Of Tbi Sleep and Psychiatric mentioning

confidence: 99%

Traumatic Brain Injury, Sleep Disorders, and Psychiatric Disorders: An Underrecognized Relationship

Morse

Garner

2018

Medical Sciences

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Traumatic brain injury (TBI) is commonplace among pediatric patients and has a complex, but intimate relationship with psychiatric disease and disordered sleep. Understanding the factors that influence the risk for the development of TBI in pediatrics is a critical component of beginning to address the consequences of TBI. Features that may increase risk for experiencing TBI sometimes overlap with factors that influence the development of post-concussive syndrome (PCS) and recovery course. Post-concussive syndrome includes physical, psychological, cognitive and sleep–wake dysfunction. The comorbid presence of sleep–wake dysfunction and psychiatric symptoms can lead to a more protracted recovery and deleterious outcomes. Therefore, a multidisciplinary evaluation following TBI is necessary. Treatment is generally symptom specific and mainly based on adult studies. Further research is necessary to enhance diagnostic and therapeutic approaches, as well as improve the understanding of contributing pathophysiology for the shared development of psychiatric disease and sleep–wake dysfunction following TBI.

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Circadian Clock Model Supports Molecular Link Between PER3 and Human Anxiety

Cited by 58 publications

References 75 publications

Circadian Effects on Performance and Effort in Collegiate Swimmers

Circadian Effects on Performance and Effort in Collegiate Swimmers

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

Traumatic Brain Injury, Sleep Disorders, and Psychiatric Disorders: An Underrecognized Relationship

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