Genetic dissection of psychopathological symptoms: Insomnia in mood disorders and <i>CLOCK</i> gene polymorphism

Serretti, Alessandro; Benedetti, Francesco; Mandelli, Laura; Lorenzi, Cristina; Pirovano, Adele; Colombo, Cristina; Smeraldi, Enrico

doi:10.1002/ajmg.b.20053

Cited by 231 publications

(145 citation statements)

References 26 publications

Supporting

Mentioning

134

Contrasting

Unclassified

Order By: Relevance

“…Sleep variables derived from nocturnal polysomnography did not differ between the genotypes [99]. Interestingly, clinical and restactivity data in patients with mood disorders indicate that individuals with the 3111C allele have increased occurrence of disturbed sleep both during mood episodes as well as in remission, higher motor activity levels in the evening, and a different response to lithium than patients homozygous for the T allele [102][103][104].…”

Section: Candidate Gene Approach Circadian Locomotor Output Cycles Kamentioning

confidence: 86%

Genotype-Dependent Differences in Sleep, Vigilance, and Response to Stimulants

Landolt

2008

CPD

View full text Add to dashboard Cite

Abstract:To better understand the neurobiology of sleep disorders, detailed understanding of circadian and homeostatic sleep-wake regulation in healthy volunteers is mandatory. Sleep physiology and the repercussions of experimentallyinduced sleep deprivation on sleep and waking electroencephalogram (EEG), vigilance and subjective state are highly variable, even in healthy individuals. Accumulating evidence suggests that many aspects of normal sleep-wake regulation are at least in part genetically controlled. Current heritability estimates of sleep phenotypes vary between approximately 20-40 % for habitual sleep duration, to over 90 % for the spectral characteristics of the EEG in nonREM sleep. The molecular mechanisms underlying the trait-like, inter-individual variation are virtually unknown, and the human genetics of normal sleep is only at the beginning of being explored. The first studies identified distinct polymorphisms in genes contributing to the endogenous circadian clock and neurochemical systems previously implicated in sleep-wake regulation, to modulate sleep architecture and sleep EEG, vulnerability to sleep loss, and subjective and objective effects of caffeine on sleep. These insights are reviewed here. They disclose molecular mechanisms contributing to normal sleep-wake regulation in humans, and have potentially important implications for the neurobiology of sleep-wake disorders and their pharmacological treatment.

show abstract

Section: Candidate Gene Approach Circadian Locomotor Output Cycles Kamentioning

confidence: 86%

Genotype-Dependent Differences in Sleep, Vigilance, and Response to Stimulants

Landolt

2008

CPD

View full text Add to dashboard Cite

show abstract

“…17 Although we did not perform any assessment of sleep patterns in our subjects, it is of interest that the rs1801260 polymorphism has previously been associated with sleep dysregulation in humans in many [31][32][33][34][35][36][37][38] but not all studies. 39 These findings, together with the present results may provide genetic evidence to support epidemiological studies associating sleep disturbance with the development of diabetes and obesity.…”

Section: Discussionmentioning

confidence: 99%

Association between polymorphisms in the Clock gene, obesity and the metabolic syndrome in man

2007

View full text Add to dashboard Cite

Objective: Accumulating evidence raises the hypothesis that dysregulation of intrinsic clock mechanisms are involved in the development of the metabolic syndrome, type 2 diabetes mellitus and cardiovascular disease. The aim of the present study was to investigate the relationship between three known common polymorphisms in the Clock gene and features of the metabolic syndrome in man. Methods: Genotype and haplotype analysis was carried out in a cohort of 537 individuals from 89 families characterized for inflammatory, atherothrombotic and metabolic risk associated with insulin resistance. Results: Heritability of the metabolic syndrome, defined according to International Diabetes Federation criteria, was 0.40. Haplotype analysis indicated three common haplotypes: CAT, TGT and CGC (rs4864548-rs3736544-rs1801260) with frequencies of 31, 33 and 28%, respectively. The CGC haplotype was less prevalent in subjects with the metabolic syndrome (P ¼ 0.0015) and was associated with lower waist circumference (P ¼ 0.007), lower hip circumference (P ¼ 0.023), lower body mass index (P ¼ 0.043) and lower leptin levels (P ¼ 0.028). The CAT haplotype was significantly associated with the presence of the metabolic syndrome (P ¼ 0.020). Conclusions: These findings suggest that the Clock gene CGC haplotype may be protective for the development of obesity and support the hypothesis that genetic variation in the Clock gene may play a role in the development of the metabolic syndrome, type 2 diabetes and cardiovascular disease.

show abstract

“…31 -33 Studies using more stringent criteria to defi ne insomnia have produced more realistic and reliably modest h 2 estimates ranging from 31% to 58%. 32 , 34 , 35 Candidate gene studies have identifi ed gene variants that may be involved in the pathophysiology of insomnia, including Apo ε 4, 36 PER3 4/4 , 37 HLA DQB1 * 0602, 38 homozygous Clock gene 3111C/C Clock, 39 and short (s-) allele of the 5-HTTLPR. 40 A genomewide association study found numerous single-nucleotide polymorphisms (SNPs) signifi cantly associated with insomnia symptoms.…”

Section: Genetics Of Sleep and Insomniamentioning

confidence: 99%

The Pathophysiology of Insomnia

Levenson

Kay

Buysse

2015

Chest

292

147

View full text Add to dashboard Cite

Insomnia disorder is characterized by chronic dissatisfaction with sleep quantity or quality that is associated with diffi culty falling asleep, frequent nighttime awakenings with diffi culty returning to sleep, and/or awakening earlier in the morning than desired. Although progress has been made in our understanding of the nature, etiology, and pathophysiology of insomnia, there is still no universally accepted model. Greater understanding of the pathophysiology of insomnia may provide important information regarding how, and under what conditions, the disorder develops and is maintained as well as potential targets for prevention and treatment.The aims of this report are (1) to summarize current knowledge on the pathophysiology of insomnia and (2) to present a model of the pathophysiology of insomnia that considers evidence from various domains of research. Working within several models of insomnia, evidence for the pathophysiology of the disorder is presented across levels of analysis, from genetic to molecular and cellular mechanisms, neural circuitry, physiologic mechanisms, sleep behavior, and self-report. We discuss the role of hyperarousal as an overarching theme that guides our conceptualization of insomnia. Finally, we propose a model of the pathophysiology of insomnia that integrates the various types of evidence presented.

show abstract

Genetic dissection of psychopathological symptoms: Insomnia in mood disorders and CLOCK gene polymorphism

Cited by 231 publications

References 26 publications

Genotype-Dependent Differences in Sleep, Vigilance, and Response to Stimulants

Genotype-Dependent Differences in Sleep, Vigilance, and Response to Stimulants

Association between polymorphisms in the Clock gene, obesity and the metabolic syndrome in man

The Pathophysiology of Insomnia

Contact Info

Product

Resources

About