Priscila F. Tempaku

Telomere length as a marker of sleep loss and sleep disturbances: a potential link between sleep and cellular senescence

The identification of biological markers that allow the early diagnosis, or even the prevention of age-related diseases, is an important goal that is being actively pursued in the research community. Sleep is one of the physiological processes that is most affected by aging, and there is a strong relationship between age-related sleep alterations and diseases. Changes in cellular senescence and the linked changes in telomere length might be potential markers of age-related sleep changes. In this review, we present some of the most recent evidence showing that telomere length has been associated with sleep loss and sleep disturbances in cross-sectional and case-control studies. We also present insights into the cellular senescence mechanisms relating to changes in telomere length, and we suggest that this field lacks basic and clinical research studies, especially long-term longitudinal studies, which may bring opportunities to sleep researchers to investigate this relationship in more depth.

Shorter leukocyte telomere length in patients at ultra high risk for psychosis

Telomere length attrition has been demonstrated in schizophrenia but not in individuals in ultra high risk (UHR) for psychosis. The present study aimed to compare the leukocyte telomere length (TL) between patients at UHR for psychosis and healthy controls (HC). Twenty-two participants with UHR and 88 HC were enrolled in this study. Telomere lengths were determined using a multiplex qPCR assay. After adjustment for age, sex, ethnicity, and education, patients in UHR, compared with HC groups, had shorter telomere length (RR: 0.929, p=0.031). Shorter leukocyte telomere length in UHR could represent early signs of accelerated aging in this population.

The effect of the severity of obstructive sleep apnea syndrome on telomere length

Aging is associated with an increase in the prevalence of obstructive sleep apnea syndrome (OSAS) as well as the shortening of telomeres. It is known that OSAS-related factors are stimuli that can contribute to the acceleration of cellular senescence. Thus, the present study aimed to compare the leukocyte telomere length (LTL) between OSAS patients and controls, as well as to verify the correlation between LTL and sleep parameters. We used DNA extracted of 928 individuals from EPISONO to measure the LTL by the quantitative real-time polymerase chain reaction. All individuals were subjected to one full-night polysomnography. LTL was significantly shorter in OSAS patients compared to controls. The results showed negative correlations between LTL and the following variables: apnea-hypopnea index, respiratory disturbance index, desaturation index and wake after sleep onset. LTL was positively correlated with sleep efficiency, total sleep time, basal, minimum and maximum oxygen saturation. Lastly, it was observed that OSAS severity was associated with shorter LTL even after adjusting for sex, age, years of schooling, body mass index, diabetes, stroke and heart attack. In conclusion, our study indicates the presence of an association between LTL and OSAS and a significant impact of severity of OSAS in telomeres shortening.

Characterization of bimodal chronotype and its association with sleep: A population-based study

ABSTRACT The circadian system coordinates internal events in a daily schedule to make sure that the body systems are synchronized to environmental time and internal cues. One important behavioral aspect of the circadian system is the chronotype. It is usually assessed through subjective questionnaires, being the Horne-Ostberg Morningness–Eveningness Questionnaire (MEQ) one of the most used. It classifies individuals into three major categories: morning, evening, and intermediate types. Recently, it has been hypothesized the existence of a fourth chronotype, the bimodal type, through an algorithm derived from the MEQ responses. Bimodals answer as morning-types in some questions, and as evening-types in others, resulting in an intermediate total score. To better characterize this phenotype, the present study aimed to detect and characterize the frequency of the bimodal chronotype in the EPISONO, a large population-based cohort, as well as to verify the association between bimodality and sleep parameters and genetic variation in the PER3 gene. Of the 1,042 individuals who participated of the EPISONO, 857 had MEQ filled correctly. We found that 16% of our sample were bimodal types. We observed that bimodal individuals were significantly younger and had lower body mass index. The association between PER3 VNTR genotype and gender with bimodal chronotype was not significant. However, we found an association between bimodality and Epworth Sleepiness Scale (EES) and apnea-hypopnea index (AHI). We did not find a statistically significant difference between bimodals and intermediate non-bimodals for the studied variables. Lastly, it was observed that the most significant predictors for bimodal chronotype were female gender, AHI, and EES. In conclusion, the present work provides more evidence that the bimodal type might have to be considered when classifying chronotype and its association with young age and sleepiness may be due to the influence of social and environmental factors.

Effect of male-specific childhood trauma on telomere length

Child maltreatment (CM) is a global issue with serious lifelong consequences. In fact, maltreatment during childhood might be an important risk factor for the development of psychiatric disorders. Furthermore, previous studies showed a strong relationship between telomere length (TL) and early life stress. Considering that only a few studies have evaluated this relationship in children and that even fewer considered the sex as a possible moderator, we investigated whether TL in the blood of both children and adolescents was associated with psychopathology and with a history of CM, and whether these associations were moderated by the sex. In this cross-sectional study, 561 individuals (ranging between 6 and 14 years of age) from a large prospective community school-based study, i.e., the Brazilian High-Risk Cohort (HRC), were evaluated. The Child Behavior Checklist (CBCL) score was used to assess psychopathology, whereas a latent variable encompassing some questions about history of adverse environment and trauma was employed to determine the CM history. TL was measured in blood cells using a multiplex quantitative polymerase chain reaction. Additionally, TL was inserted in two moderation models, in which the CBCL score/CM, TL and sex were the independent variables, the outcome, and the moderator variable, respectively. Although an association between psychiatric symptoms and TL was not observed, a relation between CM and TL moderated by the sex was seen, indicating that males with higher CM scores presented with shorter telomeres than did females. Our results suggest that child maltreatment could influence telomere length in both children and adolescents and that this effect is mediated by the sex.

Dopaminergic pathways for bruxism: a way forward?

The recent article entitled BSingle nucleotide polymorphisms in genes of dopaminergic pathways are associated with bruxism^ [1] published by Oporto and colleagues in Clinical Oral Investigations is noteworthy. It is hypothesized that the etiology of bruxism (BRX) is multifactorial and thus genetic variations may play a substantial role. In short, this case-control study aimed to investigate the association between single nucleotide polymorphisms (SNP) in genes related to dopaminergic pathways and the presence of bruxism (BRX) in its different entities according to a circadian influence: sleep BRX, awake BRX, and awake-sleep BRX. However, there are some methodological issues that need to be addressed to a better understanding of the association found. In this sense, we would like to make some considerations. According to a group of expertise [2], the sleep BRX diagnosis requires that, in addition to questionnaires and clinical criteria, a polysomnography (PSG) exam should be carried out. The gold standard for a definition of BRX diagnosis is based on the use of PSG analyses associated to audio and video recordings, where masticatory movements or the contraction of the masticatory muscles are evaluated. Although well stablished, subjective instruments (questionnaires and clinical examination) were used in the study; the absence of a diagnosis through PSG could possibly lead to the inclusion of an individual’s false positive for BRX and false negative controls. An epidemiological investigation, using PSG criteria, demonstrated a prevalence of 7.4% of sleep BRX in adults [3]. We point out some factors that could have influenced the results of Oporto and colleagues, such as smoking, caffeine intake, and alcohol consumption due to its alteration in dopaminergic pathway transmissions [4]. The authors cited these confounders’ factors but did not control for them, neither in the inclusion criteria nor in the statistical analysis. Considering the influence of these factors on the dopaminergic pathway is important for BRX phenotype, it is of extreme importance that the authors took into account that the results of each BRX phenotype could be different. Several neurotransmitters in different areas of the central nervous system have been associated with the hypotheses of ethiopatology [5]. Some studies have identified other possible polymorphisms involved in this complex etiological process, although they have been done with polymorphisms identified with serotonergic transmission, among them an investigation performed by the same research group [6, 7]. Although the study did not present standardized methodologies, it is very significant to increase our understanding of the pathophysiology of BRX. Evidence points out to an important participation of genetic factors within the causal factors of BRX [8]. We suggest that the best way to assess the genetic influence of BRX is through a genome-wide association study (GWAS). The GWAS has become a well-established instrument to identify genetic variants and genes associated with different phenotypes. In this way, we would possibly investigate the contribution of a range of single-nucleotide polymorphisms. Thus, these results can help and direct future studies in this topic, providing the development of effective treatments in the control of this pathology. Nowadays, the standard treatment focuses only in the consequences, preventing damages to oral and general health that the BRX causes.