Rhythms in lipid droplet content driven by a metabolic oscillator are conserved throughout evolution.

The biological clock in eukaryotes controls daily rhythms in physiology and behavior. It displays a complex organization that involves the molecular transcriptional clock and the redox oscillator which may coordinately work to control cellular rhythms. The redox oscillator has emerged very early in evolution in adaptation to the environmental changes in O2 levels and has been shown to regulate daily rhythms in glycerolipid (GL) metabolism in different eukaryotic cells. GLs are key components of lipid droplets (LDs), intracellular storage organelles, present in all living organisms, and essential for energy and lipid homeostasis regulation and survival; however, the cell bioenergetics status is not constant across time and depends on energy demands. Thus, the formation and degradation of LDs may reflect a time-dependent process following energy requirements. This work investigated the presence of metabolic rhythms in LD content along evolution by studying prokaryotic and eukaryotic cells and organisms. We found sustained temporal oscillations in LD content in Pseudomonas aeruginosa bacteria and Caenorhabditis elegans synchronized by temperature cycles, in serum-shock synchronized human embryonic kidney cells (HEK 293 cells) and brain tumor cells (T98G and GL26) after a dexamethasone pulse. Moreover, in synchronized T98G cells, LD oscillations were altered by glycogen synthase kinase-3 (GSK-3) inhibition that affects the cytosolic activity of the metabolic oscillator or by knocking down LIPIN-1, a key GL synthesizing enzyme. Overall, our findings reveal the existence of metabolic oscillations in terms of LD content highly conserved across evolutionary scales notwithstanding variations in complexity, regulation, and cell organization.

Social rhythm and implications on functionality of patients after stroke.

The study aimed to assess the regularity, intensity, frequency, and period of activities comprising social rhythm and associate them with the functionality of stroke patients. The sample consisted of 73 patients (41 men and 32 women) with a mean age of 60 years (±10). Social rhythm was assessed by Social Rhythm Metric (SRM) and Activity Level Index (ALI). The functionality was evaluated using the International Classification of Functioning, Disability, and Health (ICF). Data were analyzed using Student's t-test, ANOVA, and Chi-square test. The mean SRM was 5.1 ± 0.9, and ALI was 58.3 ± 14.9. Notably, 40% of the patients exhibited both low regularity and low intensity of activities. Six SRM activities, performed with low frequency (going outside, starting work, exercising, snacking, watching other TV programs, and going home), exhibited a tendency to have periods that deviated from the expected 24-hour daily cycle. ICF domains most associated with SRM were: d2-General tasks and demands, d3-Communication, d4-Mobility, d5-Self care, d8-Major life areas, and d9-Community, social and civic life. The results indicated changes in social rhythm with implications for patient functionality. Screening for disruptions in social rhythm could be part of the functional assessment during the rehabilitation process for post-stroke patients.

Zika Virus Infection Alters the Circadian Clock Expression in Human Neuronal Monolayer and Neurosphere Cultures.

Rhythmic regulations are virtually described in all physiological processes, including central nervous system development and immunologic responses. Zika virus (ZIKV), a neurotropic arbovirus, has been recently linked to a series of birth defects and neurodevelopmental disorders. Given the well-characterized role of the intrinsic cellular circadian clock within neurogenesis, cellular metabolism, migration, and differentiation among other processes, this study aimed to characterize the influence of ZIKV infection in the circadian clock expression in human neuronal cells. For this, in vitro models of human-induced neuroprogenitor cells (hiNPCs) and neuroblastoma cell line SH-SY5Y, cultured as monolayer and neurospheres, were infected by ZIKV, followed by RNA-Seq and RT-qPCR investigation, respectively. Targeted circadian clock components presented mRNA oscillations only after exogenous synchronizing stimuli (Forskolin) in SH-SY5Y monolayer culture. Interestingly, when these cells were grown as 3D-arranged neurospheres, an intrinsic oscillatory expression pattern was observed for some core clock components without any exogenous stimulation. The ZIKV infection significantly disturbed the mRNA expression pattern of core clock components in both neuroblastoma cell culture models, which was also observed in hiNPCs infected with different strains of ZIKV. The ZIKV-mediated desynchronization of the circadian clock expression in human cells might further contribute to the virus impairment of neuronal metabolism and function observed in adults and ZIKV-induced congenital syndrome. In vitro models of Zika virus (ZIKV) neuronal infection. Human neuroprogenitor cells were cultured as monolayer and neurospheres and infected by ZIKV. Monolayer-cultured cells received forskolin (FSK) as a coupling factor for the circadian clock rhythmicity, while 3D-arranged neurospheres showed an intrinsic oscillatory pattern in the circadian clock expression. The ZIKV infection affected the mRNA expression pattern of core clock components in both cell culture models. The ZIKV-mediated desynchronization of the circadian clock machinery might contribute to the impairment of neuronal metabolism and function observed in both adults (e.g., Guillain-Barré syndrome) and ZIKV-induced congenital syndrome (microcephaly). The graphical abstract has been created with Canva at the canva.com website.

Familiarity of Brazilian psychologists with basic concepts in sleep science and chronobiology.

Desynchronization of circadian rhythms and sleep-wake patterns impacts biochemical, physiological, and behavioral functions, including mental processes. The complex relationship between circadian rhythms and mental health makes it challenging to determine causality between circadian desynchronization and mental disorders. Regarding the fact that psychologists act as the front line for initial mental health care, we aimed to assess the knowledge and use of sleep science and basic chronobiology by professional psychologists in Brazil. Data were collected via an online questionnaire completed by 1384 professional psychologists between October 2018 and May 2019. Our findings revealed that ±80% of psychologists reported that at least half of their patients presented some sleep-related complaints; however, only ±27% routinely inquired about sleep quality even in the absence of patient complaints. Additionally, only ±66% initiated treatments to understand these complaints, potentially influenced by the lack of prior academic exposure to biological rhythms as reported by ±76% of Brazilian psychologists interviewed. Importantly, ±15% did not believe in an association between mental health and biological rhythms, and even a significant ±67% were unfamiliar with the term chronobiology and ±63% were not able to describe any other biological rhythm except for the sleep-wake cycle. These results demonstrate that fundamental concepts in chronobiology and sleep science are unknown to a substantial proportion of Brazilian psychologists. In conclusion, we propose that this subject could be more effectively integrated into psychologists' academic training, potentially promoting benefits through the incorporation of a chronobiological approach in mental health practice.

Does exposure to moonlight affect day/night changes in melatonin and metabolic parameters in Amazonian fish?

Lunar cycle modulates the rhythmic activity patterns of many animals, including fish. The effect of the moonlight cycle on daily melatonin and metabolic parameters was evaluated in matrinxã (Brycon amazonicus) subjected to external natural lighting. Eighty juvenile were distributed in 4 tanks of 1m3 (20 fish/tank) and divided into two groups. One group was exposed to the full moon and the other group to the new moon for 30 days, which corresponds to the duration of the lunar period. At the end of the lunar phase, 6 fish from each group were anesthetized to collect blood, tissue and eye samples at midday and midnight. The comparison between the light and dark periods revealed a significant increase in plasma and ocular melatonin in the last period. However, there was no significant difference for plasma melatonin between moons. Ocular melatonin presented higher concentrations during the new moon. Glucose, total proteins, cortisol, liver glutathione and gill lipid peroxidation were higher in the full moon compared to in the new moon. Plasma triglyceride was higher during the night for the full moon, and the opposite was found for the new moon. Total cholesterol values were higher at night regardless the moon phase. Glutathione in the gills and lipid peroxidation in the liver showed no significant differences. These results highlight the importance of considering both the day and lunar cycles for melatonin and metabolic parameters in species of commercial interest and susceptible to stressful situations in rearing conditions.

Trastornos circadianos del sueño / Circadian Sleep Disorders

Resumen El sistema circadiano está sincronizado al ciclo luz-oscuridad que es generado por la rotación de la tierra, asegurando que la vigilia sea durante el día y que el sueño ocurra durante la noche. Sin embargo, el ritmo de sueño-vigilia puede estar desincronizado del ciclo luz-oscuridad o desincronizado de manera endógena, dando como resultado: insomnio, fatiga y bajo rendimiento en las actividades cotidianas. Mientras que los trastornos del sueño están clasificados por la Asociación Americana de Trastornos del Sueño como: disomnias intrínsecas, disomnias extrínsecas, parasomnias o trastornos del sueño médicos/psiquiátricos. Los trastornos circadianos del sueño se han categorizado por separado, en parte para reconocer que en la mayoría de los casos la etiología de los trastornos circadianos es una mezcla de factores internos y ambientales, o por un desajuste temporal entre ambos. Los síntomas generalmente son insomnio o hipersomnia, síntomas comunes en pacientes con trastornos circadianos del sueño, aunque hay otras causas a las que pueden atribuirse y que deben excluirse antes de realizar el diagnóstico de un trastorno circadiano del sueño. En el paciente sin otra patología del sueño, un registro diario de actividades, comidas, ejercicio, siestas y la hora de acostarse es una herramienta esencial para evaluar los trastornos circadianos del sueño. Estos registros deben mantenerse durante 2 semanas o más, ya que una perturbación debida a cambios de trabajo o viajes a través de zonas horarias puede tener efectos sobre el sueño y el estado de alerta durante el día, semanas después del evento.

Abstract The circadian system is synchronized to the light-dark cycle generated by the rotation of the earth, ensuring that wakefulness is during the day and sleep occurs at night. However, the sleep-wake rhythm may be out of sync with the light-dark cycle or endogenously out of sync, resulting in insomnia, fatigue, and poor performance in activities of daily living. Sleep disorders are classified by the American Sleep Disorders Association, as intrinsic dyssomnias, extrinsic dyssomnias, parasomnias, or medical/psychiatric sleep disorders. Circadian sleep disorders have been categorized separately to recognize that in most cases the etiology of circadian disturbances is a mix of internal and environmental factors or a temporary mismatch between the two. Symptoms are usually insomnia or hypersomnia, common symptoms in patients with circadian sleep disorders although other causes can be attributed and must be excluded before a diagnosis of a circadian sleep disorder is made. In the patient without other sleep pathology, a daily record of activities, meals, exercise, naps, and bedtime is an essential tool in assessing circadian sleep disorders. These records should be kept for 2 weeks or more, as a disturbance due to job changes or travel across time zones can have effects on sleep and daytime alertness weeks after the event.

Biological rhythms disruption mediates the association between mother's diagnosis of bipolar disorder and offspring's emotional/behavioral problems.

OBJECTIVE: The current study assesses whether the association between diagnosis of Bipolar Disorder (BD) in mothers and emotional and behavioral problems (EBP) in their offspring is mediated by a disruption in the offspring's biological rhythms. METHODS: A probabilistic sample of 492 public school children (ages 7-8, 48 % female) were assessed for biological rhythms disruption and EBP using the Biological Rhythms Interview for Assessment in Neuropsychiatry for Kids and the Strengths and Difficulties Questionnaire, respectively. Mothers' mental health (BD = 64) was evaluated using a standardized clinical interview. A mediation analysis was conducted to assess the effect of the mother's diagnosis of BD on the EBP of their offspring in relation to the offspring's biological rhythms disruptions. RESULTS: When compared to offspring of mothers without BD, offspring of mothers with BD showed greater difficulty in maintaining biological rhythms and higher prevalence of EBP. Using the presence of EBP as the outcome, 75 % of the effect of mother's BD diagnosis was mediated by offspring's biological rhythms disruption. CONCLUSIONS: Biological rhythms disruption in children fully mediates the effect of the mother's diagnosis of BD on the child's EBP. These data encourage the development of further studies to find effective strategies to prevent and treat biological rhythms disruption in offspring of mothers with BD.

Circadian modulation of microglial physiological processes and immune responses.

Microglia is considered the central nervous system (CNS) resident macrophages that establish an innate immune response against pathogens and toxins. However, the recent studies have shown that microglial gene and protein expression follows a circadian pattern; several immune activation markers and clock genes are expressed rhythmically without the need for an immune stimulus. Furthermore, microglia responds to an immune challenge with different magnitudes depending on the time of the day. This review examines the circadian control of microglia function and the possible physiological implications. For example, we discuss that synaptic prune is performed in the cortex at a certain moment of the day. We also consider the implications of daily microglial function for maintaining biological rhythms like general activity, body temperature, and food intake. We conclude that the developmental stage, brain region, and pathological state are not the only factors to consider for the evaluation of microglial functions; instead, emerging evidence indicates that circadian time as an essential aspect for a better understanding of the role of microglia in CNS physiology.

Self-perceived rhythmicity in affective and cognitive functions is related to psychiatric symptoms in adolescents.

The objective of this study was to evaluate the relationship between self-perceived rhythms measured using the Mood Rhythm Instrument for adolescents (MRhI-Y) and depressive and psychiatric symptoms measured with the Children's Depressive Instrument (CDI) and the Strengths and Difficulties Questionnaire (SDQ). In this study, 186 adolescents were recruited in Rio Grande do Sul, Brazil. We performed a Spearman correlation analysis to evaluate the relationships between quantitative variables. All variables that had a statistically significant correlation were included in ANOVA multiple regression models. The dependent variables in the multiple regression analyses were CDI score and total and emotional scores on the SDQ. We found that only Cognitive self-perceived rhythmicity contributed significantly to the first multiple regression with CDI as the outcome variable. The second regression with SDQ Emotional score as the outcome variable showed that female sex, age, and self-perceived affective rhythmicity contributed significantly to the model. The third regression with SDQ total score as the outcome variable showed that chronotype, self-perceived cognitive symptoms, and affective rhythmicity contributed significantly to the model. In conclusion, we found that lower self-perceived rhythmicity in cognitive factors and higher self-perceived rhythmicity in affective factors were related to presence and intensity of psychiatric and depressive symptoms.

An increased number of individuals of a potential host facilitates non-photic synchronisation in the haematophagous insect Triatoma infestans

BACKGROUND Triatoma infestans (Kissing bug) is the main vector of the parasite causative of Chagas disease in Latin-America. This species shows clear activity rhythms easily synchronised to day-night cycles (photic cycle). The haematophagous nature of these insects lead us to think that they may temporally adapt to the particular activity rhythms of potential hosts (non-photic cycle). Our previous data showed that kissing bugs were weakly affected by the activity-inactivity rhythm of a single host. OBJETIVE To determine if by increasing the number of individuals of a potential host, T. infestans could increase the likelihood of synchronisation. METHODS Individual activity rhythms of experimental insects, maintained in constant darkness in light-tight cabinets, localised in a room with 24 rodents, were continuously monitored. Another insect group that served as control was maintained in the same conditions but in a room without rodents. FINDINGS Most of the experimental insects synchronised, expressing a 24 h period coincident with the activity-inactivity rhythms of the rodents, while the controls free ran with a period significantly longer than 24 h. CONCLUSION Analogous to what happens with high vs low light intensity in photic synchronisers, a high number of rodents, in contrast to the previous one-rodent experiment, increased the potency of this non-photic zeitgeber.

Sleep disturbances, circadian activity, and nocturnal light exposure characterize high risk for and current depression in adolescence.

STUDY OBJECTIVES: Major depressive disorder (MDD) in adolescence is associated with irregularities in circadian rhythms and sleep. The characterization of such impairment may be critical to design effective interventions to prevent development of depression among adolescents. This study aimed to examine self-reported and actimetry-based circadian rhythms and sleep-wake behavior associated with current MDD and high risk (HR) for MDD among adolescents. METHODS: Ninety-six adolescents who took part in the IDEA-RiSCo study were recruited using an empirically developed depression-risk stratification method: 26 classified as low risk (LR), 31 as HR, and 39 as a current depressive episode (MDD). We collected self-report data on insomnia, chronotype, sleep schedule, sleep hygiene as well as objective data on sleep, rest-activity, and light exposure rhythms using actimetry for 10 days. RESULTS: Adolescents with MDD exhibited more severe insomnia, shorter sleep duration, higher social jetlag (SJL), lower relative amplitude (RA) of activity, and higher exposure to artificial light at night (ALAN) compared with the other groups. They also presented poorer sleep hygiene compared with the LR group. The HR group also showed higher insomnia, lower RA, higher exposure to ALAN, and higher SJL compared with the LR group. CONCLUSIONS: HR adolescents shared sleep and rhythm alterations with the MDD group, which may constitute early signs of depression, suggesting that preventive strategies targeting sleep should be examined in future studies. Furthermore, we highlight that actimetry-based parameters of motor activity (particularly RA) and light exposure are promising constructs to be explored as tools for assessment of depression in adolescence.

Handling missing data in rest-activity time series measured by actimetry.

A handling procedure of off-wrist episodes in actimetry time series of motor activity is presented using two records (regular vs. irregular sleep-wake cycle and daytime activity) of 14 consecutive days sampled in 1-minute epochs. We generated single missing value (NA) intervals of 1 h, 2 h, 4 h, 6 h, 12 h, and 24 h as well as random NA episodes following probabilistic rules to simulate real-life off-wrist episodes. Then, we replaced these episodes with "zeroes" (i.e., the default of immobility records), mean or median of the remaining 13 days corresponding to the missing bins. Single missing episodes of up to 12 h resulted in less than 5% variation from the original values. The irregular series showed higher variability in acrophase, MESOR, L5, M10 and RA compared to the regular series. Random missing allocation simulating real-life off-wrist episodes resulted in significant changes in most parameters, and the imputation of zeroes significantly increased the variance; however, replacing NA with mean or median resulted in patterns similar to those of NA. We recommend replacing 'zeroes' with NA whenever possible, given the risk of inflating invariance using zeroes. If the parameters cannot be computed in the presence of NA, we recommend using the weekly mean of corresponding timepoints.

Melatonin receptors and Per1 expression in the inferior olivary nucleus of the Sapajus apella monkey.

Melatonin is a transducer of photic environmental information and participates in the synchronization of various physiological and behavioral phenomena. Melatonin can act directly in several areas of the central nervous system through its membrane receptors coupled to G protein, called MT1 and MT2 receptors. In some structures, such as the retina, hypothalamus and pars tuberalis, the expression of both melatonin receptors shows circadian variations. Melatonin can act in the synchronization of the clock proteins rhythm in these areas. Using the immunohistochemistry technique, we detected the immunoexpression of the melatonin receptors and clock genes clock protein Per1 in the inferior olivary nucleus (ION) of the Sapajus apella monkey at specific times of the light-dark phase. The mapping performed by immunohistochemistry showed expressive immunoreactivity (IR) Per1 with predominance during daytime. Both melatonin receptors were expressed in the ION without a day/night difference. The presence of both melatonin receptors and the Per1 protein in the inferior olivary nucleus can indicate a functional role not only in physiological, as in sleep, anxiety, and circadian rhythm, but also a chronobiotic role in motor control mechanisms.

Melatonin and Depression: A Translational Perspective From Animal Models to Clinical Studies.

Daily rhythm of melatonin synchronizes the body to the light/dark environmental cycle. Several hypotheses have been raised to understand the intersections between melatonin and depression, in which changes in rest-activity and sleep patterns are prominent. This review describes key experimental and clinical evidence that link melatonin with the etiopathology and symptomatology of depressive states, its role in the follow up of therapeutic response to antidepressants, as well as the clinical evidence of melatonin as MDD treatment. Melatonin, as an internal temporal cue contributing to circadian organization and best studied in the context of circadian misalignment, is also implicated in neuroplasticity. The monoaminergic systems that underly MDD and melatonin production overlap. In addition, the urinary metabolite 6-sulfatoxymelatonin (aMT6) has been proposed as biomarker for antidepressant responders, by revealing whether the blockage of noradrenaline uptake has taken place within 24 h from the first antidepressant dose. Even though animal models show benefits from melatonin supplementation on depressive-like behavior, clinical evidence is inconsistent vis-à-vis prophylactic or therapeutic benefits of melatonin or melatonin agonists in depression. We argue that the study of melatonin in MDD or other psychiatric disorders must take into account the specificities of melatonin as an integrating molecule, inextricably linked to entrainment, metabolism, immunity, neurotransmission, and cell homeostasis.

Relação do cronotipo nos níveis de ansiedade e consumo Máximo de oxigênio em jovens / Relation between chronotype on anxiety levels and maximum oxygen consumption in young people

O presente estudo analisou a relação entre cronotipo, níveis de ansiedade, depressão e estresse, bem como níveis de condicionamento cardiorrespiratório em jovens. Métodos: Foi analisado um total de 36 participantes com idades entre 18 e 28 a nos, saudáveis e que atendessem ao cronotipo matutino e vespertino. Análises de nível de atividade física, consumo máximo de oxigênio, níveis de depressão, ansiedade e estresse foram realizadas com testes específicos. Em todos os cálculos foram utilizados um alfa de p<0.05 para análise estatística. Resultados: O nível de atividade física mostrou que a porcentagem dos matutinos suficientemente ativos foi de 58% comparado com 23.5% dos vespertinos. Mulheres com cronotipo vespertino apresentaram níveis menores de VO2máx quando comparados com as mulheres com cronotipo matutino (p=0.04). Os participantes vespertinos apresentaram níveis maiores de ansiedade (p=0.02) comparados com os matutinos e esses dados foram evidentes nos participantes do sexo feminino onde as mulheres do cronotipo vespertino apresentaram níveis maiores de ansiedade (p=0.03) comparados com mulheres de cronotipo matutino. Conclusão: Portanto, o estudo conclui que indivíduos do cronotipo vespertino apresentaram menores níveis de atividade física e maiores níveis de ansiedade evidenciados principalmente nas mulheres.(AU)

The present study analyzed a relationship between schedule, anxiety, depression and stress levels, as well as cardiorespiratory fitness levels in young people. Methods: A total of 36 healthy participants aged 18 to 28 years who met the criteria for chronotypes morning type and evening type were analyzed. Analyzes of physical activity level, maximal oxygen uptake, depression, anxiety and stress levels were performed. In all calculations, an alpha of p <0.05 was used for statistical analysis. Results: The level of physical activity was higher in morning types 58% compared to 23.5% of evening types. Women with evening chronotype had lower VO2max levels compared with women with a morning chronotype (p= 0.04). Evening types had higher anxiety levels (p= 0.02) compared to morning types and these data were evidenced in female participants with higher anxiety levels (p=0.03) compared to women with a morning chronotype. Conclusion: Therefore, the study concludes that young people with a evening chronotype exhibited lower levels of physical activity and higher anxiety levels, especially in women.(AU)

Increased inflammatory biomarkers and changes in biological rhythms in bipolar disorder: A case-control study.

BACKGROUND: Bipolar Disorder (BD) is a chronic psychiatric disorder characterized by mood disturbances that include depressive, manic, and hypomanic episodes. Despite the severity of the symptoms, there is still a gap in the literature on the precise neurobiology and treatment of BD. The investigations of inflammatory changes in BD has increased in the last decade, evincing the importance of its role in the pathophysiology of the disorder. The present study aimed to investigate the inflammatory role in BD, through the evaluation of biomarkers and their relation to biological rhythms. METHODS: It was conducted a case-control study that included 36 BD and 46 healthy controls (HC). The Cyclooxygenase 2 (COX-2) enzyme, Arachidonic Acid (AA), interleukins (IL) IL-4, IL-5, IL-6, IL-10, IL-33, and Tumor Necrosis Factor Alpha (TNF-α) in the serum of individuals. It also was administered the Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN) to the BD and healthy control groups. RESULTS: The results indicated that the individuals with BD showed increased COX-2, AA, IL-6, and TNF-α levels in comparison to the HC without psychiatric disorders, as well as significant commitments in all domains evaluated by BRIAN. LIMITATIONS: Uncontrolled pharmacotherapy used by the included bipolar participants, which had important effects on participants' inflammatory systems and the lack of cases with bipolar manic episodes. CONCLUSIONS: The results of the present study reaffirm that inflammation has an important role in BD, as well as the significant changes in biological rhythms. It is still necessary to better characterize the inflammatory pathway of AA.

Poor sleep quality associates with self-reported psychiatric and cardiometabolic symptoms independently of sleep timing patterns in a large sample of rural and urban workers.

Poor sleep associates with mental and cardiometabolic pathological outcomes. The participation of sleep timing features in the pathways by which this relationship occurs is not clear. This study aims to evaluate the interrelationship between sleep quality and self-reported psychiatric/cardiometabolic symptoms, considering mediation and moderation effects of sleep timing patterns, and urban versus rural work environment, respectively; and to verify the association between sleep quality and polymorphisms of AANAT, RORA and TIMELESS genes. An epidemiological survey was performed in a rural area in southern Brazil. Eight-hundred and twenty-nine subjects were evaluated for sleep quality using the Pittsburgh Sleep Quality Index, and sleep timing patterns using the Munich Chronotype Questionnaire. Work characteristics and psychiatric/cardiometabolic symptoms were assessed using a structured self-report questionnaire. Three polymorphisms of AANAT, RORA and TIMELESS (rs3760138, rs782931 and rs774045, respectively) were genotyped in blood samples. We found statistically significant associations of poor sleep quality with self-reported psychiatric symptoms (B = 0.382; 95% CI 0.289-0.476; adjusted p-value <.001), and with self-reported cardiometabolic symptoms (B = 0.079; 95% CI 0.013-0.151; adjusted p-value = .048). The genetic analysis showed that RORA GA/AA genotype was associated to poor sleep quality (B = 0.146, 95% CI 0.054-0.239; adjusted p-value = .004). No moderated mediation effects were observed in the conditional analysis. TIMELESS polymorphism was not included in the analysis due to the low frequency of risk genotypes. These results yield new insights regarding the interrelationship between sleep characteristics and psychiatric/cardiometabolic self-reported symptoms, taking into account genes related to the biological clocks and melatonin pathways.

El sueño del niño con trastornos del neurodesarrollo / The sleep in children with neurodevelopmental disorders

El sueño adecuado es necesario para el desarrollo sináptico y la maduración cerebral, un sueño de mala calidad tiene efectos perjudiciales en las funciones cognitivas, de atención, memoria y conducta de los niños. La preocupación sobre la alta prevalencia de los problemas del sueño es amplia en todo el mundo; las consecuencias de estos problemas son incluso más importantes en los niños portadores de trastornos del neurodesarrollo; estos niños a menudo tienen dificultades de inicio y mantenimiento del sueño y despertares nocturnos frecuentes que afectan a sus problemas de conducta. El propósito de este escrito es revisar el estado del arte de los problemas del sueño en los niños con trastornos del neurodesarrollo. En este punto, es importante tener en cuenta el ritmo circadiano, un reloj que genéticamente dirige los ritmos celulares de transcripción, traslación y metabolismos. Este reloj se combina con el ambiente diurno y nocturno coordinando estos mecanismos durante los ciclos luz/oscuridad, sueño/vigilia, frío/calor, ingesta/ayuno, tanto diariamente como en las diferentes estaciones. En conclusión, los problemas del sueño son un factor condicionante de la evolución y calidad de vida de los niños con trastornos del neurodesarrollo, que debe ser tenido en cuenta en todos los casos y ocupar un lugar preferente tanto en la etapa diagnóstica como en la terapéutica.

Adequate sleep is of critical need for a typical synaptic development and brain maturation, a poor quality sleep can have detrimental effects on children's' cognitive attention, memory, mood regulation, and behavior functions. Great concern has been voiced out regarding the high prevalence of poor sleep in children worldwide, the effects of poor sleep may be even more pronounced in children with neurodevelopmental disorders; these children often have difficulties with falling and staying asleep and with night awakenings, this has a strong association with daytime behavior problems. The purpose of this article is to provide an overview of the state of the science of sleep in children with a neurodevelopmental disorder. In this context, it is important to take the circadian cycle into account, a genetically encoded clock that drives cellular rhythms of transcription, translation and metabolism. The circadian clock interacts with the diurnal and nocturnal environment that also drives transcription and metabolism during light/dark, sleep/wake, hot/cold and feast/fast daily and seasonal cycles In conclusion, the sleep problems are a conditioning factor in the evolution and quality of life of children with neurodevelopmental disorders that must be taken into account in all cases and occupy a preferential place in both the diagnostic and the therapeutic stages.

[The sleep in children with neurodevelopmental disorders]. / El sueño del niño con trastornos del neurodesarrollo.

Adequate sleep is of critical need for a typical synaptic development and brain maturation, a poor quality sleep can have detrimental effects on children's' cognitive attention, memory, mood regulation, and behavior functions. Great concern has been voiced out regarding the high prevalence of poor sleep in children worldwide, the effects of poor sleep may be even more pronounced in children with neurodevelopmental disorders; these children often have difficulties with falling and staying asleep and with night awakenings, this has a strong association with daytime behavior problems. The purpose of this article is to provide an overview of the state of the science of sleep in children with a neurodevelopmental disorder. In this context, it is important to take the circadian cycle into account, a genetically encoded clock that drives cellular rhythms of transcription, translation and metabolism. The circadian clock interacts with the diurnal and nocturnal environment that also drives transcription and metabolism during light/dark, sleep/wake, hot/cold and feast/fast daily and seasonal cycles In conclusion, the sleep problems are a conditioning factor in the evolution and quality of life of children with neurodevelopmental disorders that must be taken into account in all cases and occupy a preferential place in both the diagnostic and the therapeutic stages.

El sueño adecuado es necesario para el desarrollo sináptico y la maduración cerebral, un sueño de mala calidad tiene efectos perjudiciales en las funciones cognitivas, de atención, memoria y conducta de los niños. La preocupación sobre la alta prevalencia de los problemas del sueño es amplia en todo el mundo; las consecuencias de estos problemas son incluso más importantes en los niños portadores de trastornos del neurodesarrollo; estos niños a menudo tienen dificultades de inicio y mantenimiento del sueño y despertares nocturnos frecuentes que afectan a sus problemas de conducta. El propósito de este escrito es revisar el estado del arte de los problemas del sueño en los niños con trastornos del neurodesarrollo. En este punto, es importante tener en cuenta el ritmo circadiano, un reloj que genéticamente dirige los ritmos celulares de transcripción, traslación y metabolismos. Este reloj se combina con el ambiente diurno y nocturno coordinando estos mecanismos durante los ciclos luz/oscuridad, sueño/vigilia, frío/calor, ingesta/ayuno, tanto diariamente como en las diferentes estaciones. En conclusión, los problemas del sueño son un factor condicionante de la evolución y calidad de vida de los niños con trastornos del neurodesarrollo, que debe ser tenido en cuenta en todos los casos y ocupar un lugar preferente tanto en la etapa diagnóstica como en la terapéutica.

Biological Rhythm Disruption Associated with Obesity in School Children.

BACKGROUND: Biological rhythm is the daily metabolic cycle of mammals that involves the sleep-wake cycles, hormone release, eating habits and digestion, body temperature, and other important bodily functions that are repeated daily. Thus, greater difficulty in maintaining the circadian rhythms may be involved in the increased risk of obesity. This study assessed the association between biological rhythm disruption and childhood obesity among school children. METHODS: This is a cross-sectional study with 7-8-year-old school children enrolled in a public school in the city of Pelotas-RS. The sample was drawn through multistage sampling. The Biological Rhythms Interview of Assessment in Neuropsychiatry-Kids (BRIAN-Kids) was used to assess the degree of difficulty maintaining the biological rhythm. BMI was calculated as weight/height2 (kg/m2). RESULTS: A total of 596 children and their caregivers participated in this study. The prevalence of obesity was 24% among school children, 28.9% for girls, and 19.4 for boys (p = 0.009). Obese children had greater difficulties in maintaining the biological rhythm compared to nonobese children (p = 0.007). Some of these difficulties included sleep (p = 0.008), overall activities (p = 0.027), social rhythm (p = 0.033), and eating (p = 0.032) pattern. CONCLUSION: Approximately one-quarter of children were obese. This finding was associated with the caregiver characteristics and some difficulties in maintaining the biological rhythm.