Taking biological rhythms into account: From study design to results reporting.

Numerous physiological and behavioral processes in living organisms exhibit strong rhythmicity and are regulated within a 24-hour cycle. These include locomotor activity and sleep patterns, feeding-fasting cycles, hormone synthesis, body temperature, and even mood and cognitive abilities, all of which are segregated into different phases throughout the day. These processes are governed by the internal timing system, a hierarchical multi-oscillator structure conserved across all organisms, from bacteria to humans. Circadian rhythms have been seen across multiple taxonomic kingdoms. In mammals, a hierarchical internal timing system is comprised of so-called central and periphereal clocks. Although these rhythms are intrinsic, they are under environmental influences, such as seasonal temperature changes, photoperiod variations, and day-night cycles. Recognizing the existence of biological rhythms and their primary external influences is crucial when designing and reporting experiments. Neglecting these physiological variations may result in inconsistent findings and misinterpretations. Thus, here we propose to incorporate biological rhythms into all stages of human and animal research, including experiment design, analysis, and reporting of findings. We also provide a flowchart to support decision-making during the design process, considering biological rhythmicity, along with a checklist outlining key factors that should be considered and documented throughout the study. This comprehensive approach not only benefits the field of chronobiology but also holds value for various other research disciplines. The insights gained from this study have the potential to enhance the validity, reproducibility, and overall quality of scientific investigations, providing valuable guidance for planning, developing, and communicating scientific studies.

Individual light history matters to deal with the Antarctic summer.

The effect of light, main zeitgeber of the circadian system, depends on the time of day it is received. A brief trip to the Antarctic summer (ANT) allowed us to explore the impact of a sudden and synchronized increase in light exposure on activity-rest rhythms and sleep patterns of 11 Uruguayan university students, and to assess the significance of light history in determining individual circadian phase shift. Measurements collected in the peri-equinox in Montevideo, Uruguay (baseline situation, MVD) and in ANT, included sleep logs, actigraphy, and salivary melatonin to determine dim-light melatonin onset (DLMO), the most reliable marker of circadian phase. The increase in light exposure in ANT with respect to MVD (affecting both light-sensitive windows with opposite effects on the circadian phase) resulted in no net change in DLMO among participants as some participants advanced their DLMO and some others delayed it. The ultimate cause of each participant's distinctive circadian phase shift relied on the unique change in light exposure each individual was subjected to between their MVD and ANT. This study shows an association between the individual light history and the circadian phase shift.

Effective recommendations towards healthy routines to preserve mental health during the COVID-19 pandemic

Objective: To assess the adherence to a set of evidence-based recommendations to support mental health during the coronavirus disease 2019 (COVID-19) pandemic and its association with depressive and anxiety symptoms. Methods: A team of health workers and researchers prepared the recommendations, formatted into three volumes (1: COVID-19 prevention; 2: Healthy habits; 3: Biological clock and sleep). Participants were randomized to receive only Volume 1 (control), Volumes 1 and 2, Volumes 1 and 3, or all volumes. We used a convenience sample of Portuguese-speaking participants over age 18 years. An online survey consisting of sociodemographic and behavioral questionnaires and mental health instruments (Patient Health Questionnaire-9 [PHQ-9] and Generalized Anxiety Disorder-7 [GAD-7]) was administered. At 14 and 28 days later, participants were invited to complete follow-up surveys, which also included questions regarding adherence to the recommendations. A total of 409 participants completed the study - mostly young adult women holding university degrees. Results: The set of recommendations contained in Volumes 2 and 3 was effective in protecting mental health, as suggested by significant associations of adherence with PHQ-9 and GAD-7 scores (reflecting anxiety and depression symptoms, respectively). Conclusion: The recommendations developed in this study could be useful to prevent negative mental health effects in the context of the pandemic and beyond.

Effective recommendations towards healthy routines to preserve mental health during the COVID-19 pandemic.

OBJECTIVE: To assess the adherence to a set of evidence-based recommendations to support mental health during the coronavirus disease 2019 (COVID-19) pandemic and its association with depressive and anxiety symptoms. METHODS: A team of health workers and researchers prepared the recommendations, formatted into three volumes (1: COVID-19 prevention; 2: Healthy habits; 3: Biological clock and sleep). Participants were randomized to receive only Volume 1 (control), Volumes 1 and 2, Volumes 1 and 3, or all volumes. We used a convenience sample of Portuguese-speaking participants over age 18 years. An online survey consisting of sociodemographic and behavioral questionnaires and mental health instruments (Patient Health Questionnaire-9 [PHQ-9] and Generalized Anxiety Disorder-7 [GAD-7]) was administered. At 14 and 28 days later, participants were invited to complete follow-up surveys, which also included questions regarding adherence to the recommendations. A total of 409 participants completed the study - mostly young adult women holding university degrees. RESULTS: The set of recommendations contained in Volumes 2 and 3 was effective in protecting mental health, as suggested by significant associations of adherence with PHQ-9 and GAD-7 scores (reflecting anxiety and depression symptoms, respectively). CONCLUSION: The recommendations developed in this study could be useful to prevent negative mental health effects in the context of the pandemic and beyond.

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.

Circadian Strain, Light Exposure, and Depressive Symptoms in Rural Communities of Southern Brazil.

Irregular light-dark cycles and circadian/sleep disturbances have been suggested as risk or co-occurring factors in depression. Among a set of metrics developed to quantify strain on the circadian system, social jetlag (SJL) has been put forward as a measure of the discrepancy between biological and social clocks. Here, we approached the question on whether light exposure and SJL would also be associated with depressive symptoms in Quilombola communities in Southern Brazil. These rural communities are void of potential confounders of modern lifestyles and show low levels of SJL. 210 Quilombolas (age range 16-92; 56% women) were asked about their sleep times and light exposure using the Munich ChronoType Questionnaire (MCTQ). The Beck Depression Inventory (BDI) was used to assess depressive symptoms. Additionally, we analyzed 7-day actimetry recordings in 124 subjects. BDI scores higher than 10 (having clinically significant depressive symptoms; controlled for age and sex in the multivariate analysis) were positively associated with SJL >1 h and negatively associated with median light exposure during the day, especially in the morning from 8:00 to 10:00. Our results suggest that low light exposure during the day, and higher levels of SJL are associated with depressive symptoms; longitudinal and experimental studies are needed to understand the underlying mechanisms. Nevertheless, we highlight the potential of treatment strategies aimed at decreasing circadian strain and insufficient light exposure, which are suggested as areas of further research in Psychiatry.

How do stress, sleep quality, and chronotype associate with clinically significant depressive symptoms? A study of young male military recruits in compulsory service

Objective: Although studies have shown an association between poor sleep and chronotype with psychiatric problems in young adults, few have focused on identifying multiple concomitant risk factors. Methods: We assessed depressive symptoms (Beck Depression Inventory [BDI]), circadian typology (Morningness-Eveningness Questionnaire [MEQ]), sleep quality (Pittsburgh Sleep Quality Index [PSQI]), perceived stress (Perceived Stress Scale [PSS]), social rhythm (Social Rhythm Metrics [SRM]), and salivary cortisol (morning, evening and night, n=37) in 236 men (all 18 years old). Separate analyses were conducted to understand how each PSQI domain was associated with depressive symptoms. Results: Depressive symptoms were more prevalent in individuals with higher perceived stress (prevalence ratio [PR] = 6.429, p < 0.001), evening types (PR = 2.58, p < 0.001) and poor sleepers (PR = 1.808, p = 0.046). Multivariate modeling showed that these three variables were independently associated with depressive symptoms (all p < 0.05). The PSQI items subjective sleep quality and sleep disturbances were significantly more prevalent in individuals with depressive symptoms (PR = 2.210, p = 0.009 and PR = 2.198, p = 0.008). Lower levels of morning cortisol were significantly associated with higher depressive scores (r = -0.335; p = 0.043). Conclusion: It is important to evaluate multiple factors related to sleep and chronotype in youth depression studies, since this can provide important tools for comprehending and managing mental health problems.

How do stress, sleep quality, and chronotype associate with clinically significant depressive symptoms? A study of young male military recruits in compulsory service.

OBJECTIVE: Although studies have shown an association between poor sleep and chronotype with psychiatric problems in young adults, few have focused on identifying multiple concomitant risk factors. METHODS: We assessed depressive symptoms (Beck Depression Inventory [BDI]), circadian typology (Morningness-Eveningness Questionnaire [MEQ]), sleep quality (Pittsburgh Sleep Quality Index [PSQI]), perceived stress (Perceived Stress Scale [PSS]), social rhythm (Social Rhythm Metrics [SRM]), and salivary cortisol (morning, evening and night, n=37) in 236 men (all 18 years old). Separate analyses were conducted to understand how each PSQI domain was associated with depressive symptoms. RESULTS: Depressive symptoms were more prevalent in individuals with higher perceived stress (prevalence ratio [PR] = 6.429, p < 0.001), evening types (PR = 2.58, p < 0.001) and poor sleepers (PR = 1.808, p = 0.046). Multivariate modeling showed that these three variables were independently associated with depressive symptoms (all p < 0.05). The PSQI items subjective sleep quality and sleep disturbances were significantly more prevalent in individuals with depressive symptoms (PR = 2.210, p = 0.009 and PR = 2.198, p = 0.008). Lower levels of morning cortisol were significantly associated with higher depressive scores (r = -0.335; p = 0.043). CONCLUSION: It is important to evaluate multiple factors related to sleep and chronotype in youth depression studies, since this can provide important tools for comprehending and managing mental health problems.