Circadian rhythmicity in schizophrenia male patients with and without substance use disorder comorbidity.

Circadian rhythmicity is associated to clinical variables that play an important role in both schizophrenia (SZ) and substance use disorders (SUD), although the characteristics of the coexistence of these two diagnoses (SZ +) remain mostly unknown. Hence, we studied a sample of 165 male patients divided in three groups each of 55, according to their diagnoses (SZ + , SZ, and SUD), as well as a healthy control (HC; n = 90) group. Alongside with sociodemographic and clinical variables, circadian rhythms were registered through a sleep-wake data structured interview, a circadian typology questionnaire, and distal skin temperature (DST) using the Thermochron iButton every 2 min during 48 h. Analyses showed that SZ + and SZ patients presented a longer sleep (delay in wake-up time) and mostly an intermediate circadian typology, while SUD patients slept less hours, displaying a morning typology. The DST showed the highest daily activation and stability for the SUD group, even when compared with the HC group. The presence of schizophrenia (SZ + and SZ) was related to a DST pattern with a reduced amplitude determined by a wakefulness impairment, which was more pronounced for SZ patients whose sleep period was adequate. The assessment of circadian rhythms in under treatment male patients with SZ should be focused on the diurnal period as a possible marker of either treatment adherence or patient's recovery, irrespective of the presence of a comorbid SUD. Further research with additional objective measures may provide knowledge transferable to therapeutic strategies and could be useful to establish possible endophenotypes in the future.

Membrane lipids and maximum lifespan in clownfish.

The longevity-homeoviscous adaptation (LHA) theory of ageing states that lipid composition of cell membranes is linked to metabolic rate and lifespan, which has been widely shown in mammals and birds but not sufficiently in fish. In this study, two species of the genus Amphiprion (Amphiprion percula and Amphiprion clarkii, with estimated maximum lifespan potentials [MLSP] of 30 and 9-16 years, respectively) and the damselfish Chromis viridis (estimated MLSP of 1-2 years) were chosen to test the LHA theory of ageing in a potential model of exceptional longevity. Brain, livers and samples of skeletal muscle were collected for lipid analyses and integral part in the computation of membrane peroxidation indexes (PIn) from phospholipid (PL) fractions and PL fatty acid composition. When only the two Amphiprion species were compared, results pointed to the existence of a negative correlation between membrane PIn value and maximum lifespan, well in line with the predictions from the LHA theory of ageing. Nevertheless, contradictory data were obtained when the two Amphiprion species were compared to the shorter-lived C. viridis. These results along with those obtained in previous studies on fish denote that the magnitude (and sometimes the direction) of the differences observed in membrane lipid composition and peroxidation index with MLSP cannot explain alone the diversity in longevity found among fishes.

Activity-rest circadian pattern and academic achievement, executive function, and intelligence in children with obesity.

This study aimed to analyze the associations of activity-rest pattern indicators with academic achievement, executive function, and intelligence and to explore whether these associations are mediated by the total gray matter volume among children with overweight/obesity. Ninety-five children (10 ± 1 year, 37 girls) with overweight/obesity (based on the World Obesity Federation body mass index cutoff points) were included in this cross-sectional study. Hip- and wrist-worn ActiGraph GT3X + accelerometers were used to assess the activity-rest pattern. Interdaily stability (IS), intradaily variability (IV), the mean value of the lowest 5 hours (L5), and the mean value of the maximum 10 hours (M10) of activity and their respective timing (TL5, TM10) were used as indicators of the activity-rest pattern throughout the day. Chronotype and social jetlag were used as indicators of circadian preference. Academic achievement, executive function, and intelligence were assessed with standardized tests. Gray matter volume was acquired by magnetic resonance imaging (MRI). IS was positively associated with executive function (ß = 0.244, P = .014). IV was negatively associated with mathematics and academic applications (ß: -0.211 to -0.238, P's ≤ .026). Later TM10 in the day was related to lower writing, academic skills, and intelligence (ß: -0.229 to -0.271, P's ≤ .025). None of the associations found were mediated by gray matter volume. A non-fragmented and stable activity-rest pattern and earlier physical activity in the day were associated with better academic achievement, executive function, and intelligence in children with overweight/obesity. Further studies are required to corroborate or contrast our findings.

Impact of an intermittent and localized cooling intervention on skin temperature, sleep quality and energy expenditure in free-living, young, healthy adults.

Where people live and work together it is not always possible to modify the ambient temperature; ways must therefore be found that allow individuals to feel thermally comfortable in such settings. The Embr Wave® is a wrist-worn device marketed as a 'personal thermostat' that can apply a local cooling stimulus to the skin. The aim of the present study was to determine the effect of an intermittent mild cold stimulus of 25 °C for 15-20 s every 5 min over 3.5 days under free-living conditions on 1) skin temperature, 2) perception of skin temperature, 3) sleep quality and 4) resting energy expenditure (REE) in young, healthy adults. Ten subjects wore the device for 3.5 consecutive days. This intervention reduced distal skin temperature after correcting for personal ambient temperature (P < 0.05), but did not affect the subjects' the perception of skin temperature, sleep quality or REE (all P ≥ 0.051). Thus, this intermittent mild cold regime can reduce distal skin temperature, and wearing it under free-living conditions for 3.5 days does not seem to impair the perception of skin temperature and sleep quality or modify REE.

The clock is ticking. Ageing of the circadian system: From physiology to cell cycle.

The circadian system is the responsible to organise the internal temporal order in relation to the environment of every process of the organisms producing the circadian rhythms. These rhythms have a fixed phase relationship among them and with the environment in order to optimise the available energy and resources. From a cellular level, circadian rhythms are controlled by genetic positive and negative auto-regulated transcriptional and translational feedback loops, which generate 24h rhythms in mRNA and protein levels of the clock components. It has been described about 10% of the genome is controlled by clock genes, with special relevance, due to its implications, to the cell cycle. Ageing is a deleterious process which affects all the organisms' structures including circadian system. The circadian system's ageing may produce a disorganisation among the circadian rhythms, arrhythmicity and, even, disconnection from the environment, resulting in a detrimental situation to the organism. In addition, some environmental conditions can produce circadian disruption, also called chronodisruption, which may produce many pathologies including accelerated ageing. Finally, some strategies to prevent, palliate or counteract chronodisruption effects have been proposed to enhance the circadian system, also called chronoenhancement. This review tries to gather recent advances in the chronobiology of the ageing process, including cell cycle, neurogenesis process and physiology.

Age-related changes in mitochondrial membrane composition of Nothobranchius furzeri.: comparison with a longer-living Nothobranchius species.

Membrane compositions, particularly of mitochondria, could be critical factors in the mechanisms of growth and aging, especially during phases of high oxidative stress that result in molecular damage. Changes affecting lipid class or fatty acid (FA) compositions could affect phospholipid (PL) properties and alter mitochondrial function. In the present study, mitochondrial membrane PL compositions were analysed throughout the life-cycle of Nothobranchius furzeri, a species with explosive growth and one of the shortest-lived vertebrates. Mitochondrial PLs showed several changes with age. Proportions of total PLs and PC were reduced while an increase in PS, CL and PE was observed, mainly between the 2.5 and 5 months of fish age, the time during which animals doubled their weight. FA compositions of individual PLs in mitochondria were also significantly affected with age suggesting the existence of increasing damage to mitochondrial lipids during the life-cycle of N. furzeri that could be one of the main contributors to degraded mitochondrial function associated with aging. The peroxidation index values from N. furzeri mitochondrial PLs were significantly lower than those reported in N. rachovii, a species with a twofold longer life span than N. furzeri, which seems to contradict the membrane pacemaker theory of animal metabolism.

Relationship between Circadian System Status, Child-Pugh Score, and Clinical Outcome in Cirrhotic Patients on Waiting Lists for Liver Transplantation.

Background/Objectives: Many patients suffering from liver cirrhosis are eventually added to waiting lists for liver transplantation whose priority is established based on scales such as the Child-Pugh score. However, two marker rhythms of the circadian system, motor activity and distal temperature, are not evaluated. Methods: To determine the relationship between the functional status of the circadian system and the Child-Pugh scale in patients awaiting liver transplantation, distal temperature, motor activity, and light exposure rhythms were monitored for a full week using a wrist device (Kronowise 6.0) in 63 patients (17 women, 46 men) aged between 20 and 76 years. Results: Circadian parameters (amplitude, regularity, and fragmentation) of motor activity rhythms, distal temperature, and light exposure worsen in close association with liver disease severity as assessed by using the Child-Pugh score. Likewise, the worsening of rhythmic parameters and liver disease is associated with a deterioration in the markers of the red series: count, hemoglobin, and hematocrit. Conclusions: These results indicate the utility of ambulatory monitoring of marker rhythms to complement the clinical information provided by the Child-Pugh scale and to help establish nutrition, physical exercise, and sleep guidelines that promote better survival and quality of life in these patients.

A new integrated variable based on thermometry, actimetry and body position (TAP) to evaluate circadian system status in humans.

The disruption of the circadian system in humans has been associated with the development of chronic illnesses and the worsening of pre-existing pathologies. Therefore, the assessment of human circadian system function under free living conditions using non-invasive techniques needs further research. Traditionally, overt rhythms such as activity and body temperature have been analyzed separately; however, a comprehensive index could reduce individual recording artifacts. Thus, a new variable (TAP), based on the integrated analysis of three simultaneous recordings: skin wrist temperature (T), motor activity (A) and body position (P) has been developed. Furthermore, we also tested the reliability of a single numerical index, the Circadian Function Index (CFI), to determine the circadian robustness. An actimeter and a temperature sensor were placed on the arm and wrist of the non-dominant hand, respectively, of 49 healthy young volunteers for a period of one week. T, A and P values were normalized for each subject. A non-parametric analysis was applied to both TAP and the separate variables to calculate their interdaily stability, intradaily variability and relative amplitude, and these values were then used for the CFI calculation. Modeling analyses were performed in order to determine TAP and CFI reliability. Each variable (T, A, P or TAP) was independently correlated with rest-activity logs kept by the volunteers. The highest correlation (r= -0.993, p<0.0001), along with highest specificity (0.870), sensitivity (0.740) and accuracy (0.904), were obtained when rest-activity records were compared to TAP. Furthermore, the CFI proved to be very sensitive to changes in circadian robustness. Our results demonstrate that the integrated TAP variable and the CFI calculation are powerful methods to assess circadian system status, improving sensitivity, specificity and accuracy in differentiating activity from rest over the analysis of wrist temperature, body position or activity alone.

Smartphone App (2kmFIT-App) for Measuring Cardiorespiratory Fitness: Validity and Reliability Study.

BACKGROUND: There is strong evidence suggesting that higher levels of cardiorespiratory fitness (CRF) are associated with a healthier metabolic profile, and that CRF can serve as a powerful predictor of morbidity and mortality. In this context, a smartphone app based on the 2-km walk test (UKK test) would provide the possibility to assess CRF remotely in individuals geographically distributed around a country or continent, and even between continents, with minimal equipment and low costs. OBJECTIVE: The overall aim of this study was to evaluate the validity and reliability of 2kmFIT-App developed for Android and iOS mobile operating systems to estimate maximum oxygen consumption (VO2max) as an indicator of CRF. The specific aims of the study were to determine the validity of 2kmFIT-App to track distance and calculate heart rate (HR). METHODS: Twenty participants were included for field-testing validation and reliability analysis. The participants completed the UKK test twice using 2kmFIT-App. Distance and HR were measured with the app as well as with accurate methods, and VO2max was estimated using the UKK test equation. RESULTS: The validity results showed the following mean differences (app minus criterion): distance (-70.40, SD 51.47 meters), time (-0.59, SD 0.45 minutes), HR (-16.75, SD 9.96 beats/minute), and VO2max (3.59, SD 2.01 ml/kg/min). There was moderate validity found for HR (intraclass correlation coefficient [ICC] 0.731, 95% CI -0.211 to 0.942) and good validity found for VO2max (ICC 0.878, 95% CI -0.125 to 0.972). The reliability results showed the following mean differences (retest minus test): app distance (25.99, SD 43.21 meters), app time (-0.15, SD 0.94 seconds), pace (-0.18, SD 0.33 min/km), app HR (-4.5, 13.44 beats/minute), and app VO2max (0.92, SD 3.04 ml/kg/min). There was good reliability for app HR (ICC 0.897, 95% CI 0.742-0.959) and excellent validity for app VO2max (ICC 0.932, 95% CI 0.830-0.973). All of these findings were observed when using the app with an Android operating system, whereas validity was poor when the app was used with iOS. CONCLUSIONS: This study shows that 2kmFIT-App is a new, scientifically valid and reliable tool able to objectively and remotely estimate CRF, HR, and distance with an Android but not iOS mobile operating system. However, certain limitations such as the time required by 2kmFIT-App to calculate HR or the temperature environment should be considered when using the app.

Ambulatory circadian monitoring in sleep disordered breathing patients and CPAP treatment.

Our aim was to evaluate the circadian rhythm of motor activity, body position and integrated variable TAP (composed by wrist Temperature, motor Activity and body Position) in Sleep Disordered Breathing (SDB), its relation to SDB severity and the effect of continuous positive airway pressure (CPAP) on these circadian rhythms. To do this, we monitored motor activity and body position rhythms of 78 SDB patients (53.3 ± 1.2 years old, 26.9% women) and 32 healthy subjects (51.4 ± 3.2 years old, 43.8% women) for 1 week. On the last day of that week, SDB patients underwent a polysomnography followed by a Maintenance of Wakefulness Test, Multiple Sleep Latency Test and Sustained Attention to Response Task protocol. A subgroup of 18 moderate to severe SDB patients was treated with CPAP and monitored again after 3 months under treatment. A non-parametrical analysis was performed to characterize the circadian patterns to assess differences between groups and associations between sleep and circadian parameters. Circadian variables were altered in SDB, exhibiting a direct relationship to SDB severity. The motor activity pattern showed a clear improvement with CPAP treatment. Thus, circadian ambulatory monitoring, including the integrated variable TAP, could be used to evaluate the circadian alterations caused by SDB and activity pattern to monitor the effect of CPAP treatment.

Circadian Characteristics in Patients under Treatment for Substance Use Disorders and Severe Mental Illness (Schizophrenia, Major Depression and Bipolar Disorder).

Dual disorders (substance use and mental illness comorbidity) are a condition that has been strongly associated with severe symptomatology and clinical complications. The study of circadian characteristics in patients with Severe Mental Illness or Substance Use Disorder (SUD) has shown that such variables are related with mood symptoms and worse recovery. In absence of studies about circadian characteristics in patients with dual disorders we examined a sample of 114 male participants with SUD and comorbid Schizophrenia (SZ+; n = 38), Bipolar Disorder (BD+; n = 36) and Major Depressive Disorder (MDD+; n = 40). The possible differences in the sample of patients according to their psychiatric diagnosis, circadian functioning with recordings of distal skin temperature during 48 h (Thermochron iButton®), circadian typology and sleep-wake schedules were explored. MDD+ patients were more morning-type, while SZ+ and BD+ had an intermediate-type; the morning-type was more frequent among participants under inpatient SUD treatment. SZ+ patients had the highest amount of sleeping hours, lowest arousal and highest drowsiness followed by BD+ and MDD+, respectively. These observed differences suggest that treatment for patients with dual disorders could include chronobiological strategies to help them synchronize patterns with the day-light cycle, since morning-type is associated with better outcomes and recovery.

A Systematic Review of Fitness Apps and Their Potential Clinical and Sports Utility for Objective and Remote Assessment of Cardiorespiratory Fitness.

BACKGROUND: Cardiorespiratory fitness (CRF) assessment provides key information regarding general health status that has high clinical utility. In addition, in the sports setting, CRF testing is needed to establish a baseline level, prescribe an individualized training program and monitor improvement in athletic performance. As such, the assessment of CRF has both clinical and sports utility. Technological advancements have led to increased digitization within healthcare and athletics. Nevertheless, further investigation is needed to enhance the validity and reliability of existing fitness apps for CRF assessment in both contexts. OBJECTIVES: The present review aimed to (1) systematically review the scientific literature, examining the validity and reliability of apps designed for CRF assessment; and (2) systematically review and qualitatively score available fitness apps in the two main app markets. Lastly, this systematic review outlines evidence-based practical recommendations for developing future apps that measure CRF. DATA SOURCES: The following sources were searched for relevant studies: PubMed, Web of Science®, ScopusTM, and SPORTDiscus, and data was also found within app markets (Google Play and the App Store). STUDY ELIGIBILITY CRITERIA: Eligible scientific studies examined the validity and/or reliability of apps for assessing CRF through a field-based fitness test. Criteria for the app markets involved apps that estimated CRF. STUDY APPRAISAL AND SYNTHESIS METHODS: The scientific literature search included four major electronic databases and the timeframe was set between 01 January 2000 and 31 October 2018. A total of 2796 articles were identified using a set of fitness-related terms, of which five articles were finally selected and included in this review. The app market search was undertaken by introducing keywords into the search engine of each app market without specified search categories. A total of 691 apps were identified using a set of fitness-related terms, of which 88 apps were finally included in the quantitative and qualitative synthesis. RESULTS: Five studies focused on the scientific validity of fitness tests with apps, while only two of these focused on reliability. Four studies used a sub-maximal fitness test via apps. Out of the scientific apps reviewed, the SA-6MWTapp showed the best validity against a criterion measure (r = 0.88), whilst the InterWalk app showed the highest test-retest reliability (ICC range 0.85-0.86). LIMITATIONS: Levels of evidence based on scientific validity/reliability of apps and on commercial apps could not be robustly determined due to the limited number of studies identified in the literature and the low-to-moderate quality of commercial apps. CONCLUSIONS: The results from this scientific review showed that few apps have been empirically tested, and among those that have, not all were valid or reliable. In addition, commercial apps were of low-to-moderate quality, suggesting that their potential for assessing CRF has yet to be realized. Lastly, this manuscript has identified evidence-based practical recommendations that apps might potentially offer to objectively and remotely assess CRF as a complementary tool to traditional methods in the clinical and sports settings.

The Mediating Role of Brown Fat and Skeletal Muscle Measured by 18 F-Fluorodeoxyglucose in the Thermoregulatory System in Young Adults.

OBJECTIVE: This study aimed to examine whether brown adipose tissue (BAT) or skeletal muscle activity mediates the relationship between personal level of environmental temperature (Personal-ET) and wrist skin temperature (WT). Moreover, we examined whether BAT and skeletal muscle have a mediating role between Personal-ET and WT (as a proxy of peripheral vasoconstriction/vasodilation). METHODS: The levels of BAT were quantified by cold-induced 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography scan and measured the Personal-ET and WT by using iButtons (Maxim Integrated, Dallas, Texas) in 75 participants (74.6% women). RESULTS: The study found that BAT volume and metabolic activity played a positive and significant role (up to 25.4%) in the association between Personal-ET and WT. In addition, at the coldest temperatures, the participants with lower levels of WT (inducing higher peripheral vasoconstriction) had higher levels of BAT outcomes, whereas in warm temperatures, participants with higher levels of WT (inducing higher peripheral vasodilation) had lower levels of BAT outcomes. The study did not find any mediating role of skeletal muscle activity. CONCLUSIONS: BAT volume and metabolic activity play a role in the relationship between Personal-ET and WT. Moreover, the data suggest that there are two distinct phenotypes: individuals who respond better to the cold, both through nonshivering thermogenesis and peripheral vasoconstriction, and individuals who respond better to the heat.

Relationship between the Daily Rhythm of Distal Skin Temperature and Brown Adipose Tissue 18F-FDG Uptake in Young Sedentary Adults.

The present study examines whether the daily rhythm of distal skin temperature (DST) is associated with brown adipose tissue (BAT) metabolism as determined by 18F-fluorodeoxyglucose (18F-FDG) uptake in young adults. Using a wireless thermometer (iButton) worn on the nondominant wrist, DST was measured in 77 subjects (26% male; age 22 ± 2 years; body mass index 25.2 ± 4.8 kg/m2) for 7 consecutive days. The temperatures to which they were habitually exposed over the day were also recorded. The interday stability of DST was calculated from the collected data, along with the intraday variability and relative amplitude; the mean temperature of the 5 and 10 consecutive hours with the maximum and minimum DST values, respectively; and when these hours occurred. Following exposure to cold, BAT volume and mean and peak standardized 18F-FDG uptake (SUVmean and SUVpeak) were determined for each subject via static 18F-FDG positron emission tomography/computed tomography scanning. Relative amplitude and the time at which the 10 consecutive hours of minimum DST values occurred were positively associated with BAT volume, SUVmean, and SUVpeak (p ≤ 0.02), whereas the mean DST of that period was inversely associated with the latter BAT variables (p ≤ 0.01). The interday stability and intraday variability of the DST were also associated (directly and inversely, respectively) with BAT SUVpeak (p ≤ 0.02 for both). All of these associations disappeared, however, when the analyses were adjusted for the ambient temperature to which the subjects were habitually exposed. Thus, the relationship between the daily rhythm of DST and BAT activity estimated by 18F-FDG uptake is masked by environmental and likely behavioral factors. Of note is that those participants exposed to the lowest ambient temperature showed 3 to 5 times more BAT volume and activity compared with subjects who were exposed to a warmer ambient temperature.

Assessing Chronotypes by Ambulatory Circadian Monitoring.

In order to develop objective indexes for chronotype identification by means of direct measurement of circadian rhythms, 159 undergraduate students were recruited as volunteers and instructed to wear ambulatory circadian monitoring (ACM) sensors that continuously gathered information on the individual's environmental light and temperature exposure, wrist temperature, body position, activity, and the integrated TAP (temperature, activity, and position) variable for 7 consecutive days under regular free-living conditions. Among all the proposed indexes, the night phase marker (NPM) of the TAP variable was the best suited to discriminate among chronotypes, due to its relationship with the Munich ChronoType Questionnaire (ß = 0.531; p < 0.001). The NPM of TAP allowed subjects to be classified as early- (E-type, 20%), neither- (N-type, 60%), and late-types (L-type, 20%), each of which had its own characteristics. In terms of light exposure, while all subjects had short exposure times to bright light (>100 lux), with a daily average of 93.84 ± 5.72 min, the earlier chronotypes were exposed to brighter days and darker nights compared to the later chronotypes. Furthermore, the earlier chronotypes were associated with higher stability and day-night contrast, along with an earlier phase, which could be the cause or consequence of the light exposure habits. Overall, these data support the use of ACM for chronotype identification and for evaluation under free living conditions, using objective markers.

Circadian Rhythmic Characteristics in Men With Substance Use Disorder Under Treatment. Influence of Age of Onset of Substance Use and Duration of Abstinence.

There is evidence of the reciprocal influence between the alteration of circadian rhythms and Substance Use Disorders (SUD), and part of the success of the SUD treatment lays in the patient's rhythmic recovery. We aim to elucidate the effect of the SUD treatment in circadian rhythmicity considering, for the first time, the age of onset of substance use (OSU) and duration of abstinence. We registered the sleep-wake schedules, the chronotype and the distal skin temperature of 114 SUD patients with at least 3 months of abstinence, considering whether they had begun consumption at age 16 or earlier (OSU ≤ 16, n = 56) or at 17 or later (OSU ≥ 17, n = 58), and duration of abstinence as short (SA: 3 to 5 months, n = 38), medium (MA: 6 to 9 months, n = 35) or long (LA: more than 9 months, n = 41). Moreover, we compared the patients' distal skin temperature pattern with a similar sample of healthy controls (HC, n = 103). SUD patients showed a morningness tendency and higher night values, amplitude and stability, a better adjustment to the cosine model and lower minimum temperature and circadianity index in the distal skin temperature rhythm, in contrast to the HC group. The OSU ≥ 17 and LA groups showed a more robust distal skin temperature pattern, as well as milder clinical characteristics when compared to the OSU ≤ 16 and SA groups, respectively. The circadian disturbances associated to substance consumption seem to improve with treatment, although the age of OSU and the duration of abstinence are modulating variables. Our results highlight the need to include chronobiological strategies that boost circadian rhythmicity both in SUD prevention and rehabilitation programs. The measurement of distal skin temperature rhythm, a simple and reliable procedure, could be considered an indicator of response to treatment in SUD patients.

Bright light therapy versus physical exercise to prevent co-morbid depression and obesity in adolescents and young adults with attention-deficit / hyperactivity disorder: study protocol for a randomized controlled trial.

BACKGROUND: The risk for major depression and obesity is increased in adolescents and adults with attention-deficit / hyperactivity disorder (ADHD) and adolescent ADHD predicts adult depression and obesity. Non-pharmacological interventions to treat and prevent these co-morbidities are urgently needed. Bright light therapy (BLT) improves day-night rhythm and is an emerging therapy for major depression. Exercise intervention (EI) reduces obesity and improves depressive symptoms. To date, no randomized controlled trial (RCT) has been performed to establish feasibility and efficacy of these interventions targeting the prevention of co-morbid depression and obesity in ADHD. We hypothesize that the two manualized interventions in combination with mobile health-based monitoring and reinforcement will result in less depressive symptoms and obesity compared to treatment as usual in adolescents and young adults with ADHD. METHODS: This trial is a prospective, pilot phase-IIa, parallel-group RCT with three arms (two add-on treatment groups [BLT, EI] and one treatment as usual [TAU] control group). The primary outcome variable is change in the Inventory of Depressive Symptomatology total score (observer-blinded assessment) between baseline and ten weeks of intervention. This variable is analyzed with a mixed model for repeated measures approach investigating the treatment effect with respect to all three groups. A total of 330 participants with ADHD, aged 14 - < 30 years, will be screened at the four study centers. To establish effect sizes, the sample size was planned at the liberal significance level of α = 0.10 (two-sided) and the power of 1-ß = 80% in order to find medium effects. Secondary outcomes measures including change in obesity, ADHD symptoms, general psychopathology, health-related quality of life, neurocognitive function, chronotype, and physical fitness are explored after the end of the intervention and at the 12-week follow-up. DISCUSSION: This is the first pilot RCT on the use of BLT and EI in combination with mobile health-based monitoring and reinforcement targeting the prevention of co-morbid depression and obesity in adolescents and young adults with ADHD. If at least medium effects can be established with regard to the prevention of depressive symptoms and obesity, a larger scale confirmatory phase-III trial may be warranted. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00011666. Registered on 9 February 2017. ClinicalTrials.gov, NCT03371810. Registered on 13 December 2017.

Circadian Impairment of Distal Skin Temperature Rhythm in Patients With Sleep-Disordered Breathing: The Effect of CPAP.

Study objectives: Our aim was to evaluate the circadian rhythm of distal skin temperature (DST) in sleep-disordered breathing (SDB), its relation to excessive daytime sleepiness and the effect of continuous positive airway pressure (CPAP) on DST. Methods: Eighty SDB patients (53.1 ± 1.2 years old, 27.6% women) and 67 healthy participants (52.3 ± 1.6 years old, 26.9% women) wore a temperature data logger for 1 week. On the last day of that week, SDB patients underwent a polysomnography followed by a Maintenance of Wakefulness Test (MWT), Multiple Sleep Latency Test, and Sustained Attention to Response Task protocol to objectively quantify daytime sleepiness. A subset of 21 moderate to severe SDB patients were treated with CPAP during at least 3 months and revaluated with the same procedure. A nonparametric analysis was performed to characterize DST to assess differences between groups and associations among DST, polysomnography, and daytime sleepiness measures. Results: SDB patients showed an unstable, fragmented, flattened, phase-advanced, and less robust DST rhythm as compared to healthy participants. The more severe the SDB, the worse the DST pattern was, as indicated by the correlation coefficient. Sleepiness, according to MWT sleep latencies, was also associated with the higher fragmentation, lower amplitude, and less robustness of the DST rhythm. Treatment with CPAP improved DST pattern regularity and robustness. Conclusion: DST is altered in SDB, exhibiting a direct relationship to the severity of this condition, and improves with CPAP treatment. DST independently correlates with sleepiness, thus, its measurement may contribute to the understanding of the pathophysiology of sleepiness in these patients.

Fragmentation of daily rhythms associates with obesity and cardiorespiratory fitness in adolescents: The HELENA study.

BACKGROUND & AIMS: Chronobiology studies periodic changes in living organisms and it has been proposed as a promising approach to investigate obesity. We analyze the association of the characteristics of the rest-activity rhythms with obesity, cardiorespiratory fitness and metabolic risk in adolescents from nine European countries. METHODS: 1044 adolescents (12.5-17.5 y) were studied. Circadian health was evaluated by actigraphy with accelerometers (Actigraph GT1M). Characteristics of the daytime activity such as fragmentation (intradaily variability), estimated acrophase, and 10 h mean daytime activity index were obtained. Body composition was assessed using Bioelectrical-Impedance-Analysis, skinfold thickness, air-displacement-plethysmography and Dual-energy-X-ray-Absorptiometry. Cardiorespiratory fitness (VO2max) and metabolic risk were studied. RESULTS: Highly fragmented activity rhythms were associated with obesity and central adiposity (P < 0.05). Obese adolescents had ∼3 times higher odds of having a high fragmentation of daytime activity compared to normal weight adolescents OR (95% CI) = 2.8 (1.170, 6.443). A highly fragmented rhythm was also related to lower cardiorespiratory fitness and higher metabolic risk (P < 0.05) so those adolescents classified as low fitness showed a significantly higher fragmentation of daytime activity than those included in the high fitness group (P < 0.0001). Other characteristics of the rhythms such as smaller 10 h daytime mean activity index and delayed estimated acrophase were also related to obesity and metabolic risk (P < 0.05). CONCLUSIONS: Our results indicate that the daily organization of the rest-activity cycle is more fragmented in obese and less fit adolescents and correlates with higher metabolic risk. This fact reinforces our hypothesis that disturbances in daily rhythms can be considered as sensitive markers of poorer adolescent's health.

The benefits of four weeks of melatonin treatment on circadian patterns in resistance-trained athletes.

Exercise can induce circadian phase shifts depending on the duration, intensity and frequency. These modifications are of special meaning in athletes during training and competition. Melatonin, which is produced by the pineal gland in a circadian manner, behaves as an endogenous rhythms synchronizer, and it is used as a supplement to promote resynchronization of altered circadian rhythms. In this study, we tested the effect of melatonin administration on the circadian system in athletes. Two groups of athletes were treated with 100 mg day(-1) of melatonin or placebo 30 min before bed for four weeks. Daily rhythm of salivary melatonin was measured before and after melatonin administration. Moreover, circadian variables, including wrist temperature (WT), motor activity and body position rhythmicity, were recorded during seven days before and seven days after melatonin or placebo treatment with the aid of specific sensors placed in the wrist and arm of each athlete. Before treatment, the athletes showed a phase-shift delay of the melatonin circadian rhythm, with an acrophase at 05:00 h. Exercise induced a phase advance of the melatonin rhythm, restoring its acrophase accordingly to the chronotype of the athletes. Melatonin, but not placebo treatment, changed daily waveforms of WT, activity and position. These changes included a one-hour phase advance in the WT rhythm before bedtime, with a longer nocturnal steady state and a smaller reduction when arising at morning than the placebo group. Melatonin, but not placebo, also reduced the nocturnal activity and the activity and position during lunch/nap time. Together, these data reflect the beneficial effect of melatonin to modulate the circadian components of the sleep-wake cycle, improving sleep efficiency.