Case report: Diagnosis and intervention of a non-24-h sleep-wake disorder in a sighted child with a psychiatric disorder.

Circadian rhythm sleep-wake disorders (CRSWD) are sleep dysfunctions related to circadian functioning. They are characterized by symptoms of insomnia or excessive sleepiness that occur because the intrinsic circadian pacemaker is not entrained to a 24-h light/dark cycle. Affected individuals with a free-running disorder or hypernycthemeral syndrome (N24SWD) have a longer sleep-wake cycle that produces a sleep pattern that typically delays each day. The disorder is seen in 70% of blind people, and among people with healthy vision, it is a rare pathology. Among sighted cases, 80% are young men and 28% have a psychiatric disorder. The patient was a 14-year-old boy with a psychiatric pathology diagnosed with a PANDAS syndrome (pediatric autoimmune neuropsychiatric disorders associated with streptococci), a sudden acute and debilitating onset of intense anxiety and mood lability accompanied by obsessive compulsive-like issues and/or tics, in association with a streptococcal A infection that occurs immediately prior to the symptoms. As a comorbidity, he exhibited severe insomnia due to an irregular sleep pattern that strongly delayed his sleep schedule day to day. It affected his daily routines, as he was not going to school, and aggravated, furthermore, the psychiatric symptoms. He was referred for sleep consultation, where the case was explored by ambulatory circadian monitoring (ACM) using the novel system Kronowise® (Chronolab, University of Murcia) and diagnosed with a non-24-h sleep-wake disorder (N24SWD). The first treatment approach for the patient was focused on improving symptoms during the acute infection and psychiatric symptoms. Additionally, sleep pathology was treated by light therapy and melatonin. After 8 months and different trials, it was possible to establish a treatment to normalize the symptoms and fix his sleep rhythm in a normal schedule as well as to reduce anxious symptoms during the day. The association of PANDAS and N24SWD has not previously been reported in the literature.

Correlated color temperature and light intensity: Complementary features in non-visual light field.

An appropriate exposure to the light-dark cycle, with high irradiances during the day and darkness during the night is essential to keep our physiology on time. However, considering the increasing exposure to artificial light at night and its potential harmful effects on health (i.e. chronodisruption and associated health conditions), it is essential to understand the non-visual effects of light in humans. Melatonin suppression is considered the gold standard for nocturnal light effects, and the activation of intrinsically photosensitive retinal ganglion cells (ipRGCs) through the assessment of pupillary light reflex (PLR) has been recently gaining attention. Also, some theoretical models for melatonin suppression and retinal photoreceptors activation have been proposed. Our aim in this study was to determine the influence of correlated color temperature (CCT) on melatonin suppression and PLR, considering two commercial light sources, as well as to explore the possible correlation between both processes. Also, the contribution of irradiance (associated to CCT) was explored through mathematical modelling on a wider range of light sources. For that, melatonin suppression and PLR were experimentally assessed on 16 healthy and young volunteers under two light conditions (warmer, CCT 3000 K; and cooler, CCT 5700 K, at ~5·1018 photons/cm2/sec). Our experimental results yielded greater post-stimulus constriction under the cooler (5700 K, 13.3 ± 1.9%) than under the warmer light (3000 K, 8.7 ± 1.2%) (p < 0.01), although no significant differences were found between both conditions in terms of melatonin suppression. Interestingly, we failed to demonstrate correlation between PLR and melatonin suppression. Although methodological limitations cannot be discarded, this could be due to the existence of different subpopulations of Type 1 ipRGCs differentially contributing to PLR and melatonin suppression, which opens the way for further research on ipRGCs projection in humans. The application of theoretical modelling suggested that CCT should not be considered separately from irradiance when designing nocturnal/diurnal illumination systems. Further experimental studies on wider ranges of CCTs and light intensities are needed to confirm these conclusions.

Insomnio en niños y adolescentes. Documento de consenso / Insomnia in children and adolescents. A consensus document

El insomnio es una patología muy frecuente en edad pediátrica (30% en niños menores de 5 años) que ocasiona una grave repercusión cognitiva, emocional y en el aprendizaje junto con una importante comorbilidad médica y afectación de la calidad de vida del niño y la familia. La formación de los pediatras en el diagnóstico y el tratamiento del mismo suele ser deficitaria. Por todo ello, se presenta el documento de consenso sobre el manejo del insomnio en la infancia y la adolescencia elaborado por representantes de la Asociación Española de Pediatría, la Sociedad Española de Sueño, la Sociedad Española de Pediatría Extrahospitalaria y de Atención Primaria, la Sociedad Española de Medicina de la Adolescencia, la Sociedad Española de Psiquiatría Infantil y la Sociedad Española de Neurología Pediátrica. Este grupo recomienda que el diagnóstico debe ser clínico y solo en los casos dudosos o en que sea necesario un diagnóstico diferencial serán necesarias pruebas complementarias. Asimismo el tratamiento se debe basar principalmente en terapias cognitivo-conductuales y en una modificación de los hábitos de sueño. El uso de medicamentos y sustancias para facilitar el sueño es elevado, aunque no existen guías clínicas que lo apoyen

Insomnia is very common during childhood (30% of children under 5), and causes a serious cognitive and emotional consequence in learning, as well as significant medical comorbidity. It also affects the quality of life, not only of the child, but also of the whole family. Paediatrician training in its diagnosis and treatment is usually poor. For this reason a consensus document is presented on the management of insomnia in children and adolescents. This has been developed by members of the Spanish Paediatrics Association, the Spanish Sleep Society, the Spanish Society of Paediatric Outpatient and Primary Care, the Spanish Adolescent Medicine Society, the Spanish Child and Adolescent Society, and the Spanish Paediatric Neurology Society. The group suggests that diagnosis must be clinical and complementary tests will only be required in doubtful cases or when a differential diagnosis is needed. Likewise, treatment should be mainly based on cognitive-behavioural therapy and the modification of sleeping habits. Using medicines and other substances to make the sleep easier is currently quite common, even although there are no clinical guidelines to support this

Relevance of internal time and circadian robustness for cancer patients.

BACKGROUND: Adequate circadian timing of cancer treatment schedules (chronotherapy) can enhance tolerance and efficacy several-fold in experimental and clinical situations. However, the optimal timing varies according to sex, genetic background and lifestyle. Here, we compute the individual phase of the Circadian Timing System to decipher the internal timing of each patient and find the optimal treatment timing. METHODS: Twenty-four patients (11 male; 13 female), aged 36 to 77 years, with advanced or metastatic gastro-intestinal cancer were recruited. Inner wrist surface Temperature, arm Activity and Position (TAP) were recorded every 10 min for 12 days, divided into three 4-day spans before, during and after a course of a set chronotherapy schedule. Pertinent indexes, I < O and a new biomarker, DI (degree of temporal internal order maintenance), were computed for each patient and period. RESULTS: Three circadian rhythms and the TAP rhythm grew less stable and more fragmented in response to treatment. Furthermore, large inter- and intra-individual changes were found for T, A, P and TAP patterns, with phase differences of up to 12 hours among patients. A moderate perturbation of temporal internal order was observed, but the administration of fixed chronomodulated chemotherapy partially resynchronized temperature and activity rhythms by the end of the study. CONCLUSIONS: The integrated variable TAP, together with the asynchrony among rhythms revealed by the new biomarker DI, would help in the personalization of cancer chronotherapy, taking into account individual circadian phase markers.

Métodos cronobiológicos en las encuestas alimentarias: criterios de aplicación e interpretación de resultados / Methods for monitoring the functional status of the circadian system in dietary surveys studies: application criteria and interpretation of results

En 1996, la Cumbre Mundial sobre la Alimentación reafirmó el derecho inalienable de los habitantes del mundo a tener acceso a una alimentación adecuada, inocua y nutritiva, y se planteó como meta disminuir a la mitad el número de personas subnutridas en el mundo para el año 2015, es decir, este año que iniciamos. Diversos países y organizaciones se plantean la necesidad de consensuar y desarrollar indicadores para la medición de la inseguridad alimentaria en los hogares. Disponer de un método de medición simple pero con base científica para identificar los grupos de población de mayor vulnerabilidad nutricional, se considera una herramienta básica para poder implementar estrategias que permitan afrontar el problema de un forma efectiva (AU)

To evaluate the circadian system status of the subject may be of special interest in nutrition. Particularly for those studies related to the assessment of diseases related to malnutrition, as it is the case of most of the degenerative diseases such as obesity, cancer, or cardiovascular diseases. For this purpose, one of the approaches consists to measure a) the external synchronizers of the internal clock, such as light intensity, and changes from fasting to eating and from resting to activity. Indeed, “chronodisruptors” have been defined as “exogenous and endogenous exposures or effectors which are chronobiologically active and can thus disrupt the timing and order. Another approach to assess the circadian system health is to measure the b) outputs of the internal clock (circadian marker rhythms). Among such outputs, the rhythm of body temperature, motor activity, melatonin, cortisol and clock gene expression are the most commonly used. From the genetic perspective, we are now able to measure failures in the internal clock, in order to assess c) the genetics of the molecular clock. Indeed, new nutrigenetics techniques are giving us the opportunity to measure the association between different genetic variants of our clock genes and several illnesses such as obesity, cardiovascular diseases, diabetes or cancer. In addition to these techniques, selfreported questionnaires based in the morning-evening preferences have been developed as complementary procedures to assess human chronotypes (AU)

The circadian rest-activity rhythm, a potential safety pharmacology endpoint of cancer chemotherapy.

The robustness of the circadian timing system (CTS) was correlated to quality of life and predicted for improved survival in cancer patients. However, chemotherapy disrupted the CTS according to dose and circadian timing in mice. A continuous and repeated measures longitudinal design was implemented here to characterize CTS dynamics in patients receiving a fixed circadian-based chemotherapy protocol. The rest-activity rhythm of 49 patients with advanced cancer was monitored using a wrist actigraph for 13 days split into four consecutive spans of 3-4 days each, i.e., before, during, right after and late after a fixed chronotherapy course. The relative amount of activity in bed vs. out of bed (I

Rest-activity circadian rhythms in aged Nothobranchius korthausae. The effects of melatonin.

Adult (48-week-old) and senescent (72-week-old) individually-kept Nothobranchius korthausae were used as experimental subjects to characterise circadian system (CS) function and age-related changes in senescent fish. This species was specifically chosen because it has already shown potential for use as a model system in gerontological studies. The rest-activity rhythm (RAR) in fish can be easily monitored and used to characterise the state of the CS, and it has also been proposed as a reliable model to study sleep-like periods in fish. As they aged, N. korthausae experienced a significant decrease in total daily activity and a progressive impairment of the RAR, accompanied by changes in the regularity, fragmentation and amplitude of the rhythm. The ability of the CS to oscillate autonomously when the two main synchronizers, photoperiod and feeding time, were absent (continuous darkness and random feeding), was also impaired with age, as the capacity to re-synchronise to the light-dark (LD) cycle declined. Melatonin treatment improved the regularity, fragmentation and amplitude of the RAR in senescent fish, and it also improved sleep efficiency. In conclusion, N. korthausae represents a viable model for studying the aging of the circadian system and the restorative effect of chronobiotic substances, such as melatonin.

[Chronobiological aspects of obesity and metabolic syndrome]. / Aspectos cronobiológicos de la obesidad y el síndrome metabólico.

Circadian rhythms (approximately 24h) are widely characterized at molecular level and their generation is acknowledged to originate from oscillations in expression of several clock genes and from regulation of their protein products. While general entrainment of organisms to environmental light-dark cycles is mainly achieved through the master clock of the suprachiasmatic nucleus in mammals, this molecular clockwork is functional in several organs and tissues. Some studies have suggested that disruption of the circadian system (chronodisruption (CD)) may be causal for manifestations of the metabolic syndrome. This review summarizes (1) how molecular clocks coordinate metabolism and their specific role in the adipocyte; (2) the genetic aspects of and scientific evidence for obesity as a chronobiological illness; and (3) CD and its causes and pathological consequences. Finally, ideas about use of chronobiology for the treatment of obesity are discussed.