Endogenous melatonin predicts efficacy of exogenous melatonin in consolidation of fragmented wrist-activity rhythm of adult patients with developmental brain disorders: a double-blind, placebo-controlled, crossover study.

OBJECTIVE: : We studied whether the endogenous melatonin patterns in adult patients with developmental brain disorders have any role in response to exogenous melatonin given as a sleep-promoting medicine. METHODS: : Participants included 15 adults (18-60 years, five females) with developmental brain disorders of varying etiologies, motor handicaps, and long-term history of sleep problems. According to the 24-h patterns of serum melatonin, patients were divided into two subgroups: lower and higher secretors. The pretreatment sleep disorder was characterized by a structured interview, 24-h ambulatory polysomnography and 7-day wrist actigraphy. Patients received 1, 3, or 6mg fast-release melatonin tablets, each for 4 weeks in increasing order, at a constant time of 30min before the desired sleep onset. Similarly, placebos with different codes were given during 3x4 weeks. The 7-day actigraphy was repeated at the end of each drug period. Outcome measures were six different parameters of non-parametric circadian rhythm analysis. Drug effects and 40 confounding/modulating factors were evaluated by applying two-level regression analyses with co-variables. RESULTS: : Exogenous melatonin decreased the fragmentation of the rest-activity rhythm, increased the day/night ratio of activity and advanced the onset of rest period. The effects on fragmentation and day/night ratio were more pronounced in the lower than higher secretors of melatonin. Other contributing factors in the drug effects were blindness and some features of the original sleep disorder (disrupted cyclicity of the sleep architecture in polysomnography or reported daytime somnolence). CONCLUSIONS: : Exogenous melatonin consolidated the fragmented rest-activity in about half of the patients. Low endogenous serum melatonin levels at night predicted improvement by the drug. Higher doses were not more effective than the lowest dose.

Sleep disturbances in aspartylglucosaminuria (AGU): a questionnaire study.

Sleep disturbances are common in many progressive metabolic encephalopathies. The possible presence of disturbed sleep-wake behaviour in the lysosomal storage disorder aspartylglucosaminuria, has not been previously studied, however. The sleep-wake behaviour of 81 patients with aspartylglucosaminuria (AGU, age 3-55 years, median 22 years; 42 female and 39 male) and 49 controls (age 2-57 years, median 18 years; 25 female and 24 male) was assessed through a postal survey. A slightly modified version of the validated Basic Nordic Sleep Questionnaire was used. Fifty-eight per cent of the AGU patients were reported to suffer daily from a sleep-related problem (controls 31%, p < 0.01). In AGU adults (age >17 years) and children (age < or =17 years), the corresponding figures were 52% and 61%, respectively (control children 22%, p < 0.05 and control adults 38%, p = 0.06). In AGU children, settling difficulties were reported to occur significantly more commonly than in control children. Children with AGU were also reported to snore more often than were the controls. Adults with this disorder were found to suffer from severely fragmented night-time sleep, which was experienced as highly distressing by the parents and other caregivers. A long night sleep period was reported to be common in the ageing AGU patients (AGU 9.5 +/- 1.7 vs controls 7.2 +/- 1.0 h, mean +/- SD, p < 0.001). Parents and caregivers also often complained about disturbing movements during sleep in AGU patients. In conclusion, both children and adults with aspartylglucosaminuria were reported to display several types of sleep disturbances significantly more commonly than healthy controls.

The daily rhythms of melatonin and free fatty acids in goats under varying photoperiods and constant darkness.

The purpose of the study was to explore parallel and divergent features of the daily rhythms of melatonin and plasma free fatty acids (FFA) in goats exposed to different lighting conditions. From these features, we attempted to analyze whether the endogenous melatonin rhythm plays any role in the maintenance of the FFA rhythm. Seven Finnish landrace goats were kept under artificial lighting that simulated the annual changes of photoperiod at 60 degrees N (longest photoperiod, 18 h; shortest, 6 h). The ambient temperature and feeding regimen were kept constant. Blood samples were collected 6 times a year at 2 h intervals for 2 d, first in the prevailing light-dark (LD) conditions and then after 3 d in constant darkness (DD). In LD conditions, the melatonin levels always increased immediately after lights-off and declined around lights-on, except in winter (18 h darkness), when the low daytime levels were restored clearly before lights-on. The FFA levels also displayed a consistent rhythmicity, with low levels at night and a transient peak around lights-on. In DD conditions, the melatonin profiles were very similar to those found in the habitual LD conditions, but the rhythm tended to advance. The FFA rhythm persisted also in DD, and the morning peak tended to advance. There was an overall parallelism between the two rhythms, with one significant exception. In winter in LD conditions, the morning rise in FFA levels coincided with lights-on and not with the declining phase of melatonin, whereas in DD conditions, the FFA peak advanced several hours and coincided with the declining phase of melatonin. From this finding and comparisons of the calculated rhythm characteristics, i.e., phase-shifts, phase differences, and correlations, we conclude that the daily rhythm of FFA levels is most probably generated by an endogenous oscillator, primarily adjusted by dawn, whereas the melatonin rhythm in this species is regulated by an oscillator primarily adjusted by dusk. The results did not exclude a modulatory effect of melatonin on the daily FFA profiles, but melatonin secretion, alone, does not explain the patterns sufficiently.

Wrist actigraphy in estimation of sleep and wake in intellectually disabled subjects with motor handicaps.

BACKGROUND AND PURPOSE: We studied the applicability of wrist actigraphy to sleep-wake estimation in patients with motor handicaps. PATIENTS AND METHODS: Concomitant polysomnographic and actigraphic recordings (16-24 h) were compared in three groups: normally moving subjects with normal sleep (n=10), sleep-disordered subjects without motor handicaps (n=13) and sleep-disordered patients with different motor disabilities (n=16). The motor abilities of the subjects were determined by clinical evaluation using a grading scale from 0 to 10. Their actual daily activity was calculated from the recordings as average activity scores. RESULTS: In the healthy subjects, the mean difference between actigraphic and polysomnographic total sleep estimation was negligible (-1 min), while in both sleep-disordered groups, sleep was highly overestimated by actigraphy. There was a significant correlation between the motor ability score and the discrepancy between actigraphy and polysomnography, but individual data points were highly scattered. A more consistent correlation was found between the average activity score/min in actigrams and the discrepancy of actigraphic with polysomnographic total sleep estimation (Spearman's r=-0.58, P=0.0001, n=39). When the recordings with very low average activity score were rejected from the analyses (two patients without and six with motor handicaps), the overestimation of sleep by actigraphy was reduced but it still remained in both sleep-disordered groups. The mean differences of total sleep between actigraphy and polysomnography were 72 and 121 min and the rank order correlation coefficients 0.80 and 0.71 in patients without and with motor handicaps, respectively. The median discrepancy in total sleep estimation was 6% in both sleep-disordered groups. CONCLUSIONS: In subjects with rudimentary motor abilities, a standard actigraphy can produce a signal, which is related to the amount of sleep scored in polysomnograms. The sleep parameters obtained by the two methods are not equal, however. The inspection of actigrams is more reliable than the clinical scaling of motor abilities in predicting the applicability of wrist actigraphy.

Daily and annual variations of free fatty acid, glycerol and leptin plasma concentrations in goats (Capra hircus) under different photoperiods.

The aim of the study was to differentiate the impact of lighting conditions and feeding times on the regulation of lipid metabolism of goats under different photoperiods throughout the year. Seven Finnish landrace goats were kept under artificial lighting that simulated the annual changes of photoperiod at 60 degrees N (the longest light period 18 h, the shortest 6 h). Ambient temperature and feeding regime were kept constant. Blood samples were collected six times a year at 2-h intervals for 2 days, first in light/dark (LD) conditions and then after 3 days in constant darkness (DD). Significant daily variations were detected in the concentrations of plasma free fatty acids (FFA) and glycerol throughout the year. The nocturnal decrease and morning rise of FFA levels were related to the photoperiod, while the trough levels of glycerol were associated with the concentrate meal times. In DD conditions, FFA and glycerol rhythms were unstable. A significant seasonal variation was detected in the overall FFA and glycerol levels suggesting decreased lipogenesis in winter, increased lipolysis in spring and high lipogenesis in summer and fall. There was no significant daily rhythm in serum leptin levels, nor did the profiles in LD and DD conditions differ. The leptin level was slightly lower in early fall than in the other seasons, paralleling a small decrease of body mass in the goats after the grazing season. The daily or annual variations of FFA and glycerol levels were not clearly related to leptin concentrations. The results suggest that lipid metabolism of goats is regulated by light even in constant temperature and feeding conditions; however, no significant contribution of leptin levels could be shown.

Shared means and meanings in vocal expression of man and macaque.

Vocalisations of six Macaca arctoides that were categorised according to their social context and judgements of naive human listeners as expressions of plea/submission, anger, fear, dominance, contentment and emotional neutrality, were compared with vowel samples extracted from simulations of emotional-motivational connotations by the Finnish name Saara and English name Sarah. The words were spoken by seven Finnish and 13 English women. Humans and monkeys resembled each other in the following respects. 'Neutral', 'pleading' and 'commanding' had a similar F0 level. Loud vocalisations of intense 'anger' and 'fear' had both high F0, and the highest values were encountered for 'fear'. Compared with 'neutral', the audiosignal waveform of 'plea/submission' was more sinusoidal, seen in the spectrum as an attenuation of formants and an emphasis of the fundamental, whereas the signal waveform of 'commanding' was more complex corresponding to an increase in noise and a wider distribution of spectral energy. 'Frightened' samples included rather harmonic segments with emphasis of the fundamental, and 'angry' samples included more noise at the low end of the spectrum and often segments with low-frequency ( < 100 Hz) edged modulation. Sounds resembling soft and noisy 'content' grunts of the monkey do not appear in Finnish or English speech but 'content' utterances were, however, associated with low speech pressure, attenuation of harmonics and increase in noise.

Automatic blink detection: a method for differentiation of wake and sleep of intellectually disabled and healthy subjects in long-term ambulatory monitoring.

OBJECTIVES: To develop a method for automatic detection of blinks in electrooculograms and to evaluate reliability of blink rate as an indicator of wake and sleep in subjects with developmental brain disorders. DESIGN: Categorization of wake and sleep by blink rate was compared with visual sleep scoring of the polysomnograms. SETTING: Ambulatory polysomnographic recordings at home or in the sleep laboratory. PARTICIPANTS: Nine healthy volunteers for calibration, 10 for validation; 7 intellectually disabled patients for calibration, 10 for validation of the method. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Blinks were detected from electrooculograms using a weighted finite impulse response median hybrid filtering and the criterion of minimum duration at amplitude threshold. More than 80% of the visually identified electrooculographic blinks were detected in most subjects. When 30-second epochs of electrooculograms with 1 or more blinks were defined as wake and those without blinks as sleep, the average agreement with polysomnographic scoring was 95% in healthy subjects and 84% in patients. The mismatch was mostly due to the 30-second epochs without blinks during waking. A contextual redefinition of wake and sleep by expanding the inspected electrooculographic span from 1 to 20 epochs (10 minutes) increased the agreement to 93% in patients. The agreement is comparable to that of actigraphy with polysomnography. The linear correlation coefficient of the proportions of sleep epochs between visual scoring and the contextual blink rate method was 0.869. The main sleep periods detected by the blink-rate method were an average of 7 minutes longer than those determined by visual scoring. This was caused by differences in the detection of sleep onsets: blinking ceased before the first stage 1 sleep period was scored. The absolute period lengths obtained by the 2 methods did not differ significantly from each other in unpaired t-tests, and the linear correlation between the values was 0.999. CONCLUSIONS: The blinks extracted from the electrooculographic signal can be used to reliably determine the main sleep and wake periods in both healthy subjects and patients with developmental brain disorders.

Serum cortisol levels in goats exhibit seasonal but not daily rhythmicity.

The aim of the study was to find out whether there is a daily rhythm in goat serum cortisol concentrations, whether the concentration profiles differ between normal light:dark and constant dark conditions, and whether any seasonal variations might be detected in daily cortisol secretion patterns. Seven Finnish landrace goats were kept at indoor temperature (18-23 degrees C) under artficial lighting that approximately simulated the annual changes of daylength at 60 degrees N. Blood samples were collected for cortisol measurements by radioimmunoassay at 2h intervals during six times of the year: winter (light:dark 6:18h), early spring (10:14h), late spring (14:10h), summer (18:6h), early fall (14:10h), and late fall (10:14h). Cortisol profiles were determined for two consecutive days, first in light:dark (LD) conditions and then in continuous darkness (DD). There was no significant daily rhythm in serum cortisol levels in any time of the year, nor did the profiles in LD and DD conditions show any differences. A significant seasonal variation was, however, detected among the overall cortisol levels. In winter, the concentrations were higher than in any other season, and from early spring to summer they were at their lowest. Under equal photoperiods, the cortisol levels were higher in fall than spring. The difference between winter and summer was confirmed the following year in LD conditions. There was on correlation between serum cortisol and progesterone levels. The results suggest that the possible circadian variation of cortisol secretion in goats is completely masked by external factors, and lighting conditions do not have immediate effects on the daily secretion patterns. The seasonal variation in the overall cortisol levels is most probably related to the changes in photoperiod, because other conditions were relatively constant during the experiment.

Sleep fragmentation in mentally retarded people decreases with increasing daylength in spring.

We studied the sleep-wake behavior of mentally retarded people from late winter to early summer at 60 degrees N. During this time the daylength increased 8 h 51 min. The data were collected by observing the sleep-wake status of 293 subjects at 20-min intervals for five randomized 24h periods (= recording days). The intervals during which the individual recording days of the same order (1st, 2nd, etc.) were carried out, were called recording periods. Consequently, there were five recording periods, each containing 293 individual recording days. Even though there was overlap among the recording periods, the median daylength from one period to another increased approximately by 100 min. In the initial statistical analysis, the number of wake-sleep transitions was found to differ significantly among the five recording periods (Friedman test, p < 0.001). The mean ranks in the Friedman test suggested that the number of wake-sleep transitions was highest during the 1st and lowest during the 5th recording period. In further statistical analyses using a program for mixed effects regression analysis (MIXOR 2.0) it was found that the increase in daylength during the study period was associated with a simultaneous decrease of approximately 0.5 wake-sleep transitions in the whole study population (p < 0.001). The decrease in the number of wake-sleep transitions was significant only in the subgroups of subjects with a daylength change of more than 350 min between the 1st and 5th recording days (Wilcoxon tests, p < 0.005). This suggests that after a marked prolongation of the natural photoperiod, the reduction in sleep episodes was more probable than after smaller changes in daylength. It is concluded that the sleep of mentally retarded people living in a rehabilitation center at a northern latitude is more fragmented in winter than in early summer and that the change is related probably to the simultaneous increase in the length of the natural photoperiod. The sleep quality of persons living in institutional settings might be improved by increasing the intensity and/or duration of daily artificial light exposure during the darker seasons.