Pattern Of Melatonin Secretion Research Articles

Urinary levels of 6-sulphatoxymelatonin and their associations with sleep disorders and behavioural impairments in children with autism spectrum disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with sleep disturbances that may result from abnormalities in melatonin production. The correlations of melatonin levels with the severity of sleep disorder and/or severity of ASD were reported. To evaluate urinary levels of the melatonin metabolite, 6-sulphatoxymelatonin (aMT6s), in children with ASD, and their associations with sleep abnormalities and behavioural impairments. Study involved 77 children with ASD and 84 controls aged 2.5‒15.5 years. Sleep disorders were assessed by Children's Sleep Habits Questionnaire. Morning and afternoon levels of aMT6s were determined by radioimmunoassay method. Urinary creatinine levels were assessed by an enzymatic method. The urinary aMT6s/creatinine values indicate that the night-time melatonin levels are significantly lower in ASD than in controls, but there are no significant differences in the daytime levels. In the ASD group, on average, a 6.8-fold difference between night-time and daytime values of urinary aMT6s/creatinine was found, whereas for the controls a 12.5-fold difference was observed, indicating a lower night-time increase in melatonin levels. In ASD group, the difference in night-time-daytime aMT6s/creatinine value correlated with some types of sleep problems, but not with the severity of ASD. The results indicate that in ASD there are differences in the patterns of melatonin secretion that may be associated with sleep impairment (Tab. 4, Fig. 2, Ref. 28).

Effect of Monochromatic Light on Circadian Rhythm of Clock Genes in Chick Pinealocytes.

The avian circadian system is a complex of mutually coupled pacemakers residing in pineal gland, retina and suprachiasmatic nucleus. In this study, the self-regulation mechanism of pineal circadian rhythm was investigated by culturing chick primary pinealocytes exposed to red light (RL), green light (GL), blue light (BL), white light (WL) and constant darkness (DD), respectively. All illuminations were set up with a photoperiod of 12 light: 12 dark. The 24-h expression profiles of seven core clock genes (cBmal1/2, cClock, cCry1/2 and cPer2/3), cAanat and melatonin showed significant circadian oscillation in all groups, except for the loss of cCry1 rhythm in BL. Compared to WL, GL increased the amplitudes and mesors of positive elements (cClock and cBmal1/2) and reduced those of negative elements (cCry1/2 and cPer2/3), in contrast to RL. The temporal patterns of cAanatmRNA and melatonin secretion have always been consistent with the positive genes. Besides, GL advanced the acrophases of the positive elements, cAanat and melatonin, but RL and BL showed the opposite effect. Thereby, GL could promote the secretion of melatonin by enhancing the expressions of positive clock genes and repressing the expressions of negative clock genes.

Predictors of the melatonin secretion pattern in elementary school children

Predictors of the melatonin secretion pattern in elementary school children

Clinical Considerations Derived From the Administration of Melatonin to Children With Sleep Disorders

Background and ObjectivesDespite the numerous investigations carried out in relation to melatonin, there is a lack of knowledge about the specific melatonin secretion patterns in the diverse primary sleep disturbances. The objective of this study was to analyze the plasma melatonin concentrations in children with primary sleep disorders and the effects of melatonin therapy on their serum levels and their actigraphic sleep parameters. MethodsFourteen participants (nine girls; seven to 14 years old) diagnosed with diverse primary sleep disorders were recruited. Four different melatonin secretion patterns were identified: low plasma melatonin levels, absence of a circadian rhythm, advanced acrophase, and delayed acrophase. A placebo (one week) was administered followed by three months of melatonin therapy (3 mg/night). Urinary 6-sulfatoxymelatonin levels, 24-hour plasma melatonin concentrations, and a seven-day actigraphic record were collected after both treatments. ResultsAfter melatonin therapy, a significant increase (P < 0.001) of urinary 6-sulfatoxymelatonin excretion with a clear circadian variation was observed. Plasma melatonin concentrations were also significantly higher with a recovery in the circadian rhythm. Actual sleep time was significantly longer, with a substantial reduction in the sleep onset latency and night awakenings. No severe side effects were reported. ConclusionsThe main clinical implication of this study is to demonstrate the efficacy of melatonin in three main circumstances: an insufficient hormone production, a disturbed circadian rhythm, and an advanced or delayed acrophase. As ongoing work, we are exploring the effect of different doses of melatonin on the regulation of its concentrations and of its secretion rhythm.

Abstract P364: Altered Circadian Rhythm in Blood Pressure in Obstructive Sleep Apnea

Background: In people with obstructive sleep apnea (OSA), adverse cardiovascular (CV) events occur most commonly during the night, about 6 hours earlier than the morning peak of events observed in the general population. In healthy individuals, circadian rhythms in many CV risk markers peak in the morning, around the common time of occurrence of adverse CV events. We therefore tested whether circadian rhythms are advanced in those with OSA, which might explain the earlier time of adverse CV events. Methods: Eleven volunteers (4 healthy controls and 7 OSA; 55 ± 5 years of age) completed a 5-day laboratory protocol with sleep and all other behaviors evenly spaced across the 24 h circadian period. To achieve this, after a baseline night, participants completed 10 consecutive short-day cycles of 2 h 40 min each of wakefulness and sleep opportunity. Blood pressure and heart rate were recorded 10 min after each wake time. Salivary melatonin and cortisol concentration were measured at 1-1.5h intervals during wakefulness. Cosinor analyses were performed to determine the rhythmicity of the all variables. We also compared OSA data with larger groups of historical healthy controls from our laboratory. Results: The circadian times of peak systolic and diastolic blood pressure were significantly advanced (up to 7 hours) in OSA as compared to healthy controls, p&lt;0.05. Circadian peaks in all other measured variables were not different between OSA and controls. Conclusions: These results suggest that OSA is associated with a change in the timing of endogenous circadian blood pressure rhythms. This may be specific to the cardiovascular system as there was no evidence for altered phase of melatonin or cortisol secretion patterns. The relatively advanced blood pressure rhythms in OSA is similar to the advancement of the time of adverse CV events in OSA and should be further investigated.

Mechanisms regulating angiogenesis underlie seasonal control of pituitary function

Seasonal changes in mammalian physiology, such as those affecting reproduction, hibernation, and metabolism, are controlled by pituitary hormones released in response to annual environmental changes. In temperate zones, the primary environmental cue driving seasonal reproductive cycles is the change in day length (i.e., photoperiod), encoded by the pattern of melatonin secretion from the pineal gland. However, although reproduction relies on hypothalamic gonadotrophin-releasing hormone output, and most cells producing reproductive hormones are in the pars distalis (PD) of the pituitary, melatonin receptors are localized in the pars tuberalis (PT), a physically and functionally separate part of the gland. How melatonin in the PT controls the PD is not understood. Here we show that melatonin time-dependently acts on its receptors in the PT to alter splicing of vascular endothelial growth factor (VEGF). Outside the breeding season (BS), angiogenic VEGF-A stimulates vessel growth in the infundibulum, aiding vascular communication among the PT, PD, and brain. This also acts on VEGF receptor 2 (VEGFR2) expressed in PD prolactin-producing cells known to impair gonadotrophin secretion. In contrast, in the BS, melatonin releases antiangiogenic VEGF-Axxxb from the PT, inhibiting infundibular angiogenesis and diminishing lactotroph (LT) VEGFR2 expression, lifting reproductive axis repression in response to shorter day lengths. The time-dependent, melatonin-induced differential expression of VEGF-A isoforms culminates in alterations in gonadotroph function opposite to those of LTs, with up-regulation and down-regulation of gonadotrophin gene expression during the breeding and nonbreeding seasons, respectively. These results provide a mechanism by which melatonin can control pituitary function in a seasonal manner.

Melatonin Secretion Pattern in Critically Ill Patients: A Pilot Descriptive Study.

Critically ill patients have abnormal circadian and sleep homeostasis. This may be associated with higher morbidity and mortality. The aims of this pilot study were (1) to describe melatonin secretion in conscious critically ill mechanically ventilated patients and (2) to describe whether melatonin secretion and sleep patterns differed in these patients with and without remifentanil infusion. Eight patients were included. Blood-melatonin was taken every 4th hour, and polysomnography was carried out continually during a 48-hour period. American Academy of Sleep Medicine criteria were used for sleep scoring if sleep patterns were identified; otherwise, Watson's classification was applied. As remifentanil was periodically administered during the study, its effect on melatonin and sleep was assessed. Melatonin secretion in these patients followed a phase-delayed diurnal curve. We did not observe any effect of remifentanil on melatonin secretion. We found that the risk of atypical sleep compared to normal sleep was significantly lower (p < 0.001) under remifentanil infusion. Rapid Eye Movement (REM) sleep was only observed during the nonsedation period. We found preserved diurnal pattern of melatonin secretion in these patients. Remifentanil did not affect melatonin secretion but was associated with lower risk of atypical sleep pattern. REM sleep was only registered during the period of nonsedation.

Blue light therapy improves circadian dysfunction as well as motor symptoms in two mouse models of Huntington's disease

Patients with Huntington's disease (HD) exhibit movement disorders, psychiatric disturbance and cognitive impairments as the disease progresses. Abnormal sleep/wake cycles are common among HD patients with reports of delayed sleep onset, fatigue during the day, and a delayed pattern of melatonin secretion all of which suggest circadian dysfunction. Mouse models of HD confirm disrupted circadian rhythms with pathophysiology found in the central circadian clock (suprachiasmatic nucleus). Importantly, circadian dysfunction manifests early in disease, even before the classic motor symptoms, in both patients and mouse models. Therefore, we hypothesize that the circadian dysfunction may interact with the disease pathology and exacerbate the HD symptoms. If correct, early intervention may benefit patients and delay disease progression. One test of this hypothesis is to determine whether light therapy designed to strengthen this intrinsic timing system can delay the disease progression in mouse models. Therefore, we determined the impact of blue wavelength-enriched light on two HD models: the BACHD and Q175 mice. Both models received 6h of blue-light at the beginning of their daily light cycle for 3 months. After treatment, both genotypes showed improvements in their locomotor activity rhythm without significant change to their sleep behavior. Critically, treated mice of both lines exhibited improved motor performance compared to untreated controls. Focusing on the Q175 genotype, we sought to determine whether the treatment altered signaling pathways in brain regions known to be impacted by HD using NanoString gene expression assays. We found that the expression of several HD relevant markers was altered in the striatum and cortex of the treated mice. Our study demonstrates that strengthening the circadian system can delay the progression of HD in pre-clinical models. This work suggests that lighting conditions should be considered when managing treatment of HD and other neurodegenerative disorders.

Melatonin in Tuberous Sclerosis Complex Analysis Using Modern Mathematical Modeling Methods.

Purpose. The aim of the study was to assess melatonin secretion pattern in children with TSC and to compare it with the secretion patterns in children with and without epilepsy. Material and Methods. Melatonin secretion was measured every three hours using the RIA method in four children with recognized TSC. The parameters of the melatonin secretion models were interpreted and compared with those obtained for the patients with epilepsy (n = 76) and the children from the control, nonepileptic group (n = 36). To describe the diurnal melatonin secretion, mathematical model was constructed and nonlinear least squares method with the Levenberg-Marquardt optimization algorithm was applied to approximate its parameters. The dim light melatonin onset (DLMO) parameters were also estimated from the model. Results and Conclusions. Statistically significant differences were found between the TSC melatonin secretion profiles and the nonepileptic control group. The profiles for the epileptic and TSC groups were found to be similar. For the TSC group, though a small one, the variations in the MLT release amplitudes seem to be independent of the total number of seizures; however, the MLT release shift appears to depend on the number of seizures.

Developmental effect of light deprivation on synaptic plasticity of rats' hippocampus: implications for melatonin.

There are few reports have demonstrated the effect of a change-in-light experience on the structure and function of hippocampus. A change-in-light experience also affects the circadian pattern of melatonin secretion. This study aimed to investigate developmental effect of exogenous melatonin on synaptic plasticity of hippocampus of light deprived rats. The effects of intracerebroventricular (ICV) injection of 2μg/5μl melatonin was evaluated on the basic and tetanized field excitatory post-synaptic potentials (fEPSPs) recorded in the hippocampal CA3-CA1 pathway of normal light-reared (LR) and dark-reared (DR) rats at 2, 4, and 6 weeks of age. Using RT-PCR and western blotting, developmental changes in the expression of melatonin receptors, MT1 and MT2, in the hippocampus were also evaluated. The amplitude of basic responses decreased across age in the LR rats. While light deprivation increased the amplitude of baseline fEPSPs, it decreased the degree of potentiation in post-tetanus responses. Melatonin injection also increased the amplitude of fEPSPs and suppressed the induction of long-term potentiation in both LR and DR rats. The expression of melatonin receptors increased in the hippocampus during brain development, and dark rearing reversed the expression patterns of both receptors. Although melatonin changed basic and tetanized responses of CA1 neurons across age during critical period of brain development, the pattern of its effects did not match the expression pattern of melatonin receptors in the hippocampus. Thus, the effects of melatonin on hippocampal neuronal responses may be exerted through other ways, like intercellular molecules and nuclear hormone receptors.

Circadian phase typing in idiopathic generalized epilepsy: Dim light melatonin onset and patterns of melatonin secretion-Semicurve findings in adult patients.

It has been debated in the literature whether patients with idiopathic generalized epilepsy (IGE) have a distinctive, evening-oriented chronotype. The few questionnaire-based studies that are available in the literature have conflicting results. The aim of our study was to define chronotype in patients with IGE by determining dim light melatonin onset (DLMO). Twenty adults diagnosed with IGE (grand mal on awakening [GM] in 7 cases and juvenile myoclonic epilepsy in 13 cases) were investigated by means of a face-to-face semistructured sleep interview, Morningness-Eveningness Questionnaire (MEQ), Pittsburgh Sleep Quality Index (PSQI) questionnaire, and a melatonin salivary test with DLMO determination. Eighteen healthy subjects (HC) and 28 patients affected with cryptogenic focal epilepsy (FE) served as controls. The mean MEQ score was significantly lower in patients with IGE than that in patients with FE (49.1±5.9 versus 56.1±8.7 P<0.01) but not significantly lower than that in HC (49.1±5.9 versus 49.3±8.6). Midsleep on free days corrected for sleep duration did not differ significantly between the three subject groups (04:59±01:21h, 04:37±01:17h, 04:29±00:52h). The mean DLMO time in patients with IGE (22:13±01:34h) occurred 49min later than that in HC (21.24±1h), and the melatonin surge within the 30-minute time interval after DLMO in patients with IGE was significantly lower than that in HC (1.51±2.7 versus 3.8±3.6pg/mL P=0.045). Subjective measures of chronotype do not indicate a definite evening-oriented chronotype in patients with IGE. However, the data concerning endogenous melatonin secretion indicate that patients with IGE tend to have a late circadian phase. Further studies are warranted in order to better define the late pattern of endogenous melatonin secretion in patients with IGE and to ascertain the role of this pattern in influencing behavioral chronotype in these subjects.

Basing Turkey Lighting Programs on Broiler Research: A Good Idea? A Comparison of 18 Daylength Effects on Broiler and Turkey Welfare.

Simple SummaryAltering daylength in a poultry management program is a simple tool that can have immense impacts on productivity and bird welfare. It is not uncommon for lighting data derived from broiler research to be extrapolated to turkey production. This review of two studies (one with broilers and the second with turkeys), completed in the same research facility using the same lighting programs, shows evidence that some, but not all responses to graded daylengths are similar between these two species. It defines that daylength choices for turkeys should be based on research conducted with turkeys.Daylength used as a management tool has powerful implications on the welfare of both broilers and turkeys. Near-constant light results in many detrimental impacts, including lack of behavioural rhythms and circadian melatonin rhythms. Both are suggestive that sleep fragmentation could result in birds reared on long photoperiods, which can lead to the same negative health and physiological responses as total sleep deprivation. An indirect comparison of the welfare implications of graded levels of daylength on broilers and turkeys clearly indicate that long daylengths depress welfare by increasing mortality, reducing mobility, increasing ocular pathologies and changing behaviour in both species. Furthermore, long daylengths change melatonin secretion patterns and eliminate behavioural and melatonin circadian rhythms, which were measured in broilers in these works. However, feather pecking in turkeys was reduced when birds were exposed to long daylengths. Exactly how much darkness should be included in a management program to maximize welfare will depend on the species, the age of marketing, and in turkeys, bird gender.

Relationship between post-awakening salivary cortisol and melatonin secretion in healthy participants

We report the relationship between patterns of post-awakening salivary melatonin and cortisol secretion in healthy participants (n = 51; mean age 21.6 ± 5.0 years). Saliva samples were collected within the domestic setting, at 0-, 15-, 30-, and 45-min post-awakening on 2 consecutive typical weekdays. Analyses were undertaken on data with electronically verified sample timing accuracy (<5-min delay between awakening and the start of saliva sampling). Melatonin secretion declined linearly by an average of 29% within the first 45-min post-awakening. In contrast, there was a marked 112% surge in cortisol, characteristic of the cortisol awakening response. No day differences in melatonin or cortisol secretion were observed but melatonin concentrations were lower with later awakening. Despite contrasting post-awakening changes in these hormones, there was a lack of relationship between overall levels or patterns of melatonin and cortisol during this period.

Plasma Melatonin and Progesterone Profiles of Suffolk and Romney Marsh Ewes Implanted with Melatonin during Anoestrus Season at Lower Latitudes in Southern Hemisphere

Background: The subcutaneous implants of melatonin are stimulatory and mimic the positive effects of short photoperiod on reproduction in small ruminants. This study investigated the daily plasma melatonin profiles in ewes treated with melatonin implants and kept under natural photoperiod in Southeastern Brazil. The plasma progesterone concentrations were also investigated before and after melatonin implantation.Materials, Methods &amp; Results: Romney Marsh (n = 11) and Suffolk (n = 10) ewes, which had been isolated from rams for at least 2 months prior to the beginning of the trial, were randomly allocated in two groups based on melatonin implant treatment (with or without melatonin implant). For plasma melatonin concentration, 43 days after melatonin implantation and 3 days before the ram introduction blood samples were collected every 2 hours during 24 hours. For plasma progesterone concentrations, blood samples were collected every once to twice a week for 2 different periods: prior to melatonin implantation and 46 days after the melatonin implantation and at the same day of the introduction of rams. The hormonal concentrations were determined by the radioimmunoassay method (RIA). The data were analyzed according to MIXED procedure (SAS) as repeated measurements for random animal effects. The effect of melatonin treatment on plasma melatonin 24-h period varied according to the breed. At the dark-phase, there were no plasma melatonin differences (P &gt; 0.05) between implanted and no-implanted (228.02 ± 58.39 vs. 169.59 ± 48.39) Romney Marsh ewes whereas for Suffolk ewes the plasma melatonin levels were higher in implanted (305.61 ± 68.39 pg/mL) than no-implanted (151.26 ± 38.35 pg/mL) ones. At the light-phase, melatonin treatment effects could be evidenced and these differences (P &lt; 0.01) consisted of higher melatonin values for implanted ewes and basal values for no-implanted ones in both breed groups. Before the melatonin implantation, the plasma progesterone levels were ˂ 1 ng/mL for Romney Marsh (0.41 ± 0.02 ng/mL) and Suffolk (0.47 ± 0.02 ng/mL) ewes. During the ram introduction period, no melatonin treatment effect was observed on plasma progesterone concentrations in both breed groups, but 2 days after ram introduction the plasma progesterone concentrations increased the mean values &gt; than 1 ng/mL in implanted and no-implanted Suffolk ewes. In implanted Romney Marsh ewes the elevation of progesterone mean values was weak whereas in no-implanted Romney Marsh ewes the progesterone levels were maintained ˂ 1 ng/mL during all the blood sample collection times.Discussion: The melatonin treatment also produced a similar model of daily melatonin levels as reported previously by others, which is characterized by high plasma melatonin concentrations during the light phase of the day. The effect of melatonin implants on plasma melatonin profiles interacted with breed confirming an individual response to melatonin implantation which is proportional to genetic individual variation pattern of melatonin secretion. Before the melatonin implantation all Romney Marsh and Suffolk ewes were judged to be in non-ovulatory period (anoestrus) with plasma progesterone mean values lower than 1 ng/mL. The melatonin treatment helped to induce the ovulatory activity in most of the ewes that were in anestrous at the time of melatonin implantation and the efficacy of this treatment depends on the individual variation in ovulatory response to ram introduction. In Southeastern Brazil., melatonin implant altered the daily plasma melatonin profiles of Suffolk and Romney Marsh ewes by increasing the melatonin levels during the light-phase of the day. Melatonin implant also induced an ovulatory response in Suffolk and Romney Marsh after the introduction of the rams. For no-implanted Suffolk ewes, the male effect is sufficient to provoke an ovulatory response.

Central Interleukin-1β Suppresses the Nocturnal Secretion of Melatonin.

In vertebrates, numerous processes occur in a rhythmic manner. The hormonal signal reliably reflecting the environmental light conditions is melatonin. Nocturnal melatonin secretion patterns could be disturbed in pathophysiological states, including inflammation, Alzheimer's disease, and depression. All of these states share common elements in their aetiology, including the overexpression of interleukin- (IL-) 1β in the central nervous system. Therefore, the present study was designed to determine the effect of the central injection of exogenous IL-1β on melatonin release and on the expression of the enzymes of the melatonin biosynthetic pathway in the pineal gland of ewe. It was found that intracerebroventricular injections of IL-1β (50 µg/animal) suppressed (P < 0.05) nocturnal melatonin secretion in sheep regardless of the photoperiod. This may have resulted from decreased (P < 0.05) synthesis of the melatonin intermediate serotonin, which may have resulted, at least partially, from a reduced expression of tryptophan hydroxylase. IL-1β also inhibited (P < 0.05) the expression of the melatonin rhythm enzyme arylalkylamine-N-acetyltransferase and hydroxyindole-O-methyltransferase. However, the ability of IL-1β to affect the expression of these enzymes was dependent upon the photoperiod. Our study may shed new light on the role of central IL-1β in the aetiology of disruptions in melatonin secretion.

Study of Seasonal Variation of Melatonin Levels of Iraqi Awassi Ewes

This study was conducted at the Sheep Farm pertaining to the Department of Animal Resources - College of Agriculture - University of Al-Anbar that located at Latitude 33° 20´ N during the period from 1/3/2013 till 22/12/2013. The objective of this study was to investigate the plasma melatonin levels of Iraqi Awassi ewes. Ten Awassi ewes of 2-4 years old and 41-54 kg live body weight were used in this study. Blood samples were collected from each ewe every 3h for 24h during spring equinox (21-22 March). Summer solstice (22-23 June). Autumn equinox (21-22 September) and Winter solstice (21-22 December). The plasma melatonin levels were determined as well as light intensity. Temperature – humidity index (THI) and body temperature at the time of blood collected. The plasma melatonin levels showed a characteristic seasonal variation and the pattern of melatonin secretion of Iraqi Awassi ewes did not subjected to the normal rhythm of melatonin secretion (high at night and low or undetected at the day). The plasma melatonin levels seem to be highly variable among individuals. The absence of significant correlation was observed between light intensity and plasma melatonin levels. THI and plasma melatonin levels as well as between plasma melatonin levels and body temperature. It was concluded from this study that there was a significant difference in melatonin levels between different seasons.

Expression and cellular localization of the transcription factor NeuroD1 in the developing and adult rat pineal gland.

Circadian rhythms govern many aspects of mammalian physiology. The daily pattern of melatonin synthesis and secretion is one of the classic examples of circadian oscillations. It is mediated by a class of neuroendocrine cells known as pinealocytes which are not yet fully defined. An established method to evaluate functional and cytological characters is through the expression of lineage-specific transcriptional regulators. NeuroD1 is a basic helix-loop-helix transcription factor involved in the specification and maintenance of both endocrine and neuronal phenotypes. We have previously described developmental and adult regulation of NeuroD1 mRNA in the rodent pineal gland. However, the transcript levels were not influenced by the elimination of sympathetic input, suggesting that any rhythmicity of NeuroD1 might be found downstream of transcription. Here, we describe NeuroD1 protein expression and cellular localization in the rat pineal gland during development and the daily cycle. In embryonic and perinatal stages, protein expression follows the mRNA pattern and is predominantly nuclear. Thereafter, NeuroD1 is mostly found in pinealocyte nuclei in the early part of the night and in cytoplasm during the day, a rhythm maintained into adulthood. Additionally, nocturnal nuclear NeuroD1 levels are reduced after sympathetic disruption, an effect mimicked by the in vivo administration of α- and β-adrenoceptor blockers. NeuroD1 phosphorylation at two sites, Ser(274) and Ser(336) , associates with nuclear localization in pinealocytes. These data suggest that NeuroD1 influences pineal phenotype both during development and adulthood, in an autonomic and phosphorylation-dependent manner.

Intra- and inter-individual variability of longitudinal daytime melatonin secretion patterns in depressed and non-depressed individuals

Disrupted melatonin secretion is regarded as a link between circadian rhythm and major depression, but results have been contradictory. We hypothesize that this might be due to averaging across individuals and too short measurements periods. In this study, pair-matched depressed and non-depressed individuals sampled their saliva three times a day, 30 days, in their natural environment. The depressed group showed significantly more variance and higher melatonin levels (p < 0.05). Substantial interindividual heterogeneity and day-to-day variability was found. The individual time-series approach allowed us to reveal this variability. Important information remains unnoticed when analyzing melatonin only at the group level.

Putative role of monoamines in the antidepressant-like mechanism induced by striatal MT2 blockade

It has been observed that the secretion pattern of melatonin is modified in Parkinson's disease (PD). Hence, it is hypothesized that dysregulations of melatonin MT2 receptors may be involved in the installation of depression in PD patients. Together with recent evidence based on the use of the intranigral rotenone model of PD, have led to the hypothesis that modulating the striatal MT2 receptor could provide a more comprehensive understanding of the antidepressant properties triggered. To further investigate this issue, male Wistar rats were infused with intranigral rotenone (12μg/μL) and seven days later subjected to a rapid eye movement sleep deprivation (REMSD) for 24h. After, we injected within the striatum the MT2 selective agonist, 8-M-PDOT (10μg/μL), the MT2 selective antagonist, 4-P-PDOT (5μg/μL) or vehicle. Subsequently, they were tested in the forced swimming test and were allowed to perform the sleep rebound (REB). Then, the rats were re-tested, and the striatum, hippocampus and substantia nigra pars compacta (SNpc) were collected for neurochemical purposes. Results indicated substantial antidepressant effects promoted by the blockade of striatal MT2 receptors that were potentiated by REMSD. MT2 activation increased DA levels in the striatum and hippocampus, while MT2 blockade increase DA in the SNpc. 4-P-PDOT treatment of the rotenone REMSD group generated a decrement in 5-HT levels within the striatum, hippocampus and SNpc. However, increased 5-HT turnover was observed among these structures. Therefore, we demonstrated the neurochemical antidepressant effect induced by striatal MT2 blockage associated with REMSD in the rotenone model of PD.

Psychosomatic disorder may be related to circadian rhythms in physically healthy students

Students suffering from subjective psychosomatic disorder often have basic lifestyle problems. We examined 30 healthy students aged 21–22 years old. Salivary samples were collected from the subjects at home five times per day (20:00, 24:00, 04:00, 08:00 and 12:00 h). We assessed melatonin secretion patterns by fluorescence enzyme immunoassay and cortisol secretion by ELISA. We assigned the subjects to regular, semi-regular and irregular circadian rhythm groups based on whether melatonin secretion was high until midnight. A self-assessment questionnaire addressing psychosomatic disorder was completed by the same students. The subjects rated their psychosomatic symptoms twice per day (08:00 and 20:00 h). The irregular group showed lower cortisol awakening response, but high cortisol concentrations at 12:00 h; this group also reported more subjective health complaints related to psychosomatic stress compared with the regular group. Our findings suggest that psychosomatic disorder is associated with circadian rhythms in Japanese students.