Browsing by Subject "MELATONIN"

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  • Celikkayalar, Ercan; Airaksinen, Marja; Kivelä, Sirkka-Liisa; Nieminen, Jenni; Kleme, Jenni; Puustinen, Juha (2021)
    Purpose: The use of benzodiazepines and related drugs (BZD) is common among older adults although there is growing evidence of their harmful effects. This study investigated how well older people are aware of the potential risks related to the BZD they are taking and whether the risk awareness has changed in the years between 2004 and 2015. Patients and Methods: The data were collected by interviewing BZD using home-dwelling patients aged >= 65 years with normal cognitive function (MMSE >= 20) who were admitted to the hospital within a 1 month study period in the years 2004 and 2015. Patients were asked whether they were aware of the ten main potential risks related to BZD use. A risk awareness score (range 0-10) was assessed for each patient, each known potential risk yielding one point. Results: The study included 37 patients in 2004 and 31 patients in 2015. In 2004,6/37 patients (16%), while 16/31 patients (52%) in 2015 had risk awareness scores between 6 and 10. Awareness of dependence (p=0.047), interaction with alcohol (p=0.001), dizziness (p=0.002) and developing tolerance (p=0.002) had improved, while awareness of the other potential risks remained unchanged, muscle weakness being the least known (3/37 in 2004 and 4/31 in 2015 were aware of it as a potential risk). Regular BZD use had declined (p=0.043) but pro re nata (PRN; when required) BZD use had increased (p=0.003) between the years 2004 and 2015. Conclusion: Older BZD users' awareness of some potential risks related to BZD use (dependence, interaction with alcohol, dizziness and developing tolerance) had improved between 2004 and 2015, while awareness of other potential risks remained unchanged.
  • Merikanto, Ilona; Kantojärvi, Katri; Partonen, Timo; Pesonen, Anu-Katriina; Paunio, Tiina (2021)
    Objective Associations of eveningness with health hazards benefit from analyzing to what extent the polygenic score for morningness correlates with the assessments of the behavioral trait of morningness-eveningness and chronotype. Methods With a population-based sample of 17,243 Finnish adults, aged 25–74 years, this study examines the associations of four feasible assessment methods of chronotype, a) biological the genetic liability based on the polygenic score for morningness (PGSmorn), b) the widely-used single item for self-assessed morningness/eveningness (MEQi19) of the original Morningness-Eveningness Questionnaire (MEQ), c) the behavioral trait of morningness-eveningness as assessed with the score on the shortened version (sMEQ) of the original MEQ, and d) the phase of entrainment as assessed with the habitual midpoint of sleep based on the self-reported sleep-wake schedule during weekend (Sleepmid-wknd) as well as the sleep debt corrected midpoint of sleep (Sleepmid-corr). Results All self-report measures correlated with each other, but very weakly with the PGSmorn, which explained 1–2% of the variation in diurnal preference or habitual sleep-wake schedule. The influence of age was greater on Sleepmid-wknd and Sleepmid-corr than on the sMEQ or MEQi19, indicating that the diurnal preference might be a more stable indicator for morningness-eveningness than the sleep-wake schedule. Analyses of the discrepancies between sMEQ and MEQi19 indicated that eveningness can be over-estimated when relying on only the single-item self-assessment. Conclusions The current polygenic score for morningness explains only a small proportion of the variation in diurnal preference or habitual sleep-wake schedule. The molecular genetic basis for morningness-eveningness needs further elucidation.
  • Kahn, Michal; Korhonen, Topi; Leinonen, Leena; Martinmaki, Kaisu; Kuula, Liisa; Pesonen, Anu-Katriina; Gradisar, Michael (2021)
    Professional and colloquial sleep hygiene guidelines advise against evening physical activity, despite meta-analyses of laboratory studies concluding that evening exercise does not impair sleep. This study is the first to investigate the association between objectively measured evening physical activity and sleep within a real-world big-data sample. A total of 153,154 nights from 12,638 individuals aged 18-60 years (M = 40.1 SD = 10.1; 44.5% female) were analyzed. Nighttime sleep and minutes of physical activity were assessed using Polar wearable devices for 14 consecutive days. Thirty minutes or more of moderate-to-near maximal physical activity during the 3 h before sleep onset were recorded in 12.4% of evenings, and were more frequent on weekdays than weekends (13.3 vs. 10.2% respectively, p < 0.001). Linear mixed modeling revealed that sleep efficiency was not significantly associated with evening physical activity, and that sleep duration was 3.4 min longer on average on nights following evenings in which participants engaged in 30 min or more of moderate-intense physical activity. Effects were found for sleep timing metrics, as evening physical activity was linked with earlier sleep onset and offset times (-13.7 and -9.3 min, respectively). Overall, these effects were greater- but still very small- on weekdays compared to weekends. The present study provides further evidence for the lack of meaningful links between sleep duration or quality and physical activity in the hours preceding sleep. Taken together with recent meta-analytic findings, these findings suggest that changes in public health recommendations are warranted regarding evening physical activity and its relation to sleep.
  • Puustinen, Juha; Lähteenmäki, Ritva; Nurminen, Janne; Vahlberg, Tero; Aarnio, Pertti; Partinen, Markku; Räihä, Ismo; Neuvonen, Pertti J.; Kivelä, Sirkka-Liisa (2018)
    Background: Studies on persistence of benzodiazepine agonist (BZDA) withdrawal in older outpatients are few, and few studies on long-term persistence over years have yet been published. To describe the persistence of temazepam, zolpidem, and zopiclone (BZDA) withdrawal among older outpatients at 3 years from the beginning of withdrawal, as well as any changes in use of other medications. Methods: 92 outpatients (>= 55 years) with primary insomnia, long-term BZDA use as hypnotics (mean duration of BZDA use 9.9 +/- 6.2 years), and willingness to withdraw from BZDAs each received either melatonin or a placebo nightly for one month. During this period, BZDAs were meant to be gradually withdrawn. Sleep hygiene counselling and psychosocial support were provided. Three years later, use of BZDAs and other medications was determined by interview and confirmed from medical records. Results: Of the original 92 outpatients, 83 (90%) participated in the 3-year survey (mean follow-up 3.3 +/- 0.2 years). The number of BZDA-free participants decreased from 34 (37%) at 6 months to 26 (28%; intention-to-treat) at 3 years, that of irregular BZDA users decreased from 44 (48%) at 6 months to 27 (29%) at 3 years, while that of regular users increased from 11 (12%) at 6 months to 30 (33%) at 3 years (P = 0.001). Those who were regular BZDA users at 3 years had at baseline (before withdrawal) higher BMI (P = 0.001) than did other participants. At 3 years, the total number of medications remained unchanged for non-users (P = 0.432), but increased for the irregular (P = 0.011) and regular users (P = 0.026) compared to baseline. At 3 years, compared to baseline, use of antidepressants, dopamine agonists, melatonin, and NSAIDs/paracetamol was significantly more common in the whole cohort, but their use did not differ between the BZDA-user subgroups. Randomization to melatonin or placebo during BZDA withdrawal was unrelated to BZDA-withdrawal result. Conclusions: At 3 years after withdrawal, the number of BZDA-free participants had decreased, but still one-third of the subjects remained BZDA-free, and one-third had reduced their use. Successful BZDA withdrawal did not lead to any increase in total number of medications; use of symptomatic medications in the whole cohort, however, did increase.
  • Lolicato, Fabio; Juhola, Hanna; Zak, Agata; Postila, Pekka A.; Saukko, Annina; Rissanen, Sami; Enkavi, Giray; Vattulainen, Ilpo; Kepczynski, Mariusz; Rog, Tomasz (2020)
    Synaptic neurotransmission has recently been proposed to function via either a membrane-independent or a membrane-dependent mechanism, depending on the neurotransmitter type. In the membrane-dependent mechanism, amphipathic neurotransmitters first partition to the lipid headgroup region and then diffuse along the membrane plane to their membrane-buried receptors. However, to date, this mechanism has not been demonstrated for any neurotransmitter-receptor complex. Here, we combined isothermal calorimetry measurements with a diverse set of molecular dynamics simulation methods to investigate the partitioning of an amphipathic neurotransmitter (dopamine) and the mechanism of its entry into the ligand-binding site. Our results show that the binding of dopamine to its receptor is consistent with the membrane-dependent binding and entry mechanism. Both experimental and simulation results showed that dopamine favors binding to lipid membranes especially in the headgroup region. Moreover, our simulations revealed a ligand-entry pathway from the membrane to the binding site. This pathway passes through a lateral gate between transmembrane alpha-helices 5 and 6 on the membrane-facing side of the protein. All in all, our results demonstrate that dopamine binds to its receptor by a membrane-dependent mechanism, and this is complemented by the more traditional binding mechanism directly through the aqueous phase. The results suggest that the membrane-dependent mechanism is common in other synaptic receptors, too.
  • Koskela, Sanna; Turunen, Tuomas; Ala-Laurila, Petri (2020)
    Circadian clocks predictively adjust the physiology of organisms to the day/night cycle. The retina has its own clock, and many diurnal changes in its physiology have been reported. However, their implications for retinal functions and visually guided behavior are largely unresolved. Here, we study the impact of diurnal rhythm on the sensitivity limit of mouse vision. A simple photon detection task allowed us to link well-defined retinal output signals directly to visually guided behavior. We show that visually guided behavior at its sensitivity limit is strongly under diurnal control, reaching the highest sensitivity and stability at night. The diurnal differences in visual sensitivity did not arise in the retina, as assessed by spike recordings from the most sensitive retinal ganglion cell types: ON sustained, OFF sustained, and OFF transient alpha ganglion cells. Instead, we found that mice, as nocturnal animals, use a more efficient search strategy for visual cues at night. Intriguingly, they can switch to the more efficient night strategy even at their subjective day after first having performed the task at night. Our results exemplify that the shape of visual psychometric functions depends robustly on the diurnal state of the animal, its search strategy, and even its diurnal history of performing the task. The results highlight the impact of the day/night cycle on high-level sensory processing, demonstrating a direct diurnal impact on the behavioral strategy of the animal.
  • Murphy, Rachel A.; Tintle, Nathan; Harris, William S.; Darvishian, Maryam; Marklund, Matti; Virtanen, Jyrki K.; Hantunen, Sari; de Mello, Vanessa D.; Tuomilehto, Jaakko; Lindstrom, Jaana; Bolt, Matthew A.; Brouwer, Ingeborg A.; Wood, Alexis C.; Senn, Mackenzie; Redline, Susan; Tsai, Michael Y.; Gudnason, Vilmundur; Eiriksdottir, Gudny; Lindberg, Eva; Shadyab, Aladdin H.; Liu, Buyun; Carnethon, Mercedes; Uusitupa, Matti; Djousse, Luc; Riserus, Ulf; Lind, Lars; van Dam, Rob M.; Koh, Woon-Puay; Shi, Peilin; Siscovick, David; Lemaitre, Rozenn N.; Mozaffarian, Dariush (2022)
    Background: n-3 and n-6 PUFAs have physiologic roles in sleep processes. but little is known regarding circulating n-3 and n-6 PUFA and sleep parameters. Objectives: We sought to assess associations between biomarkers of n-3 and n-6 PUFA intake with self-reported sleep duration and difficulty falling sleeping in the Fatty Acids and Outcome Research Consortium. Methods: Harmonized, de novo. individual-level analyses were performed and pooled across 12 cohorts. Participants were 35-96 y old and from 5 nations. Circulating measures included alpha-linolenic acid (ALA), EPA, docosapentaenoic acid (DPA), DHA, EPA + DPA DHA, linoleic acid, and arachidonic acid. Sleep duration (10 cohorts. n = 18.791) was categorized as short (= 9 h). Difficulty falling asleep (8 cohorts, n = 12,500) was categorized as yes or no. Associations between PUFAs, sleep duration, and difficulty falling sleeping were assessed by cross-sectional multinomial logistic regression using standardized protocols and covariates. Cohort-specific multivariable-adjusted ORs per quintile of PUFAs were pooled with inverse-variance weighted meta-analysis. Results: In pooled analysis adjusted for sociodemographic characteristics and health status, participants with higher very long-chain n-3 PUFAs were less likely to have long sleep duration. In the top compared with the bottom quintiles. the multivariable-adjusted ORs (95% CIs) for long sleep were 0.78 (95% CI: 0.65, 0.95) for DHA and 0.76 (95% CI: 0.63, 0.93) for EPA + DPA + DHA. Significant associations for ALA and n-6 PUFA with short sleep duration or difficulty falling sleeping were not identified. Conclusions: Participants with higher concentrations of very long-chain n-3 PUFAs were less likely to have long sleep duration. While objective biomarkers reduce recall bias and misclassification, the cross-sectional design limits assessment of the temporal nature of this relation. These novel findings across 12 cohorts highlight the need for experimental and biological assessments of very long-chain n-3 PUFAs and sleep duration.
  • Sulkava, Sonja M; Taka, Antti-Mathias; Kantojärvi, Katri; Pölkki, Pirjo; Morales-Munoz, Isabel; Milani, Lili; Porkka-Heiskanen, Tarja; Saarenpää-Heikkilä, Outi; Kylliäinen, Anneli; Paavonen, E. Juulia; Paunio, Tiina (2020)
    Melatonin is a circadian regulatory hormone with neuroprotective properties. We have previously demonstrated the association of the genetic variant rs12506228 near the melatonin receptor 1A gene (MTNR1A) with intolerance to shift‐work. Furthermore, this variant has been connected to Alzheimer's disease. Because of the previously suggested role of melatonin signalling in foetal neurocognitive and sleep development, we studied here the association of rs12506228 with early development. The study sample comprised 8‐month‐old infants from the Finnish CHILD‐SLEEP birth cohort (n = 1,301). Parental questionnaires assessed socioemotional, communication and motor development, as well as sleep length and night awakenings. The A allele of rs12506228 showed an association with slower socioemotional (p = .025) and communication (p = .0098) development, but no direct association with sleep. However, the association of the Finnish seasons with infant sleep length interacted with rs12506228. Taken together, rs12506228 near MTNR1A, which has been previously linked to adult and elderly traits, is shown here to associate with slower early cognitive development. In addition, these results suggest that the darker seasons associate with longer infant sleep time, but only in the absence of the rs12506228 AA genotype. Because the risk allele has been connected to fewer brain MT1 melatonin receptors, these associations may reflect the influence of decreased melatonin signalling in early development.