A pilot study of serotonin-1A receptor genotypes and rapid eye movement sleep sensitivity to serotonergic/cholinergic imbalance in humans: a pharmacological model of depression

RATIONALE: The serotonergic and cholinergic systems are jointly involved in regulating sleep but this system is theorized to be disturbed in depressed individuals. We previously reported that cholinergic and serotonergic agents induce sleep changes partially consistent with monoamine models of sleep disturbances in depression. One potential cause of disturbed neurotransmission is genetic predisposition. The G(-1019) allele of the serotonin-1A (5-HT(1A)) receptor promoter region predicts an increased risk for depression compared to the wild-type C(-1019) allele. OBJECTIVE: The goal of this study was to investigate how serotonin-1A receptor genotypes mediate sleep sensitivity to pharmacological probes modeling the serotonergic/cholinergic imbalance of depression. METHODS: Seventeen healthy female participants homozygous for either C (n=11) or G (n=6) alleles aged 18–27 years were tested on four nonconsecutive nights. Participants were given galantamine (an anti-acetylcholinesterase), buspirone (a serotonergic agonist), both drugs together, or placebos before sleeping. RESULTS: As reported previously, buspirone significantly increased rapid eye movement (REM) latency (P<0.001), as well as awakenings, percentage of time spent awake, and percentage of time asleep spent in stage N1 (P<0.019). Galantamine increased awakenings, percentage of time spent awake, percentage of time asleep spent in stage N1, and percentage of time asleep spent in REM, and decreased REM latency and percentage of time asleep spent in stage N3 (P<0.019). Galantamine plus buspirone given together disrupted sleep more than either drug alone, lowering sleep efficiency and percentage of time asleep spent in stage N3 and increasing awakenings, percentage of time spent awake, and percentage of time asleep spent in stage N1 (P<0.019). There was no main effect of genotype nor was there a significant multivariate interaction between genotype and drug condition. CONCLUSION: These findings are partially consistent with the literature about sleep in depression, notably short REM latency, higher percentage of total sleep time spent in REM, lower percentage of time asleep spent in stage N3, and increased sleep fragmentation. The C/G mutation in the serotonin-1A receptor promoter region does not appear to cause noticeable differences in the sleep patterns of a relatively small sample of healthy young females. Future studies with larger sample sizes are required

Parallel Changes in Mood and Melatonin Rhythm Following an Adjunctive Multimodal Chronobiological Intervention With Agomelatine in People With Depression: A Proof of Concept Open Label Study

Background: Agomelatine is a melatonin agonist and 5HT antagonist developed for the treatment of major depressive disorder which also has some effects on the circadian system. Since circadian dysfunctions are thought to play a role in the pathophysiology of depression, some of the mechanism of action of this drug may relate to improvements in circadian rhythms.Objective: This proof of concept open-label study sought to determine if improvements in depressive symptoms following an adjunctive multimodal intervention including agomelatine intake are associated with the magnitude of circadian realignment. This was investigated in young people with depression, a subgroup known to have high rates of delayed circadian rhythms.Methods: Young people with depression received a psychoeducation session about sleep and circadian rhythms, were asked to progressively phase advance their wake up time, and completed an 8 weeks course of agomelatine (25–50 mg). Participants underwent semi-structured psychological assessments, ambulatory sleep-wake monitoring and measurement of melatonin circadian phase before and after the intervention.Results: Twenty-four young adults with depression (17–28 years old; 58% females) completed the study. After the intervention, depressive symptoms were significantly reduced [t(23) = 6.9, p &lt; 0.001] and, on average, the timing of dim light melatonin onset (DLMO) shifted 3.6 h earlier [t(18) = 4.4, p &lt; 0.001]. On average, sleep onset was phase shifted 28 min earlier [t(19) = 2.1, p = 0.047] and total sleep time increased by 24 min [t(19) = –2.6, p = 0.018]. There was no significant change in wake-up times. A strong correlation (r = 0.69, p = 0.001) was found between the relative improvements in depression severity and the degree of phase shift in DLMO.Conclusion: Although this needs to be replicated in larger randomized controlled trials, these findings suggest that the degree of antidepressant response to a multimodal intervention including psychoeducation and agomelatine intake may be associated with the degree of change in evening melatonin release in young people with depression. This offers promising avenues for targeted treatment based on the prior identification of objective individual characteristics

Adverse Childhood Experiences: Roads to Recovery

THE ALL-PARTY PARLIAMENTARY GROUP AND THE WORKING GROUP The Working Group that produced this Report is a sub-group of the All-Party Parliamentary Group on a Fit and Healthy Childhood. The purpose of the APPG is to promote evidence-based discussion and produce reports on all aspect of childhood health and wellbeing including obesity, to inform policy decisions and public debate relating to childhood; and to enable communications between interested parties and relevant parliamentarians. Group details are recorded on the Parliamentary website at: https://publications.parliament.uk/pa/cm/cmallparty/190911/fit-and-healthychildhood.htm The Working Group is chaired by Helen Clark, a member of the APPG secretariat. Working Group members are volunteers from the APPG membership with an interest in this subject area. Those that have contributed to the work of the Working Group are listed on the previous page. The Report is divided into themed subject chapters with recommendations that we hope will influence active Government policy

Adverse Childhood Experiences: Roads to Recovery

THE ALL-PARTY PARLIAMENTARY GROUP AND THE WORKING GROUP The Working Group that produced this Report is a sub-group of the All-Party Parliamentary Group on a Fit and Healthy Childhood. The purpose of the APPG is to promote evidence-based discussion and produce reports on all aspect of childhood health and wellbeing including obesity, to inform policy decisions and public debate relating to childhood; and to enable communications between interested parties and relevant parliamentarians. Group details are recorded on the Parliamentary website at: https://publications.parliament.uk/pa/cm/cmallparty/190911/fit-and-healthychildhood.htm The Working Group is chaired by Helen Clark, a member of the APPG secretariat. Working Group members are volunteers from the APPG membership with an interest in this subject area. Those that have contributed to the work of the Working Group are listed on the previous page. The Report is divided into themed subject chapters with recommendations that we hope will influence active Government policy

Status assessment and conservation priorities for a circumpolar raptor: the Snowy Owl Bubo scandiacus

The global population and status of Snowy Owls Bubo scandiacus are particularly challenging to assess because individuals are irruptive and nomadic, and the breeding range is restricted to the remote circumpolar Arctic tundra. The International Union for Conservation of Nature (IUCN) uplisted the Snowy Owl to “Vulnerable” in 2017 because the suggested population estimates appeared considerably lower than historical estimates, and it recommended actions to clarify the population size, structure, and trends. Here we present a broad review and status assessment, an effort led by the International Snowy Owl Working Group (ISOWG) and researchers from around the world, to estimate population trends and the current global status of the Snowy Owl. We use long-term breeding data, genetic studies, satellite-GPS tracking, and survival estimates to assess current population trends at several monitoring sites in the Arctic and we review the ecology and threats throughout the Snowy Owl range. An assessment of the available data suggests that current estimates of a worldwide population of 14,000–28,000 breeding adults are plausible. Our assessment of population trends at five long-term monitoring sites suggests that breeding populations of Snowy Owls in the Arctic have decreased by more than 30% over the past three generations and the species should continue to be categorised as Vulnerable under the IUCN Red List Criterion A2. We offer research recommendations to improve our understanding of Snowy Owl biology and future population assessments in a changing world. Arctic; Bubo scandiacus; Irruptive; Monitoring; Population trendspublishedVersio

Trends in outpatient and inpatient visits for separate ambulatory-care-sensitive conditions during the first year of the COVID-19 pandemic: a province-based study

BackgroundThe COVID-19 pandemic led to global disruptions in non-urgent health services, affecting health outcomes of individuals with ambulatory-care-sensitive conditions (ACSCs).MethodsWe conducted a province-based study using Ontario health administrative data (Canada) to determine trends in outpatient visits and hospitalization rates (per 100,000 people) in the general adult population for seven ACSCs during the first pandemic year (March 2020–March 2021) compared to previous years (2016–2019), and how disruption in outpatient visits related to acute care use. ACSCs considered were chronic obstructive pulmonary disease (COPD), asthma, angina, congestive heart failure (CHF), hypertension, diabetes, and epilepsy. We used time series auto-regressive integrated moving-average models to compare observed versus projected rates.ResultsFollowing an initial reduction (March–May 2020) in all types of visits, primary care outpatient visits (combined in-person and virtual) returned to pre-pandemic levels for asthma, angina, hypertension, and diabetes, remained below pre-pandemic levels for COPD, and rose above pre-pandemic levels for CHF (104.8 vs. 96.4, 95% CI: 89.4–104.0) and epilepsy (29.6 vs. 24.7, 95% CI: 22.1–27.5) by the end of the first pandemic year. Specialty visits returned to pre-pandemic levels for COPD, angina, CHF, hypertension, and diabetes, but remained above pre-pandemic levels for asthma (95.4 vs. 79.5, 95% CI: 70.7–89.5) and epilepsy (53.3 vs. 45.6, 95% CI: 41.2–50.5), by the end of the year. Virtual visit rates increased for all ACSCs. Among ACSCs, reductions in hospitalizations were most pronounced for COPD and asthma. CHF-related hospitalizations also decreased, albeit to a lesser extent. For angina, hypertension, diabetes, and epilepsy, hospitalization rates reduced initially, but returned to pre-pandemic levels by the end of the year.ConclusionThis study demonstrated variation in outpatient visit trends for different ACSCs in the first pandemic year. No outpatient visit trends resulted in increased hospitalizations for any ACSC; however, reductions in rates of asthma, COPD, and CHF hospitalizations persisted