Chronobiology of Parkinson's disease: Past, present and future

Parkinson’s disease is a neurodegenerative disorder predominately affecting midbrain dopaminergic neurons that results in a broad range of motor and non-motor symptoms. Sleep complaints are among the most common non- motor symptoms, even in the prodromal period. Sleep alterations in Parkin- son’s disease patients may be associated with dysregulation of circadian rhythms, intrinsic 24-h cycles that control essential physiological functions, or with side effects from levodopa medication and physical and mental health challenges. The impact of circadian dysregulation on sleep disturbances in Parkinson’s disease is not fully understood; as such, we review the systems, cellular and molecular mechanisms that may underlie circadian perturbations in Parkinson’s disease. We also discuss the potential benefits of chronobiology- based personalized medicine in the management of Parkinson’s disease both in terms of behavioural and pharmacological interventions. We propose that a fuller understanding of circadian clock function may shed important new light on the aetiology and symptomatology of the disease and may allow for improvements in the quality of life for the millions of people with Parkinson’s disease

“Tell Me More About Your Child’s Sleep”: A Qualitative Investigation Of Sleep Problems In Children With ADHD

Objective: To investigate parental experiences and perceptions of sleep problems in their children with Attention Deficit Hyperactivity Disorder (ADHD), the perceived impacts of sleep problems and coping strategies deployed by parents.Methods: Semi-structured interviews with twenty-six parents of pre- adolescent children with a diagnosis of ADHD, followed by thematic analysis of the interview transcripts.Results: Three themes were generated from the data: Children’s Sleep Difficulties; Impacts of Children’s Sleep; and Improving Children’s Sleep. Sleep initiation problems in children with ADHD were commonly reported by parents, were perceived to be linked in a bidirectional manner with executive and emotional problems, and were reported as being disruptive to parental sleep. Some parents reported that their children’s sleep problems were the initial prompt that lead to a diagnosis of ADHD. Parents reported utilizing a range of coping strategies to mitigate sleep problems, such as controlling the bedroom sensory environment and using emotional “wind down” as part of the bedtime routine. Some parents endorsed a beneficial effect of melatonin on their children’s sleep.Conclusions: Sleep problems in children with ADHD were perceived as important issues by parents. Equipping parents with evidence-based strate-gies for the management of their children’s sleep may lead to benefits for the children, parents and wider household

The Role of the Circadian System in Attention Deficit Hyperactivity Disorder

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental condition characterised by the core symptoms of inattention, impulsivity and hyperactivity. Similar to many other neuropsychiatric conditions, ADHD is associated with very high levels of sleep disturbance. However, it is not clear whether such sleep disturbances are precursors to, or symptoms of, ADHD. Neither is it clear through which mechanisms sleep and ADHD are linked. One possible link is via modulation of circadian rhythms. In this chapter we overview the evidence that ADHD is associated with alterations in circadian processes, manifesting as later chronotype and delayed sleep phase in ADHD, and examine some mechanisms that may lead to such changes. We also interrogate how the circadian clock may be a substrate for therapeutic intervention in ADHD (chronotherapy) and highlight important new questions to be addressed to move the field forward

ADHD 24/7:Circadian clock genes, chronotherapy and sleep/wake cycle insufficiencies in ADHD

Objectives: The current paper addresses the evidence for circadian clock characteristics associated with attention-deficit hyperactivity disorder (ADHD), and possible therapeutic approaches based on chronomodulation through bright light (BL) therapy. Methods: We review the data reported in ADHD on genetic risk factors for phase-delayed circadian rhythms and on the role of photic input in circadian re-alignment. Results: Single nucleotide polymorphisms in circadian genes were recently associated with core ADHD symptoms, increased evening-orientation and frequent sleep problems. Additionally, alterations in exposure and response to photic input may underlie circadian problems in ADHD. BL therapy was shown to be effective for re-alignment of circadian physiology toward morningness, reducing sleep disturbances and bringing overall improvement in ADHD symptoms. The susceptibility of the circadian system to phase shift by timed BL exposure may have broad cost-effective potential implications for the treatment of ADHD. Conclusions: We conclude that further research of circadian function in ADHD should focus on detection of genetic markers (e.g., using human skin fibroblasts) and development of BL-based therapeutic interventions

Seasonal and daytime variation in multiple immune parameters in humans: evidence from 329,261 participants of the UK Biobank Cohort

Seasonal disease outbreaks are perennial features of human infectious disease but the factors generating these patterns are unclear. Here we investigate seasonal and daytime variability in multiple immune parameters in 329,261 participants in UK Biobank, and test for associations with a wide range of environmental and lifestyle factors, including changes in day length, outdoor temperature and vitamin D at the time the blood sample was collected. Seasonal patterns were evident in lymphocyte and neutrophil counts, and CRP, but not monocytes, and these were independent of lifestyle, demographic and environmental factors. All the immune parameters assessed demonstrated significant daytime variation that was independent of confounding factors. At a population level, human immune parameters vary across season and across time of day, independent of multiple confounding factors. Both season and time of day are fundamental dimensions of immune function that should be considered in all studies of immuno-prophylaxis and disease transmission

Posttraumatic stress disorder, complex PTSD and subtypes of loneliness among older adults

Abstract Objectives: Research examining the relationship between loneliness and Complex Posttraumatic Stress Disorder (CPTSD) is scarce, particularly among older adults. CPTSD includes the core symptoms of PTSD along with additional symptoms reflecting “disturbances in self‐organisation” (DSO). This study examined the cross‐sectional relationships between loneliness (emotional and social loneliness) and CPTSD symptoms (i.e., PTSD and DSO symptoms) in older adults. Methods: Structural equation modelling was used to examine these relationships in a nationally representative sample of US adults aged 60–70 years (n = 456). Results: Controlling for covariates, emotional loneliness was associated with PTSD (β = 0.31) and DSO (β = 0.57) symptoms whereas social loneliness was only associated with DSO symptoms (β = 0.25). The model explained 35.0% of the variance in PTSD symptoms and 71.3% in DSO symptoms. Conclusion: These findings have important implications for treating and understanding PTSD/CPTSD and their corre�lates among older adults

A Historiometric Examination of Machiavellianism and a New Taxonomy of Leadership

Although researchers have extensively examined the relationship between charismatic leadership and Machiavellianism (Deluga, 2001; Gardner & Avolio, 1995; House & Howell, 1992), there has been a lack of investigation of Machiavellianism in relation to alternative forms of outstanding leadership. Thus, the purpose of this investigation was to examine the relationship between Machiavellianism and a new taxonomy of outstanding leadership comprised of charismatic, ideological, and pragmatic leaders. Using an historiometric approach, raters assessed Machiavellianism via the communications of 120 outstanding leaders in organizations across the domains of business, political, military, and religious institutions. Academic biographies were used to assess twelve general performance measures as well as twelve general controls and five communication specific controls. The results indicated that differing levels of Machiavellianism is evidenced across the differing leader types as well as differing leader orientation. Additionally, Machiavellianism appears negatively related to performance, though less so when type and orientation are taken into account.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Development, characterisation and in vitro evaluation of lanthanide-based FPR2/ALX-targeted imaging probes

UK Engineering and Physical Sciences Research Council (EPRSC); Royal Society Wolfson Fellowship

Circadian and photic regulation of phosphorylation of ERK1/2 and Elk-1 in the suprachiasmatic nuclei of the Syrian hamster

In this study we investigated the circadian and photic regulation of phosphorylation of the extracellular signal-related kinase (ERK) 1/2, and the transcription factor Elk-1 in the suprachiasmatic nuclei of the Syrian hamster. We report that levels of phosphorylated ERK (P-ERK) are rhythmic, peaking during the mid subjective day, whereas phosphorylated Elk-1 (P-Elk-1) shows no distinct rhythm. Light pulses during the subjective night rapidly, but transiently, induce P-ERK, whereas P-Elk-1 is also induced, albeit with a slower time course. Application of the ERK pathway inhibitor U0126 attenuates photic induction of both P-ERK and P-Elk-1 and phase advances of wheel-running behavior. The NMDA receptor channel blocker, MK-801, also significantly attenuates photic induction of P-ERK and P-Elk-1. Taken together, these results indicate a role of the ERK cascade in the regulation of free-running circadian rhythms and of photic-resetting of these rhythms and suggest that in the mammalian suprachiasmatic nuclei, Elk-1 represents a novel molecular component of the photic-induction pathway