Key Points: This is the first study to demonstrate an altered circadian phase shifting response in a circadian rhythm sleep disorder. Patients with delayed sleep-wake phase disorder (DSWPD) demonstrate greater sensitivity of the circadian system to the phase-delaying effects of light. Increased circadian sensitivity to light is associated with later circadian timing within both control and DSWPD groups. DSWPD patients had a greater sustained pupil response after light exposure. Treatments for DSWPD should consider sensitivity of the circadian system to light as a potential underlying vulnerability, making patients susceptible to relapse.
Abstract: Patients with delayed sleep-wake phase disorder (DSWPD) exhibit delayed sleep-wake behaviour relative to desired bedtime, often leading to chronic sleep restriction and daytime dysfunction. The majority of DSWPD patients also display delayed circadian timing in the melatonin rhythm. Hypersensitivity of the circadian system to phase-delaying light is a plausible physiological basis for DSWPD vulnerability. We compared the phase shifting response to a 6.5 h light exposure (∼150 lux) between male patients with diagnosed DSWPD (n = 10; aged 20.8 ± 2.3 years) and male healthy controls (n = 11; aged 22.4 ± 3.3 years). Salivary dim light melatonin onset (DLMO) was measured under controlled conditions in dim light (<3 lux) before and after light exposure. Correcting for the circadian time of the light exposure, DSWPD patients exhibited 31.5% greater phase delay shifts than healthy controls. In both groups, a later initial melatonin phase was associated with a greater magnitude phase shift, indicating that increased circadian sensitivity to light may be a factor that contributes to delayed phase, even in non-clinical groups. DSWPD patients also had reduced pupil size following the light exposure, and showed a trend towards increased melatonin suppression during light exposure. These findings indicate that, for patients with DSWPD, assessment of light sensitivity may be an important factor that can inform behavioural therapy, including minimization of exposure to phase-delaying night-time light.
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http://dx.doi.org/10.1113/JP275917 | DOI Listing |
Neurosci Biobehav Rev
January 2025
Laboratory of Molecular and Systems Neurobiology, Department of Physiology and Neurobiology, Eötvös Loránd University.
The role of prolactin in sleep regulation has been the subject of extensive research over the past 50 years, resulting in the identification of multiple, disparate functions for the hormone. Prolactin demonstrated a characteristic circadian release pattern with elevation during dark and diminution during light. High prolactin levels were linked to non-rapid eye movement sleep and electroencephalogram delta activity in humans.
View Article and Find Full Text PDFBiomed Pharmacother
January 2025
Department of Experimental Medicine, Sapienza University of Rome, Rome 00161, Italy. Electronic address:
The abundance and behaviour of all hematopoietic components display daily oscillations, supporting the involvement of circadian clock mechanisms. The daily variations of immune cell functions, such as trafficking between blood and tissues, differentiation, proliferation, and effector capabilities are regulated by complex intrinsic (cell-based) and extrinsic (neuro-hormonal, organism-based) mechanisms. While the role of the transcriptional/translational molecular machinery, driven by a set of well-conserved genes (Clock genes), in nucleated immune cells is increasingly recognized and understood, the presence of non-transcriptional mechanisms remains almost entirely unexplored.
View Article and Find Full Text PDFMetab Brain Dis
January 2025
Department of Biological Sciences (Pharmacology and Toxicology), National Institute of Pharmaceutical Education and Research (NIPER) Hyderabad, Balanagar, Hyderabad, 500037, Telangana, India.
The negative impact of repeated-mild traumatic brain injury (rmTBI) is profoundly seen in circadian-disrupted individuals. The unrelenting inflammation, glial activation, and gut dysbiosis are key neuropathological aberrations in the aftermath of rmTBI. In this study, we examined the impact of chitosan lactate (CL) on circadian disturbance (CD) + rmTBI-generated neurological dysfunctions and its prebiotic response on the gut-brain axis.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Kentucky, Lexington, KY, USA.
Background: Disruption of sleep and circadian rhythms are associated with cognitive decline, preclinical Alzheimer's Disease (AD) pathology, and increased risk of dementia. Alleviating circadian rhythm and sleep disruption may improve cognition and reduce the progression of AD and related dementias (ADRD). Time-restricted eating (TRE), a circadian behavioral intervention that corrects disrupted eating rhythms by aligning food intake to the daytime, has demonstrated improvements in metabolic dysfunction and sleep quality.
View Article and Find Full Text PDFBackground: Passively-obtained smartphone digital phenotypes may yield objective estimates of everyday cognition in older adults compared to traditional cognitive/self-report measures typically confounded by sociodemographics. However, it is currently unknown what covariates are relevant when interpreting smartphone sensor data. We aimed to clarify which intrinsic and extrinsic factors are associated with digital phenotyping versus traditional cognitive measures in a cohort of older adults.
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