Circadian Function Research Articles

Microglia are involved in the protection of memories formed during sleep deprivation

Sleep deprivation can generate inflammatory responses in the central nervous system. In turn, this inflammation increases sleep drive, leading to a rebound in sleep duration. Microglia, the innate immune cells found exclusively in the CNS, have previously been found to release inflammatory signals and exhibit altered characteristics in response to sleep deprivation. Together, this suggests that microglia may be partially responsible for the brain's response to sleep deprivation through their inflammatory activity. In this study, we ablated microglia from the mouse brain and assessed resulting sleep, circadian, and sleep deprivation phenotypes. We find that microglia are dispensable for both homeostatic sleep and circadian function and the sleep rebound response to sleep deprivation. However, we uncover a phenomenon by which microglia appear to be essential for the protection of fear-conditioning memories formed during the recovery sleep period following a period of sleep deprivation. This phenomenon occurs potentially through the upregulation of synaptic-homeostasis related genes to protect nascent dendritic spines that may be otherwise removed or downscaled during recovery sleep. These findings further expand the list of known functions for microglia in synaptic modulation.

Transdiagnostic Sleep and Circadian Intervention for Adolescents Plus Text Messaging: Randomized Controlled Trial 12-month Follow-up

ABSTRACT Objective The Transdiagnostic Sleep and Circadian Intervention for Youth (TranS-C) was developed to improve sleep and circadian functioning in adolescents. This study examined the 12-month effects for TranS-C compared with psychoeducation (PE). We also investigated whether a text messaging intervention can promote maintenance of treatment effects. Method At the baseline, adolescents (58% female, average age = 14.8 years) with an eveningness chronotype were randomized to TranS-C (n = 89) or PE (n = 87). At 6-month follow-up, participants were randomized to receive text messages that had repeated treatment information (n = 47), text messages that prompted the recall of treatment information (n = 50), or no text messages (n = 47). Results Relative to PE, TranS-C was associated with a reduced eveningness (b = 2.06, p = .005, d = 0.29) from the baseline to a 12-month follow-up. TranS-C treatment effects, relative to PE, were augmented by receiving text messages, compared to no text messages, for eveningness from baseline to 12-month follow-up (b = 1.38, p = .008, d = 0.28) and from 6- to 12-month follow-up (b = 1.07, p = .046, d = 0.21). Neither TranS-C nor text messages were significantly associated with other primary outcomes. TranS-C and text messages were significantly associated with improvements on selected secondary sleep and health outcomes through follow-up. Conclusions For adolescents with an eveningness chronotype, improved sleep and circadian functioning on selected outcomes were maintained over 12 months for TranS-C compared with PE. Text messages boosted the effects of TranS-C through 12-month follow-up.

Aging disrupts circadian gene regulation and function in macrophages.

Aging is characterized by an increased vulnerability to infection and the development of inflammatory diseases, such as atherosclerosis, frailty, cancer and neurodegeneration. Here, we find that aging is associated with the loss of diurnally rhythmic innate immune responses, including monocyte trafficking from bone marrow to blood, response to lipopolysaccharide and phagocytosis. This decline in homeostatic immune responses was associated with a striking disappearance of circadian gene transcription in aged compared to young tissue macrophages. Chromatin accessibility was significantly greater in young macrophages than in aged macrophages; however, this difference did not explain the loss of rhythmic gene transcription in aged macrophages. Rather, diurnal expression of Kruppel-like factor 4 (Klf4), a transcription factor (TF) well established in regulating cell differentiation and reprogramming, was selectively diminished in aged macrophages. Ablation of Klf4 expression abolished diurnal rhythms in phagocytic activity, recapitulating the effect of aging on macrophage phagocytosis. Examination of individuals harboring genetic variants of KLF4 revealed an association with age-dependent susceptibility to death caused by bacterial infection. Our results indicate that loss of rhythmic Klf4 expression in aged macrophages is associated with disruption of circadian innate immune homeostasis, a mechanism that may underlie age-associated loss of protective immune responses.

New Insights Into Cancer Chronotherapies.

Circadian clocks participate in the coordination of various metabolic and biological activities to maintain homeostasis. Disturbances in the circadian rhythm and cancers are closely related. Circadian clock genes are differentially expressed in many tumors, and accelerate the development and progression of tumors. In addition, tumor tissues exert varying biological activities compared to normal tissues due to resetting of altered rhythms. Thus, chronotherapeutics used for cancer treatment should exploit the timing of circadian rhythms to achieve higher efficacy and mild toxicity. Due to interpatient differences in circadian functions, our findings advocate an individualized precision approach to chronotherapy. Herein, we review the specific association between circadian clocks and cancers. In addition, we focus on chronotherapies in cancers and personalized biomarkers for the development of precision chronotherapy. The understanding of circadian clocks in cancer will provide a rationale for more effective clinical treatment of tumors.

Neurobiological and behavioral mechanisms of circadian rhythm disruption in bipolar disorder: A critical multi-disciplinary literature review and agenda for future research from the ISBD task force on chronobiology.

AimSymptoms of bipolar disorder (BD) include changes in mood, activity, energy, sleep, and appetite. Since many of these processes are regulated by circadian function, circadian rhythm disturbance has been examined as a biological feature underlying BD. The International Society for Bipolar Disorders Chronobiology Task Force (CTF) was commissioned to review evidence for neurobiological and behavioral mechanisms pertinent to BD.MethodDrawing upon expertise in animal models, biomarkers, physiology, and behavior, CTF analyzed the relevant cross‐disciplinary literature to precisely frame the discussion around circadian rhythm disruption in BD, highlight key findings, and for the first time integrate findings across levels of analysis to develop an internally consistent, coherent theoretical framework.ResultsEvidence from multiple sources implicates the circadian system in mood regulation, with corresponding associations with BD diagnoses and mood‐related traits reported across genetic, cellular, physiological, and behavioral domains. However, circadian disruption does not appear to be specific to BD and is present across a variety of high‐risk, prodromal, and syndromic psychiatric disorders. Substantial variability and ambiguity among the definitions, concepts and assumptions underlying the research have limited replication and the emergence of consensus findings.ConclusionsFuture research in circadian rhythms and its role in BD is warranted. Well‐powered studies that carefully define associations between BD‐related and chronobiologically‐related constructs, and integrate across levels of analysis will be most illuminating.

The Arabidopsis Circadian Clock and Metabolic Energy: A Question of Time

A fundamental principle shared by all organisms is the metabolic conversion of nutrients into energy for cellular processes and structural building blocks. A highly precise spatiotemporal programming is required to couple metabolic capacity with energy allocation. Cellular metabolism is also able to adapt to the external time, and the mechanisms governing such an adaptation rely on the circadian clock. Virtually all photosensitive organisms have evolved a self-sustained timekeeping mechanism or circadian clock that anticipates and responds to the 24-h environmental changes that occur during the day and night cycle. This endogenous timing mechanism works in resonance with the environment to control growth, development, responses to stress, and also metabolism. Here, we briefly describe the prevalent role for the circadian clock controlling the timing of mitochondrial activity and cellular energy in Arabidopsis thaliana. Evidence that metabolic signals can in turn feedback to the clock place the spotlight onto the molecular mechanisms and components linking the circadian function with metabolic homeostasis and energy.

Measuring Sleep, Wakefulness, and Circadian Functions in Neurologic Disorders.

Neurologic disorders impact the ability of the brain to regulate sleep, wake, and circadian functions, including state generation, components of state (such as rapid eye movement sleep muscle atonia, state transitions) and electroencephalographic microarchitecture. At its most extreme, extensive brain damage may even prevent differentiation of sleep stages from wakefulness (eg, status dissociatus). Given that comorbid sleep-wake-circadian disorders are common and can adversely impact the occurrence, evolution, and management of underlying neurologic conditions, new technologies for long-term monitoring of neurologic patients may potentially usher in new diagnostic strategies and optimization of clinical management.

Astrocytic BMAL1 regulates protein aggregation in mouse models of alpha‐synuclein and tau pathology

AbstractBackgroundThe circadian clock regulates inflammatory responses in the peripheral immune system, though its function in neuroinflammation is poorly understood. Deletion of the master circadian clock transcription factor BMAL1 abrogates cellular circadian clock function and can be used to probe cell‐type specific functions of the clock. Our lab has previously shown that Bmal1 deletion induces oxidative stress, astrocyte activation, and increased β‐amyloid plaque deposition in mice. We hypothesized that deletion of Bmal1 would increase pathology in other protein aggregation models.MethodsWe generated global inducible Bmal1 knock out mice expressing human P301S mutant tau. Pathology, aggregation state, and gliosis were quantified at nine months of age. We induced synuclein aggregation in global Bmal1 knock out mice using an alpha‐synuclein preformed fibril injection (PFF) model. Three months post‐PFF injection, mice were analyzed for synuclein pathology and gliosis. To determine a cell‐type specific effect, we generated astrocyte‐ and microglia‐specific Bmal1 knock out mice and used these for PFF injections. Pathology and gliosis were analyzed from these mice three months post‐PFF injection. We then generated astrocyte‐specific Bmal1 knock out mice expressing human P301S mutant tau to test the effect of Bmal1 deletion in astrocytes on tau aggregation.ResultsGlobal Bmal1 deletion in the P301S model resulted in a significant decrease in aggregated tau and microglia activation. Global Bmal1 knock out mice injected with PFFs had significantly decreased synuclein pathology and a decrease in microgliosis. Bmal1 deletion specifically in astrocytes was sufficient to reduce both tau and synuclein pathology. Using bioinformatics methods, we discovered an astrocytic candidate gene, Bag3, which may play a role in reducing pathology in our models. We used an in vitro PFF uptake assay and found that Bmal1 knockdown resulted in increased PFF uptake, which was reduced to baseline after simultaneous knockdown of Bag3.Conclusion Bmal1 deletion in astrocytes is sufficient to reduce tau and synuclein pathologies and attenuate microglia activation. This effect may be driven by the upregulation of the macroautophagy chaperone protein, Bag3. Our data suggests that targeting astrocytic protein degradation machinery may be a therapeutic strategy for reducing intra‐neuronal protein aggregates, such as tau and synuclein.

Effects of photoperiod and diet on BDNF daily rhythms in diurnal sand rats

Brain-derived neurotrophic factor (BDNF), its receptors and epigenetic modulators, are implicated in the pathophysiology of affective disorders, T2DM and the circadian system function. We used diurnal sand rats, which develop type 2 diabetes (T2DM), anxiety and depressive-like behavior under laboratory conditions. The development of these disorders is accelerated when animals are maintained under short photoperiod (5:19L:D, SP) compared to neutral photoperiod (12:12L:D, NP). We compared rhythms in plasma BDNF as well as BDNF and PER2 expression in the frontal cortex and suprachiasmatic nucleus (SCN) of sand rats acclimated to SP and NP. Acclimation to SP resulted in higher insulin levels, significantly higher glucose levels in the glucose tolerance test, and significantly higher anxiety- and depression-like behaviors compared with animals acclimated to NP. NP Animals exhibited a significant daily rhythm in plasma BDNF levels with higher levels during the night, and in BDNF expression levels in the frontal cortex and SCN. No significant BDNF rhythm was found in the plasma, frontal cortex or SCN of SP acclimated animals. We propose that in sand rats, BDNF may, at least in part, mediate the effects of circadian disruption on the development of anxiety and depressive-like behavior and T2DM.

Chromatin spatial organization of wild type and mutant peanuts reveals high-resolution genomic architecture and interaction alterations

BackgroundThree-dimensional (3D) chromatin organization provides a critical foundation to investigate gene expression regulation and cellular homeostasis.ResultsHere, we present the first 3D genome architecture maps in wild type and mutant allotetraploid peanut lines, which illustrate A/B compartments, topologically associated domains (TADs), and widespread chromatin interactions. Most peanut chromosomal arms (52.3%) have active regions (A compartments) with relatively high gene density and high transcriptional levels. About 2.0% of chromosomal regions switch from inactive to active (B-to-A) in the mutant line, harboring 58 differentially expressed genes enriched in flavonoid biosynthesis and circadian rhythm functions. The mutant peanut line shows a higher number of genome-wide cis-interactions than its wild-type. The present study reveals a new TAD in the mutant line that generates different chromatin loops and harbors a specific upstream AP2EREBP-binding motif which might upregulate the expression of the GA2ox gene and decrease active gibberellin (GA) content, presumably making the mutant plant dwarf.ConclusionsOur findings will shed new light on the relationship between 3D chromatin architecture and transcriptional regulation in plants.

Circadian rhythms in neurodegenerative disorders.

Endogenous biological clocks, orchestrated by the suprachiasmatic nucleus, time the circadian rhythms that synchronize physiological and behavioural functions in humans. The circadian system influences most physiological processes, including sleep, alertness and cognitive performance. Disruption of circadian homeostasis has deleterious effects on human health. Neurodegenerative disorders involve a wide range of symptoms, many of which exhibit diurnal variations in frequency and intensity. These disorders also disrupt circadian homeostasis, which in turn has negative effects on symptoms and quality of life. Emerging evidence points to a bidirectional relationship between circadian homeostasis and neurodegeneration, suggesting that circadian function might have an important role in the progression of neurodegenerative disorders. Therefore, the circadian system has become an attractive target for research and clinical care innovations. Studying circadian disruption in neurodegenerative disorders could expand our understanding of the pathophysiology of neurodegeneration and facilitate the development of novel, circadian-based interventions for these disabling disorders. In this Review, we discuss the alterations to the circadian system that occur in movement (Parkinson disease and Huntington disease) and cognitive (Alzheimer disease and frontotemporal dementia) neurodegenerative disorders and provide directions for future investigations in this field.

Chronobiology and Metabolism: Is Ketogenic Diet Able to Influence Circadian Rhythm?

Circadian rhythms underpin most physiological processes, including energy metabolism. The core circadian clock consists of a transcription-translation negative feedback loop, and is synchronized to light-dark cycles by virtue of light input from the retina, to the central clock in the suprachiasmatic nucleus in the hypothalamus. All cells in the body have circadian oscillators which are entrained to the central clock by neural and humoral signals. In addition to light entrainment of the central clock in the brain, it now emerges that other stimuli can drive circadian clock function in peripheral tissues, the major one being food. This can then drive the liver clock to be misaligned with the central brain clock, a situation of internal misalignment with metabolic disease consequences. Such misalignment is prevalent, with shift workers making up 20% of the working population. The effects of diet composition on the clock are not completely clarified yet. High-fat diet and fasting influence circadian expression of clock genes, inducing phase-advance and phase-delay in animal models. Ketogenic diet (KD) is able to induce a metabolic switch from carbohydrate to fatty acid oxidation, miming a fasting state. In recent years, some animal studies have been conducted to investigate the ability of the KD to modify circadian gene expression, and demonstrated that the KD alters circadian rhythm and induces a rearrangement of metabolic gene expression. These findings may lead to new approaches to obesity and metabolic pathologies treatment.

A Review on Role of Circadian Rhythms in Management of Prostate Cancer

The circadian clock is a molecular evolutionary mechanism that controls the time of physiology to maintain homeostasis. Circadian disorder in particular has been identified as an independent risk factor for cancer and has been classified as a carcinogen. The circadian rhythm regulates several biological pathways, including oncogenic tumors, metabolism, and cell reproduction. The new data examined in this article suggest that circadian regulatory functions play a key role in various aspects of cancer, including cell proliferation control, cell death, DNA repair, and metabolism. Circadian irregularities are incorrect input signals, such as exposure to night light, variability in circadian rhythm genes, and output changes that regulate circadian behavior, including melatonin. Night work, shift work, workday changes, urinary melatonin levels, and insomnia put older men at risk for prostate cancer. Melatonin has anti-cancer properties. Men with lower melatonin levels in the morning had a higher risk of advanced or fatal prostate cancer. Melatonin, a hormone found in the pineal gland, plays an important role in the functioning of the circadian function. The integration of circadian biology into cancer research opens up new avenues for more effective cancer treatment, including the prevention, diagnosis, and treatment of this destructive disease. This review examines the role of the circadian clock in tumor formation and cancer symptoms, and examines whether pharmacological changes in circadian clock genes may lead to new treatment options.

Circadian Functioning and Quality of Life in Substance Use Disorder Patients With and Without Comorbid Major Depressive Disorder.

Aim: Although a relationship between circadian disruption and development of several psychiatric disorders, such as major depressive disorder (MDD) and substance use disorder (SUD), has been observed, knowledge on this area is scarce yet. Therefore, this study aims to analyze the circadian functioning and quality of life (QOL) in SUD patients with and without comorbid MDD, two highly prevalent clinical entities with difficult therapeutic management.Methods: One hundred sixty-three male patients under treatment, 81 with SUD and 82 with SUD comorbid major depressive disorder (SUD + MDD), were evaluated. For the circadian functioning assessment, we calculated Social Jet Lag (SJL) and used the reduced Morningness–Eveningness Questionnaire (rMEQ) and the Pittsburgh Sleep Quality Index (PSQI). QOL was measured using the shortened version of the World Health Organization's Quality of Life Questionnaire (WHOQOL-BREF). We collected sociodemographic and clinical variables to evaluate their possible influence on the circadian functioning. Intergroup differences among the variables were examined by different analyses of covariance (ANCOVA and MANCOVA). The possible relationships of quantitative clinical variables with rMEQ, PSQI, and WHOQOL-BREF were explored using bivariate correlation analysis.Results: Lower SJL appears in the SUD + MDD group compared with SUD. The intermediate-type was more prevalent in the SUD group, while a higher percentage of morning-type patients was found in the SUD + MDD. Sleep quality (including latency and daytime dysfunction) was worse for SUD + MDD patients than for SUD even after controlling age and age of SUD onset variables. Last, QOL was poorer in patients with SUD + MDD and, for them, psychological health had a negative relationship with SJL and severity of depression.Conclusions: Our data support and extend previous findings indicating that SUD + MDD is associated with worse clinical characteristics, more sleep problems, and poorer QOL than SUD patients. These results underline the importance of a precise assessment of these measurements in future studies conducted in SUD patients with/without MDD comorbidity that could be considered from a therapeutic point of view.

Susceptibility rhythm to bacterial endotoxin in myeloid clock-knockout mice.

Local circadian clocks are active in most cells of our body. However, their impact on circadian physiology is still under debate. Mortality by endotoxic (LPS) shock is highly time-of-day dependent and local circadian immune function such as the cytokine burst after LPS challenge has been assumed to be causal for the large differences in survival. Here, we investigate the roles of light and myeloid clocks on mortality by endotoxic shock. Strikingly, mice in constant darkness (DD) show a threefold increased susceptibility to LPS as compared to mice in light-dark conditions. Mortality by endotoxic shock as a function of circadian time is independent of light-dark cycles as well as myeloid CLOCK or BMAL1 as demonstrated in conditional knockout mice. Unexpectedly, despite the lack of a myeloid clock these mice still show rhythmic patterns of pro- and anti-inflammatory cytokines such as TNFα, MCP-1, IL-18, and IL-10 in peripheral blood as well as time-of-day and site-dependent traffic of myeloid cells. We speculate that systemic time-cues are sufficient to orchestrate innate immune response to LPS by driving immune functions such as cell trafficking and cytokine expression.

Sleep Problems and Circadian Functioning in Children and Adolescents With Autism Spectrum Disorder

BackgroundSleep problems are a prevalent comorbidity in autism spectrum disorder (ASD) with a multifactorial basis in which circadian misalignment has been described. MethodsA cross-sectional study was conducted including 52 children and adolescents with ASD (9.85 ± 3.07) and 27 children and adolescent controls with normal intellectual functioning (8.81 ± 2.14). They were matched for age, sex, and body mass index, and all were drug-naïve. An ambulatory circadian monitoring device was used to record temperature and motor, body position, sleep, and light intensity. ResultsIndividuals with ASD presented longer sleep-onset latency, lower sleep efficiency, and decreased total sleep time and tended to be more sedentary and have less exposure to light. They also showed lower amplitude, low interdaily stability, and a different pattern of wrist temperature across the day, with a midpoint of sleep that did not concur with sleep midpoint indicated by the rest of circadian parameters. ConclusionsThe sleep problems observed in this sample resemble those reported previously, with the exception of nocturnal awakenings which did not show differences. The ambulatory circadian monitoring device enabled measurement of circadian parameters such as temperature which, until now, were scarcely described in children with ASD and could be used to better understand sleep and circadian system in ASD.

Adrift in time: the subjective experience of circadian challenge during COVID-19 amongst people with mood disorders

ABSTRACT Social distancing/lockdown policies during the coronavirus (COVID-19) pandemic may alter social rhythms of people through imposition of restrictions on normal daily activities. This may in turn challenge circadian function, particularly in people with mood disorders. Although objective data describing the relationship between circadian disturbances and mood disorders exist, data regarding the subjective experience of circadian challenge is sparse, and its association with mood symptoms is unclear. The present qualitative study was one component of a mixed-methods multi-national project, which took advantage of widespread disruption to daily routines due to Government COVID-related lockdowns during 2020. The Behavior Emotion and Timing during COVID-19 (BEATCOVID) survey study included three open questions generating qualitative data on participants’ subjective experience of social disruption due to social distancing/lockdown policies, two of which asked about the barriers and opportunities for stabilizing routines. Responses were coded and analyzed using Thematic Analysis. A total of N = 997 participants responded to at least one of the free-text questions. Four themes were identified: 1) loss of daily timed activities, 2) role of social interaction, 3) altered time perception and 4) disruption to motivation and associated psychological effects. Themes were organized into a provisional heuristic map, generating hypotheses for future research centered on the new concept of ‘psychological drift.’

Brain tumours in children and adolescents may affect the circadian rhythm and quality of life.

Children with brain and cervical medulla tumours may experience circadian abnormalities and poor health. We aimed to examine their circadian rhythm, fatigue and quality of life (QoL). Children with a brain or cervical medulla tumour were recruited from the Paediatric Department, Rigshospitalet, Copenhagen, Denmark, between 2016 and 2020. They were grouped by tumour location involving the circadian regulatory system, defined as diencephalon, pineal gland, brain stem and cervical medulla, or other areas. Saliva melatonin and cortisol concentrations were measured. Sleep diaries and actigraphy assessed sleep-wake patterns. The Pediatric Quality of Life Inventory, Multidimensional Fatigue Scale and Generic Core Scale measured fatigue and QoL. We included 68 children (62% males) with a median age (25th-75th percentiles) of 12.2 (7.7-16.3) years. Children with tumours involving the circadian regulatory system typically had a lower melatonin peak (p=0.06) and experienced significantly more fatigue and poorer QoL. Low melatonin profiles were observed in 31% and 4% had a phase-shifted daytime peak, compared with 14% and 0%, respectively, in children with tumours located elsewhere. Children with low melatonin profiles had significantly lower inter-daily stability than those with normal profiles. Tumours involving the circadian regulatory system adversely affected circadian function, fatigue and QoL.

The Effect of Emotional Intelligence on Facial Expression Recognition: An ERP Study

Brain-derived neurotrophic factor (BDNF), its receptors and epigenetic modulators, are implicated in the pathophysiology of affective disorders, T2DM and the circadian system function. We used diurnal sand rats, which develop type 2 diabetes (T2DM), anxiety and depressive-like behavior under laboratory conditions. The development of these disorders is accelerated when animals are maintained under short photoperiod (5:19L:D, SP) compared to neutral photoperiod (12:12L:D, NP). We compared rhythms in plasma BDNF as well as BDNF and PER2 expression in the frontal cortex and suprachiasmatic nucleus (SCN) of sand rats acclimated to SP and NP. Acclimation to SP resulted in higher insulin levels, significantly higher glucose levels in the glucose tolerance test, and significantly higher anxiety- and depression-like behaviors compared with animals acclimated to NP. NP Animals exhibited a significant daily rhythm in plasma BDNF levels with higher levels during the night, and in BDNF expression levels in the frontal cortex and SCN. No significant BDNF rhythm was found in the plasma, frontal cortex or SCN of SP acclimated animals. We propose that in sand rats, BDNF may, at least in part, mediate the effects of circadian disruption on the development of anxiety and depressive-like behavior and T2DM.

A time to wander: exploring associations between components of circadian functioning, mind wandering typology, and time-of-day

ABSTRACT Eveningness has previously been associated with more frequent mind wandering (MW). The current study re-investigated this association for components of circadian functioning, and MW typology. Questionnaire measures of Morning Affect, Eveningness, and (amplitude) Distinctness, deliberate and spontaneous MW, problem-solving daydreams, sleep quality, personality, affect, and life satisfaction were completed by 265 university students (aged 18–33, mean = 20.78), who also reported the peak time for daily MW and problem-solving daydreams. Spontaneous MW correlated with low Morning Affect and stronger Distinctness; these all correlated with poor sleep quality, less conscientiousness, less positive affect, less life satisfaction, more neuroticism, and more negative affect. Problem-solving daydreams positively correlated with Morning Affect. Significant mediators between morningness-eveningness and spontaneous MW were sleep quality, positive affect, and conscientiousness, which were also significant with Morning Affect as the predictor for spontaneous MW; sleep quality and positive affect were significant with Distinctness as the predictor for spontaneous MW. Exploratory path analysis indicated inter-relationships between Eveningness, Morning Affect, subjective sleep quality, conscientiousness, spontaneous MW, and negative affect. Spontaneous and deliberate MW showed some evidence of peak frequency at the non-preferred time-of-day. These results indicate that components of circadian functioning have varying relationships with different types of mind wandering/daydreaming.