Objective: Sleep is a state of physical and mental rest and is a major focus of chronobiological research. This study aimed to assess sleep quality in relation to sleep habits among young female college students in their daily routine. Methods: This was a cross-sectional, observational, questionnaire-based study. Participants (n=1,186; age [mean±SE]: 19.08±0.05 years) were randomly selected from undergraduate and postgraduate female students in Raipur, Chhattisgarh, India. They completed the Munich Chronotype Questionnaire, Morningness–Eveningness Questionnaire (MEQ), and Pittsburgh Sleep Quality Index to record sleep–wake behaviors, chronotype, and sleep quality. Results: One-way analysis of variance revealed a significant group difference in bedtime and MEQ score. The Mann–Whitney U test showed significantly earlier mean bedtime, wake time, and midsleep time in the good sleep quality group compared to the poor sleep quality group. Pearson’s correlation indicated that delayed bedtime and evening chronotype were associated with poor sleep quality. Binary logistic regression identified late bedtime, late wake time, internet usage, and irregular menstrual cycles as significant predictors of poor sleep quality. Conclusion: To promote good sleep quality and a morning chronotype, students should maintain early bed and wake times. Raising awareness of sleep hygiene, circadian rhythms, and the impact of sleep on health and academic performance is essential for this population.
Objective: This study investigated the association between chronotype and dysfunctional sleep-related beliefs in psychiatric outpatients presenting with sleep disturbance. Methods: This study analyzed medical records of 117 psychiatric outpatients with sleep disturbance (mean age 54.24±15.02 years; 65.8% female). Chronotype was assessed using the reduced Morningness-Eveningness Questionnaire (rMEQ). Sleep-related beliefs were evaluated using the Dysfunctional Beliefs and Attitudes about Sleep scale (DBAS-16). The relationship between chronotype and sleep-related beliefs and the interaction effect of age on their relationship were examined. Results: There was a significant negative association between rMEQ and DBAS-16 (r=-0.267, p<0.01, n=117), indicating that a stronger evening preference was associated with more pronounced dysfunctional sleep beliefs. This association remained significant after adjusting for age and sex (β=-0.299, p<0.01) or after controlling for depression, anxiety, insomnia, daytime sleepiness, and sleep quality (β=-0.277, p<0.01). The rMEQ score was independently associated with DBAS-16, accounting for 7% of the total variance. This negative relationship remained robust even after adjusting for all potential covariates including clinical and demographic factors (β=-0.277, p=0.003). There was a significant interaction of age group on the association between rMEQ and DBAS-16 (F(4, 108)=3.211, p=0.016). The effect of chronotype on dysfunctional beliefs was more evident among middle-aged and older patients. Conclusion: Chronotype is independently associated with dysfunctional beliefs about sleep in psychiatric outpatients with sleep disturbance.
Objective: Alcohol use disorder is associated with compulsive drinking and impaired self-control, often leading to poor sleep quality. This study aimed to assess the effect of metacognitive-based training on sleep quality in persons with alcohol use disorder. Methods: A quasi-experimental design was used with 30 male patients aged 25–45 years with alcohol use disorder and poor sleep quality, recruited from Recovery Home Foundation, Chennai. They were divided into control (conventional occupational therapy) and experimental (metacognitive-based training) groups. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) before and after the 12-week intervention. Data were analyzed using paired and independent t-tests. Results: The results showed a significant improvement in sleep quality in the experimental group compared to the control group (mean PSQI score: control 8.53 vs. experimental 4.87; p<0.001). Conclusion: The study concluded that metacognitive-based training was effective in improving sleep quality among male patients with alcohol use disorder.
Objective: Insomnia is one of the most common psychiatric symptoms among inpatients, frequently accompanied by sleep–wake and circadian disruption and showing distinct consultation patterns. This study aimed to examine the consultation request patterns and clinical implications of insomnia in hospitalized patients, and to compare them with those of patients with anxiety and depressive disorders. Methods: A retrospective chart review was conducted for 1,286 patients who received psychiatric consultations at a general hospital between 2005 and 2011. The sample included 236 patients with insomnia, 601 with anxiety disorders, and 449 with depressive disorders based on DSM-IV-TR criteria. Demographic characteristics, referring departments, reconsultation status, number of consultations, and consultation request types (CR1–CR5, based on the Vaz-Salcedo functional model) were analyzed. Results: Patients with insomnia were especially older and had a higher proportion of males compared with the other diagnostic groups. The insomnia group showed the lowest mean number of consultations and the lowest reconsultation rate. More than half of consultation requests for insomnia patients were classified as CR3 (Mending type), a proportion more than twice that observed in the anxiety disorder group. After adjustment for age and sex, insomnia remained independently associated with a significantly higher likelihood of CR3 consultation requests. Conclusion: Insomnia in hospitalized patients exhibits distinct consultation-liaison patterns, with a predominance of CR3, indicating a largely symptom-oriented management approach. Future multicenter, prospective studies with longitudinal follow-up are needed to evaluate the effectiveness of pharmacological and non-pharmacological interventions and to clarify the impact of early insomnia-focused psychiatric consultation on long-term clinical outcomes.
Sleep and inflammation are closely connected due to circadian regulation of immune pathways. The present review provides an overview of contemporary evidence on molecular interplay of sleep disruption and inflammasome upregulation, with consideration of NLRP3 as the primary complex. Attention was given to molecular mechanisms, including clock genes (BMAL1, CLOCK, PER, CRY), mitochondrial malfunction, as well as cytokine signaling. Articles were selected according to their relevance to inflammasome dynamics, neuroimmune modulation, and chronobiological manipulations. Circadian misalignment and sleep deprivation resulted in a uniform increase of NLRP3 inflammasome activation, interleukin-1 beta (IL-1β) and IL-18 secretion, and oxidative stress. Two important modulators of inflammatory priming are CRY inhibition and BMAL1 loss. Clinical associations include a higher risk of autoimmune, cardiometabolic, and neurodegenerative diseases in people who suffer from sleep disturbances frequently. Via circadian and mitochondrial processes, sleep disturbance is a potent modulator of systemic inflammation. Novel treatment options may be provided by modifying the inflammasome through lifestyle, melatonin, and chronotherapy. To comprehend the connection between inflammation and sleep, it becomes crucial to prioritize more mechanism-based research in the future.
Fibromyalgia (FM) is a multifactorial chronic pain disorder characterized by widespread pain, sleep disturbance, fatigue, cognitive dysfunction, and neuroendocrine-immune imbalance. Growing evidence indicates that circadian dysregulation plays a role in FM pathophysiology, although current evidence is largely associative and mechanistic. Altered molecular clock function—including disruptions in the PER-CRY-CLOCK-BMAL1 transcriptional feedback loop—affects sleep–wake timing, hormone secretion, neurotransmission, and immune activity, all of which are systems consistently impaired in FM. Clinical studies reveal blunted or phase-shifted melatonin and cortisol rhythms, dampened rest-activity cycles, and an overrepresentation of evening chronotypes, which are associated with higher pain severity and poorer sleep. Genetic and epigenetic findings further implicate circadian biology: PER3 VNTR polymorphisms increase FM susceptibility, while differential DNA methylation patterns, microRNA dysregulation, and transcriptomic signatures highlight abnormalities in inflammatory, glutamatergic, adrenergic, and immune pathways that are themselves under circadian control. These mechanistic disturbances have direct therapeutic relevance. Core FM medications—including analgesics, antidepressants, anticonvulsants, and sleep aids—exhibit circadian variation in pharmacokinetics and pharmacodynamics, suggesting that dosing time may influence efficacy, toxicity, and symptom relief. Emerging evidence supports chronotherapeutic strategies such as morning bright-light therapy, nighttime melatonin, structured sleep–wake scheduling, and time-aligned medication administration to reinforce circadian alignment and improve pain, fatigue, sleep quality, and mood. While clinical trials suggest symptomatic improvement with melatonin supplementation, effect sizes vary, and long-term randomized evidence remains limited. This review integrates current molecular, genetic, and clinical evidence linking circadian biology to FM and outlines how chronopharmacology and chronotherapy could advance precision medicine in this population. Future integration of multi-omics profiling, wearable-based digital phenotyping, and personalized circadian biomarkers may enable mechanism-guided, rhythm-informed management of FM.
Objective: This study aims to evaluate whether short-term behavioral history improves the prediction of transitions into sustained inactivity in continuous rest–activity data beyond the instantaneous activity level alone.Methods: Minute-level wrist actigraphy data from individuals with major depressive disorder, schizophrenia, attention-deficit/hyperactivity disorder, and healthy controls were analyzed (2.53 million observations). Activity was transformed into trajectory-based features capturing instantaneous level, short-timescale variability, and directional drift memory. The primary outcome, D20_onset, was defined as the onset of ≥20 consecutive minutes of zero recorded activity and treated as an operational marker of transition into sustained inactivity. Logistic regression models with interaction terms evaluated whether recent trajectory features improved prediction beyond memoryless formulations.Results: Transition probability exhibited a stable and reproducible structure within the behavioral state space. Sustained activity level showed a strong suppressive association with D20_onset probability across diagnostic groups. Variability and drift memory exerted conditional effects, amplifying transition probability primarily within low-activity regimes. A significant three-way interaction among activity level, variability, and drift indicated a nonlinear, history-sensitive structure. Predicted probability surfaces showed concentration of transition probability within a low-activity, high-instability region, consistent with a structured region of the state space.Conclusion: Transitions into sustained inactivity in naturalistic settings are temporally embedded and depend on short-term behavioral history. Because actigraphy reflects behavior within circadian rest–activity organization, these transitions likely represent a mixture of behavioral disengagement, rest, and phase-related quiescence rather than a single process. The findings support history-aware, state-space modeling of rest–activity dynamics without presupposing a specific underlying mechanism.
Objective: This study aimed to examine the association between sleep quality and emotional symptoms/well-being in university students.Methods: This analytical cross-sectional study included 297 participants (aged 15–47 years; 70.37% female). Nonparametric tests, Spearman correlations, and OLS/WLS regressions with robust errors were applied to model Pittsburgh Sleep Quality Index (PSQI) scores.Results: Poor sleep quality was reported by 66.7% of participants, and 26.9% presented mild insomnia. Strong correlations were observed between depression and stress, insomnia and PSQI, and anxiety and stress (all p<0.001). Variables differed significantly across PSQI categories with moderate-to-large effects. Regression models explained approximately 58% of PSQI variance; insomnia, stress, and anxiety were associated with poorer sleep quality, while depression showed a marginal suppression effect, and sex was not significant.Conclusion: Poor sleep quality is highly prevalent and closely linked to greater emotional distress and reduced well-being, underscoring the need for screening and intervention in university settings.
Objective: This study aimed to evaluate the preliminary effectiveness of a five-session modular cognitive behavioral therapy for insomnia (CBT-I)– based sleep intervention in psychiatric outpatients presenting with sleep complaints.Methods: Fifty-six psychiatric outpatients (mean age 39.38±15.30 years; 16 men) with clinically diagnosed psychiatric disorders and insomnia symptoms or related sleep disturbances participated. The program consisted of sleep hygiene education (Sessions 1–2) followed by the modular CBT-I–based sleep intervention (Sessions 3–5) tailored to the primary sleep problem. Nine standardized questionnaires were administered at baseline (T0), post-intervention (T1), and 3-month follow-up (T2; n=20). Participants completed a sleep diary during treatment; 41 met criteria for early- versus late-treatment diary analyses (T0 vs. T1). Questionnaire outcomes were analyzed using linear mixed-effects models, and diary parameters using paired t-tests.Results: Improvements were observed at T1 across multiple domains, including insomnia severity (Insomnia Severity Index), sleep quality (Pittsburgh Sleep Quality Index), fatigue (Fatigue Severity Scale), anxiety (Beck Anxiety Inventory), depression (Patient Health Questionnaire-9), and health-related quality of life (36-Item Short Form Health Survey) (all p<0.001). These improvements were largely sustained at the 3-month follow-up. Sleep diary analyses showed increased mean sleep efficiency (SE) (p<0.001) and significantly reduced wake after sleep onset (WASO), nap time (NT), and snoozing (p<0.01 for WASO and NT; p<0.05 for snoozing). Reduced SE variability (p=0.01) was consistent with enhanced sleep stability, while time in bed and WASO variability showed positive improvement trends (p<0.10).Conclusion: In this single-arm outpatient study, the modular CBT-I–based sleep intervention was associated with improvements in subjective sleep and diary-derived sleep continuity. These findings suggest that a modular CBT-I–based sleep intervention may be a feasible adjunctive approach for improving sleep and psychiatric symptoms in routine psychiatric outpatient care.
Objective: This study evaluated the effectiveness of a Person-Environment-Occupation-Performance (PEOP) model–based sleep intervention on sleep quality among parents of children with special needs, compared with conventional occupational therapy.Methods: A quasi-experimental design with convenience sampling was used, involving 30 parents. Participants were nonrandomly allocated by site: Center A to the PEOP intervention (n=15) and Center B to conventional occupational therapy (n=15). To minimize selection bias, both centres followed identical recruitment procedures and inclusion criteria. Assessor blinding was not implemented. Interventions were delivered over 12 weeks (36 sessions). Sleep quality was assessed pre- and post-intervention using the Pittsburgh Sleep Quality Index (PSQI). Within-group and between-group differences were analyzed using appropriate inferential statistics.Results: The PEOP-based intervention group showed a significant improvement in sleep quality, with PSQI scores decreasing from 10.94±3.06 at baseline to 5.40±1.72 post-intervention (p<0.001). The conventional occupational therapy group also demonstrated a statistically significant but smaller improvement (11.27±3.41 to 10.20±3.10; p=0.001). Between-group analysis revealed significantly greater improvement in sleep quality in the PEOP-based intervention group compared with the control group (p<0.001).Conclusion: The PEOP-based sleep intervention was more effective than conventional occupational therapy in improving sleep quality among parents of children with special needs. These findings support the use of occupation-focused, contextually driven interventions in sleep management for caregiver populations.
Circadian measures are increasingly used in sleep medicine and aging research, but different measures do not capture the same aspect of circadian biology. Chronotype questionnaires, sleep diaries, actigraphy, dim light melatonin onset, patient-derived cellular rhythms, and blood-based omics profiles each provide different types of information. Wearable-derived or sensor-derived rhythms mainly describe the patient’s current rhythm state in daily life. Controlled in vivo markers such as dim light melatonin onset estimate internal circadian phase. Patient-derived cellular period measured under controlled ex vivo conditions may reflect endogenous, trait-like circadian properties. Blood-based transcriptomic, metabolomic, and proteomic approaches may estimate molecular body time, but they also reflect systemic biological state. This review summarizes these circadian measures and discusses how they may be interpreted along a trait-state continuum. It also discusses how different measures may be compared to understand circadian misalignment, including phase-related, period-related, zeitgeber-related, central-peripheral, and trait-state misalignment. These concepts are not yet validated clinical biomarkers. However, they may help organize hypotheses for individualized interventions, including timed light, melatonin, sleep-wake scheduling, activity timing, meal timing, social rhythm stabilization, and treatment timing. A cautious integration of multiple circadian measures may support a systems-level interpretation of patient-specific temporal biology and contribute to personalized circadian intervention as one component of precision medicine.
Strengthening the core circadian oscillator, here operationally described as “circadian amplification,” has been proposed as a novel therapeutic concept. This mini-review examines the preclinical and limited clinical evidence regarding three naturally derived compounds, nicotinamide mononucleotide (NMN), resveratrol, and nobiletin, as potential candidate circadian amplifiers. NMN and resveratrol are proposed to influence the NAD+/SIRT1 axis, which may affect circadian clock function. Nobiletin appears to act through a distinct pathway, including ROR-related clock modulation within the auxiliary feedback loop, and has shown circadian-enhancing effects in preclinical models. Preclinical studies suggest that these compounds may restore circadian gene expression and improve metabolic parameters, while human studies remain nascent. NMN, resveratrol, and nobiletin are promising compounds of chronobiological interest that may modulate circadian clock-related pathways. However, direct evidence supporting true “circadian amplification” in humans remains insufficient at present.
Objective: This study aimed to investigate the prevalence of probable REM sleep behavior disorder (pRBD) and identify associated factors among psychiatric sleep clinic outpatients. Methods: We retrospectively reviewed records of first-visit outpatients aged ≥18 years who presented with sleep-related complaints at the psychiatric sleep clinic at a single tertiary university hospital between January 1, 2023, and December 31, 2024. Of 522 patients, 387 (74.1%) completed the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ), and 356 were included in the analysis. RBDSQ scores ≥5 defined the pRBD group. Demographic and clinical variables, including diagnoses and medication use, were collected. Univariable and multivariable logistic regression analyses identified factors associated with pRBD. Results: Among participants, 179 (50.3%) were classified as pRBD and 177 (49.7%) as non-RBD. The pRBD group was significantly younger, had a higher body mass index, and showed higher scores for insomnia, depression, anxiety, and trauma exposure, and risk of obstructive sleep apnea (OSA). They were also more likely to be diagnosed with trauma- and stressor-related disorders and selective serotonin reuptake inhibitors (SSRIs). In multivariable analysis, higher anxiety scores (odds ratio [OR]=1.07, 95% confidence interval [CI]=1.02–1.12), sleep-related breathing disorders (OR=7.60, 95% CI=2.05–28.17), and SSRIs use (OR=6.91, 95% CI=1.91–22.11) were independently associated with pRBD. Conclusion: RBD symptoms were common among psychiatric sleep clinic outpatients. These results suggest that psychiatric patients with marked anxiety, SSRIs use, and sleep-related breathing disorders should be prioritized for screening, particularly before antidepressant initiation, with careful differentiation from OSA.
Objective: This study aims to determine whether time-of-day (12:00 h vs. 00:00 h) and season (rainy vs. dry) modify liver injury induced by gentamicin and artesunate in male Wistar rats. Methods: A total of 128 male Wistar rats were randomized to 16 groups (n=7–8/group) and treated once daily intraperitoneal for 7 days with normal saline, gentamicin (120 mg/kg), artesunate (100 mg/kg), or the combination during the rainy (August 2023) and dry (February 2024) seasons. Primary outcomes were serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP); secondary outcomes included superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and liver histology. Normality and homogeneity of variance were assessed using the Shapiro–Wilk and Levene tests. Two-way analysis of variance (ANOVA; season×dosing time) with Bonferroni correction was used to evaluate effect sizes (partial η2) and 95% confidence intervals (CIs). Results: Two-way ANOVA revealed significant season×dosing-time interactions for ALT, AST, and ALP (all p<0.01; partial η2≈0.10–0.25). Overall, dry-season exposure produced larger enzyme elevations and greater reductions in antioxidant activities than rainy-season exposure. Nighttime dosing (00:00 h) in the dry season produced the largest ALT increases compared with rainy-season daytime saline (p<0.001). Histology corroborated biochemical findings, showing more pronounced necrosis and inflammatory infiltration with dry-season night dosing. Artesunate attenuated some gentamicin-induced changes in the rainy season but not in the dry season. Conclusion: Season and dosing time jointly modulate artesunate–gentamicin hepatotoxicity in rats; dry-season nighttime dosing markedly increases injury. These results support chronotherapeutic consideration in settings where seasonal environmental stressors vary.
Night-shift work is essential to modern industries but disrupts circadian rhythms, increasing risks of cardiometabolic disease, cancer, and mental health conditions. The International Agency for Research on Cancer (IARC) classifies “night-shift work involving circadian disruption” as “probably carcinogenic to humans” (Group 2A). Advances in chronobiology now enable precise estimation of internal circadian phase using transcriptomic, metabolomic, and wearable-based assessments. This protocol outlines a 24-month prospective cohort study evaluating the association between circadian misalignment and adverse health outcomes among 500 night-shift workers and 250 day-shift controls. Circadian phase will be assessed using multi-modal biomarkers and machine-learning models. Outcomes include metabolic, cardiovascular, inflammatory, and mental-health indicators. Mixed-effects regression models will examine longitudinal associations while adjusting for lifestyle and occupational covariates. The study aims to determine the feasibility of body-clock testing for personalized health interventions and improved shift-schedule design. Findings may inform occupational health policies and contribute to circadian-based preventive strategies for shift-dependent sectors.
In humans, the sleep-reproductive endocrinology interface is likely overly conserved due to the neuroendocrine regulation of circadian rhythms, pulsatile hormonogenesis, and ovarian physiology. This review explores the bidirectional relationship between sleep architecture and the hypothalamic-pituitary-ovarian axis, emphasizing how circadian timing, sleep-wake patterns, and melatonin release influence the pulsatile secretion of gonadotropin-releasing hormone, luteinizing hormone, follicle-stimulating hormone, and ovarian steroidogenesis. Sleep disturbances, such as insomnia, obstructive sleep apnoea, and circadian misalignment, can disrupt follicular development, ovulation, and menstrual regularity, all associated with subfecundity and endocrine disorders like polycystic ovary syndrome and endometriosis. Melatonin, with its antioxidant and chronobiotic properties, appears central to reproductive timing and the synchronization of light-dark cycles. This neuroendocrine interaction evolves across key sexual milestones (puberty, pregnancy, menopause) and is influenced by age and chronotype. Emerging neural imaging tools, biomarker assays, and chronotherapy studies now offer potential for personalized treatments that normalize melatonin levels. When combined with cognitive behavioral therapy for insomnia, such approaches may help restore hormonal balance and optimize reproductive outcomes. Sleep health should be integrated into reproductive medicine, requiring a holistic approach that incorporates circadian biology, stress responses, and environmental influences to support hormone regulation and women’s health across the lifespan.
