Search Results (98)

Background: Attention-deficit/hyperactivity disorder (ADHD) has traditionally been understood through executive and frontostriatal models, but increasing evidence suggests that metabolic, inflammatory, circadian, and neuroendocrine mechanisms may also contribute to clinical heterogeneity. The hypothalamus is a central regulatory hub for appetite, sleep–wake organization, stress responsivity, autonomic function, and endocrine signalling. Objective: This review evaluated evidence linking ADHD with hypothalamic inflammation and related metabolic, inflammatory, circadian, and neuroendocrine dysregulation, with particular emphasis on appetite regulation, sleep and circadian function, stress reactivity, and pharmacological treatment response and tolerability. Methods: A systematic literature search was conducted in PubMed/MEDLINE, Embase, PsycINFO, Scopus, and Web of Science Core Collection from database inception to 31 May 2026. Human observational and intervention studies formed the primary evidence base. Evidence was synthesized narratively. Where available, quantitative findings from previously published meta-analyses were summarized to provide an overview of the strength and consistency of the evidence. Results: The reviewed evidence indicates that ADHD is associated with increased obesity risk, altered appetite-related hormones, immune-inflammatory changes, delayed circadian timing, atypical cortisol responsivity, and treatment-related effects on appetite, sleep, cardiovascular physiology, and tolerability. The strongest quantitative evidence concerned obesity, inflammatory markers, appetite hormones, and type 2 diabetes risk. Direct evidence for hypothalamic inflammation in ADHD remains limited, but converging indirect findings support hypothalamic and neuroendocrine mechanisms as biologically plausible contributors in a subgroup of individuals with ADHD. Conclusions: ADHD appears to be associated with broader metabolic, inflammatory, circadian, and neuroendocrine vulnerabilities beyond its core attentional and behavioural symptoms. Hypothalamic pathways should be interpreted as a mechanistic hypothesis rather than an established causal mechanism. Future longitudinal and multimodal studies are needed to clarify causality and identify biologically defined ADHD subgroups. Full article

Background: Smith–Magenis syndrome (SMS) is a rare neurodevelopmental disorder characterized by severe sleep disturbances, circadian rhythm dysregulation, and prominent behavioral difficulties. Objective: To examine associations between subjective and objective sleep and circadian characteristics and behavioral difficulties in children with SMS in real life. Methods: Children aged 5–13 years with genetically confirmed SMS were included in a prospective single-center cohort study. Sleep and circadian rhythms were assessed using parent-reported questionnaires (Sleep Disturbance Scale for Children (SDSC), Horne and Östberg Morningness–Eveningness Questionnaire (H&O)) and 15-day home-based wrist actigraphy. Behavioral difficulties were evaluated using the Aberrant Behavior Checklist-Community (ABC-C). Associations between subjective and objective sleep and circadian measures with behavioral difficulties were studied using Spearman correlations for each ABC-C subscale. Results: Among the 20 children included (55% female, mean age 10 ± 2.5 years), 75% were carriers of a 17p11.2 microdeletion and 25% had an RAI1 mutation. Overall, 95% of children were treated with melatonin, 55% with psychostimulants and 20% with beta-blockers. According to the SDSC results, pathological sleep disturbances were present in 14/20 (70%) children and concerned mainly complaints of insomnia (10/20, 50%) and excessive daytime sleepiness (8/20, 40%). The H&O chronotypes confirmed the morning type in 70% of patients. Sleep and circadian measures obtained by actigraphy showed reduced total sleep time in 71% of the children, reduced sleep efficiency in 88%, long wake after sleep onset (WASO > 60 min) in 59%, as well as an early L5 onset (5 h period with the least movements < 23:38) and M10 onset (10 h period with the highest activity levels < 09:12) in 92% and 62% of children, respectively. The behavioral domains of the ABC-C with the highest scores were hyperactivity (mean 52.1, range 2.1–97.9) and irritability, agitation, and crying (mean 46.9, range 17.8–82.2). In the analysis of the relationship between behavior and sleep, a positive correlation was found between sleep disorders and stereotyped behaviors (r = 0.472, p = 0.048), insomnia and irritability, social withdrawal and stereotyped behaviors (r = 0.472, p = 0.048; r = 0.701, p = 0.001; and r = 0.648, p = 0.004, respectively), and non-restorative sleep and inappropriate speech (r = 0.476, p = 0.046). No significant association was found between objective sleep measures and behaviors. While subjective assessments suggested that a stronger morning chronotype was associated with lower irritability (r = −0.565, p = 0.015), actigraphy-derived circadian rhythm analyses revealed that an earlier L5 onset was associated with greater social withdrawal and hyperactivity (r = −0.556, p = 0.048 and r = −0.560, p = 0.049, respectively). Conclusions: The present cohort study of children with SMS studied in real-life conditions, using both objective and subjective measures, shows that patients continued to experience sleep and behavioral disturbances despite treatment. Exploratory analyses identified distinct associations between subjective sleep disturbances, circadian rhythm characteristics, and specific behavioral domains. While subjective sleep disturbances were associated with irritability, stereotypic behavior, and inappropriate speech, circadian rhythm parameters are specifically associated with hyperactivity. Both were also associated with social withdrawal. As these findings arise from an exploratory observational secondary analysis, they should be considered hypothesis-generating and require confirmation in larger prospective studies. If confirmed, they may help identify sleep and circadian rhythm characteristics as potential targets for future interventions in children with SMS. Full article

Human African trypanosomiasis (HAT) or sleeping sickness is a neglected tropical disease with a progressive central nervous system (CNS) involvement and marked sleep and circadian rhythm abnormalities. Even though this is a prominent feature of HAT, the connection between parasite neuroinvasion, neuroinflammation, circadian dysfunction, and neurological impairment is not fully understood. This narrative review aims to summarize the most up-to-date knowledge about sleep and circadian disturbance in HAT and proposes an integrated approach for the Trypanosome-Associated Sleep Disorder (TASD). The relevant literature was identified by searching major biomedical databases for HAT, sleep disorders, circadian rhythms, neuroinflammation, and CNS invasion. The review covers the steps by which the CNS becomes invaded, how the barriers are disrupted, how the CNS becomes activated by inflammatory responses, and how the hypothalamic and circadian regulatory networks are disrupted. The evidence suggests that excessive daytime sleepiness, fragmented nocturnal sleep, circadian misalignment, and neuropsychiatric manifestations are related to the activation of inflammatory cytokines, altered neurotransmitter signaling, activation of the kynurenine pathway, dysregulation of clock genes, and disruption of the suprachiasmatic nucleus. We also discuss TASD as a syndrome-like phenotype of CNS involvement and propose a three-stage model of sleep–wake dysfunction in HAT. The review unites these integral mechanisms in a single mechanistic framework to offer a unified understanding of the sleep pathology associated with HAT. There are still important gaps in our knowledge of biomarkers, disease staging, and irreversible neuronal damage, which indicate priorities for future research and better clinical management. Full article

Melatonin occupies a paradoxical position in contemporary sleep medicine: despite its physiological role as a regulator of circadian timing, it is frequently used and perceived as a nonspecific “natural” hypnotic. Although melatonin demonstrates modest benefits for sleep initiation and clearer efficacy in circadian rhythm sleep–wake disorders, its clinical use is often undermined by diagnostic imprecision, inappropriate dosing, mistimed administration, inconsistent formulations, and inadequate patient counseling. Circadian disorders can be misclassified as primary insomnia, leading to symptomatic treatment approaches that fail to address the underlying phase misalignment. At the same time, supraphysiological doses and reflexive bedtime administration have become normalized despite evidence that melatonin acts primarily as a chronobiotic whose effects depend more on timing than dose. Regulatory inconsistencies and substantial variability in over-the-counter preparations further complicate safe and reproducible use. These factors contribute to avoidable treatment failure, inaccurate labeling of nonresponse, and persistent misconceptions regarding melatonin’s mechanism of action. Therefore, melatonin should be approached as a pharmacological intervention requiring the same diagnostic rigor, individualized dosing, and longitudinal assessment expected of other sleep therapeutics, particularly when integrated with behavioral and circadian interventions. Full article

Sleep is a cardinal biological process that backstops central nervous system function, which also plays a crucial role in regulating systemic homeostasis, including immune activities. Cytokines, particularly interleukin-1β and tumor necrosis factor-α, act as mediators bridging sleep and inflammation, also influencing both sleep architecture and sleep–wake cycle. Sleep deprivation and sleep disorders such as insomnia, narcolepsy, hypersomnia, or obstructive sleep apnoea may disrupt cytokine production, alter their circadian rhythm of release, and shift secretion peaks from night to day. These changes contribute to daytime fatigue, impaired cognitive and physical performance, increased susceptibility to infections and/or systemic inflammation. Molecular studies indicate that insufficient sleep primes immune cells to enhance pro-inflammatory responses, creating a feedback loop with neuroendocrine pathways that further exacerbates sleep patterns and inflammatory dysregulation. Understanding the bidirectional relationship between sleep and cytokines may highlight the role of sleep as an active component of immunity regulation and underscore the potential usefulness of multilevel interventions that include complementary and integrative health approaches restoring sleep, normalizing cytokine rhythms and mitigating inflammation. Full article

Insomnia is one of the most common sleep disorders. Traditionally, its pathophysiology has been interpreted mainly from the perspective of the central nervous system (CNS). However, accumulating evidence suggests that the microbiota–gut–brain axis (MGBA), a bidirectional communication network linking the gut and the CNS, may play an important role in the development, maintenance, and treatment of insomnia. This review summarizes the major signaling pathways of the MGBA and discusses its potential mechanisms in insomnia. Current evidence indicates that gut microbiota and their metabolites may influence sleep–wake homeostasis through neural, immune, endocrine, and circadian pathways. At the same time, insomnia-related stress responses, immune imbalance, and lifestyle disturbances may in turn affect the gut microbiota, thereby forming a bidirectional regulatory network. Animal and clinical studies further support a close association between gut microbial dysbiosis and insomnia. In addition, this review systematically summarizes factors that may affect the MGBA, including diet, lifestyle, psychosocial stress, medications, and medical exposures. On this basis, MGBA-targeted interventions, such as dietary modification, prebiotics and probiotics, lifestyle interventions, fecal microbiota transplantation, and natural medicines, may provide promising new strategies for the prevention and treatment of insomnia. Nevertheless, the current evidence still relies largely on animal studies and cross-sectional research, and further longitudinal studies and high-quality interventional trials are needed to clarify causality, long-term efficacy, and standardized therapeutic approaches. Full article

Background/Objectives: Schizophrenia is a severe psychiatric disorder frequently characterised by sleep and circadian disturbances, which are closely linked to cognitive dysfunction, symptom exacerbation, and poor functional outcomes. A growing body of evidence implicates the orexin (hypocretin) system—an essential regulator of arousal, sleep–wake stability, metabolic processes, and motivated behaviour—in the pathophysiology and treatment response of psychotic disorders. We aimed to investigate the relationships between the orexinergic system and psychoses. Methods: On 3 March 2026, we searched the PubMed, Scopus, PsycInfo/Articles and Cinahl databases for studies dealing with the orexin system and psychotic disorders and treatment response. Results: We found 20 eligible studies reporting variable and inconsistent alterations in orexin signalling in patients with schizophrenia. Studies were mostly cross-sectional and heterogeneous in design. Antipsychotic medications interfere with orexin-dependent pathways, potentially contributing to both therapeutic effects and adverse outcomes such as sleep disruption and metabolic dysregulation. Conclusions: While evidence from preclinical studies could point to an influence of dopaminergic activity through orexinergic mechanisms, with possible attenuation of antipsychotic-induced motor side effects and improvement of attentional deficits associated with NMDA receptor hypofunction, the utility of dual orexin receptor antagonists (DORAs) in psychoses is unclear. Despite the high prevalence of insomnia in schizophrenia, its pharmacological management remains suboptimal, with current treatments often limited by reduced efficacy or tolerability concerns. DORAs, which are currently approved medications for the treatment of insomnia, represent a novel and mechanistically distinct therapeutic option that may improve sleep while modulating arousal- and cognition-related circuits relevant to psychosis. Full article

Sleep is a fundamental biological process essential for physical, cognitive, and mental health, yet sleep disorders remain underrecognized in primary care. Given the central role of primary care physicians (PCPs) in early identification and management, this study aimed to assess sleep and sleep disorder knowledge among PCPs working within the Primary Health Care Corporation in Qatar. A cross-sectional study was conducted using the validated 30-item Assessment of Sleep Knowledge in Medical Education (ASKME) questionnaire, alongside demographic and clinical practice variables. The primary outcomes were the overall ASKME percentage score and participants achieving adequate sleep knowledge (≥60%). A total of 110 PCPs were included in the analysis. The mean overall ASKME score was 56.5%, and 44.5% of participants achieved adequate sleep knowledge. Knowledge was highest in circadian sleep–wake regulation and basic sleep principles, and lowest in common sleep disorders, sleep architecture, and the effects of drugs and alcohol on sleep. In multivariable logistic regression, years of clinical experience was the only factor independently associated with adequate sleep knowledge. These findings indicate persistent gaps in clinically relevant sleep knowledge among PCPs and underscore the need for targeted sleep education within primary care to support early and effective management of sleep disorders. However, the achieved sample size was substantially smaller than the initially calculated target of 260, limiting statistical power; therefore, the non-significant findings may reflect a Type II error, and the regression analyses should be interpreted with caution. Full article

Purpose of Review—sleep disturbance is the main complaint associated with patients who suffer acute postoperative pain. Sleep disturbance may also increase the pain sensitivity and contribute to the development and maintenance of chronic pain. The pathophysiology of pain is complex; management of perioperative pain and preventing chronic pain are challenges in clinical. Use of opioids for pain management are still a therapeutic mainstay and generally safe when taken, in a short time, for severe postoperative pain relief. For long-term use tolerance may be developed, and for their euphoric property, addiction, overdose incidents, and even death may be the social problems. Therefore, the opioid-sparing multimodal analgesia (MMA) for pain management is recommended in current postoperative pain management. The successful MMA for pain management will enhance patient recovery after surgery with less chronic CPSP and long-term opioid use disorder (OUD). The present review discusses all currently used analgesics actions and interactions, and opioid-sparing or opioid-free analgesia in perioperative pain management. Acute pain following major trauma or surgery may originate from both nociceptive and neuropathic mechanisms. Approximately 10–50% of surgical patients develop chronic postoperative pain, which not only causes persistent discomfort but also leads to functional limitations and psychological distress. Growing evidence highlights a close and bidirectional relationship between sleep and pain: pain disrupts sleep architecture, while sleep deprivation intensifies pain sensitivity and impairs recovery. This reciprocal interaction forms a vicious cycle that poses challenges for effective pain management. Melatonin—a neurohormone secreted by the pineal gland—plays a crucial role in regulating circadian rhythm and sleep–wake cycles. Beyond its chronobiotic action, melatonin exhibits anti-nociceptive, anti-inflammatory, and opioid-sparing properties. Recent preclinical studies have demonstrated that exogenous melatonin can attenuate nociceptive responses to noxious stimuli and enhance morphine analgesia while attenuating morphine tolerance. Moreover, environmental light manipulation preserving the circadian rhythm has been shown to synergistically maintain melatonin secretion, improve sleep quality, and modulate neuroimmune responses involved in pain regulation. Together, these findings suggest that circadian alignment and melatonin supplementation may represent a promising integrative approach for improving both pain control and sleep health in perioperative and chronic pain conditions. Chronic pain patients frequently experience opioid tolerance during long-term therapy, resulting in diminished analgesic efficacy and a need for escalating doses. Our recent work revealed that constant light exposure suppresses endogenous melatonin, heightens pro-inflammatory cytokines (TNF-α, IL-1β), reduces IL-10, and accelerates morphine tolerance in a neuropathic pain model. In contrast, maintaining circadian light–dark cycles or supplementing melatonin preserves melatonin rhythm, reduces glial activation, and sustains morphine antinociception. Melatonin’s co-administration not only attenuates morphine tolerance but also enhances morphine efficacy through the modulation of inflammatory and glial pathways. These findings underscore melatonin’s multifaceted role as both a chronotherapeutic and neuroprotective agent, integrating circadian regulation with pain modulation. Clinically, the application of melatonin or circadian-aligned strategies could guide personalized pain and sleep management, offering safer and more effective multimodal analgesic protocols with reduced opioid dependence and improved quality of life. Full article

Burnout is increasingly recognized as both a psychosocial and a chronobiological disorder characterized by endocrine dysregulation and circadian disruption. It arises from chronic occupational stress and manifests through psychological, physical, and physiological symptoms. Although psychosocial determinants are well established, the biological and chronobiological mechanisms, particularly those involving cortisol and melatonin, remain less explored. This systematic review synthesizes current evidence on hormonal and circadian dysregulation in burnout and complements it with exploratory observational data from healthcare professionals. Peer-reviewed studies evaluating endocrine or circadian biomarkers in individuals with burnout were systematically reviewed. In addition, an exploratory observational analysis was carried out among 195 Romanian clinicians using an adapted Maslach Burnout Inventory. Morning salivary cortisol was measured once at 9 a.m. in a small subsample (n = 26) to provide preliminary physiological data. Because only a single time point was obtained, these values were interpreted as indicative of stress-related activation rather than circadian rhythm. Thirty-seven studies met the inclusion criteria. Across the literature, burnout was associated with altered HPA-axis activity, blunted diurnal cortisol variation, and irregular melatonin secretion related to shift work and disrupted sleep–wake cycles. Complementary exploratory data from our Romanian cohort indicated strong correlations between burnout severity, physical symptoms, and higher morning cortisol values among shift-working clinicians. These findings are preliminary and not representative of full circadian profiles. Burnout should be considered both a psychosocial and a systemic disorder influenced by endocrine and circadian dysregulation. Recognizing alterations in cortisol and melatonin as objective indicators may facilitate earlier detection and inform chronobiological interventions such as optimized scheduling, light exposure management, or melatonin therapy. The observational data presented here is preliminary and intended to generate hypotheses; future research should employ repeated cortisol sampling under controlled Zeitgeber conditions to confirm circadian associations. Full article

Background/Objectives: Smith–Magenis Syndrome (SMS) is a rare neurodevelopmental disorder characterized by severe sleep disturbances and an advanced melatonin rhythm. Current treatments, mainly exogenous melatonin and β-blockers, have not been evaluated in children. This study aimed to characterize the clinical, sleep, and chronobiological profiles of children with SMS under treatment and to assess the effects of melatonin and β-blockers. Methods: In this prospective, single-center study, 20 children with genetically confirmed SMS (aged 5–13 years; 55% female) underwent 15-day home actimetry and 48 h hospitalization, during which questionnaires, polysomnography (PSG), and salivary melatonin/cortisol profiling were performed. Melatonin and psychostimulants were discontinued 36 h before hospitalization. Results: Overall, 95% of children received melatonin and 20% β-blockers. Despite treatment, insomnia was reported in 90%, excessive daytime sleepiness in 65%, and learning problems in 90%. On actimetry, melatonin improved the mean nocturnal awakening duration (1.4 vs. 2.3 min, p = 0.040), wake-up time (06:50 vs. 06:11, p = 0.004), and longest continuous sleep episode (398 vs. 317 min, p = 0.040), but had little effect on the total sleep time, efficiency, and midpoint of sleep. Very high daytime salivary melatonin persisted (median peak 169.50 pg/mL) despite the last exogenous melatonin intake being more than 48 h prior to sampling, suggesting possible iatrogenic accumulation. The median peak in melatonin occurred at 11:57 and that in cortisol at 08:22. In children with β-blockers, there was a tendency toward an earlier melatonin peak but also toward delayed sleep onset, increased nocturnal awakenings, and reduced total sleep. Conclusions: Children with SMS showed persistent sleep difficulties and an advanced circadian phase despite sleep treatments. Exogenous melatonin provides partial benefit but may lead to daytime accumulation, while β-blockers may have adverse sleep effects despite beneficial effects on melatonin peak secretion, warranting further study. Full article

Introduction: Tumor- and/or treatment-associated hypothalamic damage results in reduced quality of life and increased morbidity due to sleep disorders in survivors of craniopharyngioma. Methods: The narrative review is based on a search of Web of Science, MEDLINE/PubMed, and Embase databases for the identification of publications. The search terms craniopharyngioma, sleep disorders, fatigue, and daytime sleepiness were used. Selected English language papers published 1970–2025 were included. Results: Circadian rhythms (wakefulness and sleep) are controlled by hypothalamic suprachiasmatic nuclei and regulated by melatonin. A dysregulation of circadian rhythms due to altered melatonin secretion can be observed in craniopharyngioma with hypothalamic involvement. Furthermore, sleep quality is regulated by lateral hypothalamic areas, the ventrolateral preoptic nucleus, and monoaminergic nuclei which function as the arousal system. Flexible changes between sleep and wakefulness can be achieved through interaction of arousal and sleep-promoting systems named “flip–flop” switch. Insomnia can be the result of damage to the ventrolateral preoptic nucleus. Excessive daytime sleepiness and disrupted sleep patterns can be observed due to dysregulation of lateral hypothalamic areas. Obesity, chronic fatigue, headache, and excessive daytime sleepiness can be the result of poor sleep quality. “Primary” hypothalamic sleep dysfunction, including narcolepsy, dysregulated sleep–wake cycles, and hypersomnia, can be observed due to hypothalamic dysfunction. “Secondary” sleep disturbances including obstructive sleep apnea, insufficient substitution medication for arginine vasopressin deficiency (nocturia), or psychosocial factors are sequelae in patients with craniopharyngioma and hypothalamic lesions. Conclusions: Further research on novel treatment approaches for sleep disorders due to hypothalamic syndrome are warranted to improve the outcome after craniopharyngioma. Full article

Background/Objectives: Breakfast skipping has been associated with a wide range of adverse health outcomes, including metabolic disorders, disrupted circadian rhythm, and impairments of memory and attention in adolescents and adults. Although partial associations between sleep and breakfast behaviors have been reported, few studies have examined multi-dimensional sleep health simultaneously in relation to breakfast skipping, especially comprehensive studies systematically examining this relationship, particularly under controlled social conditions, remain insufficient. Methods: We here demonstrate the association between sleep health and breakfast skipping among 2969 Japanese high school students. Participants provided between one and eight days of sleep diary data, including meal timing records; most (78.1%) completed all eight days, while the remainder contributed fewer days. Additionally, the Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality, and the Pediatric Daytime Sleepiness Scale (PDSS) was used to evaluate daytime sleepiness. Results: Later wake-up times, lower sleep quality, and stronger daytime sleepiness were each associated with a higher likelihood of breakfast skipping. In additional analyses, no significant pairwise interactions were detected among wake-up time, PSQI, and PDSS, suggesting that these factors may be separately associated with breakfast skipping. Conclusions: These findings suggest that multi-dimensional sleep health, including wake-up time, sleep quality, and daytime sleepiness, is relevant to breakfast skipping. This study offers a novel contribution by linking multiple downstream indicators influenced by sleep health to breakfast behavior. Full article

Insomnia is a common and complex disorder, rooted in the dysregulation of circadian rhythms, impaired neurotransmitter function, and disturbances in sleep–wake homeostasis. While conventional hypnotics such as benzodiazepines and Z-drugs are effective in the short term, their use is limited by a high potential for dependence, cognitive side effects, and withdrawal symptoms. In contrast, melatonergic receptor agonists—melatonin, ramelteon, tasimelteon, and agomelatine—represent a pharmacologically targeted alternative that modulates MT1 and MT2 receptors, which are pivotal to the regulation of circadian timing and sleep initiation. Clinical evidence supports the efficacy of these agents in reducing sleep onset latency, extending total sleep duration, and re-aligning disrupted circadian rhythms, particularly among older individuals and patients with non-24 h sleep–wake disorders. Notably, agomelatine offers additional antidepressant properties through selective antagonism of the 5-HT_2C receptor in micromolar concentrations. In contrast, its agonistic activity at melatonergic receptors is observed in the low sub-nanomolar range, which illustrates the complexity of this drug’s interactions with the human body. All compounds reviewed demonstrate a generally favorable safety and tolerability profile. Accumulating evidence highlights that selected medicinal plants, such as chamomilla, lemon balm, black cumin, valeriana, passionflower and lavender, may exert relevant hypnotic or anxiolytic effects, thus complementing melatonergic strategies in the management of insomnia. This structured narrative review presents a comprehensive analysis of the molecular pharmacology, receptor affinity, signaling pathways, and clinical outcomes associated with melatonergic agents. It also examines their functional interplay with serotonergic, GABAergic, dopaminergic, and orexinergic systems involved in arousal and sleep regulation. Through comparative synthesis of pharmacokinetics and neurochemical mechanisms, this work aims to inform the development of evidence-based strategies for the treatment of insomnia and circadian rhythm sleep–wake disorders. Full article

Cortisol follows a 24 h circadian rhythm that plays a pivotal role in maintaining the optimal function of various physiological systems in alignment with behavioural cycles. Its synthesis and secretion are regulated by the hypothalamic–pituitary–adrenal (HPA) axis. The 24 h fluctuations of cortisol may result from physiological changes influencing its regulation, or conversely, hormone-mediating physiological changes within the body. This review mainly aims to synthesize current evidence on methods for detecting cortisol. In addition, it focuses on evaluating cortisol’s potential as a biomarker for circadian disruption and related health impacts. A literature search was conducted across databases, including Google Scholar, PubMed, and Scopus, using search terms such as “circadian rhythm OR circadian clock OR circadian disruption OR circadian dysregulation” and “cortisol OR hydrocort* OR corticoid OR corticosteroid”. A total of 47 articles were included on methods of cortisol detection, and 41 articles were reviewed for their health implications. Cortisol measured via saliva, blood serum, urine, interstitial fluid (ISF), and sweat has been reported as suitable for 24 h monitoring, reflecting circadian regulation. In contrast, hair cortisol is suitable for identifying chronic changes and prolonged elevations in cortisol levels. This review highlights the stability, suitability, and challenges of each detection method, including reported cortisol levels across studies. Additionally, it provides a comprehensive overview of health implications associated with changes in cortisol, offering insights into its potential as a marker for circadian disruption and related health outcomes. Full article