Publications

Peer-reviewed articles are listed from newest to oldest. For the complete bibliography, visit ORCID, Stanford Profiles, or Google Scholar.

Editorial overview: Sleep and wakefulness are fundamental biological functions supporting adaptation, cognition, emotional regulation, and behavior. Their disturbances should not be treated merely as secondary features of psychiatric illness. Across several psychiatric disorders, sleep-wake alterations may precede the full syndrome, intensify during symptomatic periods, persist during partial remission, and predict recurrence or poorer outcomes. They therefore provide an important clinical window into the mechanisms that shape biological resilience and vulnerability.

Oxidative stress and antioxidant defense occupy a central place in this framework. Reactive oxygen species generated through mitochondrial metabolism are necessary for signaling and adaptation, but oxidative imbalance can disrupt signaling, amplify inflammation, and reduce energetic efficiency. Sleep deprivation, sleep fragmentation, intermittent hypoxia, circadian desynchronization, metabolic stress, aging, inflammation, and chronic psychosocial burden can all increase mitochondrial load. The clinical consequences may include unstable vigilance, fatigue, non-restorative sleep, cognitive slowing, impaired motivation, mood dysregulation, and reduced tolerance to stress.

The article proposes mitochondrial resilience as the capacity to maintain redox equilibrium, energetic efficiency, and functional stability under changing demands. Dopaminergic, orexinergic, and noradrenergic systems provide a bridge between sleep-wake regulation, motivation, vigilance, and stress responsiveness. Antioxidant defenses, including mitochondrial buffering systems such as SOD2, are viewed as active components of this regulatory architecture. The resulting framework is dimensional and transdiagnostic, and supports integrated molecular, physiological, clinical, and epidemiological research on sleep, wakefulness, oxidative regulation, and psychiatric outcomes.

Abstract: This study estimated the prevalence of obstructive sleep apnoea syndrome and its burden on workplace productivity in the United States and the United Kingdom. Self-reported breathing pauses combined with excessive daytime sleepiness were used as a proxy for the syndrome. The estimated prevalence was 22.8% in the United States and 19.5% in the United Kingdom. Annual productivity losses were estimated at US$180.2 billion in the United States and £4.22 billion in the United Kingdom. In both countries, the productivity loss attributable to an affected individual exceeded the estimated cost of continuous positive airway pressure treatment. These findings suggest that better identification of obstructive sleep apnoea, broader access to treatment, and improved adherence could produce substantial clinical and economic benefits.

Background: Adult-onset food allergy is increasingly recognized as a clinically important condition, but longitudinal population-based information on its incidence and persistence remains limited. This study estimated the prevalence, annualized incidence, and three-year persistence of physician-diagnosed food allergy among U.S. adults and examined associated demographic and clinical factors.

Methods: Adults from 15 U.S. states participated in structured telephone interviews at baseline between 2002 and 2012 and were re-interviewed approximately three years later between 2006 and 2015. Of 19,136 people contacted, 15,929 completed the baseline assessment, corresponding to an 83.2% cooperation rate, and 10,931 completed both waves. A structured diagnostic module recorded physician-diagnosed food allergies, implicated foods, and cutaneous, respiratory, and gastrointestinal reactions. Digestive intolerance without a physician diagnosis was not classified as food allergy. Interviews were administered with the Adinfer/EVAL system. Analyses were weighted to U.S. census distributions and adjusted for age, sex, and race.

Results: At baseline, 7.3% of participants reported a physician-diagnosed food allergy; weighted prevalence at follow-up was 7.2%. Women reported food allergy more often than men at both waves. Among participants without food allergy at baseline, cumulative incidence over approximately three years was 5.1%, corresponding to an annualized incidence of 1.7%. Among adults with food allergy at baseline, 65.7% continued to report it at follow-up. Persistence was greater among participants with coexisting asthma, 78.4%, than among those without asthma, 60.1%. Female sex, younger age, non-food allergies, asthma, chronic medical conditions, moderate-to-severe fatigue, ADHD, migraine, and anxiety disorders were associated with persistence. Female sex, higher body mass index, chronic pain, non-food allergies, asthma, and ADHD were associated with incident food allergy.

Conclusion: Food allergy is common among U.S. adults, continues to arise during adulthood, and frequently persists over three years. Its clustering with asthma and other atopic conditions suggests a subgroup with broader allergic susceptibility. Associations with neurobehavioral conditions warrant further mechanistic investigation but should not be interpreted causally.

Introduction: Chronic nausea and vomiting can have persistent effects on health and quality of life. This study investigated whether chronic nausea and vomiting contribute to the development of sleep-related leg cramps in 10,931 participants representative of the U.S. adult general population.

Methods: Participants were interviewed by telephone twice, approximately three years apart, using the Sleep-EVAL expert system. The interviews collected information on sleep habits and sleep disorders according to the International Classification of Sleep Disorders, mental disorders according to DSM-IV-TR criteria, and medical conditions. Chronic nausea and vomiting were defined, in accordance with Rome IV recommendations, as episodes occurring at least five times per month for at least one month outside pregnancy.

Results: Chronic nausea and vomiting were reported by 3.0% of participants at baseline and 2.5% at follow-up; the three-year incidence was 1.4%. Sleep-related leg cramps were reported by 12.4% at baseline and 11.5% at follow-up. In multivariable models, participants who reported chronic nausea and vomiting at both interviews were 4.1 times more likely to report sleep-related leg cramps at follow-up than participants without nausea or vomiting. Magnesium intake at baseline was associated with a lower risk of subsequent sleep-related leg cramps.

Discussion: Persistent chronic nausea and vomiting strongly predicted sleep-related leg cramps in this longitudinal survey. One possible mechanism is depletion of potassium or magnesium resulting from recurrent gastrointestinal symptoms. The findings support greater physician awareness of this association and consideration of relevant nutritional and metabolic factors.

Objective: Narcolepsy is a rare chronic disorder of hypersomnolence characterized by excessive daytime sleepiness, hypnagogic or hypnopompic hallucinations, sleep paralysis, disrupted nighttime sleep, and, in type 1 narcolepsy, cataplexy. This study assessed the prevalence of narcolepsy in large representative general-population samples from North America, Europe, and Asia.

Methods: The cross-sectional epidemiological analysis used the Sleep-EVAL research database and included 61,754 participants from ten countries interviewed between 1992 and 2016. Sleep-EVAL conducted standardized interviews and applied positive and differential diagnostic procedures. For each participant, the system explored symptoms and diagnostic pathways to determine whether criteria for narcolepsy type 1 or type 2 were met according to the International Classification of Sleep Disorders, Third Edition.

Results: The estimated prevalence of narcolepsy type 1 was 19.1 per 100,000 persons and that of narcolepsy type 2 was 23.3 per 100,000. Prevalence estimates were similar across countries and between men and women. Narcolepsy type 1 was most prevalent among participants aged 35 years or younger, whereas narcolepsy type 2 was most prevalent among those aged 35 to 54 years.

Conclusion: Across representative samples from ten countries, narcolepsy affected an estimated 42.4 persons per 100,000. The results confirm that narcolepsy is rare and provide standardized international population estimates for both major diagnostic types.

Abstract: RNA-DNA differences challenge the conventional view that RNA is always a faithful copy of its DNA template. They may arise through regulated RNA editing, transcriptional errors, or oxidative damage. Reactive oxygen species can produce lesions such as 8-oxo-guanine that impair transcription and translation and may lead to dysfunctional proteins. This review examines the biochemical origins of RNA-DNA differences, their amplification under oxidative stress, and their potentially adaptive as well as pathological roles.

RNA-DNA differences may contribute to genomic instability and have been implicated in cancer, neurodegenerative conditions, and autoimmune diseases, while also contributing to phenotypic diversity. Evidence from terrestrial and spaceflight studies illustrates the convergence of oxidative stress, RNA-DNA difference formation, and cellular dysfunction. Improved methods for detecting and quantifying these differences, combined with strategies for managing reactive oxygen species, may offer new ways to restore cellular homeostasis and strengthen biological resilience.

The review positions RNA-DNA differences as a marker of genomic entropy and of the limits of biological adaptation. Guanine-rich codons in antioxidant genes may be especially vulnerable to oxidative lesions, creating a link among redox stress, transcriptional fidelity, genomic instability, and constrained adaptation. These mechanisms have implications for aging, disease progression, and adaptation in both terrestrial and space environments.

Abstract: Long-duration spaceflight beyond Earth's magnetosphere creates major health risks, including muscle atrophy, bone loss, liver and kidney injury, and spaceflight-associated neuro-ocular syndrome. RNA sequencing of mice housed aboard the International Space Station for 37 days revealed an unusually high frequency of changes in tissue-specific genes, with guanine base conversions predominating.

The findings suggest that the accelerated, genome-wide changes were not explained solely by radiation dose. They were consistent with oxidative damage related to elevated carbon dioxide exposure and increased reactive oxygen species aboard the International Space Station. The observed changes appeared more rapidly through RNA transcription than through DNA replication and were more numerous than would be expected from radiation alone, revealing previously unrecognized hotspots in the mammalian proteome.

These hotspots overlapped with genes commonly mutated in human cancers, supporting the use of the International Space Station as a model for studying accelerated mutation, genomic instability, and the emergence of disease-associated changes. The study suggests that metabolic processes can contribute to somatic mutation and potentially to carcinogenesis, with implications for human health both in space and on Earth.

Background: In the REST-ON clinical trial, extended-release once-nightly sodium oxybate significantly improved mean sleep latency on the Maintenance of Wakefulness Test compared with placebo in participants with narcolepsy. This post hoc analysis examined the magnitude of individual treatment response and improvement in excessive daytime sleepiness.

Methods: Participants aged 16 years or older with narcolepsy were randomized in equal proportions to once-nightly sodium oxybate or placebo. Active treatment was titrated from 4.5 g in week 1 to 6 g in weeks 2 and 3, 7.5 g through week 8, and 9 g through week 13. Mean sleep latency was measured across five Maintenance of Wakefulness Test trials, each lasting up to 30 minutes. Post hoc outcomes included the proportions of participants whose mean sleep latency improved by at least 5, 10, 15, or 20 minutes, and the proportion who remained awake for the full 30 minutes.

Results: Significantly more participants receiving once-nightly sodium oxybate than placebo achieved improvements of at least 5 and 10 minutes at every evaluated dose. Improvements of at least 15 minutes were significant at 6, 7.5, and 9 g, and improvements of at least 20 minutes were also more frequent with active treatment. At 7.5 g, 10.5% of treated participants remained awake for the full 30 minutes compared with 1.3% receiving placebo. At 9 g, the corresponding proportions were 13.2% and 5.1%.

Conclusion: Once-nightly sodium oxybate produced clinically meaningful improvements in objective wakefulness across a range of response thresholds. At the two highest doses, more than 10% of treated participants remained awake throughout the Maintenance of Wakefulness Test, supporting once-at-bedtime extended-release sodium oxybate as a treatment option for adults with narcolepsy.

Abstract: No abstract was published or indexed for this short French-language article.

Background: Major depressive disorder (MDD) is largely managed in primary care, but physicians vary widely in their understanding of symptoms and treatments. This study aims to better understand the evolution of depression from initial diagnosis over a 3-year period.
Methods: This was a noninterventional, retrospective, longitudinal study, with 2 waves of participant interviews approximately 3 years apart. Phone interviews were conducted using the hybrid artificial intelligence (AI) Sleep-EVAL system, an AI-driven diagnostic deep learning tool. Participants were noninstitutionalized adults representative of the general population in 8 US states. Diagnosis was confirmed according to the DSM-5 using the Sleep-EVAL System.
Results: 10,931 participants completed Wave 1 and 2 (W1, W2) interviews. The prevalence of MDD, including partial and complete remission, was 13.4 % and 19.6 % in W1 and W2, respectively. About 42 % of MDD participants at W1 continued to report depressive symptoms at W2. Approximately half of antidepressant (AD) users in W1 were moderately to completely dissatisfied with their treatment; 29.6 % changed their AD for a different one, with 16.4 % switching from one SSRI to another between W1 and W2. Primary care physicians were the top AD prescribers, both in W1 (45.7 %) and W2 (59%), respectively.
Limitations: Data collected relied on self-reporting by participants. As such, the interpretation of the data may be limited.
Conclusions: Depression affects a sizeable portion of the US population. Dissatisfaction with treatment, frequent switching of ADs, and changing care providers are associated with low rates of remission. Residual symptoms remain a challenge that future research must address.

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Objective: The objectives of this study are to evaluate the prevalence and incidence of Narcolepsy type 1 and type 2 and to determine the prevalence of narcolepsy diagnosis criteria in the US general population.
Methods: This longitudinal study was conducted in the adult US general population in two occasions. The initial interviews included 15 states (Arizona, California, Colorado, Florida, Idaho, Missouri, New York, North Carolina, North Dakota, Oregon, Pennsylvania, South Dakota, Texas, Washington, and Wyoming). The follow-up interviews, was done three years later in eight of these states. Of the 19,136 contacted individuals, 15,929 completed the initial interview and 10,931 completed the follow-up. Participants were interviewed using the Sleep-EVAL system, an artificial intelligence tool. Narcolepsy Type 1 (with cataplexy) and Narcolepsy Type 2 (without cataplexy) were defined according to the ICSD-3 classification. Symptoms of narcolepsy were assessed by frequency per week and duration. Medical visits and diagnoses were also collected.
Results: Participants were aged between 18 and 102 years of age (mean 45.8 ± 17.9 years), 51.3 % were women. The prevalence of narcolepsy with cataplexy was 12.6 per 100,000 individuals (95 % C.I., 0 to 30) and narcolepsy without cataplexy was 25.1 per 100,000. The incidence per year was 2.6 per 100,000 individuals (95 % C.I., 0 to 11).
Conclusions: Narcolepsy is a rare condition affecting 37.7/100,000 individuals (126,191 individuals in the current US population). Our US general population prevalence is in line with rates found in community-based studies but lower than what is reported in claim database studies.

Epidemiological studies can provide information not only on specific diagnostic entities but also on their underlying symptomatic constellations. For this purpose, an expert system was developed for the assessment of sleep disorders and endowed with the fuzzy logic capabilities necessary to determine the degree to which a given symptom corresponds to a specific diagnosis.
Uncertainty is inherent in fields such as sleep medicine and psychiatry, and becomes evident in clinical practice at the stages of data collection and diagnostic formulation, when the clinician must determine whether a symptom is present and must choose from several diagnostic possibilities. The process involves a considerable degree of subjectivity on the part of the patient in trying to describe his or her symptoms, and of the clinician whose final diagnosis will depend on his or her clinical experience and interpretation of what is normal and what is pathological.
Inferential models of the probabilistic or fuzzy logic type take into account such uncertainty.
The Sleep-Eval system has been used in epidemiological and clinical studies involving 34,044 interviews collected by close to 300 interviewers.
The diagnostic potential of these models is illustrated using data collected in an epidemiological study of the noninstitutionalized general population of Italy and underlines the advantages and limits of the binary, bayesian, and fuzzy logic methods and analyses.

To validate the Sleep-EVAL expert system, a computerized tool designed for the assessment of sleep disorders, against polysomnographic data and clinical assessments by sleep specialists. Patients were interviewed twice, once by a physician using Sleep-EVAL and again by a sleep specialist. Polysomnographic data were also recorded to ascertain diagnoses.
Agreement between diagnoses generated by Sleep-EVAL and those formulated by sleep specialists was determined via the kappa statistic. Settings: Sleep disorder centers at Stanford University (USA) and Regensburg University (Germany); 105 patients aged 18 years or over were included.
Results: Sleep-EVAL made an average of 1.32 diagnoses per patient, compared with 0.93 for the sleep specialists. Overall agreement on any sleep-breathing disorder was 96.9% (Kappa .94). More than half of the patients were diagnosed with obstructive sleep apnea syndrome (OSAS); the agreement rate for this specific diagnosis was 96.7% (Kappa .93).
The findings indicate that the Sleep-EVAL system is a valid instrument for the recognition of major sleep disorders, particularly insomnia and OSAS.

Our study aims to explore the associations between outdoor nighttime lights (ONL) and sleep patterns in the human population. Cross-sectional telephone study of a representative sample of the general US population age 18 y or older. 19,136 noninstitutionalized individuals (participation rate: 83.2%) were interviewed by telephone. The Sleep-EVAL expert system administered questions on life and sleeping habits; health; sleep, mental and organic disorders (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision; International Classification of Sleep Disorders, Second Edition; International Classification of Diseases, 10th Edition).
Individuals were geolocated by longitude and latitude. Outdoor nighttime light measurements were obtained from the Defense Meteorological Satellite Program's Operational Linescan System (DMSP/OLS), with nighttime passes taking place between 19:30 and 22:30 local time. Light data were correlated precisely to the geolocation of each participant of the general population sample.
Living in areas with greater ONL was associated with delayed bedtime (P < 0.0001) and wakeup time (P < 0.0001), shorter sleep duration (P < 0.01), and increased daytime sleepiness (P < 0.0001). Living in areas with greater ONL also increased the dissatisfaction with sleep quantity and quality (P < 0.0001) and the likelihood of having a diagnostic profile congruent with a circadian rhythm disorder (P < 0.0001).
Although they improve the overall safety of people and traffic, nighttime lights in our streets and cities are clearly linked with modifications in human sleep behaviors and also impinge on the daytime functioning of individuals living in areas with greater ONL.