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1.  Association of Per3 length polymorphism with bipolar I disorder and schizophrenia 
Background
Sleep–wake disturbances have frequently been reported in bipolar disorder and schizophrenia, and are considered to be caused by an underlying circadian rhythm disorder. The study presented here was designed to investigate the existence of Per3 polymorphism in bipolar disorder type I (BD-I) and schizophrenic patients in South India.
Methods
Blood samples were collected from 311 BD-I patients, 293 schizophrenia patients, and 346 age- and sex-matched normal controls. Per3 genotyping was performed on DNA by polymerase chain reaction using specific primers.
Results
An increased prevalence of five repeat homozygotes was seen in BD-I patients as compared with healthy controls (odds ratio =1.72 [95% confidence interval: 1.08–2.76, P=0.02]). In BD-I patients, the frequency of the five repeat allele was higher (allele frequency =0.41), and that of the four repeat allele lower (allele frequency =0.36) (χ2=4.634; P<0.03) than in the control group. No significant association was observed in the allele frequencies of four and five repeat alleles in schizophrenia patients when compared with controls.
Conclusion
The occurrence of the five repeat allele of Per3 may be a risk factor for BD-I onset in this ethnic group.
doi:10.2147/NDT.S73765
PMCID: PMC4267513  PMID: 25525361
circadian rhythms; clock genes; Per3 polymorphism; bipolar disorder; schizophrenia
2.  Prevalence of sleep-related accidents among drivers in Saudi Arabia 
Annals of Thoracic Medicine  2014;9(4):236-241.
INTRODUCTION:
The prevalence of sleepy driving and sleep-related accidents (SRA) varies widely, and no data exist regarding the prevalence of sleepy driving in Saudi Arabia. Therefore, this study was designed to determine the prevalence and predictors of sleepy driving, near-misses, and SRA among drivers in Saudi Arabia.
MATERIALS AND METHODS:
A questionnaire was developed to assess sleep and driving in detail based on previously published data regarding sleepy driving. The questionnaire included 50 questions addressing socio-demographics, the Epworth Sleepiness Scale (ESS), driving items, and the Berlin Questionnaire. In total, 1,219 male drivers in public places were interviewed face-to-face.
RESULTS:
The included drivers had a mean age of 32.4 ± 11.7 years and displayed a mean ESS score of 7.2 ± 3.8. Among these drivers, 33.1% reported at least one near-miss accident caused by sleepiness. Among those who had actual accidents, 11.6% were attributed to sleepiness. In the past six months, drivers reported the following: 25.2% reported falling asleep at least once during, driving and 20.8% had to stop driving at least once because of severe sleepiness. Young age, feeling very sleepy during driving, and having at least one near-miss accident caused by sleepiness in the past six months were the only predictors of accidents.
CONCLUSION:
Sleepy driving is prevalent among male drivers in Saudi Arabia. Near-miss accidents caused by sleepiness are an important risk factor for car accidents and should be considered as a strong warning signal of future accidents.
doi:10.4103/1817-1737.140138
PMCID: PMC4166072  PMID: 25276244
Accidents; drowsiness; near-miss accidents; sleepiness; sleepy driving
3.  Diurnal Intermittent Fasting during Ramadan: The Effects on Leptin and Ghrelin Levels 
PLoS ONE  2014;9(3):e92214.
We aimed to assess the effect of Islamic intermittent fasting, during and outside of Ramadan, on plasma levels of leptin and ghrelin while controlling for several potential confounding variables. Eight healthy male volunteers with a mean age of 26.6±4.9 years reported to the sleep disorders center (SDC) at King Saud University on four occasions: 1) adaptation; 2) 4 weeks before Ramadan while performing Islamic fasting for 1 week (baseline fasting) (BLF); 3) 1 week before Ramadan (non-fasting baseline) (BL); and 4) during the second week of Ramadan while fasting. Plasma leptin and ghrelin levels were measured using enzyme-linked immunoassays at 22:00, 02:00, 04:00, 06:00, and 11:00. During BLF, there were significant reductions in plasma leptin concentrations at 22:00 and 02:00 compared with the baseline concentrations (at 22:00: 194.2±177.2 vs. 146.7±174.5; at 02:00: 203.8±189.5 vs. 168.1±178.1; p<0.05). During Ramadan, there was a significant reduction in plasma leptin levels at 22:00 (194.2±177.2 vs. 132.6±130.4, p<0.05). No significant difference in plasma ghrelin concentrations was detected during the BL, BLF, or Ramadan periods. Cosinor analyses of leptin and ghrelin plasma levels revealed no significant changes in the acrophases of the hormones during the three periods. The nocturnal reduction in plasma leptin levels during fasting may be the result of the changes in meal times during fasting.
doi:10.1371/journal.pone.0092214
PMCID: PMC3956913  PMID: 24637892
4.  Narcolepsy or Sleep Apnea?: Not Everything is What it Appears to be! 
doi:10.3389/fneur.2013.00152
PMCID: PMC3792551  PMID: 24115943
excessive daytime sleepiness; elderly; narcolepsy; rapid eye movement; multiple sleep latency test; sleep apnea; sleep onset REM periods; epworth sleepiness scale
5.  Objective assessment of drowsiness and reaction time during intermittent Ramadan fasting in young men: a case-crossover study 
Background
Ramadan fasting and its attendant lifestyle changes induce changes in the circadian rhythm and in associated physiological and metabolic functions. Previous studies that have assessed psychomotor performance during Ramadan fasting have reported conflicting results. Therefore, we designed this study to objectively assess the effects of intermittent fasting during and outside Ramadan (to control for lifestyle changes) on drowsiness, blink total duration and mean reaction time (MRT) test while controlling for potential confounders.
Methods
Eight healthy volunteers with a mean age of 25.3 ± 2.9 years and a mean body mass index (BMI) of 23.4 ± 3.2 kg/m2 reported to the sleep laboratory on four occasions for polysomnography (PSG) and drowsiness and psychomotor assessments as follows: 1) adaptation; 2) 4 weeks before Ramadan while performing the Islamic fasting for 1 week (baseline fasting) (BLF); 3) 1 week before Ramadan (non-fasting baseline) (BL); and 4) during the second week of Ramadan while fasting (Ramadan). OPTALERT™ was used to objectively assess daytime drowsiness using the Johns Drowsiness Scale (JDS), and blink total duration and a visual reaction time test were used to assess MRT.
Results
Rapid eye movement (REM) sleep percentage was significantly lower at BLF (17.7 ± 8.1%) and at Ramadan (18.6 ± 10.7%) compared with BL (25.6 ± 4.8%) (p < 0.05). There were no significant differences between JDS scores and blink total duration during the two test periods in BL, BLF and Ramadan. There were no significant changes in MRT during BL, BLF and Ramadan.
Conclusions
Under controlled conditions of fixed light/dark exposure, caloric intake, sleep/wake schedule and sleep quality, the Islamic intermittent fasting has no impact on drowsiness and vigilance as measured by the JDS, total blink duration and MRT.
doi:10.1186/1744-9081-9-32
PMCID: PMC3751553  PMID: 23937904
Ramadan; Fasting; REM sleep; Vigilance; Mean reaction time; Blink duration; Optalert; Johns Drowsiness Scale
6.  Sleep Disorders as a Cause of Motor Vehicle Collisions 
Studies have shown that a large proportion of traffic accidents around the world are related to inadequate or disordered sleep. Recent surveys have linked driver fatigue to 16% to 20% of serious highway accidents in the UK, Australia, and Brazil. Fatigue as a result of sleep disorders (especially obstructive sleep apnea), excessive workload and lack of physical and mental rest, have been shown to be major contributing factors in motor vehicle accidents. A number of behavioral, physiological, and psychometric tests are being used increasingly to evaluate the impact of fatigue on driver performance. These include the oculography, polysomnography, actigraphy, the maintenance of wakefulness test, and others. Various strategies have been proposed for preventing or reducing the impact of fatigue on motor vehicle accidents. These have included: Educational programs emphasizing the importance of restorative sleep and the need for drivers to recognize the presence of fatigue symptoms, and to determine when to stop to sleep; The use of exercise to increase alertness and to promote restorative sleep; The use of substances or drugs to promote sleep or alertness (i.e. caffeine, modafinil, melatonin and others), as well as specific sleep disorders treatment; The use of CPAP therapy for reducing excessive sleepiness among drivers who have been diagnosed with obstructive sleep apnea. The evidence cited in this review justifies the call for all efforts to be undertaken that may increase awareness of inadequate sleep as a cause of traffic accidents. It is strongly recommended that, for the purpose of promoting highway safety and saving lives, all disorders that cause excessive sleepiness should be investigated and monitored.
PMCID: PMC3634162  PMID: 23626880
Alertness; fatigue; rest; sleep; traffic accident
7.  Sleep architecture of consolidated and split sleep due to the dawn (Fajr) prayer among Muslims and its impact on daytime sleepiness 
Annals of Thoracic Medicine  2012;7(1):36-41.
BACKGROUND:
Muslims are required to wake up early to pray (Fajr) at dawn (approximately one and one-half hours before sunrise). Some Muslims wake up to pray Fajr and then sleep until it is time to work (split sleep), whereas others sleep continuously (consolidated sleep) until work time and pray Fajr upon awakening.
AIM:
To objectively assess sleep architecture and daytime sleepiness in consolidated and split sleep due to the Fajr prayer.
SETTING AND DESIGN:
A cross-sectional, single-center observational study in eight healthy male subjects with a mean age of 32.0 ± 2.4 years.
METHODS:
The participants spent three nights in the Sleep Disorders Center (SDC) at King Khalid University Hospital, where they participated in the study, which included (1) a medical checkup and an adaptation night, (2) a consolidated sleep night, and (3) a split-sleep night. Polysomnography (PSG) was conducted in the SDC following the standard protocol. Participants went to bed at 11:30 PM and woke up at 7:00 AM in the consolidated sleep protocol. In the split-sleep protocol, participants went to bed at 11:30 PM, woke up at 3:30 AM for 45 minutes, went back to bed at 4:15 AM, and finally woke up at 7:45 AM. PSG was followed by a multiple sleep latency test to assess the daytime sleepiness of the participants.
RESULTS:
There were no differences in sleep efficiency, the distribution of sleep stages, or daytime sleepiness between the two protocols.
CONCLUSION:
No differences were detected in sleep architecture or daytime sleepiness in the consolidated and split-sleep schedules when the total sleep duration was maintained.
doi:10.4103/1817-1737.91560
PMCID: PMC3277040  PMID: 22347349
Consolidated sleep; daytime sleepiness; Fajr prayer; sleep architecture; split sleep
8.  Therapeutic potential of melatonin and its analogs in Parkinson’s disease: focus on sleep and neuroprotection 
Sleep disorders constitute major nonmotor features of Parkinson’s disease (PD) that have a substantial effect on patients’ quality of life and can be related to the progression of the neurodegenerative disease. They can also serve as preclinical markers for PD, as it is the case for rapid eye movement (REM)-associated sleep behavior disorder (RBD). Although the etiology of sleep disorders in PD remains undefined, the assessment of the components of the circadian system, including melatonin secretion, could give therapeutically valuable insight on their pathophysiopathology. Melatonin is a regulator of the sleep/wake cycle and also acts as an effective antioxidant and mitochondrial function protector. A reduction in the expression of melatonin MT1 and MT2 receptors has been documented in the substantia nigra of PD patients. The efficacy of melatonin for preventing neuronal cell death and for ameliorating PD symptoms has been demonstrated in animal models of PD employing neurotoxins. A small number of controlled trials indicate that melatonin is useful in treating disturbed sleep in PD, in particular RBD. Whether melatonin and the recently developed melatonergic agents (ramelteon, tasimelteon, agomelatine) have therapeutic potential in PD is also discussed.
doi:10.1177/1756285611406166
PMCID: PMC3187674  PMID: 22010042
agomelatine; insomnia; light therapy; melatonin; oxidative stress; Parkinson’s disease; ramelteon; REM sleep behavior disorder; tasimelteon
9.  Melatonin in Mitochondrial Dysfunction and Related Disorders 
Mitochondrial dysfunction is considered one of the major causative factors in the aging process, ischemia/reperfusion (I/R), septic shock, and neurodegenerative disorders like Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD). Increased free radical generation, enhanced mitochondrial inducible nitric oxide (NO) synthase activity, enhanced NO production, decreased respiratory complex activity, impaired electron transport system, and opening of mitochondrial permeability transition pore all have been suggested as factors responsible for impaired mitochondrial function. Melatonin, the major hormone of the pineal gland, also acts as an antioxidant and as a regulator of mitochondrial bioenergetic function. Both in vitro and in vivo, melatonin was effective for preventing oxidative stress/nitrosative stress-induced mitochondrial dysfunction seen in experimental models of PD, AD, and HD. In addition, melatonin is known to retard aging and to inhibit the lethal effects of septic shock or I/R lesions by maintaining respiratory complex activities, electron transport chain, and ATP production in mitochondria. Melatonin is selectively taken up by mitochondrial membranes, a function not shared by other antioxidants. Melatonin has thus emerged as a major potential therapeutic tool for treating neurodegenerative disorders such as PD or AD, and for preventing the lethal effects of septic shock or I/R.
doi:10.4061/2011/326320
PMCID: PMC3100547  PMID: 21629741
10.  Pharmacotherapy of Insomnia with Ramelteon: Safety, Efficacy and Clinical Applications 
Ramelteon is a tricyclic synthetic analog of melatonin that acts specifically on MT1 and MT2 melatonin receptors. Ramelteon is the first melatonin receptor agonist approved by the Food and Drug Administration (FDA) for the treatment of insomnia characterized by sleep onset difficulties. Ramelteon is both a chronobiotic and a hypnotic that has been shown to promote sleep initiation and maintenance in various preclinical and in clinical trials. The efficacy and safety of ramelteon in patients with chronic insomnia was initially confirmed in short-term placebo-controlled trials. These showed little evidence of next-day residual effects, withdrawal symptoms or rebound insomnia. Other studies indicated that ramelteon lacked abuse potential and had a minimal risk of producing dependence or adverse effects on cognitive or psychomotor performance. A 6-month placebo-controlled international study and a 1-year open-label study in the USA demonstrated that ramelteon was effective and well tolerated. Other potential off-label uses of ramelteon include circadian rhythm sleep disorders such as shift-work and jet lag. At the present time the drug should be cautiously prescribed for short-term treatment only.
doi:10.4137/JCNSD.S1611
PMCID: PMC3663615  PMID: 23861638
circadian rhythms; hypnotic; insomnia; melatonin; ramelteon; sleep

Results 1-10 (10)