Thesis (Ph. D.)--University of Wyoming, 2005. / Includes bibliographical references. Also available online.

Background: Sleep disorders have been poorly described in children and adolescents diagnosed with FASD. The objective of this study is to describe the sleep and circadian rhythm characteristics of children with FASD using overnight polysomnography, sleep questionnaires, and the Dim Light Melatonin Onset (DLMO) test. To our knowledge, no comprehensive studies of this nature have been conducted. Methods: Children ages 6-18 years diagnosed with Fetal Alcohol Spectrum Disorder (FASD) were recruited from various FASD clinics to the Youthdale Child and Adolescent Sleep Centre in Toronto. After medical consultation, each participant had one night of overnight polysomnography, as well as an additional night of DLMO. Participants completed various sleep and FASD questionnaires. Results: Significant differences were found when comparing the sleep architecture of FASD participants to normative data. There was a high prevalence of sleep disorders in this sample. Most of the melatonin profiles of the FASD participants were found to be abnormal.

Background: Sleep disorders have been poorly described in children and adolescents diagnosed with FASD. The objective of this study is to describe the sleep and circadian rhythm characteristics of children with FASD using overnight polysomnography, sleep questionnaires, and the Dim Light Melatonin Onset (DLMO) test. To our knowledge, no comprehensive studies of this nature have been conducted. Methods: Children ages 6-18 years diagnosed with Fetal Alcohol Spectrum Disorder (FASD) were recruited from various FASD clinics to the Youthdale Child and Adolescent Sleep Centre in Toronto. After medical consultation, each participant had one night of overnight polysomnography, as well as an additional night of DLMO. Participants completed various sleep and FASD questionnaires. Results: Significant differences were found when comparing the sleep architecture of FASD participants to normative data. There was a high prevalence of sleep disorders in this sample. Most of the melatonin profiles of the FASD participants were found to be abnormal.

Mood and cognition, along with numerous other physiological processes, are under circadian regulation. The synthesis and secretion rhythm of the pineal hormone melatonin is under the direct regulation of the central circadian pacemaker and the secretion rhythm of melatonin can be used to assess circadian alterations. In this thesis, it was demonstrated that low levels of endogenous nocturnal melatonin was associated with subsyndromal depression and alterations in sleep architecture. Studies in individuals with endogenous circadian rhythm disorder, with and without comorbid depressive symptoms, revealed that individuals with depressive symptoms had a greater phase delay in melatonin profiles as compared to individuals without depressive symptoms. Furthermore, in the same study, exogenous melatonin administered to induce phase advances significantly improved depression scores and sleep initiation. In addition to endogenous circadian disruption, circadian rhythms can also be disrupted by repeated atypical alterations in environmental time cues. In mammals, light is the strongest environmental cue that can modulate circadian rhythms. Recent studies suggest that circadian response to photic stimuli is preferentially sensitive to short wavelengths in the range of 450-480 nm. Using an animal model it was demonstrated that filtering a 10 nm bandwidth between 470-480 nm from polychromatic white light prevents nocturnal light exposure induced disruptions in melatonin and corticosterone secretion as well as central and peripheral clock gene expression. These findings were further investigated in humans and revealed that filtering short wavelengths below 480 nm attenuates 12 h nocturnal light exposure induced suppression of melatonin secretion, increased cortisol secretion and disrupted peripheral clock gene expression. Furthermore, attenuation of these changes was associated with improvements in mood, alertness and vigilance at a time close to the endogenous circadian wake drive. However, filtering short wavelengths below 460 nm or reducing the optical transmission by up to 30% below 480 nm did not attenuate the disruptive effects of nocturnal light exposure on physiological and behavioural variables. Overall, the results presented in this thesis support the role of circadian dysfunction in neuropsychometric impairment and presents evidence supporting spectral modulation as a promising approach to attenuate light-mediated chronodisruption.

No description available.

The effects of one night of 3h sleep on cortisol levels were assessed in two groups of women at different points in their menstrual cycles: mid-follicular and mid-luteal. Eighteen women (age: 21.8 ± 0.54; BMI: 22.6 ± 0.63, mean ± SEM) were studied. Salivary samples were collected at six times during two consecutive days: first after a 10 h overnight sleep opportunity and then after a night with a 3 h sleep opportunity. Secondary analysis examined the impact of sleep restriction on self-reports of hunger ratings and mood. Women in the follicular phase showed a significant decrease (p =0.004) in their cortisol awakening responses after sleep restriction and an elevation in afternoon/evening cortisol levels (p =0.008), whereas women in the luteal phase showed no change. Overall group increases in hunger and deterioration in fatigue and vigour were observed. Menstrual cycle phase dramatically altered the responses of women to a single night of sleep restriction.

The clk-1 gene was found in the screen for the maternal effect viable mutants in Caenorhabditis elegans. It is believed to be involved in controlling timing of various biological processes in the nematode including lengthening it's life span, and, as such, it belongs to the Clock group of genes. The CLK-1 homologue in yeast, COQ7, was shown to be involved in ubiquinone biosynthesis and gluconeogenic gene activation. The Drosophila clk-1 gene has been cloned. As a means to assay probable correlation between the timing mechanism of clk-1 and the circadian clocks, well studied in Drosophila, the clk-1 circadian mRNA expression has been monitored. At the middle of the dark phase, the level of clk-1 transcript decreases by approximately 30%. The Drosophila clk-1 mRNA expression during developmental stages was also analyzed. The amount of clk-1 mRNA is doubled during the larvae stage, the most metabolically active stage in the early Drosophila development.

We investigated the relationship between rhythms occurring at different time-scales, namely circadian and ultradian rhythms. Furthermore, we examined the potential role of the period (per) gene, a known clock gene initially isolated in Drosophila, for regulating these rhythms in the wild-type cricket, Teleogryllus oceanicus . Here we report a positive correlation between circadian and ultradian rhythms in crickets. Thus, crickets with a slow endogenous circadian rhythm also have a slow ultradian rhythm, and conversely, animals with a fast endogenous circadian rhythm have a fast ultradian rhythm. In addition to this correlation, we observed PER-like immunoreactivity in the regions of the cricket nervous system involved in regulating these rhythms, namely the brain, in particular the optic lobes, and the meso- and metathoracic ganglia. We thus conclude that different time-scale rhythms may be regulated by a common setting element, a role potentially played by the per gene.

Mood and cognition, along with numerous other physiological processes, are under circadian regulation. The synthesis and secretion rhythm of the pineal hormone melatonin is under the direct regulation of the central circadian pacemaker and the secretion rhythm of melatonin can be used to assess circadian alterations. In this thesis, it was demonstrated that low levels of endogenous nocturnal melatonin was associated with subsyndromal depression and alterations in sleep architecture. Studies in individuals with endogenous circadian rhythm disorder, with and without comorbid depressive symptoms, revealed that individuals with depressive symptoms had a greater phase delay in melatonin profiles as compared to individuals without depressive symptoms. Furthermore, in the same study, exogenous melatonin administered to induce phase advances significantly improved depression scores and sleep initiation. In addition to endogenous circadian disruption, circadian rhythms can also be disrupted by repeated atypical alterations in environmental time cues. In mammals, light is the strongest environmental cue that can modulate circadian rhythms. Recent studies suggest that circadian response to photic stimuli is preferentially sensitive to short wavelengths in the range of 450-480 nm. Using an animal model it was demonstrated that filtering a 10 nm bandwidth between 470-480 nm from polychromatic white light prevents nocturnal light exposure induced disruptions in melatonin and corticosterone secretion as well as central and peripheral clock gene expression. These findings were further investigated in humans and revealed that filtering short wavelengths below 480 nm attenuates 12 h nocturnal light exposure induced suppression of melatonin secretion, increased cortisol secretion and disrupted peripheral clock gene expression. Furthermore, attenuation of these changes was associated with improvements in mood, alertness and vigilance at a time close to the endogenous circadian wake drive. However, filtering short wavelengths below 460 nm or reducing the optical transmission by up to 30% below 480 nm did not attenuate the disruptive effects of nocturnal light exposure on physiological and behavioural variables. Overall, the results presented in this thesis support the role of circadian dysfunction in neuropsychometric impairment and presents evidence supporting spectral modulation as a promising approach to attenuate light-mediated chronodisruption.

Rats are nocturnal animals, their ingestive behaviours show circadian rhythms and the suprachiasmatic nuclei (SCN) of the hypothalamus are the primary pacemaker of these rhythms. Serotonin (5-HT) is one of the most abundant neurotransmitter in the SCN and it is involved in the regulation of ingestive behaviour. In this study, we compared food and water intakes of male adult Wistar rats infused during 7 days with serotonin (2.5 nmol/24h) or artificial cerebrospinal fluid (CSF) in the SCN in a three-way selection of macronutrients. Within 5-HT infusion, nocturnal and diurnal water intakes, and the nocturnal caloric intake from the protein diet were significantly lower than those of the CSF infused group. Decrease in water consumption was most significant in the early and middle dark phases. Besides, increased diurnal energy intake and decreased nocturnal energy intake were observed during 5-HT and CSF infusion. In conclusion, this first chronic and continuous infusion work on 5-HT in the SCN specifically disrupted the circadian rhythmicities in water and protein consumptions.