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Biomedical subjects

Timothy H Monk

Publications and source records attributed to Timothy H Monk.

At least 19 recordsLinked to original sources

Age-related differences in the lifestyle regularity of seniors experiencing bereavement, care-giving, insomnia, and advancement into old-old age.

Compared to younger adults, seniors (> or = 60 yrs) often adopt a highly regular lifestyle, perhaps as an adaptive response to age-related changes in their sleep and circadian rhythms. At baseline, diary measures of lifestyle regularity (SRM-5) were obtained from 104 seniors of three separate groups. Thirty-three subjects were challenged by spousal bereavement or the need to care for a spouse at home with dementia (Challenged); 33 were suffering from formally diagnosed (DSM-IV) insomnia (Insomnia); and 38 were healthy, well-functioning older seniors in the second half of their eighth decade of life or later (Healthy Older). The objective of this study was to determine whether lifestyle regularity increased as a function of age within each of these three senior groups. Overall, age was significantly correlated with SRM-5 (r=0.41, p<0.001), with the SRM score increasing by 0.67 units/decade. The same was true for the Challenged and Insomnia groups, which also showed a significant correlation between SRM and age (Challenged: r=0.48, p<0.01; Insomnia: r=0.36, p<0.05), though with a slightly faster rate of SRM increase in the Challenged (0.95 units/decade) than Insomnia (0.55 units/decade) group. Perhaps there was no correlation between age and SRM (r=0.07, n.s.) in the Healthy Older group due to the small age range, although this group did have a higher overall SRM score than the other two groups (p<0.01). The study thus confirmed that the previously observed increase in lifestyle regularity over the adult lifespan persists into later life. This may represent an adaptive behavioral response that might be used in future therapeutic approaches.

Aged↗

Sleep in healthy seniors: a diary study of the relation between bedtime and the amount of sleep obtained.

The aim of this study was to determine whether naturally occurring inter-individual and intra-individual differences in bedtime selection in the elderly might be lawfully related to the amount of sleep that is obtained. A total of 128 seniors (63f, 65m) aged 70-92 years each provided a week of sleep diary data yielding a total of 896 subject-nights for analysis. From each subject-night the diary was used to derive measures of time in bed (TIB) and total sleep time (TST). These measures were used as dependent variables in mixed-effect linear models (nights nested within subjects) with the independent variable being bedtime for that subject-night, arbitrarily expressed as minutes since 19:00 hours. Although there were strong inter-individual and intra-individual differences, for both genders, bedtime had a statistically significant effect (P < 0.001) on both TIB and TST. We observed that later bedtimes were associated with less time in bed and less time asleep. On average between 7 and 8 min of less TIB and TST were associated with each 10-min delay in bedtime from 19:00 hours. These results are interpreted in terms of increases in sleep being derived from living in a better harmony with an earlier peaking circadian pacemaker characteristic of older age, although other possible mechanisms are also considered (e.g. age-dependent alterations in phase angle and homeostatic sleep need).

Aged↗

Treating complicated grief: effects on sleep quality.

Complicated grief (CG) is characterized by recurrent distressing emotions and intrusive thoughts related to the loss of a loved one and avoidance of reminders of the deceased. Poor sleep quality characterizes CG. Cognitive-behavioral therapy and interpersonal psychotherapy reduce CG symptom severity. The effect of these treatments on sleep quality is not known, however. We investigated whether complicated grief treatments (CGTs) improve sleep quality, as assessed by the Pittsburgh Sleep Quality Index. Data collected from 95 adults who participated in a randomized controlled trial were reviewed. Poor sleep quality persisted despite clinically significant improvements in CG severity posttreatment. Given that sleep disturbance is a risk factor for poor health outcomes, adjunctive sleep interventions may be necessary to enhance CGT outcomes.

Adjustment Disorders↗

Using daily 30-min phase advances to achieve a 6-hour advance: circadian rhythm, sleep, and alertness.

INTRODUCTION: A ground-based study was undertaken to determine whether circadian and sleep dysfunction could be avoided by "trickling in" a 6-h phase advance in sleep/wake schedule by 12 consecutive 30-min phase advances as per NASA's Appendix K. METHODS: We simulated a 16-d (384 h) mission for each of 10 subjects. Temporal cues and light levels approximated those experienced in space. All sleep periods were exactly 8 h. Before the study, for 14 d, subjects were required to live on a schedule with a 23:00 bedtime and 07:00 wake time. Laboratory sessions then started with a 4-d baseline segment on that schedule. The fourth night and the day following it were then taken as baseline. Repeated 30-min phase advances in bedtime were then required on each of the next 12 successive nights, resulting in an eventual movement of bedtimes to a 6-h phase-advanced position (bedtime: 17:00, wake time: 01:00). Polysomnographic sleep, circadian rhythms in urinary free cortisol, urinary volume (every void), and core body temperature (once per minute), and ratings of performance, mood, and alertness (five per day) were measured. RESULTS: While circadian dysfunction was largely avoided by trickling in the phase shift, there remained slight differences in phase between the endogenous circadian pacemaker and the imposed routine which disrupted sleep and daytime alertness. CONCLUSION: Though statistically significant, the disruption was less than we observed from repeated 2-h phase delays reported in a 2004 ASEM paper. Evidence would thus seem to favor repeated 30-min phase advances over repeated 2-h phase delays.

Adult↗

The post-lunch dip in performance.

For some performance variables, and some individuals, there is a dip in performance during the midafternoon hours (referred to as the post-lunch dip) that is linked to an increase in sleep propensity at that time of day. The post-lunch dip is a real phenomenon that can occur even when the individual has had no lunch and is unaware of the time of day. This dip has its roots in human biology, and may be linked to the size of the 12-hour harmonic in the circadian system. It is certainly exacerbated by a high-carbohydrate lunch, and may be more likely to occur in extreme morning-type individuals.

Adult↗

Heritability of morningness-eveningness and self-report sleep measures in a family-based sample of 521 hutterites.

Individual variation in the phase and amplitude of human circadian rhythms is well known, but the impact of heritable factors on such variation is less clear. We estimated the narrow-sense heritability for selected circadian and sleep timing, quality, and duration measures among related members of the Hutterites, an endogamous, religious community (n=521 participants). "Morningness-eveningness" (M/E), a stable trait reflecting circadian phase, was evaluated using the Composite Scale (CS). Subjective sleep measures were assessed using the Sleep Timing Questionnaire. Initial analyses reconfirmed the impact of age on M/E. Previously reported correlations between M/E scores and the sleep measures were also noted, demonstrating the construct validity of the questionnaires among the participants. Following corrections for age, gender, and colony of residence, significant narrow-sense heritability was noted for M/E (23%). The heritability for subjective sleep measures (related to timing, duration, and quality) were statistically significant for all but one variable, and varied between 12.4% and 29.4%. Thus, significant heritable influences on human circadian phase and subjective sleep indices can be detected through family-based studies. In view of the impact of circadian malfunction on human health, it may be worthwhile to map genetic factors impacting circadian and sleep variation.

Circadian Rhythm↗

Circadian genes and bipolar disorder.

Bipolar disorder (BD) is a chronic, potentially disabling illness with a lifetime morbid risk of approximately 1%. There is substantial evidence for a significant genetic etiology, but gene-mapping efforts have been hampered by the complex mode of inheritance and the likelihood of multiple genes of small effect. In view of the complexity, it may be instructive to understand the biological bases for pathogenesis. Extensive disruption in circadian function is known to occur among patients in relapse. Therefore, it is plausible that circadian dysfunction underlies pathogenesis. Evidence for such a hypothesis is mounting and is reviewed here. If circadian dysfunction can be established as an 'endophenotype' for BD, this may not only enable identification of more homogenous sub-groups, but may also facilitate genetic analyses. For example, it would be logical to investigate polymorphisms of genes encoding key proteins that mediate circadian rhythms. Association studies that analyzed circadian genes in BD have been initiated and are reviewed. Other avenues for research are also discussed.

ARNTL Transcription Factors↗

Circadian phase variation in bipolar I disorder.

Abnormalities in circadian rhythms are prominent features of bipolar I disorder (BD1). To investigate circadian variation in BD1, we evaluated morningness-eveningness (M/E), a stable trait reflecting circadian phase, using the composite scale (CS) among BD1 patients (DSM IV criteria; n = 75), unscreened controls (n = 349), and patients with schizophrenia (SZ) or schizoaffective disorder (SZA) (n = 81). Our analyses showed that CS scores correlated significantly with age but did not differ by gender among the controls. BD1 patients differed significantly from controls and from SZ/SZA patients when age was considered. CS scores were distributed bi-modally among BD1 cases. There are several possible reasons for the observed heterogeneity. Younger BD1 patients, and those with rapid mood swings, were significantly more likely to have lower CS scores (i.e., to score in the 'evening' range and to have later circadian phase). CS scores were also positively correlated with the age at onset and the duration of the most severe depressive episodes. These relationships were not observed among the SZ/SZA groups. Thus, distinct patterns of M/E were noted among BD1 patients and among BD1 subgroups. The impact of medication, mood state, and chronicity on CS scores needs to be considered.

Age Factors↗

Circadian patterns of sleep, sleepiness, and performance in older and younger adults.

STUDY OBJECTIVE: To compare circadian patterns of sleep, subjective sleepiness, and psychomotor performance in older and younger adults. DESIGN: Controlled experimental laboratory study. SETTING: General Clinical Research Center. PARTICIPANTS: Healthy older adults (n = 17, mean age 76 years) and healthy younger adults (n = 19, mean age 23 years). INTERVENTIONS: Subjects lived for 60 consecutive hours on a 90-minute sleep-wake cycle (30 minutes in bed, 60 minutes awake). Electroencephalographic recordings were conducted during bedrest periods. Self-ratings and psychomotor performance tests were conducted during 60-minute wake periods. MEASUREMENTS AND RESULTS: Data were analyzed with cosinor and linear mixed models. Amplitude and phase of the core body temperature rhythm did not significantly differ by age group. Older adults had significantly reduced mean levels and amplitude of rhythms in total sleep time and sleep efficiency and increased mean levels and amplitude of rhythms in sleep latency and wake after sleep onset. Age groups did not differ in mean level of subjective sleepiness, but older adults had reduced amplitude. Older adults had worse overall psychomotor performance, with evidence of larger circadian amplitude in some of these rhythms. Age groups did not differ on the phase position of any rhythm. CONCLUSIONS: Older adults had a lower level and smaller circadian variation of sleep propensity compared with younger adults, whereas wakefulness and psychomotor performance rhythms tended to show increased circadian variation among older subjects. These findings likely result from a combination of age-related changes in cortical function, homeostatic sleep mechanisms, and circadian regulation.

Adult↗

Aging human circadian rhythms: conventional wisdom may not always be right.

This review discusses the ways in which the circadian rhythms of older people are different from those of younger adults. After a brief discussion of clinical issues, the review describes the conventional wisdom regarding age-related changes in circadian rhythms. These can be summarized as four assertions regarding what happens to people as they get older: 1) the amplitude of their circadian rhythms reduces, 2) the phase of their circadian rhythms becomes earlier, 3) their natural free-running period (tau) shortens, and 4) their ability to tolerate abrupt phase shifts (e.g., from jet travel or night work) worsens. The review then discusses the empirical evidence for and against these assertions and discusses some alternative explanations. The conclusions are that although older people undoubtedly have earlier circadian phases than younger adults, and have more trouble coping with shift work and jet lag, evidence for the assertions about rhythm amplitude and tau are, at best, mixed.

Adult↗

Morningness-eveningness and lifestyle regularity.

The relation between morningness (M) - eveningness (E) and lifestyle regularity was studied in a convenience sample of 100 healthy subjects aged between 20 and 59 yrs (47 males and 53 females; mean age 33.6 yrs). Morningness-eveningness was measured by a single administration of the 13-item Composite Scale for Morningness (CSM). Lifestyle regularity was measured by requiring subjects to complete a five-item Social Rhythm Metric diary (SRM-5) each evening for two weeks. Each week of SRM-5 was analyzed separately and the two SRM scores averaged to yield the lifestyle regularity measure for the subject. Subjects were categorized by morningness into top and bottom quartiles of CSM score (denoted M-types and E-types, respectively), with the remaining 50% of subjects denoted as intermediate (I-types). Mean SRM scores significantly differed between the three morningness groups (p <0.001) in the order E-types (SRM = 3.6), then I-types (SRM=4.0), then M-types (SRM=4.9), with higher scores indicating greater daily lifestyle regularity. The effect size of the E-type versus M-type difference was approximately 1.3. The relationship between the CSM and SRM scores was also confirmed using a correlational analysis (rho = 0.428; p < 0.001). This correlational finding was substantially weaker when age was partialed out (r=0.186; p=0.065), although there was still a trend toward a significan relationship. Thus it appears that morning types appear to be more regular in their daily lifestyle than are evening types, suggesting a relationship between these two aspects of human circadian behavior.

Adult↗

Using nine 2-h delays to achieve a 6-h advance disrupts sleep, alertness, and circadian rhythm.

UNLABELLED: A ground-based study was undertaken to determine whether circadian and sleep dysfunction could be avoided by "trickling in" a 6-h phase advance in sleep/wake schedule by nine consecutive 2-h phase delays, as would be recommended by NASA's Appendix K guidelines. METHODS: A 16-d (384-h) mission was simulated in 10 subjects (5 men, 5 women, mean age: 41.2 yr), studied singly or in pairs. After 14 d on a 23:00-07:00 sleep/wake cycle, the subject entered the laboratory. After a 4-d baseline segment, repeated 2-h phase delays were then required on each of the next nine successive nights of the study (i.e., bedtimes at 01:00, 03:00, 05:00, etc.), resulting in an eventual movement of bedtimes to an 18-h phase delayed (equivalent to a 6-h phase advanced) position with bedtime at 17:00. Measures taken throughout the laboratory study included polysomnographically measured sleep, circadian rhythms in rectal temperature, and subjective ratings of mood and alertness. RESULTS: Circadian dysfunction and sleep disruption were not avoided by trickling in the phase shift. The circadian pacemaker appeared to delay its phase by an average of about 1 h later per night, rather than the 2 h later per night required by the imposed routine. This resulted in a progressive decrease in circadian temperature rhythm amplitude, a progressive disruption in sleep, and a progressive lowering in subjective ratings of alertness. CONCLUSION: Doubt must be cast on the assertion that circadian dysfunction and sleep loss can be avoided by limiting repeated phase delays in routine to 2 h.

Adult↗

Measuring sleep habits without using a diary: the sleep timing questionnaire.

STUDY OBJECTIVES: To develop a single-administration instrument yielding equivalent measures of sleep to those obtained from a formal (2-week) sleep diary. DESIGN & SETTING: A single-administration Sleep riming Questionnaire (STQ) is described (and reproduced in the Appendix). Test-retest reliability was examined in 40 subjects who were given the STQ on two occasions separated by less than 1 year. Convergent validity was measured both by comparing STO-derived measures with objective measures derived from wrist actigraphy (n=23) and by comparing STQ-derived measures with other subjective measures derived from a detailed 2-week sleep diary in two nonoverlapping samples (n=101, 93). Correlations of STQ measures with age and momingness-eveningness (chronotype) were also examined. SUBJECTS: The analyses used sample sizes of 40, 23, 101, and 93 (both genders, overall age range 20y-89y). Most subjects were healthy volunteers; some Study 4 subjects were patients (enrolled in research protocols). RESULTS: Test-retest reliability for the STQ was demonstrated for estimates of bedtime (r = 0.705, p < 0.001) and waketime (r = 0.826, p < 0.001). Convergent validity using wrist actigraphy was demonstrated by correlations of 0.592 (p < 0.005) for bedtime, and of 0.769 (p < 0.001) for waketime. Diary studies indicated STQ bedtime and waketime data to be highly correlated (at about 0.8) with those obtained from a formal 2-week sleep diary. The STQ also provided data on estimated sleep latency and wake after sleep onset (WASO), which correlated reliably (at about 0.7) with average nightly ratings of these variables from a 2-week sleep diary. Mean estimated values of sleep latency and WASO from the two instruments were within 1 minute of each other. ST-derived bedtimes and waketimes correlated with both age and chronotype in the expected direction (older subjects earlier, morning types earlier). CONCLUSION: The STQ may be a reliable valid measure of sleep timing that could provide a time-efficient alternative to traditional sleep diaries.

Adult↗

Hormonal changes during 17 days of head-down bed-rest.

We investigated in six men the impact of 17 days of head-down bed rest (HDBR) on the daily rhythms of the hormones involved in hydroelectrolytic regulation. This HDBR study was designed to mimic a real space flight. Urine samples were collected at each voiding before, during and after HDBR. Urinary excretion of Growth Hormone (GH), Cortisol, 6 Sulfatoxymelatonin, Normetadrenaline (NMN) and Metadrenaline (NM) was determined. A decrease in urinary cortisol excretion during the night of HDBR was noted. For GH, a rhythm was found before and during HDBR. The rhythm of melatonin, evaluated with the urine excretion of 6 Sulfatoxymelatonin (aMT6S), the main hepatic metabolite, persisted throughout the experiment without any modification to the level of phase. A decrease during the night was noted for normetadrenaline urinary derivates, but only during the HDBR.

Adult↗

The role of chronobiology in sleep disorders medicine.

This review is concerned with circadian (approximately 24 h) aspects of chronobiology, and how they relate to sleep disorders medicine. We begin with an introduction to the key concepts and paradigms of circadian rhythms research in general, including a description of homeostatic and circadian determinants of sleep timing. This is followed by a brief history of chronobiology in relation to sleep disorders medicine. Both animal and human circadian rhythm studies are considered. We trace historical changes in the relative emphasis placed on social contacts, light, and melatonin in human circadian rhythms research. Special attention is given to free-running, forced desynchrony, and ultra-short sleep/wake cycle findings of particular relevance to sleep disorders medicine. The latter part of the review comprises a description of the circadian rhythm sleep disorders, highlighting insights derived from basic circadian rhythms research, including recent advances in molecular genetics. We conclude that the role of chronobiology in sleep disorders medicine is profound and pervasive, and that the two disciplines will move ever closer as a natural function of important new insights into sleep and sleep disorders provided by basic circadian rhythms research.

Chronobiology Phenomena↗

The relationship between lifestyle regularity and subjective sleep quality.

In previous work we have developed a diary instrument-the Social Rhythm Metric (SRM), which allows the assessment of lifestyle regularity-and a questionnaire instrument--the Pittsburgh Sleep Quality Index (PSQI), which allows the assessment of subjective sleep quality. The aim of the present study was to explore the relationship between lifestyle regularity and subjective sleep quality. Lifestyle regularity was assessed by both standard (SRM-17) and shortened (SRM-5) metrics; subjective sleep quality was assessed by the PSQI. We hypothesized that high lifestyle regularity would be conducive to better sleep. Both instruments were given to a sample of 100 healthy subjects who were studied as part of a variety of different experiments spanning a 9-yr time frame. Ages ranged from 19 to 49 yr (mean age: 31.2 yr, s.d.: 7.8 yr); there were 48 women and 52 men. SRM scores were derived from a two-week diary. The hypothesis was confirmed. There was a significant (rho = -0.4, p < 0.001) correlation between SRM (both metrics) and PSQI, indicating that subjects with higher levels of lifestyle regularity reported fewer sleep problems. This relationship was also supported by a categorical analysis, where the proportion of "poor sleepers" was doubled in the "irregular types" group as compared with the "non-irregular types" group. Thus, there appears to be an association between lifestyle regularity and good sleep, though the direction of causality remains to be tested.

Adult↗

A simple way to measure daily lifestyle regularity.

A brief diary instrument to quantify daily lifestyle regularity (SRM-5) is developed and compared with a much longer version of the instrument (SRM-17) described and used previously. Three studies are described. In Study 1, SRM-17 scores (2 weeks) were collected from a total of 293 healthy control subjects (both genders) aged between 19 and 92 years. Five items (1) Get out of bed, (2) First contact with another person, (3) Start work, housework or volunteer activities, (4) Have dinner, and (5) Go to bed were then selected from the 17 items and SRM-5 scores calculated as if these five items were the only ones collected. Comparisons were made with SRM-17 scores from the same subject-weeks, looking at correlations between the two SRM measures, and the effects of age and gender on lifestyle regularity as measured by the two instruments. In Study 2 this process was repeated in a group of 27 subjects who were in remission from unipolar depression after treatment with psychotherapy and who completed SRM-17 for at least 20 successive weeks. SRM-5 and SRM-17 scores were then correlated within an individual using time as the random variable, allowing an indication of how successful SRM-5 was in tracking changes in lifestyle regularity (within an individual) over time. In Study 3 an SRM-5 diary instrument was administered to 101 healthy control subjects (both genders, aged 20-59 years) for two successive weeks to obtain normative measures and to test for correlations with age and morningness. Measures of lifestyle regularity from SRM-5 correlated quite well (about 0.8) with those from SRM-17 both between subjects, and within-subjects over time. As a detector of irregularity as defined by SRM-17, the SRM-5 instrument showed acceptable values of kappa (0.69), sensitivity (74%) and specificity (95%). There were, however, differences in mean level, with SRM-5 scores being about 0.9 units [about one standard deviation (SD)] above SRM-17 scores from the same subject-weeks. SRM-5 scores also deviated more from a Gaussian distribution than did SRM-17 ones. In a study with a sample size of 101, the new SRM-5 instrument yielded scores with a mean of 4.11 and an SD of 1.13. Correlations between lifestyle regularity and age, and between lifestyle regularity and morningness appeared similar whether 5-item or 17-item SRM measures were used. When a gender difference in lifestyle regularity appeared, it was detected by both SRM-5 and SRM-17 measures.

Adult↗

Human regional cerebral glucose metabolism during non-rapid eye movement sleep in relation to waking.

Sleep is an essential human function. Although the function of sleep has generally been regarded to be restorative, recent data indicate that it also plays an important role in cognition. The neurobiology of human sleep is most effectively analysed with functional imaging, and PET studies have contributed substantially to our understanding of both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. In this study, PET was used to determine patterns of regional glucose metabolism in NREM sleep compared with waking. We hypothesized that brain structures related to waking cognitive function would show a persistence of function into the NREM sleep state. Fourteen healthy subjects (age range 21-49 years; 10 women, 4 men) underwent concurrent EEG sleep studies and [(18)F]fluoro-2-deoxy-D-glucose PET scans during waking and NREM sleep. Whole-brain glucose metabolism declined significantly from waking to NREM sleep. Relative decreases in regional metabolism from waking to NREM sleep occurred in wide areas of frontal, parietal, temporal and occipital association cortex, primary visual cortex, and in anterior/dorsomedial thalamus. After controlling for the whole-brain declines in absolute metabolism, relative increases in regional metabolism from waking to NREM were found bilaterally in the dorsal pontine tegmentum, hypothalamus, basal forebrain, ventral striatum, anterior cingulate cortex and extensive regions of the mesial temporal lobe, including the amygdala and hippocampus, and in the right dorsal parietal association cortex and primary somatosensory and motor cortices. The reductions in relative metabolism in NREM sleep compared with waking are consistent with prior findings from blood flow studies. The relative increases in glucose utilization in the basal forebrain, hypothalamus, ventral striatum, amygdala, hippocampus and pontine reticular formation are new observations that are in accordance with the view that NREM sleep is important to brain plasticity in homeostatic regulation and mnemonic processing.

Adult↗