Louis Fogg

Individual Differences in the Amount and Timing of Salivary Melatonin Secretion

Background The aim of this study was to examine individual differences in a large sample of complete melatonin profiles not suppressed by light and search for possible associations between the amount and timing of melatonin secretion and a multitude of lifestyle variables. The melatonin profiles were derived from saliva samples collected every 30 minutes in dim light from 85 healthy women and 85 healthy men aged 18–45 years. There was a large individual variability in the amount of melatonin secreted with peak values ranging from 2 to 84 pg/ml. The onset of melatonin secretion ranged from 18:13 to 00:26 hours. The use of hormonal birth control, reduced levels of employment, a smaller number of days on a fixed sleep schedule, increased day length and lower weight were associated with an increased amplitude of melatonin secretion. The use of hormonal birth control, contact lenses, a younger age, and lower ratings of mania and paranoia were associated with a longer duration of melatonin secretion. An earlier occurrence of the onset of melatonin secretion was associated with an earlier wake time, more morningness and the absence of a bed partner. Lifestyle and behavioral variables were only able to explain about 15% of the individual variability in the amount of melatonin secretion, which is likely because of a substantial genetic influence on the levels of melatonin secretion.

Effects of melatonin administration on daytime sleep after simulated night shift work

Disturbed sleep and on‐the‐job sleepiness are widespread problems among night shift workers. The pineal hormone melatonin may prove to be a useful treatment because it has both sleep‐promoting and circadian phase‐shifting effects. This study was designed to isolate melatonin’s sleep‐promoting effects, and to determine whether melatonin could improve daytime sleep and thus improve night time alertness and performance during the night shift. The study utilized a placebo‐controlled, double‐blind, cross‐over design. Subjects (n=21, mean age=27.0u2003±u20035.0u2003years) participated in two 6‐day laboratory sessions. Each session included one adaptation night, two baseline nights, two consecutive 8‐h night shifts followed by 8‐h daytime sleep episodes and one recovery night. Subjects took 1.8u2003mg sustained‐release melatonin 0.5u2003h before the two daytime sleep episodes during one session, and placebo before the daytime sleep episodes during the other session. Sleep was recorded using polysomnography. Sleepiness, performance, and mood during the night shifts were evaluated using the multiple sleep latency test (MSLT) and a computerized neurobehavioral testing battery. Melatonin prevented the decrease in sleep time during daytime sleep relative to baseline, but only on the first day of melatonin administration. Melatonin increased sleep time more in subjects who demonstrated difficulty in sleeping during the day. Melatonin had no effect on alertness on the MSLT, or performance and mood during the night shift. There were no hangover effects from melatonin administration. These findings suggest that although melatonin can help night workers obtain more sleep during the day, they are still likely to face difficulties working at night because of circadian rhythm misalignment. The possibility of tolerance to the sleep‐promoting effects of melatonin across more than 1u2003day needs further investigation.

Alerting effects of light are sensitive to very short wavelengths

In humans a range of non-image-forming (NIF) light responses (melatonin suppression, phase shifting and alertness) are short wavelength sensitive (440-480 nm). The aim of the current study was to assess the acute effect of three different short wavelength light pulses (420, 440 and 470 nm) and 600 nm light on subjective alertness. Healthy male subjects (n = 12, aged 27 +/- 4 years, mean +/- S.D.) were studied in 39, 4-day laboratory study sessions. The subjects were maintained in dim light (<8 lx) and on day 3 they were exposed to a single 4-h light pulse (07:15-11:15 h). Four monochromatic wavelengths were administered at two photon densities: 420 and 440 nm at 2.3 x 10(13)photons/cm(2)/s and 440, 470 and 600 nm at 6.2 x 10(13)photons/cm(2)/s. Subjective mood and alertness were assessed at 30 min intervals during the light exposure, using four 9-point VAS scales. Mixed model regression analysis was used to compare alertness and mood ratings during the 470 nm light to those recorded with the other four light conditions. There was a significant effect of duration of light exposure (p < 0.001) on alertness but no significant effect of subject. Compared to 470 nm light, alertness levels were significantly higher in 420 nm light and significantly lower in the 600 nm light (p < 0.05). These data (420 nm>470 nm>600 nm) suggest that subjective alertness may be maximally sensitive to very short wavelength light.

A critical analysis of the intent-to-treat principle in prevention research

Nonadherence to experimental protocols in randomized clinical trials (RCT) is a ubiquitous problem that can lead to erroneous estimations of treatment effects. The most widely advocated strategy for addressing the problem of nonadherence is based on the principle of intent-to-treat (ITT) in which all participants are analyzed according to their randomized condition regardless of actual adherence to the assigned protocol. However, there are numerous problems with using the ITT principle, all of which can be magnified in prevention RCTs. We describe the rationale underlying the use of the ITT principle and the potential problems it can create when interpreting results from prevention RCTs. Four alternative solutions for analyzing nonadherence to experimental protocols that would advance the science and practice of prevention are described. Editors’ Strategic Implications: This paper details a strategy that shows promise. This paper speaks to all research methods when treatment and comparisons are involved. The authors’ recommendations for analyzing nonadherence to protocols—in both experimental and control conditions—are sound; if followed, they would improve research practice and push the knowledge base forward about how to ensure translation from research to practice. The authors’ lessons may be just as relevant to researchers in applied settings as they are to those conducting clinical trials.

The circadian rhythm of temperature during light treatment for winter depression

Circadian rhythm abnormalities have been implicated in winter seasonal affective disorder. We examined the circadian temperature rhythm of 22 patients with winter depression and 10 normal controls who had participated in various high-intensity light treatment experiments. We did not find abnormalities in the baseline phase or amplitude of the temperature rhythm in patients compared to controls. Nor did we find abnormalities in the phase-shifting response to morning light. There was some evidence that the phase-delayed half of the patients responded poorly to phase advances produced by morning light, whereas the phase-advanced half of the patients responded poorly when their rhythms delayed. However, the antidepressant responses during the best week (week of lowest depression score) were unrelated to temperature rhythm phase shifts. In general, there was not strong support for a relationship between circadian rhythms changes and antidepressant response.

Threats to validity in randomized clinical trials

The purposes of this article are to present an overview of randomized clinical trials (RCTs) and describe some of the methodological problems inherent in using RCTs in nursing research. Many nursing intervention studies are fraught with problems that defy the stringent control criteria required for RCTs, leading to biased estimates of intervention efficacy. Five threats to validity in RCTs are presented, including problems related to (a) differential dropout, (b) random assignment, (c) identifying and maintaining an adequate control condition, (d) nonadherence to research protocols, and (e) assessment of clinically meaningful change. Three strategies are recommended for addressing some of the problems posed by RCTs and improving inference.

Bright light therapy for winter depression - Is phase advancing beneficial?

Bright light is the recommended treatment for winter seasonal affective disorder (SAD). Previously we showed that the antidepressant effect of morning (but not evening) light was greater than placebo after 3 weeks of treatment. Here, we determined if the magnitude and direction of circadian rhythm phase shifts produced by the bright light in the previous study were related to the antidepressant effects. Twenty-six SAD patients from the original sample of 96 had their rectal temperature continuously monitored while they participated in a placebo-controlled parallel design conducted over six winters. After a baseline week, there were three treatments for 4 weeks—morning light, evening light, or morning placebo. Bright light was produced by light boxes (˜6000 lux). Placebos were sham negative ion generators. All treatments were 1.5 h in duration. Depression ratings were made weekly by blind raters. Circadian phase shifts were determined from changes in the timing of the core body temperature minimum (Tmin). Morning light advanced and evening light delayed the Tmin by about 1 h. The placebo treatment did not alter circadian phase. As the sleep schedule was held constant, morning light increased and evening light decreased the Tmin to wake interval, or phase angle between circadian rhythms and sleep. Phase advance shifts and increases in the phase angle were only weakly associated with antidepressant response. However, there was an inverted U-shaped function showing that regardless of treatment assignment the greatest antidepressant effects occurred when the phase angle was about 3 h, and that patients who moved closer to this phase angle benefited more than those who moved farther from it. However 46% of our sample had a phase angle within 30 min of this 3 h interval at baseline. So it does not appear that an abnormal phase angle can entirely account for the etiology of SAD. A majority (75%) of the responders by strict joint criteria had a phase angle within this range after treatment, so it appears that obtaining the ideal phase relationship may account for some, but not all of the antidepressant response. In any case, regardless of the mechanism for the antidepressant effect of morning light, it can be enhanced when patients sleep at the ideal circadian phase and reduced when they sleep at a more abnormal circadian phase.

Outcomes of a Life Skills Intervention for Homeless Adults with Mental Illness

A manualized life skills intervention based on empowerment theory and situated learning was tested on 51 homeless adults with mental illness living in emergency or single room occupancy housing. The intervention improved skills in food, money, room, and self-care management and safe community participation. Participation included baseline measures with intervention post-tests and three and six month follow up measures. Comparisons were made to examine effectiveness between modules. There were significant improvements over time for the room and self-care and safe community participation modules, whereas the other modules did not reach statistical significance. The results suggest that through intervention this population may develop and retain the life skills needed to maintain residential stability.

What does the NCATS measure

The purpose of this study was to examine what aspects of the mother-child relationship are measured by the Nursing Child Assessment Teaching Scale (NCATS). A racially heterogeneous sample of 128 mothers completed questionnaires measuring maternal depression, parenting self-efficacy, knowledge of developmental and parenting principles, and perceived difficult toddler temperament. Mothers and children were also videotaped during home visits while completing two teaching tasks that were later scored using the NCATS. NCATS Parent subscale scores were significantly related to maternal knowledge and education but unrelated to depression and self-efficacy. Child subscale scores were unrelated to all of the study variables, including perceived difficult temperament. Significant differences were noted among African-American, Hispanic, and white mothers. The findings suggest that the NCATS taps cognitive factors more reliably than affective factors underlying the mother-child relationship and the cognitive factors may be culturally biased.

Concordance of symptoms in recurrent depressive episodes

The presence or absence of 12 depressive symptoms was examined in 93 bipolar and 108 unipolar patients who had two discrete episodes of major depression over a 5-year period. For each symptom the concordance of its presence or absence across episodes was low. The agreement observed was largely that to be expected by chance. A substantial amount of concordance was obtained if differences in episode intensity (propensity to have symptoms) were taken into account. This suggests that although there may be factors related to depression which remain stable across episodes, symptom presentation is moderated by other factors, such as intensity, which vary from episode to episode.