Diurnal mood variation in depression: a signal of disturbed circadian function?

BACKGROUND: Diurnal variation in mood is a prominent symptom of depression, and is typically experienced as positive mood variation (PMV - mood being worse upon waking and better in the evening). The present study sought to advance understanding of PMV by measuring daily mood variation in non-clinical individuals with varying levels of depressed mood. Based on research into normative variation in mood and evidence that circadian amplitudes may be decreased in depression, it was hypothesised that compared to those with low levels of depression, individuals meeting Centre for Epidemiological Studies-Depression Scale (CES-D) cut-off for probable depression would exhibit an attenuated circadian component in diurnal variation of Positive Affect (PA). METHOD: Ninety-nine young healthy women (mean age=21.5, SD=3.0) living on a normal sleep-wake schedule provided mood reports every two hours between 0800 h and 2200 h for 7 days. RESULTS: The high depression group (CES-D > or = 23, n=22) exhibited a pattern of diurnal variation consistent with PMV (increased PA in the evening relative to the morning). As predicted, evidence was also found that the high depression group was characterized by a decreased circadian component to diurnal variation in PA relative to the low depression group (CES-D < 23, n=77). CONCLUSIONS: It is provisionally concluded that diurnal mood variation in depression can usefully be understood from the perspective of weakened circadian function. Findings are discussed in terms of limitations of the study's naturalistic design and future research avenues identified.     

Relations between depressed mood and vocal parameters before, during and after sleep deprivation: a circadian rhythm study

The mechanism underlying improvement after total sleep deprivation (TSD) was studied in 14 major depressed patients. The suggestions that (1) circadian processes and/or (2) dimensions of arousal may play a role in the response to TSD were investigated. Diurnal variation of depressed mood and of mood- and arousal-related vocal parameters was studied in relation to the effect of TSD on depressed mood and vocal parameters. During 3 baseline days, during TSD and 2 days after TSD vocal parameters and depressed mood were assessed 6 and 3 times daily respectively. The mean fundamental frequency (frequency of vocal fold vibration, F0) (presumably reflecting aspects of arousal) as well as the range of the F0 (proposed to reflect sadness) showed a clear circadian pattern with a peak at about 4.00 p.m. TSD affected the circadian organization of the mean F0 and advanced the peak of the curve. After one night of subsequent sleep this effect disappeared. In addition, improvement after TSD coincided with an increase of the mean F0. The diurnal variation of mood before TSD predicted the mood response to TSD, whereas diurnal variation of vocal parameters did not. Moreover, circadian changes in vocal parameters were not related to changes in depressed mood. These findings suggest that the diurnal variations in mood and vocal parameters are regulated by different mechanisms. Data support the presumption that circadian as well as arousal processes are involved in the mood response to TSD. Circadian changes in vocal parameters due to TSD are not likely to reflect changes in the biological clock.     

The daily course of the symptomatology and the impaired time estimation in endogenous depression (melancholia)

The importance of 'typical' diurnal variations in mood (depression worse in the morning) as a diagnostic criterion of endogenous depression has been challenged in previous investigations. Disturbance in time experience may contribute towards an understanding of diurnal variation in depressive symptomatology. To examine this hypothesis a series of time estimation experiments was conducted in the course of the day. Twenty-five endogenous depressive patients (according to ICD-9) and 12 healthy controls were asked to estimate prospectively a 30-s interval on two successive days at 7.30 a.m., 11.30 a.m., 3.30 p.m. and 7.30 p.m. Simultaneously the subjects assessed their state of well-being using a visual analogue mood scale. A circadian rhythm of time estimation errors could not be detected; even in daily courses with 'typical' diurnal variations an increasingly favourable self-assessment of well-being was not accompanied by a corresponding diurnal fluctuation of time estimation. These results cast additional doubts on the significance of 'typical' diurnal variations in depressive symptomatology.     

Circadian variation in portal pressure: appropriate use of non-selective beta blockers in the prevention of variceal bleed

The circadian variation in some biologic functions may have clinical, fiscal and therapeutic implications. The authors discuss circadian variation in portal pressure in cirrhotic patients and nocturnal occurrence of bleeding from varices in these patients. The pathogenesis of the diurnal variation in portal pressure is presented. The authors submit the hypothesis that an optimal dosing regimen for non-selective beta blocker therapy in the prevention of variceal bleed must include an evening dose of beta blocker medication. In studies reporting comparative efficacy of beta blocker therapy with other modalities in the prevention of variceal bleeding, the optimal dosing schedule for beta blocker therapy must be emphasized.     

Reversed diurnal variation in depression: associations with a differential antidepressant response, tryptophan: large neutral amino acid ratio and serotonin transporter polymorphisms

BACKGROUND: Although diurnal variation of mood is a widely recognized symptom of depression, the clinical, neurobiological and psychopharmacological significance of this symptom has not previously been reported. METHOD: A total of 195 depressed out-patients underwent a detailed clinical and neurobiological assessment, and were then randomized to treatment with either fluoxetine or nortriptyline. RESULTS: Of the 195 depressed patients, 62 had a pattern of reversed diurnal variation (i.e. worse in the evening). Those with reversed diurnal variation had a poorer response to a serotonergic anti-depressant, were less likely to have bipolar II disorder, had a higher tryptophan: large neutral amino acid ratio and had different allele frequencies of the polymorphisms in the promoter region of the serotonin transporter. CONCLUSIONS: These findings raise the possibility of serotonergic influence on diurnal variation, and that the symptom of reversed diurnal variation is of relevance to antidepressant prescribing.     

Diurnal variation: reliability of measurement and relationship to typical and atypical symptoms of depression.

We used three rating scales to study diurnal variation of mood in 37 patients with major depressive disorder (17 drug-free patients and 20 treatment refractory patients on stable regimens of antidepressant medication). The three rating scales included global self-ratings administered twice a day; an itemized, prospective, observer-rated scale administered twice a day; and the retrospective item on the Hamilton Depression Rating Scale. Z scores and Intraclass Correlation Coefficients demonstrated a poor level of agreement between the itemized, prospective scale and the self-ratings. In addition, stepwise multiple regression analysis and point bi-serial correlation showed no systematic relationship between atypical diurnal variation (i.e., mood worsening in the evening) and atypical depressive symptoms (weight gain, hypersomnia, etc.), or between typical diurnal variation (i.e., mood worsening in the morning) and typical depressive symptoms (weight loss, insomnia, etc.). This lack of relationship was observed in both drug-free and medicated patients using each of the three rating scales. We discuss possible explanations for these negative findings.     

Diurnal variations of mood in depressed patients in relation to severity of depression

This study investigates the relationship between the severity of the depressive syndrome and the occurrence of diurnal mood variation. Several authors have proposed that diurnal variations of mood cease in the severest states of depression. By contrast, others suggest a rhythm-inducing effect of depression. We could not find any correlation between the severity of depression and various measures of diurnal mood variation in a group of 70 patients. These findings are discussed against the background of chronobiological hypotheses.     

Optimism,positive affectivity,and salivary cortisol

Objectives. Research on stress and salivary cortisol has focused almost exclusively on the effects of negative psychological conditions or emotional states. Little attention has been drawn to the impact associated with positive psychological conditions, which have been shown recently to have significant influences on neuroendocrine regulation. The aim of this study is to examine the impact of optimism and positive affect on salivary cortisol with the effects of their negative counterparts controlled for. Design. Optimism and pessimism, and positive and negative affectivity were studied in relation to the diurnal rhythm of salivary cortisol in a group of 80 Hong Kong Chinese, who provided six saliva samples over the course of a day on two consecutive days. The separate effects of optimism and positive affect on two dynamic components of cortisol secretion, awakening response, and diurnal decline were examined. Methods. Optimism and pessimism were measured using the Chinese version of the revised Life Orientation Test while generalized affects and mood states were assessed by the Chinese Affect Scale. An enzyme‐linked immunoabsorbent assay kit (EIA) developed for use in saliva was adopted for the biochemical analysis of cortisol. Testing of major group differences associated with positive psychological conditions was carried out using two‐way (group by saliva collection time) ANOVAs for repeated measures with negative psychological conditions and mood states as covariates. Results. Participants having higher optimism scores exhibited less cortisol secretion in the awakening period when the effect of pessimism and mood were controlled. This effect was more apparent in men than in women who had higher cortisol levels in the awakening period. Optimism did not have similar effect on cortisol levels during the underlying period of diurnal decline. On the other hand, higher generalized positive affect was associated with lower cortisol levels during the underlying period of diurnal decline after the effects of negative affect and mood states had been controlled. Generalized positive affect did not significantly influence cortisol secretion during the awakening period. Conclusions. These findings suggest that positive psychological resources including optimism and generalized positive affect had higher impact on cortisol secretion than their negative counterparts, and point to the need for increased attention to the potential contribution of positive mental states to well‐being.     

The treatment of early-morning awakening insomnia with 2 evenings of bright light

STUDY OBJECTIVE: To assess the effectiveness of brief bright-light therapy for the treatment of early-morning awakening insomnia. PARTICIPANTS: Twenty-four healthy adults with early-morning awakening insomnia were assigned to either the bright-light condition (2,500-lux white light) or the control (dim red light) condition. MEASUREMENTS AND RESULTS: The circadian phase of rectal temperature and urinary melatonin rhythms were assessed with 26-hour constant routines before and after 2 evenings of light therapy. Sleep and daytime functioning were monitored using sleep diaries, activity monitors, and mood scales before light therapy and for 4 weeks during the follow-up period. While there were no significant circadian phase changes in the dim-light control group, the bright-light group had significant 2-hour phase delays of circadian temperature and melatonin rhythm. Compared to pretreatment measures, over the 4-week follow-up period, the bright-light group had a greater reduction of time awake after sleep onset, showed a trend toward waking later, and had a greater increase of total sleep time. Participants in the bright-light condition also tended to report greater reductions of negative daytime symptoms, including significantly fewer days of feeling depressed at the 4-week follow-up, as compared with the control group. CONCLUSION: Two evenings of bright-light exposure phase delayed the circadian rhythms of early-morning awakening insomniacs. It also improved diary and actigraphy sleep measures and improved some indexes of daytime functioning for up to 1 month after light exposure. The study suggests that a brief course of evening bright-light therapy can be an effective treatment for early-morning awakening insomniacs who have relatively phase advanced circadian rhythms.     

Circadian rhythms of early morning awakening insomniacs

SUMMARY It has been suggested that two types of insomnia, sleep onset insomnia and early morning awakening insomnia, may be caused by delays and advances respectively of circadian rhythms. Evidence supports the circadian rhythm phase delay of sleep onset insomniacs. The present study investigated the phase timing of circadian rhythms of early morning awakening insomniacs compared with a group of age matched good sleepers. A 24-h bed rest laboratory session was used to evaluate the endogenous core body temperature and urinary melatonin rhythms. Objective and subjective sleepiness were also measured every 30 min across the session with 10 min multiple sleep latency tests and Stanford Sleepiness Scale. Maximum and minimum phases of each individual's rhythm were identified using two-component cosine curve fitting. Compared with the good sleepers, the insomniacs had significant phase advances of 2 4 h for the temperature and melatonin rhythms. However, the 0-4 h advances of the sleepiness rhythms were not significant. This latter unexpected result was explained on the basis of variability of sleepiness measures. It was suggested that early morning awakening insomnia arises from phase advanced circadian rhythms which evoke early arousal's from sleep.     

Diurnal courses of cortisol, pain, fatigue, negative mood, and stiffness in patients with recently diagnosed rheumatoid arthritis

To investigate the diurnal courses of cortisol and the daytime states: pain, fatigue, negative mood, and stiffness of patients with rheumatoid arthritis, as well as the association between the cortisol and state courses, 9 repeated measurementson 2consecutive days were taken in the real-life environment of 25 recently diagnosed patients (19 women, 6 men; mean age 55.2 years) and 28 healthy controls (20 women, 8 men; mean age 55.8 years). Patients showed a highly characteristic diurnal course of cortisol (F_{8, 15} = 7.4, p < .001) and a significant diurnal fatigue (F_{7, 18} = 2.6, p < .05) and early morning stiffness course (F3, 22 = 6.2, p < .01), but the temporal association between these courses was low. Daytime states, notably fatigue (r = 0.40, p < .05), were positively correlated with the early morning rise of cortisol and nighttime pain (r ≥ 0.53, p < .01) but not with cortisol level or inflammatory activity. Cortisol level and inflammatory activity were positively correlated (r = 0.47, p < .05). These results suggest that in patients with rheumatoid arthritis, cortisol has a strong endogenous rhythm that is not disturbed by inflammatory activity. It appears that diurnal fluctuations in fatigue and stiffness are independent of the circadian rhythm of cortisol or inflammatory activity, but rather reflect temporal changes as a consequence of sleep, rest, and physical activity throughout the day.     

Sleep inertia,sleep homeostatic and circadian influences on higher‐order cognitive functions

Sleep inertia, sleep homeostatic and circadian processes modulate cognition, including reaction time, memory, mood and alertness. How these processes influence higher‐order cognitive functions is not well known. Six participants completed a 73‐day‐long study that included two 14‐day‐long 28‐h forced desynchrony protocols to examine separate and interacting influences of sleep inertia, sleep homeostasis and circadian phase on higher‐order cognitive functions of inhibitory control and selective visual attention. Cognitive performance for most measures was impaired immediately after scheduled awakening and improved during the first ~2–4 h of wakefulness (decreasing sleep inertia); worsened thereafter until scheduled bedtime (increasing sleep homeostasis); and was worst at ~60° and best at ~240° (circadian modulation, with worst and best phases corresponding to ~09:00 and ~21:00 hours, respectively, in individuals with a habitual wake time of 07:00 hours). The relative influences of sleep inertia, sleep homeostasis and circadian phase depended on the specific higher‐order cognitive function task examined. Inhibitory control appeared to be modulated most strongly by circadian phase, whereas selective visual attention for a spatial‐configuration search task was modulated most strongly by sleep inertia. These findings demonstrate that some higher‐order cognitive processes are differentially sensitive to different sleep–wake regulatory processes. Differential modulation of cognitive functions by different sleep–wake regulatory processes has important implications for understanding mechanisms contributing to performance impairments during adverse circadian phases, sleep deprivation and/or upon awakening from sleep.     

Diurnal variation of visual field size in patients with postretinal lesions

Summary Perimetry at various times of day in patients with large visual field defects due to postretinal lesions showed significant variations of visual field size. The largest visual fields were observed at noon, the smallest in the evening. Such systematic variations were observed only in patients who showed a gradual increase of increment threshold between the intact parts of the visual field and the scotoma. In two patients who showed an abrupt transition between intact and blind areas of the visual field, no obvious diurnal variation was observed. It is suggested that an endogenous modulation of neuronal sensitivity coupled to a hypothetical circadian oscillator is the basis of the diurnal variation.     

Altered circadian rhythms in rheumatoid arthritis patients play a role in the disease's symptoms

The circadian changes in the metabolism or nocturnal secretion of endogenous corticosteroids (reduction) observed in rheumatoid arthritis (RA) patients are responsible, in part, for the time-dependent changes that are observed in the inflammatory response and related early morning clinical symptoms of the disease. Melatonin (MLT), another circadian nocturnal hormone that is the secretory product of the pineal gland, has been implicated in the time-dependent RA inflammatory reaction with effects that are opposite to those of corticosteroids. As a consequence, altered functioning of the HPA axis (early morning reduced corticosteroid production) and of the pineal gland (night increased MLT production) found in RA patients, seem to be important factors in the appearance and perpetuation of the clinical circadian symptoms of the disease. Consistently, human proinflammatory Th1-type cytokine production (related to MLT stimulation) exhibits a diurnal rhythmicity with peak levels during the night and early morning, at a time when plasma cortisol (inducing the Th2-type cytokine production) is lowest and MLT is highest. Reduced daily light exposure as observed in northern Europe (Estonia), at least during the winter, might explain the higher and more prolonged serum MLT concentrations that were observed in northern RA patients, as well as some epidemiological features versus southern Europe patients.     

Alertness, mood and performance rhythm disturbances associated with circadian sleep disorders in the blind

Blind people report disturbances in alertness, mood and performance. In laboratory studies, these waking functions can only be maintained when the wake-dependent deterioration is opposed by appropriately-timed endogenous circadian rhythms. We aimed to quantify whether variations in waking function experienced by blind people living in society were dependent on the phase relationship between the sleep-wake cycle and the circadian pacemaker. The time course of alertness, mood and performance was assessed in 52 blind subjects with and without circadian rhythm disorders every 2 h for 2 days per week for 4 weeks. Sleep-wake timing and circadian phase were assessed from diaries and weekly measurements of urinary 6-sulphatoxymelatonin rhythms, respectively. In those subjects who woke at either a normal circadian phase (n = 26) or abnormally early (n = 5), alertness, mood and performance deteriorated significantly with increased time awake (P < 0.05). In 17 non-entrained ('free-running') subjects, waking function varied significantly with circadian phase such that subjects rated themselves most sleepy (P = 0.03) and most miserable (P = 0.02) when they were awake during the time of peak melatonin production. The internal phase relationship between sleep-wake behaviour and the circadian melatonin rhythm in entrained subjects contributed to predictable differences in the daily profile of alertness, mood and performance. Disruption of this phase relationship in non-entrained blind individuals with circadian rhythm sleep disorders resulted in impaired waking function during the day equivalent to that usually only experienced when awake during the night. Treatment for circadian rhythm disorders should be targeted in normalizing these phase relationships.     

Loss of the circadian variation of platelet [3H]imipramine binding in delusional compared with non-delusional endogenously depressed patients

BACKGROUND: The circadian variations of the serotonin reuptake sites were studied in 16 patients meeting DSM-IV criteria for major depression with melancholia, either with (n=8) or without (n=8) psychotic symptomatology. METHOD: The [3H]imipramine binding sites were measured in platelet samples. RESULTS: While no statistically significant difference was found between the morning (09:00 h) and evening (21:00 h) [3H]imipramine B(max) values in the control group, both the non-delusional and delusional melancholic patients showed higher evening than morning B(max) values, which were only statistically significant in the former. When both diagnostic groups were compared, the delusional patients showed significantly lower [3H]imipramine binding values than the non-delusional patients both in the morning and evening samples. Within the non-delusional depressed patients, those individuals with mood circadian variation, assessed by the 18th item of the HDRS, showed significantly lower B(max) values than those without mood variation. Lowest morning and evening B(max) values were noted in the delusional depressed group without mood variations. CONCLUSIONS: These results suggest that delusional depressions might have a different neurobiological substrate with loss of chronobiological rhythms.     

Level of glucocorticoid hormones in early postnatal ontogenesis and circadian rhythms of endocrine-metabolic functions in adult rats

The disturbance of the glucocorticoid balance in early postnatal ontogenesis (17–19 days) as the result of prednisolone administration has been shown to lead to partial suppression of circadian adrenocortical activity in adult rats. The circadian rhythm of FFA in these groups of animals was not detectable and the circadian acrophase of blood glucose concentration changed, while diurnal urine periodicity remained unchanged. The diurnal rhythm of locomotor activity in prednisolone-pretreated rats was characterized by a later onset of increase in its activity and a shorter duration.Translated from Problemy Éndokrinologii, Vol. 34, No. 5, pp. 56–59, September–October, 1988.     

Circadian variation in salivary testosterone across age classes in Ache Amerindian males of Paraguay

Testosterone levels exhibit a circadian rhythm in healthy men, with morning levels tending to be higher compared to evening titers. However, circadian rhythms wane with age. Although this has been described in males living within industrialized settings, age‐related changes have not received similar attention in populations outside these contexts. Because many nonindustrialized populations, such as Ache Amerindians of Paraguay, exhibit testosterone levels that are lower than what is commonly reported in the clinical literature and lack age‐associated variation in testosterone, it was hypothesized that Ache men would not show age‐related variation in testosterone circadian rhythms. Diurnal rhythmicity in testosterone within and between Ache men in association with age (n = 52; age range, 18–64) was therefore examined. A significant negative association was evident between the ratio of morning and evening salivary testosterone and age (r = ?0.28, P = 0.04). Men in their third decade of life exhibited significant diurnal variation (P = 0.0003), whereas older and younger age classes did not. Men between the ages of 30 and 39 also exhibited a higher AM:PM testosterone ratio compared to 40–49 and 50< year old men (P = 0.002, 0.006). Overall, declines in testosterone with aging may not be universal among human males, however, within‐individual analyses of diurnal variation capture age‐related contrasts in daily testosterone fluctuations. Circadian rhythmicity differs with age among the Ache and may be a common aspect of reproductive senescence among men regardless of ecological context. Am. J. Hum. Biol., 2010. © 2009 Wiley‐Liss, Inc.     

Behavioral and psychophysiological correlates of irregularity in chronic sleep routines.

Behavioral and psychophysiological correlates of irregularity in chronic sleep routines were studied. Two groups each of 18 healthy male university students were classified as either irregular sleepers or control subjects according to retrospective questionnaires, and sleep chart criteria. The control group was composed of persons who slept naturally from 12-8:00 a.m. for 7-8 hr. Irregular sleepers were defined as those whose retiring and awakening times varied by about 2-4 hr. Measurements were obtained from an auditory reaction time task, a mood adjective check list, of sublingual temperature and pulse rate 30 min. after awakening in the (a) morning, at (b) noon, in the (c) afternoon and (d) early evening following an electroencephalographically recorded 12-8:00 a.m. sleep night. At various points in the diurnal cycle irregular sleepers compared with the control group had significantly lower levels of pulse rate and body temperature, but significantly longer reaction times. During the four time periods negative affects (deactivation-sleep, depression, general deactivation, inert-fatigued) were significantly greater and positive mood states (cheerful, energetic, general activation--significantly less in the irregular sleepers. The irregular sleepers averaged significantly less stage 4, and REM, but more stage 2 and transitions between sleep stages. The present results indicate that relatively lowered levels of physiological arousal indexes, psychomotor performance and subjective mood are associated with irregularity in chronic sleep routines of young adult males. These psychobehavioral correlates of chronically maintained sleep pattern variations complement and extend previous findings on degradations in waking functions following acute 2-4 hr temporal shifts of habitual sleep periods. It is postulated that there were psychobehavioral deficits in the irregular sleepers attributable either to selective sleep stage (REM and/or stage 4) deprivation or to the more general consequence of disturbed sleeping patterns per se or to both of these factors.     

The circadian patterns of spontaneous seminal emission, sexual activity and penile reflexes in the rat

Spontaneous seminal emission (SSE) by sexually naive and experienced rats occurred almost exclusively in the light period of a 14:10 LD cycle. The circadian pattern of SSE slowly shifted following an LD reversal and was completely reversed by three weeks. The diurnal variation in parameters of sexual activity which are associated with sexual arousal shifted much more readily such that it was reversed within one week of the LD reversal. In contract, parameters of sexual behavior which are associated with the ejaculatory mechanism were altered following the LD shift with a phase-shifting pattern more similar to that exhibited for SSE, such that the diurnal variation seen before the LD shift was not reestablished until the third week after the shift. The characteristic pattern of SSE in 14:10 LD lighting was disrupted with two weeks of a shift to constant illumination, but the number and weight of spontaneously produced plugs did not change. Finally, there were no differences in any component of the display of penile reflexes by 29 rats tested in the dark period compared to 19 rats tested in the light period, despite significant circadian variation in the copulatory activity of these animals.