Diurnal Mood Research Articles

Daily Associations Between Presenteeism and Health-Related Factors Among Office Workers: An Ecological Momentary Assessment Approach.

The study examined daily associations between presenteeism and health-related factors among office workers using ecological momentary assessment (EMA). Diurnal mood and physical symptoms were repeatedly recorded over 2 weeks with EMA. Daily work performance (WP) was also recorded. Recalled WP and baseline health conditions were assessed via questionnaires. Daily sleep was assessed using actigraphy. Reliability between recalled and daily WP was compared. Hierarchical linear modeling (HLM) was used to analyze the effects of sleep, mood, and physical symptoms on daily WP. Weak yet significant agreement was found between recalled and daily WP, with EMA capturing occasional declines in performance overlooked by recalled assessments. HLM indicated that longer sleep, reduced depressive mood, and decreased shoulder stiffness were significantly associated with increased daily WP. These factors are associated with daily fluctuations in presenteeism, suggesting potential targets of intervention.

Treatment-emergent symptoms during short-term ketamine administration in treatment-resistant bipolar depression: A retrospective cross-sectional descriptive study

Symptoms that emerge during pharmacological treatment of bipolar depression are frequently observed, underscoring the necessity for comprehensive treatment monitoring. This observational study sought to observe the correlation of eight intravenous ketamine infusions with treatment-emergent depressive symptoms in treatment-resistant bipolar depression patients who maintained their baseline psychotropic and chronic somatic treatments. Depressive symptoms were evaluated using the Inventory of Depressive Symptomatology Self-Report 30 (IDS-SR30). Treatment-emergent symptoms TES were defined as symptoms absent at baseline but present at the conclusion of the study. The most common TES included decreased appetite, increased weight, hypersomnia, and diurnal mood variation. Conversely, feelings of sadness, altered perceptions of the future, decreased interest in sex, and physical discomfort were absent in all patients. Notably, 13.6 % of patients reported thoughts of death or suicide. Larger-scale studies, integrating clinician-rated and patient-reported outcome measures, are essential to deepen our understanding of treatment-emergent symptoms. Establishing regulatory or professional definitions for treatment-emergent symptoms is warranted to improve the robustness of future research endeavors.

Affective and somatic symptom clusters in depression and their relationship to treatment outcomes in the STAR*D sample

BackgroundThe heterogenous nature of depression continues to stymie efforts to identify biomarkers or predict treatment response. Efforts leveraging large datasets to define more uniform subtypes of depression or subgroups of depressed patients have considered only small subsets of symptoms. We aimed to understand how inclusion of more diverse complaints would impact data-emergent symptom and patient clusters. MethodsWe applied principal components analysis to baselineInventory of Depressive Symptomatology data from 1491 patients with major depressive disorder to derive naturally co-occurring symptom subsets before utilizing k-means clustering to divide patients into groups based on standardized residuals of each symptom subset score. We evaluated the clinical utility of our approach by comparing how cluster membership impacted response to citalopram. ResultsPrinicpal components analysis identified nine naturally co-occurring symptom subsets: core affective symptoms, appetite/weight loss, anxiety, somatic symptoms, insomnia, negative intrusive thoughts, leaden paralysis/mood quality, diurnal mood variation, and irritability. Cluster analysis identified two patient groups, differing significantly in 7 of 9 c symptom subsets. Patients distinguished by the prominence of somatic versus core affective symptoms exhibited less reduction in depression severity with citalopram treatment. LimitationsResults depend not only on raw data, but also parameter selection, and interpretation. Replication is indicated. ConclusionsFindings are consistent with previous reports linking somatic symptoms to treatment resistance and demonstrating that SSRIs are most effective in treating affective symptoms. A novel distinction between physical somatic symptoms and psychic anxiety highlights the utility of assessing a broad spectrum of symptoms when exploring heterogeneity in depression and the need for treatments targeting physical somatic symptoms specifically.

Circadian preference and sleep quality in healthy controls and psychiatric inpatients with major depressive disorder – An actigraphy study incorporating morning and evening mood assessments

ABSTRACT Major depressive disorder (MDD) is frequently accompanied by sleep disturbance. Regarding diurnal preference (chronotype), sleep problems and low mood have been associated with evening orientation. Considering diurnal preference, we investigated subjective restorative value of sleep and actigraphy sleep parameters together with mood assessments twice a day, i.e. in the morning and evening, during weekdays and weekends in MDD psychiatric inpatients and healthy controls (HCs). The restorative value of sleep was higher during the weekend in HC, and bedtimes and risetimes were delayed during the weekend compared to weekdays in HC and MDD. Morning mood affected subjective sleep ratings in both groups, while association with symptom severity (BDI) in MDD remained insignificant. In HC, better evening mood was associated with later bedtimes. Regarding the chronotype in HC, evening orientation was associated with relatively low restorative value of sleep during weekdays, and morning orientation was associated with relatively higher actigraphy sleep efficiency during weekdays compared to weekend. In MDD, an association of evening orientation with later rise times could be observed, while no chronotype dependent effect emerged regarding the restorative value of sleep or sleep efficiency. Our results emphasize that research on sleep in MDD should incorporate weekdays as well as weekends, chronotype assessment, and measures of morning and evening mood, as these can be associated with ratings of the subjective restorative value of sleep (i.e. in our study, better morning mood was associated with higher restorative values), but also with behavioral sleep parameters (i.e. in our study, more positive evening mood was associated with later bedtimes). Potentially, the restorative value of sleep in MDD evening types can be improved by maintaining a regular sleep schedule, which needs to be investigated in an experimental design.

Diurnal mood variation symptoms in major depressive disorder associated with evening chronotype: Evidence from a neuroimaging study

BackgroundMajor depressive disorder (MDD) is often accompanied with classic diurnal mood variation (DMV) symptoms. Patients with DMV symptoms feel a mood improvement and prefer activities at dusk or in the evening, which is consistent with the evening chronotype. Their neural alterations are unclear. In this study, we aimed to explore the neuropathological mechanisms underlying the circadian rhythm of mood and the association with chronotype in MDD. MethodsA total of 126 depressed patients, including 48 with DMV, 78 without, and 67 age/gender-matched healthy controls (HC) were recruited and underwent a resting-state functional magnetic resonance imaging. Spontaneous neural activity was investigated using amplitude of low-frequency fluctuation (ALFF) and region of interest (ROI)-based functional connectivity (FC) analyses were conducted. The Morningness-Eveningness Questionnaire (MEQ) was utilized to evaluate participant chronotypes and Pearson correlations were calculated between altered ALFF/FC values and MEQ scores in patients with MDD. ResultsCompared with NMV, DMV group exhibited lower MEQ scores, and increased ALFF values in the right orbital superior frontal gyrus (oSFG). We observed that increased FC between the left suprachiasmatic nucleus (SCN) and supramarginal gyrus (SMG). ALFF in the oSFG and FC of rSCN-SMG were negatively correlated with MEQ scores. LimitationSome people's chronotypes information is missing. ConclusionPatients with DMV tended to be evening type and exhibited abnormal brain functions in frontal lobes. The synergistic changes between frontotemporal lobe, SCN-SMG maybe the characteristic of patients with DMV symptoms.

Difference in the regulation of biological rhythm symptoms of Major depressive disorder between escitalopram and mirtazapine

BackgroundBiological rhythm plays an important role in major depressive disorder (MDD). The efficacy of antidepressant in biological rhythm remains unclear. This study is designed to explore the efficiency of escitalopram and mirtazapine in improving circadian rhythm, diurnal mood variation(DMV) and daily activity in MDD patients. MethodsFour-hundred and fifty participants diagnosed with MDD were randomized to receive treatment with escitalopram (TWE), treatment with mirtazapine (TWM) or treatment as usual (TAU). Biological rhythm symptoms were assessed by relevant biological subscale in the Hamilton depression scale (HAMD) and the quick inventory of depressive symptomatology self-report (QIDS). The participants were assessed by trained evaluators at baseline and week 2, 4, 6 and 8. ResultsThe differences of HAMD score among TWE(58%, 69%, 72%), TWM(56%, 64%, 76%) and TAU(49%, 57%, 68%) were significant(P<0.05). But the differences were significant only in patients without DMV; (2) Sleep rhythm items (difficulty falling asleep and early-wake) were significantly improved in TWM (P <0 .05) for both HAMD and QIDS. Decreased appetite and weight were significantly improved in TWM (P<0 .05) for both scales. (3) For daily activity-related items, feeling slowed down and concentration were significantly improved in TWE. And the retardation was significantly improved in TWE and in TWM. ConclusionsBoth escitalopram and mirtazapine have superior anti-depressive effect, especially for MDD patients without DMV. Escitalopram was significantly more effective in daily activity, feeling slowed down and concentration difficulty, while mirtazapine was significantly more effective in improving sleep, appetite and weight of MDD.

Seasonal variation in neurohormones, mood and sleep in patients with primary open angle glaucoma – implications of the ipRGC-system

ABSTRACT Primary open angle glaucoma is associated with an increased risk of mood and sleep disorders. These adversities have been suggested to relate to a disrupted function of the intrinsically photosensitive retinal ganglion cells (ipRGCs). The ipRGCs are key components in the nonvisual photoreceptive system that mediates light effects on mood, sleep and circadian rhythm. We assessed the diurnal hormone levels, pupillary responses and mood and sleep under seasons with different photoperiods in 24 patients with glaucoma and 24 age- and sex-matched healthy controls to investigate responses to naturalistic seasonal changes in daylight. The patients had moderate-to-advanced glaucoma with substantial visual field defects and reductions in the ipRGC-mediated pupillary responses (p < .001). In winter, compared with summer, patients with glaucoma had higher daytime melatonin concentration (p < .001) and lower nighttime cortisol (p = .002). In winter, the daytime melatonin level was inversely correlated with the ipRGC-mediated pupillary responses in the control group (p = .04). In the control group, there were no significant changes in hormone levels between seasons or any correlations between neurohormone levels and the ipRGC-mediated responses. The two groups showed a similar response to season with lower depression scores in summer compared with winter. In between-group comparison, the nocturnal melatonin level (area under curve from 20:00 h to 08:00 h) in summer was lower in glaucoma compared with controls (p = .03). In winter, nocturnal cortisol (at 04:00 h) was lower (p = .004) and daytime cortisol (12:00 h and 16:00 h) was higher (p = .007) in glaucoma compared with controls. In conclusion, we found that patients with glaucoma displayed a seasonal variation in diurnal hormone levels that was not present in healthy controls. Such neurohormonal changes may contribute to the increased risk of mood and sleep disorders seen in patients with glaucoma.

Aberrant functional connectivity between the suprachiasmatic nucleus and the superior temporal gyrus: Bridging RORA gene polymorphism with diurnal mood variation in major depressive disorder

Diurnal mood variation (DMV), a common symptom of major depressive disorder (MDD), is associated with circadian related genes and dysregulation of the suprachiasmatic nucleus (SCN). Previous research confirmed that the RORA gene is involved in the regulation of circadian rhythms. In this study, we hypothesized that polymorphisms of RORA may affect DMV symptoms of MDD through functional changes in the SCN. A total of 208 patients diagnosed with depression and 120 control subjects were enrolled and underwent a resting-state functional magnetic resonance imaging (rs-fMRI). Blood samples were collected and genotyping of 9 RORA gene SNPs were performed using next-generation sequencing technology. Patients were categorized as an AA genotype or C allele carriers based on RORA rs72752802 polymorphism. SCN-seed functional connectivity (FC) was compared between the two groups and correlation with severity of DMV was analyzed. Finally, a mediation analysis was performed to further determine FC intermediary effects. We observed that rs72752802 was significantly associated with patients’ DMV symptoms. C allele carriers of rs72752802 showed significantly decreased FC between the right SCN and right superior temporal gyrus (rSTG). This was also correlated with DMV symptoms. In addition, the rs72752802 SNP influenced DMV symptoms through intermediary effects of SCN-rSTG connectivity. The study presented here provides a neurological and genetic basis for understanding depressed patients experiencing DMV.

The therapeutic effect of repetitive transcranial magnetic stimulation in elderly depression patients.

Background:Depression, a common psychiatric disorder in elderly, serves as a remarkable precipitating factor for suicide among the elderly people. Here, a randomized double-blinded study was performed to investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) on improving the clinical symptoms and reducing suicidal ideation in elderly patients with depression.Methods:In this study, 103 elderly patients with depression and suicidal ideation were randomly divided into 2 groups, 48 cases in the rTMS group and 55 cases in the control group (sham rTMS). Both groups received routine drug therapy with rTMS or sham rTMS. The patients received evaluation by Hamilton depression scale and self-rating idea of suicide scale before treatment and after 2 and 4 weeks of treatment, respectively.Results:The measurement from the present study demonstrated that Hamilton depression scale and self-rating idea of suicide scale scores decreased to varying degrees in the 2 groups after treatment, and the decrease was more significant in rTMS group. The rate of marked effectiveness was much higher in rTMS group after 2 weeks of treatment compared with the control group. Furthermore, the rate of moderate effectiveness at 4 weeks after treatment was significantly higher in rTMS group compared with the control group.Conclusion:Together, the present study shows that rTMS with routine drug therapy exhibited effect with quick onset to improve the clinical symptoms and reduce suicidal ideation in elderly patients with depression.

Molecular basis for the association between depression and circadian rhythm.

Depression is a life-threatening psychiatric disorder and a major public health concern worldwide with an incidence of 5% and a lifetime prevalence of 15%–20%. It is related with the social disability, decreased quality of life, and a high incidence of suicide. Along with increased depressive cases, health care cost in treating patients suffering from depression has also surged. Previous evidence have reported that depressed patients often exhibit altered circadian rhythms. Circadian rhythm involves physical, mental, and behavioral changes in a daily cycle, and is controlled by the suprachiasmatic nucleus of the hypothalamus in responding to light and darkness in an environment. Circadian rhythm disturbance in depressive patients causes early morning waking, sleep disturbances, diurnal mood variation, changes of the mean core temperature, endocrine release, and metabolic functions. Many medical interventions have been used to treat depression; however, several adverse effects are noted. This article reviews the types, causes of depression, mechanism of circadian rhythm, and the relationship between circadian rhythm disturbance with depression. Pharmaceutical and alternative interventions used to treat depressed patients are also discussed.

Overnight worsening of emotional distress indicates maladaptive sleep in insomnia.

Mechanisms underlying the distress of hyperarousal in people with insomnia remain enigmatic. We investigated whether insomnia impedes the overnight adaptation to emotional distress. We induced the distressful self-conscious emotion of shame four times across three consecutive days by exposing 64 participants to their often embarrassingly out-of-tune singing, recorded earlier during a Karaoke session. Perceived physical, emotional, and social distress was assessed with the Experiential Shame Scale. Compared to exposures followed by wakefulness, exposures followed by sleep resulted in overnight relief of physical component of shame in normal sleepers, but in a striking opposite overnight worsening in people with insomnia. Our findings are the first to experimentally show that the benefits of sleep are not only lost when sleep is poor; people with insomnia experience a maladaptive type of sleep that actually aggravates physically perceived distress. Maladaptive sleep could shed new light on posttraumatic stress disorder (PTSD) and on diurnal mood fluctuation and the counterintuitive favorable effects of sleep deprivation in depression.

Longitudinal association between inflammatory markers and specific symptoms of depression in a prospective birth cohort

BackgroundLow-grade inflammation is associated with depression, but studies of specific symptoms are relatively scarce. Association between inflammatory markers and specific symptoms may provide insights into potential mechanism of inflammation-related depression. Using longitudinal data, we have tested whether childhood serum interleukin 6 (IL-6) and C-reactive protein (CRP) levels are associated with specific depressive symptoms in early adulthood. MethodsIn the ALSPAC birth cohort, serum IL-6 and CRP levels were assessed at age 9 years and 19 depressive symptoms were assessed at age 18 years. We used modified Poisson generalised linear regression with robust error variance to estimate the risk ratio (RR) and 95% confidence interval (95% CI) for each depressive symptom. In addition, we used confirmatory factor analysis to create two continuous latent variables representing somatic/neurovegetative and psychological dimension scores. Structural equation modelling was used to test the associations between IL-6 and these dimension scores. ResultsBased on data from 2731 participants, IL-6 was associated with diurnal mood variation, concentration difficulties, fatigue and sleep disturbances. The adjusted RRs for these symptoms at age 18 years for participants in top, compared with bottom, third of IL-6 at age 9 years were 1.75 (95% CI, 1.13–2.69) for diurnal mood variation, 1.50 (95% CI, 1.11–2.02) for concentration difficulties, 1.31 (95% CI, 1.12–1.54) for fatigue, and 1.24 (95% CI, 1.01–1.52) for sleep disturbances. At dimension level, IL-6 was associated with both somatic/neurovegetative (β = 0.059, SE = 0.024, P = 0.013) and psychological (β = 0.056, SE = 0.023, P = 0.016) scores. ConclusionsInflammation is associated with specific symptoms of depression. Associations with so-called somatic/neurovegetative symptoms of depression such as fatigue, sleep disturbances and diurnal mood variation indicate that these symptoms could be useful treatment targets and markers of treatment response in clinical trials of anti-inflammatory treatment for depression.

Diurnal Variations of Depression-Related Health Information Seeking: Case Study in Finland Using Google Trends Data.

BackgroundSome of the temporal variations and clock-like rhythms that govern several different health-related behaviors can be traced in near real-time with the help of search engine data. This is especially useful when studying phenomena where little or no traditional data exist. One specific area where traditional data are incomplete is the study of diurnal mood variations, or daily changes in individuals’ overall mood state in relation to depression-like symptoms.ObjectiveThe objective of this exploratory study was to analyze diurnal variations for interest in depression on the Web to discover hourly patterns of depression interest and help seeking.MethodsHourly query volume data for 6 depression-related queries in Finland were downloaded from Google Trends in March 2017. A continuous wavelet transform (CWT) was applied to the hourly data to focus on the diurnal variation. Longer term trends and noise were also eliminated from the data to extract the diurnal variation for each query term. An analysis of variance was conducted to determine the statistical differences between the distributions of each hour. Data were also trichotomized and analyzed in 3 time blocks to make comparisons between different time periods during the day.ResultsSearch volumes for all depression-related query terms showed a unimodal regular pattern during the 24 hours of the day. All queries feature clear peaks during the nighttime hours around 11 PM to 4 AM and troughs between 5 AM and 10 PM. In the means of the CWT-reconstructed data, the differences in nighttime and daytime interest are evident, with a difference of 37.3 percentage points (pp) for the term “Depression,” 33.5 pp for “Masennustesti,” 30.6 pp for “Masennus,” 12.8 pp for “Depression test,” 12.0 pp for “Masennus testi,” and 11.8 pp for “Masennus oireet.” The trichotomization showed peaks in the first time block (00.00 AM-7.59 AM) for all 6 terms. The search volumes then decreased significantly during the second time block (8.00 AM-3.59 PM) for the terms “Masennus oireet” (P<.001), “Masennus” (P=.001), “Depression” (P=.005), and “Depression test” (P=.004). Higher search volumes for the terms “Masennus” (P=.14), “Masennustesti” (P=.07), and “Depression test” (P=.10) were present between the second and third time blocks.ConclusionsHelp seeking for depression has clear diurnal patterns, with significant rise in depression-related query volumes toward the evening and night. Thus, search engine query data support the notion of the evening-worse pattern in diurnal mood variation. Information on the timely nature of depression-related interest on an hourly level could improve the chances for early intervention, which is beneficial for positive health outcomes.

Chronotype influences response to antidepressant chronotherapeutics in bipolar patients

ABSTRACTPatient diurnal mood fluctuation, sleep characteristics and factors affecting sleep homeostasis predict antidepressant response to the combination of total sleep deprivation and light therapy (TSD + LT). In order to study if chronotype could influence response to TSD+LT, we considered 194 bipolar depressed patients. Severity of depression was rated with Hamilton Depression Rating Scale; perceived mood levels were assessed by a self-administered 10-cm visual analogue scale and chronotype was assessed using the Mornigness-Eveningness Questionnaire.More than 60% of patients resulted responders to treatment with chronotype influencing the antidepressant response with evening type subjects showing higher response rates.

Application of Empirical Mode Decomposition to Mother and Infant Physical Activity.

The mutual dependencies between mother and infant circadian rhythms are important for examining disturbances of maternal circadian rhythms, which are considered substantial risk factors for the development of maternal depression during childrearing periods. We characterized the mutual dependencies of maternal-infant circadian rhythms by an index of synchronization properties and then tested the hypothesis that such an index, specifically the instantaneous phase differences between their rhythms, is associated with maternal mental health. We performed longitudinal recordings of maternal symptoms of fatigue, stress, and mood states by ecological momentary assessment, together with simultaneous measurements of mother and infant physical activity data in daily life, on 20 mother-infant pairs for a period of >1 week. The circadian components in their physical activity data were extracted by ensembled bivariate empirical mode decomposition, and the corresponding instantaneous phases were then obtained based on the Hilbert transformation. The associations between diurnal maternal symptoms and absolute phase differences between mother and infant circadian rhythms were tested by multilevel models. Diurnal fatigue and depressive mood scores showed positive and significant correlations (p < 0.05) with the increase in instantaneous mother-infant phase differences, indicating the significant role of synchronization of mother-infant circadian rhythms for maintaining maternal mental health. These findings suggest that modifications of maternal and/or infant circadian rhythms may lead to the improvement of maternal mental health during child-rearing periods.

Subjective Mood in Young Unmedicated Depressed Women under High and Low Sleep Pressure Conditions.

Diurnal mood variations are one of the core symptoms in depression, and total sleep deprivation (SD) can induce rapid, short-lasting clinical improvement in depressed patients. Here, we investigated if differential sleep pressure conditions impact on subjective mood levels in young women with major depressive disorder (MDD) without sleep disturbances, and in healthy controls. Eight healthy and eight MDD women underwent 40-h SD (high sleep pressure) and 40-h multiple NAP (low sleep pressure) protocols under constant routine conditions during which subjective mood was assessed every 30-min. MDD women rated overall significantly worse mood than controls, with minimal values for both groups during the biological night (ca. 4 a.m.), under high and low sleep pressure conditions. During SD, nighttime mood ratings in MDD women were lower than in controls and partially recovered during the second day of SD, but never attained control levels. The degree of this diurnal time-course in mood under SD correlated positively with sleep quality in MDD women. Our data indicate that MDD women without sleep disturbances did not exhibit a SD-induced antidepressant response, suggesting that the mood enhancement response to sleep deprivation might be related to the co-existence of sleep disturbances, which is an association that remains to be fully established.

CHRONOTYPE ASSOCIATIONS WITH DEPRESSION AND ANXIETY DISORDERS IN A LARGE COHORT STUDY.

The chronotype, being a morning or an evening type, can influence an individual's psychological health. Studies have shown a link between depressed mood and being an evening type; however, most studies have used symptom scales and not diagnostic criteria, and confounding factors such as sleep patterns and somatic health factors have often not been considered. This study aims to examine the association between chronotype and depressive (major depressive disorder (MDD), dysthymia) and anxiety (generalized anxiety disorder, panic disorder, agoraphobia, and social phobia) disorders diagnosed using clinical interviews, while taking into account relevant sociodemographic, clinical, somatic health, and sleep parameters. Data from a large cohort, the Netherlands Study of Depression and Anxiety were used (n = 1,944), which included 676 currently depressed and/or anxious patients, 831 remitted patients, and 437 healthy controls. Chronotype was assessed using the Munich Chronotype Questionnaire. Our results showed that current depressive and/or anxiety disorders were associated with a late chronotype (β = .10, P = .004) even when adjusting for sociodemographic, somatic health, and sleep-related factors (β = .09, P = .03). When examining each type of disorder separately, MDD only, but not dysthymia or specific anxiety disorders, was associated with the late chronotype. The late chronotype also reported significant diurnal mood variation (worse mood in the morning). Our findings show a clear association between MDD and late chronotype (being an evening type), after controlling for a range of pertinent factors. A late chronotype is therefore associated with a current status of MDD and deserves the relevant clinical attention when considering treatments.

Depression: chronophysiology and chronotherapy

Depressed patients often show altered circadian rhythms, sleep disturbances, and diurnal mood variation. Decreased latency of rapid eye movement (REM) sleep, reduction in slow wave sleep, and abnormalities in the timing of REM/nonREM sleep cycles have all been reported in patients with major depressive disorder (MDD). It is thus evident that an understanding of the basic mechanisms of sleep regulation is essential, for a better analysis of the pathophysiology of depressive disorders. The aim of this article is to review progress in understanding the mechanisms that underlie circadian and sleep rhythms, and their role in the treatment of depression. Chronotherapies including, bright light exposure, sleep deprivation, melatonin treatment, and social rhythm therapies, may provide novel insights into the development of new pharmacological and behavioral treatment strategies for mood disorders. The novel antidepressant, agomelatine, which combines the properties of a serotonin 5-HT2C antagonist and a melatonergic MT1/MT2 receptor agonist, has been found to be very effective for resetting the disturbed sleep/wake cycle and improving the clinical status of depressed patients. Agomelatine may fill the gap in the current therapeutic armoury, by combining tolerability profile with efficacy, in treating MDD.

The Melatonergic System in Mood and Anxiety Disorders and the Role of Agomelatine: Implications for Clinical Practice

Melatonin exerts its actions through membrane MT1/MT2 melatonin receptors, which belong to the super family of G-protein-coupled receptors consisting of the typical seven transmembrane domains. MT1 and MT2 receptors are expressed in various tissues of the body either as single ones or together. A growing literature suggests that the melatonergic system may be involved in the pathophysiology of mood and anxiety disorders. In fact, some core symptoms of depression show disturbance of the circadian rhythm in their clinical expression, such as diurnal mood and other symptomatic variation, or are closely linked to circadian system functioning, such as sleep-wake cycle alterations. In addition, alterations have been described in the circadian rhythms of several biological markers in depressed patients. Therefore, there is interest in developing antidepressants that have a chronobiotic effect (i.e., treatment of circadian rhythm disorders). As melatonin produces chronobiotic effects, efforts have been aimed at developing agomelatine, an antidepressant with melatonin agonist activity. The present paper reviews the role of the melatonergic system in the pathophysiology of mood and anxiety disorders and the clinical characteristics of agomelatine. Implications of agomelatine in “real world” clinical practice will be also discussed.

Mood patterns based on momentary assessment of positive and negative moods over a day and coronary artery calcification in the CARDIA study.

Retrospective assessments of negative mood have predicted coronary artery disease development and progression. Using momentary assessment, we evaluated associations between average positive and negative mood states and diurnal mood patterns, with prevalent and incident coronary artery calcification (CAC), a measure of calcified atherosclerosis. In a prospective cohort study of 669 white and African American men and women, aged 33 to 45 years, from the Coronary Artery Risk Development in Young Adults Study, mood was assessed at Year 15 examination, six times over a weekday. Prevalent, progressive, and 5-year incident CAC (any detectable CAC [score >0]) and substantial CAC (CAC score ≥ 20) were assessed at examinations at Years 15 and 20 by electron-beam tomographic scans. We employed a modified Poisson regression approach for binary data with robust error estimation to quantify relative risk. In multivariate-adjusted analyses, those with high-average positive mood that improved over a day had a lower risk of prevalent CAC higher than 0 (relative risk [RR] = 0.17 [95% confidence interval {CI} = 0.04-0.67]) and substantial CAC (RR = 0.25 [95% CI = 0.06-0.95]). In contrast, those with high-average, increasingly negative mood over a day had a higher risk of prevalent CAC (RR = 1.85 [95% CI = 0.86-3.99]) and substantial CAC (RR = 3.11 [95% CI = 1.29-7.49]). Findings were similar for progressive CAC at Year 20. This pattern of high/worsening negative mood (not positive mood) during the day was also predictive of 5-year incident CAC (RR = 2.99 [95% CI = 1.00-8.93]). Diurnal mood patterns were associated with the progression of calcified atherosclerosis, with negative mood predicting greater progression and positive mood predicting lower progression.