Maria Paz Loayza Hidalgo

Circadian typology: a comprehensive review.

The interest in the systematic study of the circadian typology (CT) is relatively recent and has developed rapidly in the two last decades. All the existing data suggest that this individual difference affects our biological and psychological functioning, not only in health, but also in disease. In the present study, we review the current literature concerning the psychometric properties and validity of CT measures as well as individual, environmental and genetic factors that influence the CT. We present a brief overview of the biological markers that are used to define differences between CT groups (sleep–wake cycle, body temperature, cortisol and melatonin), and we assess the implications for CT and adjustment to shiftwork and jet lag. We also review the differences between CT in terms of cognitive abilities, personality traits and the incidence of psychiatric disorders. When necessary, we have emphasized the methodological limitations that exist today and suggested some future avenues of work in order to overcome these. This is a new field of interest to professionals in many different areas (research, labor, academic and clinical), and this review provides a state of the art discussion to allow professionals to integrate chronobiological aspects of human behavior into their daily practice.

Obesity and shift work: chronobiological aspects.

The present review has the objective of summarising chronobiological aspects of shift work and obesity. There was a systematic search in PubMed databases, using the following descriptors: shift work; obesity; biological clock. Shift work is extremely frequent in several services and industries, in order to systematise the needs for flexibility of the workforce, necessary to optimise productivity and business competitiveness. In developing countries, this population represents a considerable contingent workforce. Recently, studies showed that overweight and obesity are more prevalent in shift workers than day workers. In addition, the literature shows that shift workers seem to gain weight more often than those workers submitted to a usual work day. In conclusion, there is considerable epidemiological evidence that shift work is associated with increased risk for obesity, diabetes and CVD, perhaps as a result of physiological maladaptation to chronically sleeping and eating at abnormal circadian times. The impact of shift work on metabolism supports a possible pathway to the development of obesity and its co-morbities. The present review demonstrated the adverse cardiometabolic implications of circadian misalignment, as occurs chronically with shift workers.

Depression Scores Associate With Chronotype and Social Jetlag in a Rural Population

In public health, mood disorders are among the most important mental impairments. Patients with depressive episodes exhibit daily mood variations, abnormal patterns in sleep-wake behavior, and in the daily rhythms of several endocrine-metabolic parameters. Although the relationship between the sleep/circadian processes and mood disorders is poorly understood, clock-related therapies, such as light therapy, sleep deprivation, and rigid sleep schedules, have been shown to be effective treatments. Several studies investigated the relationship between circadian phenotype (chronotype) and depression. These focused mainly on urban populations and assessed diurnal preferences (Morningness-Eveningness score) rather than the actual timing of sleep and activity. Here, we used the Beck Depression Inventory (BDI) in an essentially rural population (N = 4051), and investigated its relation to circadian phenotype (chronotype and social jetlag), assessed with the Munich Chronotype Questionnaire (MCTQ). In our study design, we (i) normalized both chronotype and BDI scores for age and sex (MSFsas and BDIas, respectively); (ii) calculated individual social jetlag (misalignment of the biological and social time); and (iii) investigated the relationship between circadian phenotypes and BDI scores in a population homogeneous in respect to culture, socioeconomic factors, and daily light exposure. A 15.65% (N = 634) of the participants showed mild to severe depressive BDI scores. Late chronotypes had a higher BDIas than intermediate and early types, which was independent of whether or not the participants were smokers. Both chronotype and BDIas correlated positively with social jetlag. BDIas was significantly higher in subjects with >2 h of social jetlag than in the rest of the population—again independent of smoking status. We also compared chronotype and social jetlag distributions between BDI categories (no symptoms, minimal symptoms, and mild to severe symptoms of depression) separately for men and women and for four age groups; specifically in the age group 31–40 yrs, subjects with mild to severe BDI scores were significantly later chronotypes and suffered from higher social jetlag. Our results indicate that misalignment of circadian and social time may be a risk factor for developing depression, especially in 31- to 40-yr-olds. These relationships should be further investigated in longitudinal studies to reveal if reduction of social jetlag should be part of prevention strategies. (Author correspondence: karla.allebrandt@med.uni-muenchen.de)

Relationship between depressive mood and chronotype in healthy subjects.

Aim:  The endogenous circadian clock generates daily variations of physiological and behavior functions such as the endogenous interindividual component (morningness/eveningness preferences). Also, mood disorders are associated with a breakdown in the organization of ultradian rhythm. Therefore, the purpose of the present study was to assessed the association between chronotype and the level of depressive symptoms in a healthy sample population. Furthermore, the components of the depression scale that best discriminate the chronotypes were determined.

Antidepressant-like effects of melatonin in the mouse chronic mild stress model.

Melatonin is a hormone primarily synthesized by the pineal gland and has been shown to govern seasonal and circadian rhythms, as well as the immune system, certain behaviours, and responses to stress. Chronic exposure to stress is involved in the etiology of human depression, and depressed patients present changes in circadian and seasonal rhythms. This study investigated the effects of daily exogenous melatonin (1 and 10 mg/kg, p.o.) and imipramine (20 mg/kg, i.p.) on the changes in the coat state, grooming behaviour and corticosterone levels induced by the unpredictable chronic mild stress model of depression in mice. As expected, the 5 weeks of unpredictable chronic mild stress schedule induced significant degradation of the coat state, decreased grooming and increased serum corticosterone levels. All of these unpredictable chronic mild stress-induced changes were counteracted by melatonin (P<0.05) and imipramine (P<0.01). Especially in view of the relevance of stress as a major contributing factor in depression, as well as the alleged importance of normalizing a hyperfunctioning HPA axis and resynchronizing circadian rhythms for a successful treatment of depression, this study reassesses the potential of melatonin as an antidepressant.

Preoperative Anxiolytic Effect of Melatonin and Clonidine on Postoperative Pain and Morphine Consumption in Patients Undergoing Abdominal Hysterectomy: A Double-Blind, Randomized, Placebo-Controlled Study

UNLABELLED Recent evidence has demonstrated analgesic, anti-inflammatory, and anxiolytic properties of melatonin. Taking into account that higher anxiety makes the control of postoperative pain more difficult, one can hypothesize that melatonin anxiolytic and analgesic effects improve the control of postoperative pain. Thus, we conducted a randomized, double-blind, placebo-controlled study with 59 patients undergoing abdominal hysterectomy to test the hypothesis that melatonin is as effective as clonidine and that both are more effective than placebo in reducing postoperative pain. Additionally, we compared their anxiolytic effects on postoperative pain. Patients were randomly assigned to receive oral melatonin (5 mg) (n = 20), clonidine (100 microg) (n = 19), or placebo (n = 20) orally. In addition to primary outcomes of pain intensity and analgesic consumption, secondary outcome measures included postoperative state anxiety. In anxious patients 6 hours after surgery, the number of patients needed to be to prevent moderate to intense pain during the first 24 hours after surgery was 1.52 (95% CI, 1.14 to 6.02) and 1.64 (95% CI, 1.29 to 5.93), respectively, in the melatonin and clonidine groups compared with placebo. Also, the anxiolytic effect of melatonin and clonidine resulted in reduced postoperative morphine consumption by more than 30%. However, in the mildly anxious, it was not observed the treatment effect on pain. PERSPECTIVES The preoperative anxiolysis with melatonin or clonidine reduced postoperative pain and morphine consumption in patients undergoing abdominal hysterectomy. The effects these 2 drugs were equivalent and greater than with placebo.

The clinical impact of preoperative melatonin on postoperative outcomes in patients undergoing abdominal hysterectomy.

BACKGROUND:Melatonin has sedative, analgesic, antiinflammatory, antioxidative, and chronobiotic effects. We determined the impact of oral melatonin premedication on anxiolysis, analgesia, and the potency of the rest/activity circadian rhythm. METHODS:This randomized, double-blind, placebo-controlled study included 33 patients, ASA physical status I–II, undergoing abdominal hysterectomy. Patients were randomly assigned to receive either oral melatonin 5 mg (n = 17) or placebo (n = 16) the night before and 1 h before surgery. The analysis instruments were the Visual Analog Scale, the State-Trait Anxiety Inventory, and the actigraphy. RESULTS:The number of patients that needed to be treated to prevent one additional patient reporting high postoperative anxiety and moderate to intense pain in the first 24 postoperative hours was 2.53 (95% CI, 1.41–12.22) and 2.20 (95% CI, 1.26–8.58), respectively. The number-needed-to-treat was 3 (95% CI, 1.35–5.0) to prevent high postoperative anxiety in patients with moderate to intense pain, when compared with 7.5 (95% CI, 1.36–∞) in the absence of pain or mild pain. Also, the treated patients required less morphine by patient-controlled analgesia, as assessed by repeated measures ANOVA (F[1,31] = 6.05, P = 0.02). The rest/activity cycle, assessed by actigraphy, showed that the rhythmicity percentual of 24 h was higher in the intervention group in the first week after discharge ([21.16 ± 8.90] versus placebo [14.00 ± 7.10]; [t = −2.41, P = 0.02]). CONCLUSIONS:This finding suggested that preoperative melatonin produced clinically relevant anxiolytic and analgesic effects, especially in the first 24 postoperative hours. Also, it improved the recovery of the potency of the rest/activity circadian rhythm.

Development and use of a biological rhythm interview.

INTRODUCTION As several lines of evidence point to irregular biological rhythms in bipolar disorder, and its disruption may lead to new illness episodes, having an instrument that measures biological rhythms is critical. This report describes the validation of a new instrument, the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), designed to assess biological rhythms in the clinical setting. METHODS Eighty-one outpatients with a diagnosis of bipolar disorder and 79 control subjects matched for type of health service used, sex, age and educational level were consecutively recruited. After a pilot study, 18 items evaluating sleep, activities, social rhythm and eating pattern were probed for discriminant, content and construct validity, concurrent validity with the Pittsburgh Sleep Quality Index (PSQI), internal consistency and test-retest reliability. RESULTS A three-factor solution, termed sleep/social rhythm factor, activity factor and feeding factor, provided the best theoretical and most parsimonious account of the data; items essentially loaded in factors as theoretically intended, with the exception of the sleep and social scales, which formed a single factor. Test-retest reliability and internal consistency were excellent. Highly significant differences between the two groups were found for the whole scale and for each BRIAN factor. Total BRIAN scores were highly correlated with the global PSQI score. DISCUSSION The BRIAN scale presents a consistent profile of validity and reliability. Its use may help clinicians to better assess their patients and researchers to improve the evaluation of the impact of novel therapies targeting biological rhythm pathways.

Evaluation of the structure of Brazilian State-Trait Anxiety Inventory using a Rasch psychometric approach

OBJECTIVE This study evaluates the State-Trait Anxiety Inventory (STAI) structure using a Rasch psychometric approach, and a refined and shorter STAI version is proposed. METHODS A cross-sectional study was performed with 900 inpatients scheduled for elective surgery. Age varied from 18 to 60 years (American Society of Anesthesiologists physical status I-III). Demographic information was collected using a structured questionnaire. The measuring instrument (the STAI) was applied to all patients in the afternoon before the surgery and prior to the patients receiving preoperative sedatives. RESULTS Rasch analysis of the state and trait anxiety scales was performed separately. This analysis demonstrated that the original format of state and trait scales fails to show invariance across the trait-state anxiety level, which results in the unstable performance of items. The refined scale was retested in two subsequent random samples of 300 subjects each, and the results were confirmed. The performance was adequate regardless of gender. In the analysis, some items of the state scale (items 3,4,9,10,12,15, and 20) were deleted due to poor fit statistics. The remaining 13 items showed unidimensionality, local independence, and adequate index of internal consistency. Also, the original trait scale displayed several weaknesses. First, the four-point Likert response scale proved to be inadequate, and threshold disorders were found in all 20 items. Also, the original trait scale showed insufficient item-trait interaction and several individual item misfits. Following the rescoring process, and retesting in a second random sample, items were excluded (namely Items 3, 4, 11, 13, 14, 15, 18, and 19). The refined version showed local independence, unidimensionality, and adequate fit statistics. DISCUSSION The results indicate that the application of the Rasch model led to the refinement of the classic STAI state and trait scales. In addition, they suggest that these shorter versions have a more suitable psychometric performance and are free of threshold disorders and differential item functioning problems.

Clinical efficacy of dexmedetomidine alone is less than propofol for conscious sedation during ERCP

BACKGROUND Propofol is an accepted method of sedation for an ERCP and generally achieves deep sedation rather than conscious sedation, and dexmedetomidine has sedative properties of equivalent efficacy. OBJECTIVE To examine the hypothesis that dexmedetomidine is as effective as propofol combined with fentanyl for providing conscious sedation during an ERCP. DESIGN AND SETTING Randomized, blind, double-dummy clinical trial. PATIENTS Twenty-six adults, American Society of Anesthesiologists status I to III, underwent an ERCP. INTERVENTIONS Patients were randomized to receive either propofol (n = 14) (target plasma concentration range 2-4 microg/mL) combined with fentanyl 1 microg/kg, or dexmedetomidine (n = 12) 1 microg/kg for 10 minutes, followed by 0.2 to 0.5 microg/kg/min. Additional sedatives were used if adequate sedation was not achieved at the maximum dose allowed. MAIN OUTCOMES MEASUREMENTS The sedation level was assessed by the Richmond alertness-sedation scale and the demand for additional sedatives. Furthermore, heart rate, blood pressure, oxygen saturation, and respiratory rate were continuously assessed. RESULTS The relative risk (RR) was 2.71 (95% CI, 1.31-5.61) and the number of patients that needed to be treated (NNT) was 1.85 (95% CI, 1.19-4.21) to observe one additional patient with drowsiness 15 minutes after sedation in the dexmedetomidine group. Also, the RR was 9.42 (95% CI, 1.41-62.80), and the NNT was 1.42 (95% CI, 1.0-2.29) to require additional analgesic. However, there was also a greater reduction in blood pressure, a lower heart rate, and greater sedation after the procedure. CONCLUSIONS Dexmedetomidine alone was not as effective as propofol combined with fentanyl for providing conscious sedation during an ERCP. Furthermore, dexmedetomidine was associated with greater hemodynamic instability and a prolonged recovery.