Greater within- and between-day instability is associated with worse anxiety and depression symptoms.

BACKGROUND: Depression and anxiety affect hundreds of millions of people worldwide, and their prevalence increased during the COVID-19 pandemic as social schedules were disrupted. This study explores the associations between anxiety and depression and within- and between-day instability of affective, somatic, and cognitive symptoms during the early pandemic stages. METHODS: Participants (n = 153, ages 18-77, 72 % female) reported daily levels of affective (anxiety/sadness), somatic (appetite/sleepiness), and cognitive (concentration/energy) symptoms for 14-44 days at five timepoints: 0, 3, 6, 9, and 12 h after awakening. At the end of the study, participants completed validated scales for anxiety (GAD-7) and depression (PHQ-9). Symptom instability was assessed using the Absolute Real Variability (ARV) index. Regression models examined within-day instability (WD-I) and between-day instability (BD-I) with GAD-7 and PHQ-9 scores as outcomes. RESULTS: Greater instability (both WD-I and BD-I) of affective symptoms correlated with elevated GAD-7 and PHQ-9 scores. For somatic and cognitive symptoms, greater BD-I was associated with higher scores. LIMITATIONS: The study used retrospective daily data, which could benefit from real-time assessments for improved accuracy. CONCLUSIONS: This study provides empirical evidence of a connection between greater anxiety and depression severity and increased instability in daily mood and physiological symptoms. The findings underscore the importance of consistent symptom monitoring to understand overall mental health trajectories. Additionally, it highlights the role of daily routines in stabilizing the circadian system, potentially regulating physiological and psychological processes and reducing symptom instability.

Is chronodisruption a vulnerability factor to stress?

Since the circadian system seems to modulate stress responses, this study aimed to evaluate if the combination of circadian strain and stress amplifies changes expected from each factor alone. Control Balb/c mice (12:12-NS) kept in standard 12:12 light:dark cycles (LD) and submitted to no stress procedures (NS) were compared to groups submitted to shortened LD (10:10-NS), chronic mild stress (CMS) but no circadian strain (12:12-CMS), or shortened LD followed by CMS (10:10-CMS). Rest-activity/temperature rhythms and body weight were assessed throughout the experiments. In Experiment 1 mice were submitted to 3 weeks of CMS; in Experiment 2 sucrose preference and light-dark tests were performed. Also, blood samples were collected at the end of Experiment 2 to assess metabolic parameters. Relative amplitude of temperature after CMS was increased only in the 10:10-CMS group, while body weight change was reduced during CMS regardless of LD intervention. During the CMS, the relative amplitude of temperature was negatively correlated with body weight gain. No differences in behavior and metabolic parameters were seen among groups. Identifying suitable research designs to investigate our hypothesis that circadian disturbances may increase vulnerability to stress-induced depression and anxiety is warranted.

Differential susceptibility of BALB/c, C57BL/6N, and CF1 mice to photoperiod changes

Objective:Circadian disturbances common to modern lifestyles have been associated with mood disorders. Animal models that mimic such rhythm disturbances are useful in translational research to explore factors contributing to depressive disorders. This study aimed to verify the susceptibility of BALB/c, C57BL/6N, and CF1 mice to photoperiod changes.Methods:Thermochron iButtons implanted in the mouse abdomen were used to characterize temperature rhythms. Mice were maintained under a 12:12 h light-dark (LD) cycle for 15 days, followed by a 10:10 h LD cycle for 10 days. Cosinor analysis, Rayleigh z test, periodograms, and Fourier analysis were used to analyze rhythm parameters. Paired Student's t test was used to compare temperature amplitude, period, and power of the first harmonic between normal and shortened cycles.Results:The shortened LD cycle significantly changed temperature acrophases and rhythm amplitude in all mouse strains, but only BALB/c showed altered period.Conclusion:These findings suggest that BALB/c, the preferred strain for stress-induced models of depression, should also be favored for exploring the relationship between circadian rhythms and mood. Temperature rhythm proved to be a useful parameter for characterizing rhythm disruption in mice. Although disruption of temperature rhythm has been successfully documented in untethered mice, an evaluation of desynchronization of other rhythms is warranted.

Differential susceptibility of BALB/c, C57BL/6N, and CF1 mice to photoperiod changes.

OBJECTIVE: Circadian disturbances common to modern lifestyles have been associated with mood disorders. Animal models that mimic such rhythm disturbances are useful in translational research to explore factors contributing to depressive disorders. This study aimed to verify the susceptibility of BALB/c, C57BL/6N, and CF1 mice to photoperiod changes. METHODS: Thermochron iButtons implanted in the mouse abdomen were used to characterize temperature rhythms. Mice were maintained under a 12:12 h light-dark (LD) cycle for 15 days, followed by a 10:10 h LD cycle for 10 days. Cosinor analysis, Rayleigh z test, periodograms, and Fourier analysis were used to analyze rhythm parameters. Paired Student's t test was used to compare temperature amplitude, period, and power of the first harmonic between normal and shortened cycles. RESULTS: The shortened LD cycle significantly changed temperature acrophases and rhythm amplitude in all mouse strains, but only BALB/c showed altered period. CONCLUSION: These findings suggest that BALB/c, the preferred strain for stress-induced models of depression, should also be favored for exploring the relationship between circadian rhythms and mood. Temperature rhythm proved to be a useful parameter for characterizing rhythm disruption in mice. Although disruption of temperature rhythm has been successfully documented in untethered mice, an evaluation of desynchronization of other rhythms is warranted.

Effects of N-acetylcysteine and imipramine in a model of acute rhythm disruption in BALB/c mice.

Circadian rhythm disturbances are among the risk factors for depression, but specific animal models are lacking. This study aimed to characterize the effects of acute rhythm disruption in mice and investigate the effects of imipramine and N-acetylcysteine (NAC) on rhythm disruption-induced changes. Mice were exposed to 12:12-hour followed by 10:10-hour light:dark cycles (LD); under the latter, mice were treated with saline, imipramine or NAC. Rhythms of rest/activity and temperature were assessed with actigraphs and iButtons, respectively. Hole-board and social preference tests were performed at the beginning of the experiment and again at the 8th 10:10 LD, when plasma corticosterone and IL-6 levels were also assessed. Actograms showed that the 10:10 LD schedule prevents the entrainment of temperature and activity rhythms for at least 13 cycles. Subsequent light regimen change activity and temperature amplitudes showed similar patterns of decline followed by recovery attempts. During the 10:10 LD schedule, activity and temperature amplitudes were significantly decreased (paired t test), an effect exacerbated by imipramine (ANOVA/SNK). The 10:10 LD schedule increased anxiety (paired t test), an effect prevented by NAC (30 mg/kg). This study identified mild but significant behavioral changes at specific time points after light regimen change. We suggest that if repeated overtime, these subtle changes may contribute to lasting behavioral disturbancess relevant to anxiety and mood disorders. Data suggest that imipramine may contribute to sustained rhythm disturbances, while NAC appears to prevent rhythm disruption-induced anxiety. Associations between sleep/circadian disturbances and the recurrence of depressive episodes underscore the relevance of potential drug-induced maintenance of disturbed rhythms.

The concept of the immune-pineal axis tested in patients undergoing an abdominal hysterectomy.

OBJECTIVE: Activation of the immune-pineal axis induces a transient reduction in nocturnal melatonin in the plasma during the proinflammatory phase of an innate immune response to allow the proper migration of leukocytes to the lesion site. This transient reduction should be regulated by inflammatory mediators, which are responsible for the fine-tuning of the process. In the present study, we measured the pre- and postoperative serum concentrations of melatonin, tumor necrosis factor (TNF) and cortisol in women who underwent an elective hysterectomy and correlated the variation in melatonin with postoperative pain. METHODS: We evaluated 12 women who had an abdominal hysterectomy. Blood was collected at 10.00 and 22.00 h 1 week and 1 day before the surgery, on the 1st and 2nd days after the surgery and at 22.00 h on the day of the surgery. RESULTS: On the night after the surgery, there was no melatonin detected at 22.00 h. High TNF levels were accompanied by a lower nocturnal melatonin output, higher postoperative pain according to a visual analog scale and the request of higher doses of analgesics. In addition, low cortisol levels were accompanied by a lower nocturnal melatonin output. CONCLUSION: Our results confirm that the same antagonistic pattern between TNF and glucocorticoids observed in cultured pineal glands also occurs in humans. This integrative pattern suggests that the cross talk between the immune and endocrine system orchestrates longitudinal changes in pineal activity, reinforcing the hypothesis of an immune-pineal axis.

Desenvolvimento da versão breve da Escala de Ritmo Social / Development of brief version of the Social Rhythm Metric

OBJETIVO: O objetivo deste trabalho é o estabelecimento de uma versão abreviada da Escala de Ritmo Social, com vistas à aplicação em pesquisa. MÉTODOS: Tomando como padrão-ouro a Escala de Ritmo Social de 17 itens, estabelecidas três versões breves a partir de três critérios diferentes. Comparados escores de regularidade e quantidade de atividades desenvolvidas em um período de uma semana de 167 sujeitos saudáveis, 25 portadores de epilepsia mioclônica juvenil e 16 portadores de transtorno depressivo. RESULTADOS: A versão breve de seis itens mostrou melhor concordância com relação ao padrão-ouro k = 0,51; p < 0,001. A análise bivariada demonstrou significativa correlação entre a versão breve-6 e o padrão-ouro: (r = 0,87; p < 0,001). Houve correlação com idade na versão breve-6 (r = 0,2; p < 0,001), ainda mais significativa do que no padrão-ouro (r = 0,2; P < 0,01). Na análise ANOVA, o grupo saudável apresentou escores mais altos de regularidade em ambas as escalas. Com relação à quantidade de atividades, o grupo saudável assemelhou-se ao dos portadores de epilepsia e o dos portadores de depressão apresentou médias mais baixas. CONCLUSÃO: A simplificação da escala diminui a porcentagem de itens não preenchidos e custo em material impresso e facilita a padronização. O processo envolveu cuidadosa análise da adequação do instrumento à cultura-alvo.

OBJECTIVE: The objective of this work was to establish a brief version of the Social Rhythm Metric, aimed at applying it in research. METHODS: Taking the 17-item Social Rhythm Metric as the gold standard, three brief versions were created based on three different criteria. compared the scores of the regularity and quantity of activities carried out in a week for 167 healthy subjects and 25 individuals with juvenile myoclonic epilepy and 16 with depressive disturbance. RESULTS: The brief version of 6 items showed better concordance in relation to the gold standard; k = 0.51, p < 0.001. Bivariate analysis demonstrated a significant correlation between the brief version 6 and the gold standard (r = 0.87; p < 0.001). There was a correlation with age in the brief 6 version (r = 0.2; p < 0.001), even more significant than in the gold standard (r = 0.2; P < 0.01). ANOVA showed higher scores for regularity in the healthy using both scales. However, in relation to the quantity of activities, the healthy group resembled the epilepsy group, and the individuals with depression showed lower means. CONCLUSION: The simplification of the Social Rhythm Metric decreased the percenta-ge of items not filled in and the cost of printed matter and facilitate the standardization. The process involved a careful analysis of suitability of the instrument for the target culture.

Effects of restraint stress on the daily rhythm of hydrolysis of adenine nucleotides in rat serum.

BACKGROUND: Adenosine 5-triphosphate (ATP) and its breakdown products ADP and adenosine can act as extracellular messengers in a range of biological processes. Extracellular adenine nucleotides are metabolized by a number of enzymes including NTPDases and 5'-nucleotidase, which are considered to be the major regulators of purinergic signaling in the blood. Previous work by our group demonstrated that ATPase and ADPase activities in rat serum exhibit a 24-h temporal pattern, with higher enzyme activity during the dark (activity) phase. It was found that stress can cause disruptions in biological circadian rhythms and in the cardiovascular system. Therefore, the aim of the present study was to examine the influence of acute stress exposure upon temporal patterns of NTPDase and 5-nucleotidase enzyme activities in rat blood serum. METHODS: Adult male Wistar rats were divided into 4 groups: ZT0, ZT6, ZT12 and ZT18. Each group was subdivided in 4 groups: control, immediately, 6 h and 24 h after one hour of restraint stress. ATP, ADP and AMP hydrolysis were assayed in the serum. RESULTS: All stressed groups showed significant decreases in all enzyme activities at ZT 12 and ZT 18 when compared with control. CONCLUSION: Acute stress provokes a decrease in nucleotidase activities dependent on the time that this stress occurs and this effect appears to persist for at least 24 hours. Stress can change levels of nucleotides, related to increased frequency of cardiovascular events during the activity phase. Altered levels of nucleotides in serum may be involved in cardiovascular events more frequent during the activity phase in mammals, and with their etiology linked to stress.

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.

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.

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-infinity) 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.