Högskolan i Skövde

Despite a surge of studies on the effects of COVID-19 on our well-being, we know little about how the pandemic is reflected in people's spontaneous thoughts and experiences, such as mind-wandering (or daydreaming) during wakefulness and dreaming during sleep. We investigated whether and how COVID-19-related general concern, anxiety, and daily worry are associated with the daily fluctuation of the affective quality of mind-wandering and dreaming, and to what extent these associations can be explained by poor sleep quality. We used ecological momentary assessment by asking participants to rate the affect they experienced during mind-wandering and dreaming in daily logs over a 2-week period. Our preregistered analyses based on 1,755 dream logs from 172 individuals and 1,496 mind-wandering logs from 152 individuals showed that, on days when people reported higher levels of negative affect and lower levels of positive affect during mind-wandering, they experienced more worry. Only daily sleep quality was associated with affect experienced during dreaming at the within-person level: on nights with poorer sleep quality people reported experiencing more negative and less positive affect in dreams and were more likely to experience nightmares. However, at the between-person level, individuals who experienced more daily COVID-19 worry during the study period also reported experiencing more negative affect during mind-wandering and during dreaming. As such, the continuity between daily and nightly experiences seems to rely more on stable trait-like individual differences in affective processing. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Objectives: The objective of this study was to investigate how blood pressure, sleep architecture, sleep-disordered breathing, body habitus, and levels of serum follicle-stimulating hormone are associated with symptoms of insomnia and sleep quality during menopausal transition.

Methods: 64 healthy premenopausal women (aged 45–47 years) were recruited to the study. Data were collected at baseline and at 10-year follow-up during sleep laboratory and laboratory visits. A sleep questionnaire was used to evaluate sleep quality and insomnia symptoms. Data were analysed using multiple linear and logistic regression with a backward method.

Results: During the menopausal transition, a change in insomnia symptoms was associated with a change in morning systolic blood pressure (β = 0.114 (CI95% 0.023–0.205), p = 0.016). At follow-up, at the age of 56, a higher percentage of REM sleep was associated with a lower odds of restless sleep (OR = 0.842 (95 % CI 0.742–0.954), p = 0.007), while both higher systolic and diastolic evening blood pressure was associated with an increased odds of morning tiredness. OR = 1.047 (95 % CI 1.003–1.092), p = 0.034 and OR = 1.126 (95 % CI 1.018–1.245), p = 0.007, respectively.

Conclusions: In healthy midlife women, a change blood pressure is related to the development of insomnia symptoms during menopausal transition. In postmenopausal women, a high evening blood pressure may be associated with morning tiredness and a reduced amount of REM sleep may be perceived as restless sleep. 

Nightmares are vivid, extended, and emotionally negative or negative dreams that awaken the dreamer. While sporadic nightmares and bad dreams are common and generally harmless, frequent nightmares often reflect underlying pathologies of emotional regulation. Indeed, insomnia, depression, anxiety, or alcohol use have been associated with nightmares in epidemiological and clinical studies. However, the connection between nightmares and their comorbidities are poorly understood. Our goal was to examine the genetic risk factors for nightmares and estimate correlation or causality between nightmares and comorbidities. We performed a genome-wide association study (GWAS) in 45,255 individuals using a questionnaire-based assessment on the frequency of nightmares during the past month and genome-wide genotyping data. While the GWAS did not reveal individual risk variants, heritability was estimated at 5%. In addition, the genetic correlation analysis showed a robust correlation (rg > 0.4) of nightmares with anxiety (rg = 0.671, p = 7.507e−06), depressive (rg = 0.562, p = 1.282e−07) and posttraumatic stress disorders (rg = 0.4083, p = 0.0152), and personality trait neuroticism (rg = 0.667, p = 4.516e−07). Furthermore, Mendelian randomization suggested causality from insomnia to nightmares (beta = 0.027, p = 0.0002). Our findings suggest that nightmares share genetic background with psychiatric traits and that insomnia may increase an individual’s liability to experience frequent nightmares. Given the significant correlations with psychiatric and psychological traits, it is essential to grow awareness of how nightmares affect health and disease and systematically collect information about nightmares, especially from clinical samples and larger cohorts. 

Previous research indicates that the COVID-19 pandemic has affected dreaming negatively. We compared 1132 dreams collected with prospective two-week dream diary during the pandemic to 166 dreams collected before the pandemic. We hypothesized that the pandemic would increase the number of threatening events, threats related to diseases, and the severity of threats. We also hypothesized that dreams that include direct references to the pandemic will include more threatening events, more disease-related threats, and more severe threats. In contradiction with our hypotheses, results showed no differences between pandemic and pre-pandemic samples in the number of threats, threats related to diseases, or severe threats. However, dreams with direct references to the pandemic had more threats, disease-related threats, and severe threats. Our results thus do not suggest a significant overall increase in nightmarish or threatening dream content during the pandemic but show a more profound effect on a minority of dreams. 

Episodic memories of emotionally salient and personally significant events are often incorporated into dreams, although rarely replayed identically to the original waking event except in replicative posttraumatic nightmares. We investigated, in five Swedish female 2004 Indian Ocean tsunami survivors, how episodic memories of the catastrophe were reflected in their dreams after trauma, both in retrospectively recalled nightmares and bad dreams, and in prospective dream diaries completed several months after the catastrophe. We also assessed whether the emotional and threatening dream content differed between the trauma and a matched control group. Based on the threat simulation theory, we predicted that the trauma group dreams would portray notable similarities with elements related to the original tsunami trauma, and that the trauma group would demonstrate a higher prevalence of negative emotional states, and a higher frequency of threatening dream events as well as more severe threats in their dreams. Only the first hypothesis was partially supported, with retrospective nightmares bearing higher similarity to the trauma experience than the prospective dream diary dreams. However, we observed no statistically significant differences in emotional or threatening dream content between the groups, suggesting that the trauma group participants were not suffering from significant posttraumatic dreaming at the time of systematic dream data collection. Yet, specific features of the trauma group dreams might be interpreted as remnants of episodic tsunami-related memories: Their dreams had a higher percentage of life-threatening events depicting realistic but improbable threats, and an analysis of water-related themes evidenced stressful themes related to waves.

Establishing the neural mechanisms responsible for the altered global states of consciousness during anesthesia and dissociating these from other drug-related effects remains a challenge in consciousness research. We investigated differences in brain activity between connectedness and disconnectedness by administering various anesthetics at concentrations designed to render 50% of the subjects unresponsive. One hundred and sixty healthy male subjects were randomized to receive either propofol (1.7 μg/ml; n = 40), dexmedetomidine (1.5 ng/ml; n = 40), sevoflurane (0.9% end-tidal; n = 40), S-ketamine (0.75 μg/ml; n = 20), or saline placebo (n = 20) for 60 min using target-controlled infusions or vaporizer with end-tidal monitoring. Disconnectedness was defined as unresponsiveness to verbal commands probed at 2.5-min intervals and unawareness of external events in a postanesthesia interview. High-resolution positron emission tomography (PET) was used to quantify regional cerebral metabolic rates of glucose (CMRglu) utilization. Contrasting scans where the subjects were classified as connected and responsive versus disconnected and unresponsive revealed that for all anesthetics, except S-ketamine, the level of thalamic activity differed between these states. A conjunction analysis across the propofol, dexmedetomidine and sevoflurane groups confirmed the thalamus as the primary structure where reduced metabolic activity was related to disconnectedness. Widespread cortical metabolic suppression was observed when these subjects, classified as either connected or disconnected, were compared with the placebo group, suggesting that these findings may represent necessary but alone insufficient mechanisms for the change in the state of consciousness.

Background: Anaesthetic-induced unresponsiveness and non-rapid eye movement (NREM) sleep share common neural pathways and neurophysiological features. We hypothesised that these states bear resemblance also at the experiential level. Methods: We compared, in a within-subject design, the prevalence and content of experiences in reports obtained after anaesthetic-induced unresponsiveness and NREM sleep. Healthy males (N=39) received dexmedetomidine (n=20) or propofol (n=19) in stepwise doses to induce unresponsiveness. Those rousable were interviewed and left unstimulated, and the procedure was repeated. Finally, the anaesthetic dose was increased 50%, and the participants were interviewed after recovery. The same participants (N=37) were also later interviewed after NREM sleep awakenings. Results: Most subjects were rousable, with no difference between anaesthetic agents (P=0.480). Lower drug plasma concentrations were associated with being rousable for both dexmedetomidine (P=0.007) and propofol (P=0.002) but not with recall of experiences in either drug group (dexmedetomidine: P=0.543; propofol: P=0.460). Of the 76 and 73 interviews performed after anaesthetic-induced unresponsiveness and NREM sleep, 69.7% and 64.4% included experiences, respectively. Recall did not differ between anaesthetic-induced unresponsiveness and NREM sleep (P=0.581), or between dexmedetomidine and propofol in any of the three awakening rounds (P>0.05). Disconnected dream-like experiences (62.3% vs 51.1%; P=0.418) and memory incorporation of the research setting (88.7% vs 78.7%; P=0.204) were equally often present in anaesthesia and sleep interviews, respectively, whereas awareness, signifying connected consciousness, was rarely reported in either state. Conclusions: Anaesthetic-induced unresponsiveness and NREM sleep are characterised by disconnected conscious experiences with corresponding recall frequencies and content. Clinical trial registration: Clinical trial registration. This study was part of a larger study registered at ClinicalTrials.gov (NCT01889004). 

Background

This exploratory study aimed to investigate whether dexmedetomidine, propofol, sevoflurane, and S-ketamine affect oxylipins and bile acids, which are functionally diverse molecules with possible connections to cellular bioenergetics, immune modulation, and organ protection.

Methods

In this randomised, open-label, controlled, parallel group, Phase IV clinical drug trial, healthy male subjects (n=160) received equipotent doses (EC50 for verbal command) of dexmedetomidine (1.5 ng ml−1; n=40), propofol (1.7 μg ml−1; n=40), sevoflurane (0.9% end-tidal; n=40), S-ketamine (0.75 μg ml−1; n=20), or placebo (n=20). Blood samples for tandem mass spectrometry were obtained at baseline, after study drug administration at 60 and 130 min from baseline; 40 metabolites were analysed.

Results

Statistically significant changes vs placebo were observed in 62.5%, 12.5%, 5.0%, and 2.5% of analytes in dexmedetomidine, propofol, sevoflurane, and S-ketamine groups, respectively. Data are presented as standard deviation score, 95% confidence interval, and P-value. Dexmedetomidine induced wide-ranging decreases in oxylipins and bile acids. Amongst others, 9,10-dihydroxyoctadecenoic acid (DiHOME) –1.19 (–1.6; –0.78), P<0.001 and 12,13-DiHOME –1.22 (–1.66; –0.77), P<0.001 were affected. Propofol elevated 9,10-DiHOME 2.29 (1.62; 2.96), P<0.001 and 12,13-DiHOME 2.13 (1.42; 2.84), P<0.001. Analytes were mostly unaffected by S-ketamine. Sevoflurane decreased tauroursodeoxycholic acid (TUDCA) –2.7 (–3.84; –1.55), P=0.015.

Conclusions

Dexmedetomidine-induced oxylipin alterations may be connected to pathways associated with organ protection. In contrast to dexmedetomidine, propofol emulsion elevated DiHOMEs, oxylipins associated with acute respiratory distress syndrome, and mitochondrial dysfunction in high concentrations. Further research is needed to establish the behaviour of DIHOMEs during prolonged propofol/dexmedetomidine infusions and to verify the sevoflurane-induced reduction in TUDCA, a suggested neuroprotective agent.

Clinical trial registration

NCT02624401.

BACKGROUND: Pharmacometabolomics uses large-scale data capturing methods to uncover drug-induced shifts in the metabolic profile. The specific effects of anaesthetics on the human metabolome are largely unknown.

OBJECTIVE: We aimed to discover whether exposure to routinely used anaesthetics have an acute effect on the human metabolic profile.

DESIGN: Randomised, open-label, controlled, parallel group, phase IV clinical drug trial.

SETTING: The study was conducted at Turku PET Centre, University of Turku, Finland, 2016 to 2017.

PARTICIPANTS: One hundred and sixty healthy male volunteers were recruited. The metabolomic data of 159 were evaluable.

INTERVENTIONS: Volunteers were randomised to receive a 1-h exposure to equipotent doses (EC50 for verbal command) of dexmedetomidine (1.5 ng ml-1; n = 40), propofol (1.7 μg ml-1; n = 40), sevoflurane (0.9% end-tidal; n = 39), S-ketamine (0.75 μg ml-1; n = 20) or placebo (n = 20).

MAIN OUTCOME MEASURES: Metabolite subgroups of apolipoproteins and lipoproteins, cholesterol, glycerides and phospholipids, fatty acids, glycolysis, amino acids, ketone bodies, creatinine and albumin and the inflammatory marker GlycA, were analysed with nuclear magnetic resonance spectroscopy from arterial blood samples collected at baseline, after anaesthetic administration and 70 min postanaesthesia.

RESULTS: All metabolite subgroups were affected. Statistically significant changes vs. placebo were observed in 11.0, 41.3, 0.65 and 3.9% of the 155 analytes in the dexmedetomidine, propofol, sevoflurane and S-ketamine groups, respectively. Dexmedetomidine increased glucose, decreased ketone bodies and affected lipoproteins and apolipoproteins. Propofol altered lipoproteins, fatty acids, glycerides and phospholipids and slightly increased inflammatory marker glycoprotein acetylation. Sevoflurane was relatively inert. S-ketamine increased glucose and lactate, whereas branched chain amino acids and tyrosine decreased.

CONCLUSION: A 1-h exposure to moderate doses of routinely used anaesthetics led to significant and characteristic alterations in the metabolic profile. Dexmedetomidine-induced alterations mirror α2-adrenoceptor agonism. Propofol emulsion altered the lipid profile. The inertness of sevoflurane might prove useful in vulnerable patients. S-ketamine induced amino acid alterations might be linked to its suggested antidepressive properties.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02624401. URL: https://clinicaltrials.gov/ct2/show/NCT02624401.