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BMJ Open May 2024Late-life treatment-resistant depression (LL-TRD) is common and increases risk for accelerated ageing and cognitive decline. Impaired sleep is common in LL-TRD and is a...
INTRODUCTION
Late-life treatment-resistant depression (LL-TRD) is common and increases risk for accelerated ageing and cognitive decline. Impaired sleep is common in LL-TRD and is a risk factor for cognitive decline. Slow wave sleep (SWS) has been implicated in key processes including synaptic plasticity and memory. A deficiency in SWS may be a core component of depression pathophysiology. The anaesthetic propofol can induce electroencephalographic (EEG) slow waves that resemble SWS. Propofol may enhance SWS and oral antidepressant therapy, but relationships are unclear. We hypothesise that propofol infusions will enhance SWS and improve depression in older adults with LL-TRD. This hypothesis has been supported by a recent small case series.
METHODS AND ANALYSIS
SWIPED (Slow Wave Induction by Propofol to Eliminate Depression) phase I is an ongoing open-label, single-arm trial that assesses the safety and feasibility of using propofol to enhance SWS in older adults with LL-TRD. The study is enrolling 15 English-speaking adults over age 60 with LL-TRD. Participants will receive two propofol infusions 2-6 days apart. Propofol infusions are individually titrated to maximise the expression of EEG slow waves. Preinfusion and postinfusion sleep architecture are evaluated through at-home overnight EEG recordings acquired using a wireless headband equipped with dry electrodes. Sleep EEG recordings are scored manually. Key EEG measures include sleep slow wave activity, SWS duration and delta sleep ratio. Longitudinal changes in depression, suicidality and anhedonia are assessed. Assessments are performed prior to the first infusion and up to 10 weeks after the second infusion. Cognitive ability is assessed at enrolment and approximately 3 weeks after the second infusion.
ETHICS AND DISSEMINATION
The study was approved by the Washington University Human Research Protection Office. Recruitment began in November 2022. Dissemination plans include presentations at scientific conferences, peer-reviewed publications and mass media. Positive results will lead to a larger phase II randomised placebo-controlled trial.
TRIAL REGISTRATION NUMBER
NCT04680910.
Topics: Humans; Propofol; Cognitive Dysfunction; Aged; Sleep, Slow-Wave; Electroencephalography; Male; Anesthetics, Intravenous; Depressive Disorder, Treatment-Resistant; Female; Middle Aged; Clinical Trials, Phase I as Topic
PubMed: 38816055
DOI: 10.1136/bmjopen-2024-087516 -
Child and Adolescent Psychiatry and... May 2024Unhealthy lifestyle behaviors among adolescents have emerged as a significant public health concern worldwide, however, there is little investigation on the impact of...
BACKGROUND
Unhealthy lifestyle behaviors among adolescents have emerged as a significant public health concern worldwide, however, there is little investigation on the impact of unhealthy behaviors on non-suicidal self-injury (NSSI), suicidal ideation (SI) and suicide attempt (SA). This study aimed to investigate the prevalence of seven unhealthy behaviors as well as their associations with NSSI, SI and SA, and to explore whether the aforementioned associations differ across sex.
METHODS
A total of 74,152 adolescents were included in this study via a multi-stage, stratified cluster, random sampling method in 2021. Information about unhealthy behaviors (insufficient physical activity, current smoking, current drinking, excessive screen time, long homework time, insufficient sleep and unhealthy BMI), NSSI, SI, SA and other demographics was collected. Sampling weights were used to estimate the prevalence, and the weighted logistic regression models were performed. Stratified analyses by sex and sensitive analyses were conducted.
RESULTS
Overview, the weighted prevalence of adolescents had more than five unhealthy behaviors were 5.2%, with boys showing a higher prevalence than girls (6.5% vs.3.8%). Current smoking, current drinking, excessive screen use, long homework time, insufficient sleep, and unhealthy BMI were significantly associated with NSSI, SI and SA. Moreover, adolescents with high lifestyle risk scores were associated with an increased risk of NSSI (5-7 vs. 0: OR 6.38, 95% CI 5.24-7.77), SI (5-7 vs. 0: OR 7.67, 95% CI 6.35-9.25), and SA (5-7 vs. 0: OR 9.57, 95% CI 6.95-13.17). Significant sex differences were found in the associations of unhealthy behaviors with NSSI, SI and SA.
CONCLUSION
Unhealthy behaviors are quite common among Chinese adolescents. Adolescents with multiple unhealthy behaviors are associated with increased risks of NSSI, SI, and SA. The implementation of school and family-based interventions to promote healthy lifestyles is recommended as a preventive measure against self-injurious behavior and suicidality in adolescents.
PubMed: 38812024
DOI: 10.1186/s13034-024-00742-y -
Frontiers in Human Neuroscience 2024Parkinson's disease (PD) generally progresses slowly, but it is controversial whether delaying treatment accelerates the progression.
BACKGROUND
Parkinson's disease (PD) generally progresses slowly, but it is controversial whether delaying treatment accelerates the progression.
OBJECTIVE
Determine the correlation between the time of dopaminergic replacement treatment initiation and the severity of clinical symptoms in PD, including motor and non-motor symptoms.
METHODS
PD patients were divided between 155 people who were diagnosed and 165 PD patients receiving dopamine replacement therapy. Basic patient characteristics included gender, age, age at onset, disease duration, and the time of dopaminergic replacement treatment initiation. We used MDS-UPDRS scores to evaluate the severity of motor symptoms and we also used the scale to assess the severity of non-motor symptoms such as cognition, mood, sleep, and quality of life.
RESULTS
The mean time between symptom onset and the initiation of drug treatment was 31.0 (22.5) months. After adjusting for age, sex, age at onset, and disease duration, we found that the MDS-Unified Parkinson's Disease Rating Scale (UPDRS)-III score increased faster in the group with a similar disease duration (F = 8.7, = 0.0034) than the treatment group. The cumulative incidence of progression to H-Y score 3 in de novo PD group over disease duration was 39.7% in 50months and 92.2% in 100 months, while in treated group such cumulative incidence was 15.5% in 50 months, 51.4% in 100 months and 81.5% in 150 months. The cumulative incidence of patients in the PD group was higher than that in the treated group ( = 0.001), suggesting that untreated patients were more likely to progress to the advanced stages. Symptoms onset, the time between symptom onset and treatment initiation, age, sex, and disease duration explained 28.95% of the total variation in the MDS-UPDRS-III score for motor symptoms. In drug-naïve patients, the time between symptom onset and treatment initiation explained 20.1% of the total variation in the MDS-UPDRS-III score for motor symptoms ( = 6.15, < 0.001).
CONCLUSIONS
These data in our study showed that early dopaminergic replacement treatment have played a positive role in PD patients, while dopaminergic replacement delayed treatment might be detrimental to motor symptoms and non-motor state of PD patient. Recognizing early stage symptoms of PD and early diagnosis are of great significance to treatment.
PubMed: 38807633
DOI: 10.3389/fnhum.2024.1325324 -
Supportive Care in Cancer : Official... May 2024To evaluate the effects of complete decongestive therapy (CDT) on cancer-related fatigue, sleep quality, and lymphedema-specific quality of life using validated and...
OBJECTIVE
To evaluate the effects of complete decongestive therapy (CDT) on cancer-related fatigue, sleep quality, and lymphedema-specific quality of life using validated and reliable questionnaires in cancer patients being commendable.
MATERIAL AND METHODS
This prospective study includes 94 patients who had postmastectomy lymphedema syndrome. The demographic characteristics of the patients were recorded. The participants' stages of lymphedema (The International Society of Lymphology), Hirai Cancer Fatigue Scale (HCFS) score, Pittsburgh Sleep Quality Index (PSQI) Global score, lymphedema-specific quality of life questionnaire (LYMQOL-ARM) score, and Global health status were recorded before and after CDT.
RESULTS
The mean age of the patients was 58.49 ± 10.96 years. Strong correlations were found between the severity of edema and global health status. There was a significant positive relationship between the HCFS score, PSQI Global score, LYMQOL-ARM score, and CDT. After decongestive physiotherapy, the majority of the lymphedema stages were downstaging (p < 0.05), respectively. There was also a trend toward improvement in general well-being (p < 0.05).
CONCLUSION
Cancer-related fatigue and sleep disturbance can persist for years after surgery in women with breast cancer. This can negatively affect the patient physically, socially and cognitively. Our study, which is the first study to investigate the HCFS score in postmastectomy patients and the relationship between PSQI Global score and CDT. The findings identify the risk factors that affect these outcomes in women with lymphedema and can provide valuable insights for targeted interventions and improved patient care.
Topics: Humans; Middle Aged; Female; Prospective Studies; Mastectomy; Quality of Life; Aged; Surveys and Questionnaires; Fatigue; Sleep Quality; Lymphedema; Breast Neoplasms; Severity of Illness Index; Adult; Physical Therapy Modalities
PubMed: 38806742
DOI: 10.1007/s00520-024-08590-4 -
Frontiers in Psychiatry 2024To examine serum concentrations of neurotensin, pannexin-1 and sestrin-2, and their correlations with subjective and objective sleep quality and cognitive function in...
OBJECTIVES
To examine serum concentrations of neurotensin, pannexin-1 and sestrin-2, and their correlations with subjective and objective sleep quality and cognitive function in the patients with chronic insomnia disorder (CID).
METHODS
Sixty-five CID patients were enrolled continuously and fifty-six good sleepers in the same period were served as healthy controls (HCs). Serum levels of neurotensin, pannexin-1 and sestrin-2 were measured by enzyme-linked immunosorbent assays. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and polysomnography, and mood was evaluated by 17-item Hamilton Depression Rating Scale. General cognitive function was assessed with the Chinese-Beijing Version of Montreal Cognitive Assessment and spatial memory was evaluated by Blue Velvet Arena Test (BVAT).
RESULTS
Relative to the HCs, the CID sufferers had higher levels of neurotensin (=5.210, <0.001) and pannexin-1 (=-4.169, <0.001), and lower level of sestrin-2 (=-2.438, =0.015). In terms of objective sleep measures, pannexin-1 was positively associated with total sleep time (=0.562, =0.002) and sleep efficiency (=0.588, =0.001), and negatively with wake time after sleep onset (=-0.590, =0.001) and wake time (=-0.590, =0.001); sestrin-2 was positively associated with percentage of rapid eye movement sleep (=0.442, =0.016) and negatively with non-rapid eye movement sleep stage 2 in the percentage (=-0.394, =0.034). Adjusted for sex, age and HAMD, pannexin-1 was still associated with the above objective sleep measures, but sestrin-2 was only negatively with wake time (=-0.446, =0.022). However, these biomarkers showed no significant correlations with subjective sleep quality (PSQI score). Serum concentrations of neurotensin and pannexin-1 were positively associated with the mean erroneous distance in the BVAT. Adjusted for sex, age and depression, neurotensin was negatively associated with MoCA score (=-0.257, =0.044), pannexin-1 was positively associated with the mean erroneous distance in the BVAT (=0.270, =0.033).
CONCLUSIONS
The CID patients had increased neurotensin and pannexin-1 and decreased sestrin-2 in the serum levels, indicating neuron dysfunction, which could be related to poor sleep quality and cognitive dysfunction measured objectively.
PubMed: 38803679
DOI: 10.3389/fpsyt.2024.1360305 -
Frontiers in Neurology 2024The rising prevalence of Parkinson's disease (PD) globally presents a significant public health challenge for national healthcare systems, particularly in low-to-middle...
The rise of Parkinson's disease is a global challenge, but efforts to tackle this must begin at a national level: a protocol for national digital screening and "eat, move, sleep" lifestyle interventions to prevent or slow the rise of non-communicable diseases in Thailand.
The rising prevalence of Parkinson's disease (PD) globally presents a significant public health challenge for national healthcare systems, particularly in low-to-middle income countries, such as Thailand, which may have insufficient resources to meet these escalating healthcare needs. There are also many undiagnosed cases of early-stage PD, a period when therapeutic interventions would have the most value and least cost. The traditional "passive" approach, whereby clinicians wait for patients with symptomatic PD to seek treatment, is inadequate. Proactive, early identification of PD will allow timely therapeutic interventions, and digital health technologies can be scaled up in the identification and early diagnosis of cases. The Parkinson's disease risk survey (TCTR20231025005) aims to evaluate a digital population screening platform to identify undiagnosed PD cases in the Thai population. Recognizing the long prodromal phase of PD, the target demographic for screening is people aged ≥ 40 years, approximately 20 years before the usual emergence of motor symptoms. Thailand has a highly rated healthcare system with an established universal healthcare program for citizens, making it ideal for deploying a national screening program using digital technology. Designed by a multidisciplinary group of PD experts, the digital platform comprises a 20-item questionnaire about PD symptoms along with objective tests of eight digital markers: voice vowel, voice sentences, resting and postural tremor, alternate finger tapping, a "pinch-to-size" test, gait and balance, with performance recorded using a mobile application and smartphone's sensors. Machine learning tools use the collected data to identify subjects at risk of developing, or with early signs of, PD. This article describes the selection and validation of questionnaire items and digital markers, with results showing the chosen parameters and data analysis methods to be robust, reliable, and reproducible. This digital platform could serve as a model for similar screening strategies for other non-communicable diseases in Thailand.
PubMed: 38803644
DOI: 10.3389/fneur.2024.1386608 -
Clinical and Translational Science May 2024Sleep deprivation is a prevalent problem in critically ill patients, which leads to delayed recovery and delirium. Slow-wave sleep (SWS) is essential to energy... (Randomized Controlled Trial)
Randomized Controlled Trial
Sleep deprivation is a prevalent problem in critically ill patients, which leads to delayed recovery and delirium. Slow-wave sleep (SWS) is essential to energy restoration, tissue repair, and immune system strengthening. This study aimed to investigate the effects of gabapentin on SWS in critically ill patients. We performed a prospective open-label randomized controlled study to compare SWS and the clinical outcomes of gabapentin versus a control intervention in critically ill adult patients admitted to the intensive care unit (ICU) within 24 h. The patients' characteristics and sleep-related outcomes were recorded. The sleep-related outcomes, namely, bispectral analysis (BIS), the Richards-Campbell Sleep Questionnaire (RCSQ), and insulin-like growth factor-1 (IGF-1) levels, were evaluated. Furthermore, clinical outcomes and safety were assessed. Sixty patients from 348 cases were eligible for randomization. On day 3 of the study, patients in the gabapentin group had significantly increased SWS (66.79 vs. 0.00 min; p < 0.001), total sleep time (TST) (331.39 vs. 46.16 min; p = 0.001), RCSQ score (55.05 ± 20.18 vs. 32.80 ± 15.31; p < 0.001), and IGF-1 concentrations (84.33 ± 12.40 vs. 44.00 ± 10.20 ng/mL, p < 0.001) compared with the control group. Improvements in clinical outcomes, such as delirium, ICU-free days, and mechanical ventilator-free days, were observed; however, these differences did not reach statistically significant. Gabapentin at bedtime increased SWS, TST, and IGF-1 concentrations in critically ill patients. This regimen might be beneficial to critically ill patients for improving their sleep quality.
Topics: Humans; Gabapentin; Critical Illness; Male; Female; Middle Aged; Aged; Prospective Studies; Sleep, Slow-Wave; Adult; Intensive Care Units; Insulin-Like Growth Factor I; Sleep Deprivation; Treatment Outcome
PubMed: 38803031
DOI: 10.1111/cts.13815 -
ENeuro May 2024Sleep's contribution to affective regulation is insufficiently understood. Previous human research has focused on memorizing or rating affective pictures and less on...
Sleep's contribution to affective regulation is insufficiently understood. Previous human research has focused on memorizing or rating affective pictures and less on physiological affective responsivity. This may result in overlapping definitions of affective and declarative memories, and inconsistent deductions for how rapid eye movement sleep (REMS) and slow-wave sleep (SWS) are involved. Literature associates REMS theta (4-8Hz) activity with emotional memory processing, but its contribution to social stress habituation is unknown.Applying selective sleep stage suppression and oscillatory analyses, we investigated how sleep modulated affective adaptation towards social stress and retention of neutral declarative memories. Native Finnish participants (N=29, age M=25.8y) were allocated to REMS or SWS suppression conditions. We measured physiological (skin conductance response, SCR) and subjective stress response and declarative memory retrieval three times: before laboratory night, the next morning, and after three days. Linear mixed models were applied to test the effects of condition and sleep parameters on emotional responsivity and memory retrieval.Greater overnight increase in SCR towards the social stressor emerged after suppressed SWS (intact REMS) relative to suppressed REMS (20.1% vs. 6.1%, p=.016). The overnight SCR increase was positively associated with accumulated REMS theta energy irrespective of the condition (r=.601, p=.002). Subjectively rated affective response and declarative memory recall were comparable between the conditions.The contributions of REMS and SWS to habituation of social stress are distinct. REMS theta activity proposedly facilitates the consolidation of autonomic affective responses. Declarative memory consolidation may not have greater dependence on intact SWS relative to intact REMS. Disrupted sleep is a common problem with negative effects on affective regulation. While research indicates that rapid eye movement sleep has a central role in off-line affective processing, the mechanisms are not well defined. We used selective sleep stage suppression to investigate how disrupted sleep and stage-specific neural activity modulated the affective responsivity towards a self-conscious stressor inducing shame. We show that theta band oscillatory activity during rapid eye movement sleep is especially important for preserving the physiological stress response overnight. Understanding sleep-driven affective regulation facilitates development of applications aiming at improving mental wellbeing.
PubMed: 38802242
DOI: 10.1523/ENEURO.0453-23.2024 -
General Psychiatry 2024Understanding the evolution of circadian rhythm dysfunction and psychopathology in the high-risk population has important implications for the prevention of bipolar...
BACKGROUND
Understanding the evolution of circadian rhythm dysfunction and psychopathology in the high-risk population has important implications for the prevention of bipolar disorder. Nevertheless, some of the previous studies on the emergence of psychopathologies and circadian dysfunction among high-risk populations were inconsistent and limited.
AIMS
To examine the prevalence rates of sleep and circadian dysfunctions, mental disorders and their symptoms in the offspring of parents with (O-BD) and without bipolar disorder (O-control).
METHODS
The study included 191 O-BD and 202 O-control subjects aged 6-21 years from the Greater Bay Area, China. The diagnoses and symptoms of sleep/circadian rhythm and mental disorders were assessed by the Diagnostic Interview for Sleep Patterns and Disorders, and the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version, respectively. Generalised estimating equations and shared frailty proportional hazards models of survival analysis were applied to compare the outcomes in the offspring.
RESULTS
Adjusting for age, sex and region of recruitment, there was a significantly higher risk of delayed sleep phase symptoms (9.55% vs 2.58%, adjusted OR: 4.04) in O-BD than in O-control. O-BD had a nearly fivefold higher risk of mood disorders (11.70% vs 3.47%, adjusted OR: 4.68) and social anxiety (6.28% vs 1.49%, adjusted OR: 4.70), a fourfold higher risk of depressive disorders (11.17% vs 3.47%, adjusted OR: 3.99) and a threefold higher risk of mood symptoms (20.74% vs 10.40%, adjusted OR: 2.59) than O-control. Subgroup analysis revealed that O-BD children (aged under 12 years) had a nearly 2-fold higher risk of any mental and behavioural symptoms than O-control, while there was a nearly 4-fold higher risk of delayed sleep phase symptoms, a 7.5-fold higher risk of social anxiety and a 3-fold higher risk of mood symptoms in O-BD adolescents (aged 12 years and over).
CONCLUSIONS
There was an increase in delayed sleep phase symptoms in O-BD adolescents compared with their control counterparts, confirming the central role of circadian rhythm dysfunction in bipolar disorder. The findings of the specific age-related and stage-related developmental patterns of psychopathologies and circadian dysfunction in children and adolescent offspring of parents with bipolar disorder paved the way to develop specific and early clinical intervention and prevention strategies.
TRIAL REGISTRATION NUMBER
NCT03656302.
PubMed: 38800632
DOI: 10.1136/gpsych-2023-101239 -
Frontiers in Neurology 2024This study aimed to validate a sleep staging algorithm using in-hospital video-electroencephalogram (EEG) in children without epilepsy, with well-controlled epilepsy...
OBJECTIVES
This study aimed to validate a sleep staging algorithm using in-hospital video-electroencephalogram (EEG) in children without epilepsy, with well-controlled epilepsy (WCE), and with drug-resistant epilepsy (DRE).
METHODS
Overnight video-EEG, along with electrooculogram (EOG) and chin electromyogram (EMG), was recorded in children between 4 and 18 years of age. Classical sleep staging was performed manually as a ground truth. An end-to-end hierarchical recurrent neural network for sequence-to-sequence automatic sleep staging (SeqSleepNet) was used to perform automated sleep staging using three channels: C4-A1, EOG, and chin EMG.
RESULTS
In 176 children sleep stages were manually scored: 47 children without epilepsy, 74 with WCE, and 55 with DRE. The 5-class sleep staging accuracy of the automatic sleep staging algorithm was 84.7% for the children without epilepsy, 83.5% for those with WCE, and 80.8% for those with DRE (Kappa of 0.79, 0.77, and 0.73 respectively). Performance per sleep stage was assessed with an F1 score of 0.91 for wake, 0.50 for N1, 0.83 for N2, 0.84 for N3, and 0.86 for rapid eye movement (REM) sleep.
CONCLUSION
We concluded that the tested algorithm has a high accuracy in children without epilepsy and with WCE. Performance in children with DRE was acceptable, but significantly lower, which could be explained by a tendency of more time spent in N1, and by abundant interictal epileptiform discharges and intellectual disability leading to less recognizable sleep stages. REM sleep time, however, significantly affected in children with DRE, can be detected reliably by the algorithm.: ClinicalTrials.gov, identifier NCT04584385.
PubMed: 38798709
DOI: 10.3389/fneur.2024.1390465