The association between urbanization and depression in the elderly: A network analysis from the complexity science perspective.

IMPORTANCE: The global increase in urbanization has coincided with a rise in depression prevalence. However, the effect of urbanization on depression remains controversial, especially for the elderly. OBJECTIVE: To clarify how urbanization impacts depression in the elderly from a network perspective. DESIGN, SETTING, AND PARTICIPANTS: This sectional cohort study used data from China Health and Retirement Longitudinal Study (CHARLS). MAIN OUTCOMES AND MEASURES: The occurrence of depressive symptoms in urban and rural elderly residents. Network metrics of depressive symptoms. RESULTS: Of the 13,993 participants, lower incidence of depressive symptoms was observed in urban (26.3 %, 95 % CI, 24.7 %-27.8 %) than in rural (40.4 %, 95 % CI, 39.5 %-41.3 %, P < 0.0001) residents. However, higher incidence of depressive symptoms was observed in urban (26.3 %, 95 % CI, 25.2 %-28.4 %) than in rural (17.5 %, 95 % CI, 16.1 %-18.9 %, P < 0.0001) residents in a subset of 2898 pairs of participants after PSM. No difference in the network structure and metrics between urban and rural residents before (M = 0.071, p = 0.054, S = 0.037, p = 0.80) and after (M = 0.085, p = 0.133, S = 0.086, p = 0.47) PSM was detected. The networks structure revealed that negative affect was strongly connected to somatic symptoms and that the two anhedonic symptoms were also strongly connected. CONCLUSIONS: The current study indicated the homogeneity of the ultimate nature of depression between rural and urban residents from the network perspective, supporting the viewpoint that urbanization might not impose influence on depression. Further researches delving deeper into the complexity of the issue may provide new insights into our understanding of depression in an urban environment among the elderly.

Association of sleep timing with all-cause and cardiovascular mortality: the Sleep Heart Health Study and the Osteoporotic Fractures in Men Study.

STUDY OBJECTIVES: Previous studies have highlighted the importance of sleep patterns for human health. This study aimed to investigate the association of sleep timing with all-cause and cardiovascular disease mortality. METHODS: Participants were screened from two cohort studies: the Sleep Heart Health Study (SHHS; n = 4,824) and the Osteoporotic Fractures in Men Study (n = 2,658). Sleep timing, including bedtime and wake-up time, was obtained from sleep habit questionnaires at baseline. The sleep midpoint was defined as the halfway point between the bedtime and wake-up time. Restricted cubic splines and Cox proportional hazards regression analyses were used to examine the association between sleep timing and mortality. RESULTS: We observed a U-shaped association between bedtime and all-cause mortality in both the SHHS and Osteoporotic Fractures in Men Study groups. Specifically, bedtime at 11:00 pm and waking up at 7:00 am was the nadir for all-cause and cardiovascular disease mortality risks. Individuals with late bedtime (> 12:00 am) had an increased risk of all-cause mortality in SHHS (hazard ratio 1.53, 95% confidence interval 1.28-1.84) and Osteoporotic Fractures in Men Study (hazard ratio 1.27, 95% confidence interval 1.01-1.58). In the SHHS, late wake-up time (> 8:00 am) was associated with increased all-cause mortality (hazard ratio 1.39, 95% confidence interval 1.13-1.72). No significant association was found between wake-up time and cardiovascular disease mortality. Delaying sleep midpoint (> 4:00 am) was also significantly associated with all-cause mortality in the SHHS and Osteoporotic Fractures in Men Study. CONCLUSIONS: Sleep timing is associated with all-cause and cardiovascular disease mortality. Our findings highlight the importance of appropriate sleep timing in reducing mortality risk. CITATION: Ma M, Fan Y, Peng Y, et al. Association of sleep timing with all-cause and cardiovascular mortality: the Sleep Heart Health Study and the Osteoporotic Fractures in Men Study. J Clin Sleep Med. 2024;20(4):545-553.

Incidence and risk factors of depression in patients with metabolic syndrome.

BACKGROUND: Many studies have explored the relationship between depression and metabolic syndrome (MetS), especially in older people. China has entered an aging society. However, there are still few studies on the elderly in Chinese communities. AIM: To investigate the incidence and risk factors of depression in MetS patients in mainland China and to construct a predictive model. METHODS: Data from four waves of the China Health and Retirement Longitudinal Study were selected, and middle-aged and elderly patients with MetS (n = 2533) were included based on the first wave. According to the center for epidemiological survey-depression scale (CESD), participants with MetS were divided into depression (n = 938) and non-depression groups (n = 1595), and factors related to depression were screened out. Subsequently, the 2-, 4-, and 7-year follow-up data were analyzed, and a prediction model for depression in MetS patients was constructed. RESULTS: The prevalence of depression in middle-aged and elderly patients with MetS was 37.02%. The prevalence of depression at the 2-, 4-, and 7-year follow-up was 29.55%, 34.53%, and 38.15%, respectively. The prediction model, constructed using baseline CESD and Physical Self-Maintenance Scale scores, average sleep duration, number of chronic diseases, age, and weight had a good predictive effect on the risk of depression in MetS patients at the 2-year follow-up (area under the curve = 0.775, 95% confidence interval: 0.750-0.800, P < 0.001), with a sensitivity of 68% and a specificity of 74%. CONCLUSION: The prevalence of depression in middle-aged and elderly patients with MetS has increased over time. The early identification of and intervention for depressive symptoms requires greater attention in MetS patients.

Sleep architecture and the incidence of depressive symptoms in middle-aged and older adults: A community-based study.

BACKGROUND: Rapid eye movement (REM) sleep and three stages of non-REM (NREM) sleep comprise the full sleep cycle. The changes in sleep have been linked to depression risk. This study aimed to explore the association between sleep architecture and depressive symptoms. METHODS: A total of 3247 participants from the Sleep Heart Health Study (SHHS) were included in this cohort study. REM and NREM sleep were monitored by in-home polysomnography at SHHS visit 1. Depressive symptoms was reported as the first occurrence between SHHS visits 1 and 2 (mean follow-up of 5.3 years). Multivariable logistic regression was used to investigate the relationship between sleep stages and depressive symptoms. RESULTS: In total, 225 cases of depressive symptoms (6.9 %) were observed between SHHS visits 1 and 2. A significant linear association between NREM Stage 1 and depressive symptoms was found after adjusting for potential covariates. Multivariable logistic regression analysis showed that percentage in NREM Stage 1 was associated with the incidence of depressive symptoms (odds ratio [OR], 1.06; 95 % confidence interval [CI], 1.02-1.10; P = 0.001), as were time in NREM Stage 1 and depressive symptoms (OR, 1.02; 95 % CI, 1.01-1.03; P = 0.001). However, no significant association with depressive symptoms was found for other sleep stage. LIMITATIONS: The specific follow-up time for depressive symptoms diagnosis was missing. CONCLUSIONS: Increased time or percentage in NREM Stage 1 was associated with a higher risk of developing depressive symptoms. The early change in sleep architecture were important for incidence of depressive symptoms and warrants constant concerns.

Immune dysregulation is associated with symptom dimensions and cognitive deficits in schizophrenia: accessible evidence from complete blood count.

BACKGROUND: Schizophrenia (SCZ) is a psychotic disorder with an unknown pathogenesis accompanied by varying degrees of cognitive deficits. Recent studies have shown that immune dysregulation plays an important role in developing symptoms and cognitive deficits in SCZ. This study aimed to determine the complete blood count (CBC), including white blood cells, neutrophils, monocytes, lymphocytes, platelets, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR), in patients with SCZ and explore their correlations with SCZ symptom dimensions and cognitive function. METHODS: Seventy-four patients with SCZ and 57 age- and sex-matched healthy controls with available demographic and clinical information were recruited for this study. Blood samples were collected, and symptom dimensions and cognitive function were evaluated using the Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery (MCCB) separately. RESULTS: Our results demonstrate that SCZ patients showed higher monocyte counts, PLR, MLR, and worse performance in the total MCCB than healthy controls. Neutrophil and lymphocyte counts and NLR were positively related to symptom severity and negatively related to depressive symptoms. White blood cell (WBC) count, monocyte count, and MLR were positively correlated with cognitive performance in patients with SCZ. CONCLUSION: In summary, this study suggests that cognitive deficits and symptom severity in patients were associated with dysregulation of immunity. Moreover, we found that WBC could be used as a marker for symptom severity and cognitive deficits in SCZ and that neutrophils are more closely related to the former and monocytes to the latter. We hope that clinicians will pay more attention to dysregulated immunity in patients with SCZ in the future.

Longitudinal Gut Microbiota Dysbiosis Underlies Olanzapine-Induced Weight Gain.

Olanzapine is one of the most effective medicines available for stabilizing schizophrenia spectrum disorders. However, it has been reported to show the greatest propensity for inducing body weight gain and producing metabolic side effects, which cause a great burden in patients with psychiatric disorders. Since the gut microbiota has a profound impact on the initiation and development of metabolic diseases, we conducted a longitudinal study to explore its role in olanzapine-induced obesity and metabolic abnormalities. Female Sprague-Dawley rats were treated with different doses of olanzapine, and metabolic and inflammatory markers were measured. Olanzapine significantly induced body weight gain (up to a 2.1-fold change), which was accompanied by hepatic inflammation and increased plasma triglyceride levels (up to a 2.9-fold change), as well as gut microbiota dysbiosis. Subsequently, fuzzy c-means clustering was used to characterize three clusters of longitudinal trajectories for microbial fluctuations: (i) genera continuing to increase, (ii) genera continuing to decrease, and (iii) genera temporarily changing. Among them, Enterorhabdus (r = 0.38), Parasutterella (r = 0.43), and Prevotellaceae UCG-001 (r = 0.52) positively correlated with body weight gain. In addition, two MetaCyc metabolic pathways were identified as associated with olanzapine-induced body weight gain, including the superpathway of glucose and xylose degradation and the superpathway of l-threonine biosynthesis. In conclusion, we demonstrate that olanzapine can directly alter the gut microbiota and rapidly induce dysbiosis, which is significantly associated with body weight gain. This may suggest gut microbiota targets in future studies on metabolic abnormalities caused by olanzapine. IMPORTANCE Olanzapine is one of the most effective second-generation antipsychotics for stabilizing schizophrenia spectrum disorders. However, olanzapine has multiple drug-induced metabolic side effects, including weight gain. This study provides insight to the gut microbiota target in olanzapine-induced obesity. Specifically, we explored the longitudinal gut microbiota trajectories of female Sprague-Dawley rats undergoing olanzapine treatment. We showed that olanzapine treatment causes a dynamic alteration of gut microbiota diversity. Additionally, we identified three genera, Parasutterella, Enterorhabdus, and Prevotellaceae UCG-001, that may play an important role in olanzapine-induced obesity. In this case, the supply or removal of specific elements of the gut microbiota may represent a promising avenue for treatment of olanzapine-related metabolic side effects.

Dexmedetomidine alleviates host ADHD-like behaviors by reshaping the gut microbiota and reducing gut-brain inflammation.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders that affects children and even continues into adulthood. Dexmedetomidine (DEX), a short-term sedative, can selectively activate the α2-adrenoceptor. Treatment with α2-adrenergic agonists in patients with ADHD is becoming increasingly common. However, the therapeutic potential of DEX for the treatment of ADHD is unknown. Here, we evaluated the effect of DEX on ADHD-like behavior in spontaneously hypertensive rats (SHRs), a widely used animal model of ADHD. DEX treatment ameliorated hyperactivity and spatial working memory deficits and normalized θ electroencephalogram (EEG) rhythms in SHRs. We also found that DEX treatment altered the gut microbiota composition and promoted the enrichment of beneficial gut bacterial genera associated with anti-inflammatory effects in SHRs. The gut pathological scores and permeability and the level of inflammation observed in the gut and brain were remarkably improved after DEX administration. Moreover, transplantation of fecal microbiota from DEX-treated SHRs produced effects that mimicked the therapeutic effects of DEX administration. Therefore, DEX is a promising treatment for ADHD that functions by reshaping the composition of the gut microbiota and reducing inflammation in the gut and brain.

Association of Objective and Self-Reported Sleep Duration With All-Cause and Cardiovascular Disease Mortality: A Community-Based Study.

Background Previous studies found an association between self-reported sleep duration and mortality. This study aimed to compare the effects of objective and self-reported sleep duration on all-cause and cardiovascular disease (CVD) mortality. Methods and Results A total of 2341 men and 2686 women (aged 63.9±11.1 years) were selected from the SHHS (Sleep Heart Health Study). Objective sleep duration was acquired using in-home polysomnography records, and self-reported sleep duration on weekdays and weekends was based on a sleep habits questionnaire. The sleep duration was categorized as ≤4 hours, 4 to 5 hours, 5 to 6 hours, 6 to 7 hours, 7 to 8 hours, and >8 hours. Multivariable Cox regression analysis was used to investigate the association of objective and self-reported sleep duration with all-cause and CVD mortality. During a mean follow-up period of 11 years, 1172 (23.3%) participants died, including 359 (7.1%) deaths from CVD. All-cause and CVD mortality rates decreased gradually with increasing objective sleep duration. In multivariable Cox regression analysis, the greatest association for all-cause and CVD mortality was with an objective sleep duration of 5 hours or shorter. In addition, we found a J-shaped association of self-reported sleep duration on both weekdays and weekends with all-cause and CVD mortality. Self-reported short (≤4 hours) and long (>8 hours) sleep duration on weekdays and weekends were associated with an increased risk of all-cause and CVD mortality compared with 7 to 8 hours sleep duration. Furthermore, a weak correlation was observed between objective and self-reported sleep duration. Conclusions This study showed that both objective and self-reported sleep duration were associated with all-cause and CVD mortality, but with different characteristics. Registration URL: https://clinicaltrials.gov/ct2/show/NCT00005275; Unique identifier: NCT00005275.

A comparison of clinical characteristics of psychiatric inpatients in three hospitals from Western China and America.

BACKGROUND: Different countries have differences in social and cultural context and health system, which may affect the clinical characteristics of psychiatric inpatients. This study was the first to compare cross-cultural differences in the clinical characteristics of psychiatric inpatients in three hospitals from Western China and America. METHODS: Overall, 905 and 1318 patients from three hospitals, one in America and two in Western China, respectively, were included. We used a standardised protocol and data collection procedure to record inpatients' sociodemographic and clinical characteristics. RESULTS: Significant differences were found between hospitals from the two countries. Positive symptoms were the main reason for admission in the Chinese hospitals, while reported suicide and self-injury symptoms more frequently led to hospital admission in America. Moreover, there were more inpatients with combined substance abuse in the American hospital (97.6% vs. 1.9%, P < 0.001). The length of stay (LOS) in America was generally shorter than in China (10.5 ± 11.9 vs. 20.7 ± 13.4, P < 0.001). The dosage of antipsychotic drugs used in the American hospital was higher than in China (275.1 ± 306.9 mg vs. 238.3 ± 212.5 mg, P = 0.002). Regression analysis showed that male sex, older age, retirees, being admitted because of physical symptoms, and using higher doses of antipsychotic drugs were significantly associated with longer hospitalisation in the American hospital (P < 0.05). Comparatively, patients who were divorced, experiencing suicidal ideation, admitted involuntarily, admitted because of physical, depression, or anxiety symptoms, and using higher doses of antipsychotic drugs had longer hospitalisation in Chinese hospitals (P < 0.05). CONCLUSION: Significant variations in clinical characteristics of inpatients were found between hospitals from Western China and America. The LOS in Chinese hospitals was significantly longer, but patients used higher doses of antipsychotic drugs in the American hospital. Admission due to physical symptoms and the use of higher dosage drugs were related to longer LOS in both countries.

Bacteriophages allow selective depletion of gut bacteria to produce a targeted-bacterium-depleted mouse model.

The gut microbiome is essential for human health. Mouse microbiota models, including gnotobiotic mice, are the most prominent tools to elucidate the functions of gut bacteria. Here, we propose a targeted-bacterium-depleted (TBD) model using lytic bacteriophage to selectively deplete gut bacterium of healthy or otherwise defined mice. These phage-treated animals should have a near-complete spectrum of gut bacteria except for the depleted bacterium. To prove the concept, we employed Escherichia coli-specific phage T7 to repress E. coli in the healthy mice. Our results showed that the E. coli-depleted mice exhibited bravery-like behaviors, correlated to the presence of E. coli rather than the equilibrium among gut bacteria. Thus, we demonstrate that the TBD model is a powerful tool to elucidate the function of a specific bacterial species within a near-intact gut microbiota environment and complements gnotobiotic mice models.

Development and Validation of the Chinese Version of the Highly Sensitive Child Scale: Understanding environmental sensitivity and depressive symptoms in adolescents.

Background: Environmental sensitivity (ES) is considered a significant personality factor in the development and maintenance of depressive symptoms in adolescents. However, a clear instrument that can capture ES in Chinese adolescents is lacking. The current study aimed to investigate the psychometric properties of a Chinese version of the Highly Sensitive Child (HSC) Scale for assessing adolescent ES, and explore the potential moderation effect of ES on relationships between maternal behaviors and adolescent depressive symptoms. Methods: In total, 2,166 students from four middle and high schools and 105 depressed adolescents completed measurements of environmental sensitivity, maternal behaviors, depressive emotions, sleep duration, and academic performance. Results: First, exploratory factor and confirmatory factor analyses indicated that the HSC scale had a good model fit with the bifactor construct, total scale reliability was adequate-good, and measurement invariances across genders and different samples were supported. Furthermore, the results confirmed that the relationship between maternal behaviors and adolescent depressive symptoms had small effects. Compared to low environmentally sensitive adolescents, high environmentally sensitive adolescents exhibited less depressive emotions and better academic performance in the context of high-quality maternal behaviors. Low-quality maternal behaviors significantly predicted increased depressive emotions and worse academic performance in adolescents when environmental sensitivity was high. Moreover, on the contrary, maternal behaviors did not influence depressive emotions and academic performance in adolescents who were less sensitive to their environment. The relationship between maternal behaviors and adolescent depressive symptoms is influenced by different levels of environmental sensitivity. Conclusion: Our findings support the HSC scale as a comprehensive and psychometrically robust tool to measure ES in Chinese adolescents. In addition, the present study clarifies the moderating role of environmental sensitivity underlying the relationship between maternal behaviors and adolescent depressive symptoms. It is important to consider the role of ES in prevention and intervention strategies targeting adolescent depressive symptoms.

Grey matter volume and its association with cognitive impairment and peripheral cytokines in excited individuals with schizophrenia.

Although excited behavior in patients with schizophrenia has been linked to brain structural abnormalities, whether cortical abnormalities in this subgroup are related to cognitive impairment or peripheral immune responses is unknown. We included 28 patients with excitability (EC), 28 patients without excitability (NEC), and 48 healthy controls (HCs) to evaluate the associations. Compared with the HC group, the EC and NEC groups showed significant cognitive impairment and increased serum cytokine levels. Analysis of variance in whole-brain grey matter volume (GMV) showed that the volumes of several brain areas, including the superior frontal gyrus (SFG), superior temporal gyrus, and cingulate gyrus, were decreased in patients with schizophrenia. Notably, the left SFG volume was significantly lower in the EC group than in the NEC group. Spearman correlation analysis showed that elevated cytokines were negatively correlated with the GMV of the bilateral SFG, bilateral inferior parietal gyrus, left anterior cingulate gyrus, right fusiform gyrus and parahippocampal gyrus, which were mainly positive correlated with cognitive tests. Moreover, interleukin 4 may contribute to poor scores on Brief Assessment of Cognition and Neuropsychological Assessment Battery by reducing the left SFG volume (17%, Pmediation = 0.044; and 24%, Pmediation = 0.040, respectively). In conclusion, our results confirm GMV changes in excited patients with schizophrenia, and characterize the GMV as an important interface between inflammatory cytokines and cognitive impairment. Therefore, targeted anti-inflammatory adjuvant antipsychotic therapy may improve cognitive function and volumetric brain abnormalities in these patients.

TNF-α, IL-6 and hsCRP in patients with melancholic, atypical and anxious depression: an antibody array analysis related to somatic symptoms.

Background: The association between inflammation and major depressive disorder (MDD) remains poorly understood, given the heterogeneity of patients with MDD. Aims: We investigated inflammatory markers, such as interleukin (IL)-6, high-sensitivity C reactive protein (hsCRP) and tumour necrosis factor-α (TNF-α) in melancholic, atypical and anxious depression and explored whether baseline inflammatory protein levels could indicate prognosis. Methods: The sample consisted of participants (aged 18-55 years) from a previously reported multicentre randomised controlled trial with a parallel-group design registered with ClinicalTrials.gov, including melancholic (n=44), atypical (n=37) and anxious (n=44) patients with depression and healthy controls (HCs) (n=33). Subtypes of MDD were classified according to the 30-item Inventory of Depressive Symptomatology, Self-Rated Version and the 17-item Hamilton Depression Rating Scale. Blood levels of TNF-α, IL-6 and hsCRP were assessed using antibody array analysis. Results: Patients with MDD, classified according to melancholic, atypical and anxious depression subtypes, and HCs did not differ significantly in baseline TNF-α, IL-6 and hsCRP levels after adjustment. In patients with anxious depression, hsCRP levels increased significantly if they experienced no pain (adjusted (adj.) p=0.010) or mild to moderate pain (adj. p=0.038) compared with those with severe pain. However, the patients with anxious depression and severe pain showed a lower trend in hsCRP levels than patients with atypical depression who experienced severe pain (p=0.022; adj. p=0.155). Baseline TNF-α (adj. p=0.038) and IL-6 (adj. p=0.006) levels in patients in remission were significantly lower than those in patients with no remission among the participants with the atypical depression subtype at the eighth-week follow-up. Conclusions: This study provides evidence of differences in inflammatory proteins in patients with varied symptoms among melancholic, atypical and anxious depression subtypes. Further studies on the immunoinflammatory mechanism underlying different subtypes of depression are expected for improved individualised therapy. Trial registration number: NCT03219008.

Characterizing serum amino acids in schizophrenic patients: Correlations with gut microbes.

Amino acid abnormalities have been suggested to be a key pathophysiological mechanism in schizophrenia (SZ). Recently, gut microbes were found to be critically involved in mental and metabolic diseases. However, the relationship between serum amino acid levels and gut microbes in SZ is rarely studied. Here, we analyzed serum amino acid levels in 76 untreated SZ patients and 79 healthy controls (HC). Serum levels of 10 amino acids were significantly altered in patients with SZ. We further classified the cut-off values for serum arginine, leucine, glutamine, and methionine levels to distinguish SZ patients from controls. These classifiers were shown to be effective in another validation cohort (49 SZ and 48 HC). The correlation between serum amino acids and clinical symptoms and cognitive functions was also analyzed. Arginine, leucine, glutamine, and methionine levels were significantly correlated with clinical symptoms and cognitive impairments in SZ patients. By metagenome shotgun sequencing of fecal samples, we found that patients with SZ with a low level of serum amino acids have higher richness and evenness of the gut microbiota. At the genus level, the abundances of Mitsuokella and Oscillibacter are significantly abnormal. At the mOTU level, 15 mOTUs in the low-level SZ group were significantly different from the HC group. In addition, Mitsuokella multacida was correlated with glutamine and methionine, respectively. Our research revealed that alterations in serum amino acid levels are critically related to changes in gut microbiota composition in SZ patients. These findings may shed light on new strategies for the diagnosis and treatment of SZ.

Sleep Efficiency May Predict Depression in a Large Population-Based Study.

Objectives: The purpose of our study was to investigate the effect of objective sleep characteristics on the incidence of depression. Methods: The participants of our study (1,595 men and 1,780 women with 63.1 ± 10.7 years) were selected from the Sleep Heart Health Study (SHHS) datasets. Depression was defined as the first occurrence between SHHS visit 1 and visit 2. Objective sleep characteristics, including sleep efficiency (SE), wake after sleep onset (WASO), sleep fragmentation index (SFI) and arousal index (ArI), were monitored by polysomnography. Multivariable logistic regression was used to explore the relationship between sleep characteristics and depression. Results: A total of 248 patients with depression (7.3%) were observed between SHHS visits 1 and 2. After adjusting for covariates, SE (odds ratio [OR], 0.891; 95% confidence interval [CI] 0.811-0.978; P = 0.016) and WASO (OR, 1.021; 95% CI 1.002-1.039; P = 0.026) were associated with the incidence of depression. Moreover, the relationship between SE and depression was more pronounced in men (OR, 0.820; 95% CI 0.711-0.946; P = 0.007) than in women (OR, 0.950; 95% CI 0.838-1.078; P = 0.429) in subgroup analysis (P interaction < 0.05). Conclusions: SE and WASO may be markers for the incidence of depression. The association between SE and depression was intensified in men.

Increased Rapid Eye Movement Sleep Is Associated With a Reduced Risk of Heart Failure in Middle-Aged and Older Adults.

Objectives: Rapid eye movement (REM) sleep is closely related to all-cause mortality. The aim of this study is to explore the role of REM sleep on the incident heart failure (HF). Methods: We selected 4490 participants (2480 women and 2010 men; mean age, 63.2 ± 11.0 years) from the Sleep Heart Health Study. HF was identified as the first occurrence during a mean follow-up period of 10.9 years. REM sleep including percentage of REM sleep and total REM sleep time were monitored using in-home polysomnography at baseline. Multivariable Cox regression analysis was utilized to explore the relationship between REM sleep and HF. Results: In total, 436 (9.7%) cases of HF were observed during the entire follow-up period. After adjusting for potential covariates, an increased percentage of REM sleep (per 5%) was independently associated with a reduced incidence of HF [hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.82-0.94, P < 0.001]. A similar result was also found between total REM sleep time (increased per 5 min) and incident HF (HR 0.97, 95% CI 0.95-0.99, P < 0.001). Moreover, the fourth quartile of both percentage of REM sleep (HR 0.65, 95% CI 0.48-0.88, P = 0.005) and total REM sleep time (HR 0.64, 95% CI 0.45-0.90, P = 0.010) had lower risk of incident HF when compared with the first quartile. Conclusion: An increased percentage of REM sleep and total REM sleep time were associated with a reduced risk of HF. REM sleep may be a predictor of the incident HF. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT00005275].

Association between plasma proteome and childhood neurodevelopmental disorders: A two-sample Mendelian randomization analysis.

BACKGROUND: Childhood neurodevelopmental disorders, including autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and Tourette syndrome (TS), comprise a major cause of health-related disabilities in children. However, biomarkers towards pathogenesis or novel drug targets are still limited. Our study aims to provide a comprehensive investigation of the causal effects of the plasma proteome on ASD, ADHD, and TS using the two-sample Mendelian Randomization (MR) approach. METHODS: Genetic associations with 2994 plasma proteins were selected as exposures and genome-wide association data of ASD, ADHD, TS were utilized as outcomes. MR analyses were carried out using the inverse-variance weighted method, and the MR-Egger and weighted median methods were used for sensitivity analysis. FINDINGS: Using single-nucleotide polymorphisms as instruments, the study suggested increased levels of MAPKAPK3 (OR: 1.09; 95% CI: 1.05-1.13; P = 1.43 × 10-6) and MRPL33 (OR: 1.07; 95% CI: 1.04-1.11; P = 5.37 × 10-6) were causally associated with a higher risk of ASD, and increased MANBA level was associated with a lower risk of ADHD (OR: 0.91; 95% CI: 0.88-0.95; P = 8.97 × 10-6). The causal associations were robust in sensitivity analysis, leave-one-out analysis and Multivariable MR, and no pleiotropy was observed. No significant risk protein was identified for TS. INTERPRETATION: The study findings support the idea that the MAPK/ERK signaling pathway and mitochondrial dysfunction are involved in the pathogenesis of ASD, while a deficiency in beta-mannosidase might play a role in the development of ADHD. FUNDING: Natural Science Basic Research Program of Shaanxi (2021JQ-390).

Estimation of the bidirectional relationship between schizophrenia and inflammatory bowel disease using the mendelian randomization approach.

It has been reported that schizophrenia (SCZ) and inflammatory bowel disease (IBD) are related. However, whether there is a bidirectional interaction between them remains unclear. The aim of this study was to conduct a bidirectional Mendelian randomization (MR) analysis to elucidate the causal relationship between SCZ and IBD and its subtypes, including Crohn's disease (CD) and ulcerative colitis (UC). Single-nucleotide polymorphisms (SNPs) extracted from the summary data of genome-wide association studies were used as genetic instruments. MR was performed using the inverse-variance-weighted method. The MR-Egger and weighted median methods were used for sensitivity analyses. Analysis using 70 SNPs as genetic instruments showed that SCZ was associated with an increased risk of IBD (OR = 1.14, 95% CI: 1.09-1.20, P = 9.21 × 10-8), CD (OR = 1.16, 95% CI: 1.07-1.25, P = 1.42 × 10-4), and UC (OR = 1.14, 95% CI: 1.07-1.21, P = 2.72 × 10-5). The results of the sensitivity analyses were robust and no evidence of pleiotropy was observed. Bidirectional MR analyses showed no causal effects of IBD, CD, or UC on SCZ. This study suggests that SCZ has causal effects on IBD and its subtypes, whereas IBD has no effect on SCZ. Brain-gut axis interactions may help clarify the causal relationship between SCZ and IBD. However, further studies are needed to elucidate the biological mechanisms behind the brain-gut interactions.

The associations between sleep behaviors, lifestyle factors, genetic risk and mental disorders: A cohort study of 402 290 UK Biobank participants.

BACKGROUND: Sleep behaviors were believed to be associated with mental disorders (MD). However, the underlying mechanism of such association relationship, especially the role of multiple lifestyle factors in it remains unclear. METHODS: A total of 402,290 participants from UK Biobank who don't have MD at baseline were included. They were divided into poor, intermediate and healthy sleep patterns according to the sleep score, which was calculated based on the data collecting from five sleep behaviors. Cox proportional hazard model was used to estimate the associations between sleep behaviors and MD. The associations were further estimated when taking lifestyle factors such as physical activity, coffee intake, tea intake and genetic susceptibility into account. RESULTS: Healthy sleep pattern was associated with lower risk of overall MD status (HR,0.41, 95%CI,0.39-0.43), depressive disorders (HR,0.34, 95%CI,0.31-0.37) and anxiety disorders (HR,0.46, 95%CI,0.41-0.79), compared with poor sleep pattern. And in each subgroup of physical activity, tea intake, coffee intake, age and genetic risk scores (GRS), healthy sleep pattern could partly offset the risk of diseases. CONCLUSIONS: Our study suggested healthy sleep behaviors could diminish the negative effect from genetic predisposition and lifestyle factors on the risk of MD, highlighting the benefit of healthy sleep pattern.

Multi-Omics Analysis Reveals Aberrant Gut-Metabolome-Immune Network in Schizophrenia.

Schizophrenia (SCZ) is associated with several immune dysfunctions, including elevated levels of pro-inflammatory cytokines. Microorganisms and their metabolites have been found to regulate the immune system, and that intestinal microbiota is significantly disturbed in schizophrenic patients. To systematically investigate aberrant gut-metabolome-immune network in schizophrenia, we performed an integrative analysis of intestinal microbiota, serum metabolome, and serum inflammatory cytokines in 63 SCZ patients and 57 healthy controls using a multi-omics strategy. Eighteen differentially abundant metabolite clusters were altered in patients displayed higher cytokine levels, with a significant increase in pro-inflammatory metabolites and a significant decrease in anti-inflammatory metabolites (such as oleic acid and linolenic acid). The bacterial co-abundance groups in the gut displayed more numerous and stronger correlations with circulating metabolites than with cytokines. By integrating these data, we identified that certain bacteria might affect inflammatory cytokines by modulating host metabolites, such as amino acids and fatty acids. A random forest model was constructed based on omics data, and seven serum metabolites significantly associated with cytokines and α-diversity of intestinal microbiota were able to accurately distinguish the cases from the controls with an area under the receiver operating characteristic curve of 0.99. Our results indicated aberrant gut-metabolome-immune network in SCZ and gut microbiota may influence immune responses by regulating host metabolic processes. These findings suggest a mechanism by which microbial-derived metabolites regulated inflammatory cytokines and insights into the diagnosis and treatment of mental disorders from the microbial-immune system in the future.