Increased regional body fat is associated with depressive symptoms: a cross-sectional analysis of NHANES data obtained during 2011-2018.

AIMS: The findings from previous epidemiological studies of the association between regional body fat and depressive symptoms have been unclear. We aimed to determine the association between the body fat in different regions and depressive symptoms based on data from the National Health and Nutrition Examination Survey (NHANES). METHODS: This study included 3393 participants aged ≥ 20 years from the NHANES performed during 2011-2018. Depressive symptoms were assessed using the Patient Health Questionnaire-9. The fat mass (FM) was measured in different regions using dual-energy X-ray absorptiometry to determine the total FM, trunk FM, arm FM, and leg FM. The FM index (FMI) was obtained by dividing the FM in kilograms by the square of the body height in meters. Weighted data were calculated in accordance with analytical guidelines. Linear logistic regression models were used to quantify the association between regional FMI and depressive symptoms. Univariate and stratified analyses were also performed. RESULTS: The participants in this study comprised 2066 males and 1327 females. There were 404 (11.91%) participants with depressive symptoms, who were aged 40.89 ± 11.74 years and had a body mass index of 30.07 ± 7.82 kg/m². A significant association was found between total FMI and depressive symptoms. In the fully adjusted multivariate regression model, a higher total FMI (odds ratio = 2.18, 95% confidence interval [CI] = 1.08-4.39) was related to a higher risk of depressive symptoms, while increased total FMI (ß = 1.55, 95% CI = 0.65-2.44, p = 0.001), trunk FMI (ß = 0.57, 95% CI = 0.04-1.10, p = 0.036), and arm FMI (ß = 0.96, 95% CI = 0.33-1.59, p = 0.004) were significantly associated with PHQ-9 (Patient Health Questionnaire-9) scores, whereas the leg FMI was not (p = 0.102). The weighted association between total FMI and depressive symptoms did not differ significantly between most of the subpopulations (all p values for interaction > 0.05). The risk of having depression was higher in individuals who were non-Hispanic Whites, smokers, drinkers, obese, and had diabetes and thyroid problems (p < 0.05). CONCLUSION: These findings suggest that the population with a higher regional FMI is more likely to have depressive symptoms, especially in those who also have an increased total FMI. The association is more pronounced in individuals who are smokers, drinkers, obese, and have diabetes and thyroid problems.

The association between serum albumin and depressive symptoms: a cross-sectional study of NHANES data during 2005-2018.

AIMS: The association between serum albumin and depressive symptoms has been unclear in previous epidemiological studies. We explored whether serum albumin is associated with depressive symptoms based on the National Health and Nutrition Examination Survey (NHANES) data. METHODS: This cross-sectional study included 13,681 participants aged ≥ 20 years from the NHANES performed during 2005-2018, which produced nationally representative database. Depressive symptoms were assessed using the Patient Health Questionnaire-9. Serum albumin concentration was measured using the bromocresol purple dye method, and participants were divided into quartiles of serum albumin concentrations. Weighted data were calculated according to analytical guidelines. Logistics regression and linear regression models were used to assess and quantify the association between serum albumin and depressive symptoms. Univariate and stratified analyses were also performed. RESULTS: There were 1551 (10.23%) adults (aged ≥ 20 years) with depressive symptoms among the 13,681. A negative association was found between serum albumin concentration and depressive symptoms. Compared with the lowest albumin quartile, the multivariate-adjusted effect size (95% confidence interval) for depressive symptoms of the fully adjusted model in the highest albumin quartile was 0.77 (0.60 to 0.99) and - 0.38 (- 0.66 to - 0.09) using logistics regression and linear regression models respectively. Current smoking status modified the association between serum albumin concentration and PHQ-9 scores (p for interaction = 0.033). CONCLUSION: This cross-sectional study revealed that albumin concentration is significantly more likely to be a protective factor for depressive symptoms, with the association being more pronounced in non-smokers.

Non-suicidal self-injury and professional psychological help-seeking among Chinese left-behind children: prevalence and influencing factors.

BACKGROUND: Non-suicidal self-injury (NSSI) is a risk factor for suicide. This study aimed to investigate the prevalence of NSSI and professional psychological help-seeking status and influencing factors among left-behind children (LBC) in China. METHODS: We implemented a population-based cross-sectional study in participants aged 10-18 years. Sociodemographic characteristics, NSSI, help-seeking status and coping style were measured by self-reported questionnaires. A total of 16,866 valid questionnaires were collected, including 6096 LBC. Binary logistic regression models were used to analyze the factors influencing NSSI and professional psychological help-seeking. RESULTS: The incidence of NSSI among LBC was 4.6%, significantly higher than that of non-left-behind children (NLBC). This incidence was higher among girls. Moreover, 53.9% of LBC with NSSI did not receive any treatment and only 22.0% sought professional psychological help. LBC often adopt emotion-oriented coping styles, specifically, those with NSSI. LBC with NSSI who seek professional help tend to adopt problem-oriented coping styles. Logistic regression analysis revealed that girls, learning stage, single-parent, remarried families, patience, and emotional venting were risk factors for NSSI in LBC, while problem-solving and social support seeking were protective factors. Moreover, problem-solving was also a predictor for seeking professional psychological help, patience will prevent it. LIMITATIONS: This was an online survey. CONCLUSIONS: The prevalence of NSSI in LBC is high. Gender, grade, family structure, and coping style affect the occurrence of NSSI among LBC. Only a few LBC with NSSI seek professional psychological help, while the coping style will affect the help-seeking behavior.

The mRNA expression levels of GABAA receptor α1 and α2 subunits in patients with major depressive disorder during onset and remission.

OBJECTIVE: We aimed to investigate the expression levels of GABA and GABAA receptor α1 and α2 subunits in patients with major depressive disorder (MDD) during onset and remission. MATERIALS AND METHODS: 48 patients with MDD during onset and 45 patients with MDD during remission who were treated in our university were selected. Moreover, the control group included 46 healthy volunteers recruited in the community. The depression and anxiety symptoms were assessed by Hamilton Depression (HAMD) Scale and Hamilton Anxiety (HAMA) Scale. ELISA was used to determine the serum GABA levels. The mRNA expression of GABAA receptor α1 and α2 subunits in peripheral blood were detected by RT-PCR. RESULTS: The expression levels of serum GABA and of GABAA receptor α1 and α2 subunits in MDD depression attack group were notably decreased in comparison with those in MDD remission group and control group ((4.10 ± 0.73) v.s. (5.91 ± 1.25) and (5.83 ± 1.17) umol/L, F = 5.61, p < 0.001; (0.53 ± 0.32) v.s. (0.91 ± 0.18) and (0.93 ± 0.21), F = 8.37, p < 0.001; (1.45 ± 0.86) v.s. (2.33 ± 1.49) and (2.28 ± 1.50), F = 8.23, p < 0.001). However, there were no marked difference in the levels of these three indices between the MDD remission group and the control group (p > 0.05). Serum GABA levels were negatively correlated with HAMA total score (r = -0.34, p = 0.02), HAMD total score (r = -0.46, p = 0.01) and depression core symptom score (r = -0.32, p = 0.03). CONCLUSIONS: During the onset of MDD, there may be GABA neuronal dysfunction and abnormal expression of GABAA receptor subunits, and those changes showed a state change, which gradually returned to normal during remission.

Olfactory impairment as an early marker of Parkinson's disease in REM sleep behaviour disorder: a systematic review and meta-analysis.

Olfactory impairment and rapid eye movement sleep behaviour disorder (RBD) are prodromal symptoms of Parkinson's disease (PD) that may be associated with each other. This review aims to investigate the significance of olfaction in the diagnosis and prognosis of patients with RBD and to assess moderating factors affecting olfactory performance. We searched articles on olfaction in RBD and PD in five electronic databases. We identified 32 studies for the systematic review and used 28 of those, including 2858 participants for meta-analysis. Results revealed significant deficits in odour identification (g=-1.80; 95% CI: -2.17 to -1.43), threshold (g=-1.29; 95% CI: -1.67 to -0.91), discrimination (g=-1.08; 95% CI: -1.28 to -0.87) and overall olfactory function (g=-1.64; 95% CI: -1.94 to -1.35) in patients with RBD. Except for the Unified Parkinson's Disease Rating Scale Part III scores, none of the known moderating variables (including age, sex, disease duration and years of education) accounted for the olfactory function heterogeneity in patients with RBD. We identified similar olfactory impairments in patients with RBD and patients with PD (either with or without underlying RBD). These findings suggest that olfactory impairment may be a sensitive and stable diagnostic biomarker of RBD and appears to be useful for identifying patients with idiopathic RBD at high risk for early conversion to PD.

Classification of Unmedicated Bipolar Disorder Using Whole-Brain Functional Activity and Connectivity: A Radiomics Analysis.

The aim of this study was to develop and validate a method of disease classification for bipolar disorder (BD) by functional activity and connectivity using radiomics analysis. Ninety patients with unmedicated BD II as well as 117 healthy controls underwent resting-state functional magnetic resonance imaging (rs-fMRI). A total of 4 types of 7018 features were extracted after preprocessing, including mean regional homogeneity (mReHo), mean amplitude of low-frequency fluctuation (mALFF), resting-state functional connectivity (RSFC), and voxel-mirrored homotopic connectivity (VMHC). Then, predictive features were selected by Mann-Whitney U test and removing variables with a high correlation. Least absolute shrinkage and selection operator (LASSO) method was further used to select features. At last, support vector machine (SVM) model was used to estimate the state of each subject based on the selected features after LASSO. Sixty-five features including 54 RSFCs, 7 mALFFs, 1 mReHo, and 3 VMHCs were selected. The accuracy and area under curve (AUC) of the SVM model built based on the 65 features is 87.3% and 0.919 in the training dataset, respectively, and the accuracy and AUC of this model validated in the validation dataset is 80.5% and 0.838, respectively. These findings demonstrate a valid radiomics approach by rs-fMRI can identify BD individuals from healthy controls with a high classification accuracy, providing the potential adjunctive approach to clinical diagnostic systems.

A PET imaging study of the brain changes of glucose metabolism in patients with temporal lobe epilepsy and depressive disorder.

BACKGROUND: This study aims to compare the difference of the brain changes of glucose metabolism between temporal lobe epilepsy patients (TLE) with major depressive disorder and temporal TLE without major depressive disorder. METHODS: A total of 24 TLE patients, who met the inclusion criteria of our hospital, were enrolled in this study. They were divided into a TLE with depression group (n = 11) and a TLE without depression group (n = 13), according to the results of the HAMD-24 Scale. Two groups patients were examined using 18F-FDG PET brain imaging. RESULTS: The low metabolic regions of the TLE with depression group were mainly found in the left frontal lobe, temporal lobe and fusiform gyrus, while the high metabolic regions of the TLE with depression group were mainly located in the right frontal lobe, visual joint cortex and superior posterior cingulate cortex. Both of the TLE groups had high metabolic compensation in the non-epileptic area during the interictal period. CONCLUSIONS: There is an uptake difference of 18F-FDG between TLE patients with depression and TLE patients without depression in multiple encephalic regions.

High-dose omega-3 polyunsaturated fatty acid supplementation might be more superior than low-dose for major depressive disorder in early therapy period: a network meta-analysis.

BACKGROUND: The application of n-3 Polyunsaturated Fatty Acids (n-3 PUFAs) supplementation for major depressive disorder (MDD) has been widely discussed in recent years, but its efficacy and application are still controversial. This network meta-analysis was conducted to compare the efficacy of different dosages of n-3 PUFAs on MDD patients in the early period of treatment. METHODS: Randomized controlled trials (RCTs) exploring the efficacy of n-3 PUFA supplementation for patients with MDD were retrieved from the databases of Pubmed, Embase and the Cochrane Library. RCTs comparing the efficacy of n-3 PUFA for adult (≥18 years) MDD patients without comorbidity were eligible for our study. The score of depressive symptoms in early therapy period of the treatment (≤9 weeks) was extracted. Standardized mean deviations (SMDs) of all the sores from the eligible RCTs were synthesized in a pairwise meta-analysis in frequentist framework and a random-effects network meta-analysis in Bayesian framework for the overall and subgroups (high- and low-dose) efficacy of n-3 PUFAs. RESULTS: A total of 910 MDD patients in 10 trials with 3 adjuvant therapy strategies (high-dose n-3 PUFAs, low-dose n-3 PUFAs and placebo) were included. Results of pairwise meta-analysis showed that n-3 PUFAs were superior to placebo (SMD: 1.243 ± 0.596; 95% CI: 0.060 ~ 2.414). Results of the network meta-analysis showed that both the high (SMD: 0.908 ± 0.331; 95% CI: 0.262 ~ 1.581) and the low-dose (SMD: 0.601 ± 0.286; 95% CI: 0.034 ~ 1.18) n-3 PUFAs were superior to placebo, and the efficacy of high-dose n-3 PUFAs is superior to that of low-dose. CONCLUSIONS: High-dose n-3 PUFAs supplementation might be more superior than low-dose in the early therapy period for MDD. More head-to-head clinical trials need to be carried out to provide more direct comparison and enhance the evidence of the efficacy of n-3PUFAs for MDD.

Nr4a1 as a myogenic factor is upregulated in satellite cells/myoblast under proliferation and differentiation state.

Myogenic differentiation is precisely regulated with a cascade of genes and pathways. The previous study has demonstrated the muscle-specific deletion of Nr4a1 impairs muscle growth. However, it is still unclear whether muscular Nr4a1 deletion may directly impact myoblast physiology. Here, the present study delves into the molecular mechanism of Nr4a1 in C2C12. Through the analysis of RNAseq and microarray data, Nr4a1 was identified to highly correlate with the expression of myogenic factors. In C2C12, except confirming the induction of Nr4a1 mRNA and protein levels upon the initiation of differentiation, we observed a novel shuttling phenomenon of Nr4a1 from nucleus to cytoplasm in myoblast with a higher expression of MyoD or differentiated myotubes. Furthermore, Nr4a1 overexpression in C2C12 accelerates myoblasts' differentiation and increases myoblast fusion. In contrast, ablation of Nr4a1 expression in C2C12 inhibits the differentiation and fusion process. Meanwhile, in quiescent satellite cells, Nr4a1 expressed is not detected, while its protein level is highly induced in both BaCl2-induced muscle regeneration followed with satellite cells activation and satellite cells of cultured single myofiber. The mechanism may be through the Nr4a1-mediated expression of myogenic factors, e.g. MyoD and MyoG. In summary, the current investigation demonstrates that Nr4a1 is an essential myogenic factor involved in myoblast differentiation.

Excessive daytime sleepiness in general hospital nurses: prevalence, correlates, and its association with adverse events.

OBJECTIVE: To investigate the prevalence and correlates of excessive daytime sleepiness (EDS) in a population of hospital nurses in South China as well as the influence of EDS on the occurrence of adverse events. METHODS: A total of 1102 nurses working in a large medical center were invited to participate in this cross-sectional study (96.9% females, mean age 29.6 years). They all completed a self-reported questionnaire consisting of items on demographic variables, lifestyle factors, insomnia, anxiety, depression, and both work-related and sleep-related characteristics. RESULTS: A total of 1048 nurses gave a valid response (response rate 95.1%). Among them, 169 (16.1%) reported EDS as defined as an Epworth Sleepiness Scale ≥ 14. Depression (adjusted odds ratio = 2.24, 95% confidence interval 1.51-3.31), anxiety (1.65; 1.02-2.67), insomnia (2.29; 1.56-3.36), rotating shift work (1.98; 1.03-3.83), and low interest in work (1.74; 1.01-2.99) were all independent risk factors of the occurrence of EDS. EDS is associated with the occurrence of adverse events after controlling for confounding factors (adjusted OR 1.83, CI 1.26 to 2.67). CONCLUSIONS: EDS was common among this relatively young and healthy nurse population in south China. There were clear associations between EDS and depression, anxiety, insomnia, rotating shift work, and low work-related interest. Furthermore, EDS was an independent risk factor in the occurrence of adverse events (AEs) in our subjects.

Irisin ameliorates depressive-like behaviors in rats by regulating energy metabolism.

Depression is a common psychiatric disorder that affects millions of people around the world, however, little is known about the pathophysiology of depression and the therapeutic strategy for anti-depression. In this study, we investigated the role of irisin, a regulator of energy metabolism, in the modulation of depressive-like behaviors in chronic unpredictable stress (CUS) exposed rats. ELISA showed that irisin was aberrantly regulated by CUS in the prefrontal cortex tissues and cerebrospinal fluid (CSF) of rats. CUS-induced behavioral deficits in rats were reversed by injection treatment with recombinant irisin in a dose dependent manner. Treatment with irisin at concentrations of 100 ng/ml or higher significantly increased the sucrose preference and reduced the immobility time in CUS rats. Additionally, irisin treatment also increased the activities of mitochondrial complexes I, II and IV as well as creatine kinase, which were inhibited by CUS in the prefrontal cortex of rats. We then confirmed that irisin significantly increased the levels of glucose transport and phosphorylation, as reflected by the increased type I and type II hexokinase (Hx-1 and Hx-2) and GLUT-4 as well as the ATP level in vivo and vitro. Further studies indicated that AMPK pathway was involved in the regulation of irisin on depressive-like behaviors in CUS rats. In conclusion, we demonstrated that irisin has a crucial role in inducing antidepressant-like effects in CUS rats by regulating energy metabolism in the prefrontal cortex of brain, which may provide a new insight into the biological mechanism of depression.

Disrupted Resting-State Functional Connectivity in Nonmedicated Bipolar Disorder.

Purpose To investigate the whole-brain intrinsic functional connectivity patterns of patients with bipolar disorder (BD). Materials and Methods This prospective study was approved by the research ethics committee, and all participants provided informed consent. Thirty-seven patients with nonmedicated BD II depression and 37 healthy control participants underwent resting-state functional magnetic resonance (MR) imaging. Whole-brain connectivity was analyzed by using a graph theory approach: functional connectivity strength (FCS). Clinical state was assessed by using the 24-item Hamilton Depression Rating Scale and the Young Mania Rating Scale. Two-sample t test and nonparametric correlation analysis were used. Results Compared with healthy control participants, patients with BD II showed decreased FCS in the default mode network (ie, the bilateral medial prefrontal cortex, bilateral middle temporal gyrus, left precuneus, and right posterior cingulate cortex), right supramarginal gyrus and angular gyrus, right superior frontal gyrus, and right superior parietal gyrus and increased FCS in the bilateral temporal pole (including the parahippocampal gyrus and amygdale), left anterior cingulate cortex, left superior temporal gyrus, right lingual gyrus, and left anterior lobe of the cerebellum (P < .05; AlphaSim corrected). Conclusion These results suggest that patients with BD have disrupted intrinsic functional connectivity mainly in the default mode network and limbic system, which might be associated with the pathophysiologic structure of BD. (©) RSNA, 2016.

Interhemispheric resting state functional connectivity abnormalities in unipolar depression and bipolar depression.

OBJECTIVES: Depression in the context of bipolar disorder (BD) is often misdiagnosed as unipolar depression (UD), leading to mistreatment and poor clinical outcomes. However, little is known about the similarities and differences in interhemispheric functional connectivity between BD and UD. METHODS: Patients with bipolar II disorder (n = 36) and UD (n = 32) during a depressive episode as well as 40 healthy controls underwent resting-state functional magnetic resonance imaging. The functional connectivity between any pair of symmetric interhemispheric voxels (i.e., functional homotopy) was measured by voxel-mirrored homotopic connectivity (VMHC). RESULTS: The three groups showed significant VMHC differences in the posterior cingulate cortex (PCC), fusiform and lingual gyrus, anterior lobe of the cerebellum (CeAL), and posterior lobe of the cerebellum (CePL). In the BD group, the VMHC decreases in the fusiform/lingual gyrus, CeAL, and CePL were shown relative to controls. In the UD group, the VMHC decreases in the PCC, fusiform/lingual gyrus, and CePL were shown relative to controls. No regions of increased VMHC were detected in either patient group. There was no significant difference in the VMHC values in any brain region between the BD group and the UD group. CONCLUSIONS: Depressive episodes in BD and UD have similar impairments of interhemispheric coordination, which might imply an overlap in the neuropathology of depression.

Plasma neuropeptide Y levels in Chinese patients with primary insomnia.

PURPOSE: The present study aimed to explore the possible difference in plasma neuropeptide Y (NPY) level between patients with primary insomnia and healthy normal sleepers. METHODS: The sample comprised 42 patients with primary insomnia and 38 age- and sex-matched healthy controls. Clinical measures, including the Pittsburgh Sleep Quality Index (PSQI), State-Trait Anxiety Inventory (STAI), and Beck Depression Inventory (revised edition, BDI-R), were recorded, respectively. Morning fasting plasma NPY levels of all participants were determined by using enzyme-linked immunosorbent assay (ELISA). Student's t-test or chi-square test was used to compare the differences in demographic and clinical factors and scores of psychometric assessments between groups. Bivariate correlation test was used to analyze the relationship between NPY level and factors, such as age, body mass index (BMI), PSQI, STAI, and BDI-R score. Analysis of covariance (ANCOVA) was used to study the difference of plasma NPY level between two groups with adjustment for age, sex, BMI, STAI, and BDI-R total score. RESULTS: We found that morning plasma NPY levels in patients with primary insomnia were significantly lower than those in the normal controls (5.11 ± 2.87 vs. 7.01 ± 3.44 ng/ml, p = 0.009). The difference in plasma NPY level persisted even after adjustment for age, sex, BMI, STAI, and BDI-R total score (p = 0.026). For all subjects, plasma NPY level was found decreasing significantly with age (r = -0.232, p = 0.038). In addition, there was a trend that plasma NPY level was negatively associated with PSQI total score (r = -0.209, p = 0.063). CONCLUSIONS: Our findings suggest that NPY system may involve in the pathophysiological process of primary insomnia. Further studies are warranted to determine the causal relationship between low plasma NPY level and primary insomnia disorder.

Effects of enhanced biological phosphorus removal on rapid control of sludge bulking and fast formation of aerobic granular sludge.

This study investigated the effects of enhanced biological phosphorus removal (EBPR) on rapid sludge bulking control and fast aerobic granular sludge (AGS) formation by adding 20 % of EBPR activated sludge to the bulking activated sludge (BAS) reactor. The results indicate that activating EBPR activity swiftly improved BAS settleability within 16 days, thus resolving sludge bulking issues. Subsequently, a settling time-based selection was employed, resulting in the BAS granulation within another 16 days. The rapid achievement of EBPR activity improved the BAS settleability and facilitated the formation of sludge aggregates, thereby expediting BAS granulation. Inhibition of filamentous bacteria and enrichment of slow-growing organisms contributed to both sludge bulking control and aerobic granulation. Furthermore, the increase in proteins/polysaccharides ratio facilitated the granulation process. Additionally, total nitrogen removal increased from 59.4 % to 71.7 % because of the mature AGS formation. This study provided an approach to simultaneously control sludge bulking and promote aerobic granulation.

Markers of intestinal barrier damage in patients with chronic insomnia disorder.

Objective: Insomnia disorder stands out as one of the prevalent clinical sleep and psychiatric disorders. Prior research has unequivocally demonstrated variations in the diversity and abundance of gut microbiota among individuals with insomnia disorder. These alterations may play a direct or indirect role in the onset and progression of insomnia disorder by compromising the integrity of the intestinal barrier. This study aims to evaluate the impairment of the intestinal barrier in individuals with insomnia disorder by scrutinizing the serum functionality of this barrier. Materials and methods: 45 patients with chronic insomnia disorder and 30 matched healthy volunteers were meticulously selected based on inclusion criteria. ELISA technology was employed to measure serum levels of diamine oxidase (DAO), D-lactic acid (D-LA), intestinal fatty acid binding protein (I-FABP), and endothelin (ET). Spearman correlation analysis was used to explore the relationship between intestinal mucosal markers and clinical characteristics. Data were analyzed using SPSS 26.0. Results: Compared to the healthy control group, the insomnia disorder group exhibited significantly elevated scores on subjective mood and sleep scales (GAD-7, PHQ-9, HAMA, HAMD, PSQI, and ISI) (P < 0.05). Overnight PSG indicated a notable increase in bed time, total wake time, sleep onset latency, and wake after sleep onset in individuals with insomnia disorder. Additionally, there was a decrease in sleep efficiency and alterations in sleep structure (increased proportion of N1 and N3 stages, prolonged N1 stage) (P < 0.05). The chronic insomnia disorder group displayed significantly reduced concentrations of serum DAO, D-LA, I-FABP, and ET (P < 0.05). Furthermore, significant positive correlations were identified between intestinal epithelial barrier markers and sleep efficiency, while negative correlations were found with wake after sleep onset, total wake time, PSQI, HAMA, and HAMD. Additionally, D-LA levels were significantly positively correlated with ET concentrations. Conclusion: Individuals with chronic insomnia disorder manifest disruptions in sleep structure, heightened susceptibility to anxiety and depressive moods, and impaired intestinal barrier function. These findings suggest that the occurrence and development of insomnia disorder may be linked to the impairment of the intestinal barrier.

The effect of neuroendocrine abnormalities on the risk of psychiatric readmission after hospitalization for bipolar disorder: A retrospective study.

BACKGROUND: The correlation between the endocrine system and bipolar disorder(BD) has been well recognized, yet the influence of neuroendocrine hormones on readmission risk post-hospitalization for BD remains largely unexplored. This retrospective cohort study was to scrutinize the impact of neuroendocrine functionality on the readmission of patients with BD post-hospitalization for mental disorders. METHODS: The dataset was derived from the electronic medical records of the First Affiliated Hospital of Jinan University in Guangzhou, China. Both univariate and multivariate logistic regression analysis were conducted on all patients hospitalized for BD, and from 1 January 2017 to October 2022. RESULTS: Of the 1110 eligible patients, 83 and 141 patients experienced psychiatric readmissions within 90 and 180 days post-discharge, respectively. Multivariate analysis revealed that high serum TSH levels (aOR = 1.079; 95%CI = 1.003-1.160) and thyroid disease comorbidities (aOR = 2.899; 95%CI = 1.303-6.452) were independently correlated with the risk of 90-day readmission; while increased serum TSH levels (aOR = 1.179; 95%CI = 1.081-1.287) represented a risk factor for 180-day readmission. These results indicate that high serum TSH levels and thyroid disease comorbidities may contribute to an elevated readmission risk in patients with BD following hospitalization. CONCLUSION: Routinely evaluating and intervening in thyroid function is crucial in the treatment of BD, as it may aid in preventing re-hospitalization.

Circadian rhythm dysfunction and psychopathology in the offspring of parents with bipolar disorder: a high-risk study in the Chinese population.

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.

Dose adjustment of paroxetine based on CYP2D6 activity score inferred metabolizer status in Chinese Han patients with depressive or anxiety disorders: a prospective study and cross-ethnic meta-analysis.

BACKGROUND: Understanding the impact of CYP2D6 metabolism on paroxetine, a widely used antidepressant, is essential for precision dosing. METHODS: We conducted an 8-week, multi-center, single-drug, 2-week wash period prospective cohort study in 921 Chinese Han patients with depressive or anxiety disorders (ChiCTR2000038462). We performed CYP2D6 genotyping (single nucleotide variant and copy number variant) to derive the CYP2D6 activity score and evaluated paroxetine treatment outcomes including steady-state concentration, treatment efficacy, and adverse reaction. CYP2D6 metabolizer status was categorized into poor metabolizers (PMs), intermediate metabolizers (IMs), extensive metabolizers (EMs), and ultrarapid metabolizers (UMs). The influence of CYP2D6 metabolic phenotype on paroxetine treatment outcomes was examined using multiple regression analysis and cross-ethnic meta-analysis. The therapeutic reference range of paroxetine was estimated by receiver operating characteristic (ROC) analyses. FINDINGS: After adjusting for demographic factors, the steady-state concentrations of paroxetine in PMs, IMs, and UMs were 2.50, 1.12, and 0.39 times that of EMs, with PM and UM effects being statistically significant (multiple linear regression, P = 0.03 and P = 0.04). Sex and ethnicity influenced the comparison between IMs and EMs. Moreover, poor efficacy of paroxetine was associated with UM, and a higher risk of developing adverse reactions was associated with lower CYP2D6 activity score. Lastly, cross-ethnic meta-analysis suggested dose adjustments for PMs, IMs, EMs, and UMs in the East Asian population to be 35%, 40%, 143%, and 241% of the manufacturer's recommended dose, and 62%, 68%, 131%, and 159% in the non-East Asian population. INTERPRETATION: Our findings advocate for precision dosing based on the CYP2D6 metabolic phenotype, with sex and ethnicity being crucial considerations in this approach. FUNDING: National Natural Science Foundation of China; Academy of Medical Sciences Research Unit.

Correlation Between Chronotypes and Depressive Symptoms Mediated by Sleep Quality Among Chinese College Students During the COVID-19 Pandemic.

Purpose: The COVID-19 pandemic has adversely impacted the mental health of the population. The current study aimed to determine the prevalence of depressive symptoms and sleep disturbances among Chinese college students during the COVID-19 pandemic and investigate the correlations between chronotypes, sleep quality, and depressive symptoms. Participants and Methods: In the current study, 2526 college students responded anonymously to an online questionnaire survey from 26 May 2020 to 20 July 2020. The participants' chronotypes, sleep quality, and depressive symptoms were evaluated using the Chinese version of the Morning and Evening Questionnaire-5 (MEQ-5), Pittsburgh Sleep Quality Index (PSQI), and Patient Health Questionnaire-9 (PHQ-9). Sociodemographic information of the participants was also acquired. Statistical analyses were performed using Statistical Package for Social Sciences (SPSS) 19.0 software, with the mediating effect assessed by Hayes' PROCESS Macro. Results: During the COVID-19 pandemic, the prevalence of depressive symptoms and sleep disturbances among Chinese college students surveyed was 54.95% and 48.18%, respectively. From absolute evening chronotype to absolute morning chronotype, the surveyed college students' chronotypes were negatively correlated with their depressive symptoms. Moreover, the mediation analysis showed that the correlation between chronotypes and depressive symptoms was fully mediated by sleep quality. Eveningness college students with poorer sleep quality were more likely to report higher levels of depressive symptoms. Conclusion: Our findings suggest that during the COVID-19 pandemic, delayed circadian preference (ie, eveningness) may be linked to worse depressive symptoms among Chinese college students, and call for more attention to the sleep quality of Chinese college students as sleep quality fully mediated the correlation between chronotypes and depressive symptoms among them. Reasonable adjustment in bedtime/circadian preference and improvement in sleep quality may help to reduce the prevalence and severity of depressive symptoms among Chinese college students.