Unveiling the Interplay Between Depressive Symptoms' Alleviation and Quality of Life Improvement in Major Depressive Disorder: A Network Analysis Based on Longitudinal Data.

Background: Understanding the dynamic relationship between depressive symptoms and quality of life (QOL) is essential in improving long-term outcomes for patients with Major Depressive Disorder (MDD). While previous studies often relied on cross-sectional data, there is a pressing need for stronger evidence based on longitudinal data to better inform the development of effective clinical interventions. By focusing on key depressive symptoms, such interventions have the potential to ultimately enhance QOL in individuals with MDD. Methods: This multi-center prospective study, conducted between 2016 and 2020, enrolled outpatients and inpatients diagnosed with MDD across twelve psychiatric hospitals in China. Longitudinal data on Patient Health Questionnaire - 9 (PHQ-9) and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) was analyzed using an Extended Bayesian Information Criterion (EBIC) graphical least absolute shrinkage and selection operator (gLASSO) network model to explore the connections between depressive symptom changes and QOL changes. Flow network was applied to investigate relationships between individual symptom changes and overall QOL score change, as well as daily functional independence. Results: This study included 818 participants with complete data after 8-week antidepressant treatment. Apart from the overlapping items from PHQ-9 and Q-LES-Q-SF, the three edges between "mood" (delta-QLES2) and "anhedonia" (delta-DEP1), between "physical health" (delta-QLES1) and "sleep problems" (delta-DEP3), and between "physical health" (delta-QLES1) and "sad mood" (delta-DEP2) were the most strong bridges between the cluster of depressive symptoms alleviation and the cluster of QOL change. "Anhedonia" (delta-DEP1), "sad mood" (delta-DEP2) and "loss of energy" (delta-DEP4) had the highest bridge strength between the alleviations of depressive symptoms and the total score change of Q-LES-Q-SF. Anhedonia had the greatest connection with participants' satisfaction with function in daily life. Conclusion: This study highlighted the potential for developing highly effective interventions by targeting on central symptoms, thereby to ultimately improve QOL for patients with MDD.

Acute treatment residual depression symptoms and functional impairment among depressive patients of different age groups and education levels in China: A prospective, multicenter, randomized study.

OBJECTIVE: A prospective, multicenter, randomized study evaluated the efficacy of major depressive disorder (MDD) patients after 2-3 months of acute treatment based on the dual factors of education and age. METHODS: This study classified the included patients into four groups using two classification parameters: age (≤45 years, vs. >45 years) and education years (≤12 vs. >12). We analyzed age, gender, marital status, personal income, depression onset history, medication use, and follow-up across various groups. We evaluated residual somatic symptoms and social functioning in depression patients was conducted using the 16-item Quick Inventory of Depressive Symptomatology Self-report (QIDS-SR16), the Patient Health Questionnaire-15 (PHQ15), and the Sheehan Disability Scale (SDS). RESULTS: In China, 16 hospitals, 553 depression patients, and 428 fulfilled the inclusion criteria. Baseline patient data revealed significant differences among the different age groups in gender, marital status, income, first onset age, physical illness, combination of antipsychotics, and benzodiazepines use (all p < .05). Statistically significant differences were observed in overall comparisons among the four groups, encompassing the QIDS-SR16 score, PHQ15 score, and various SDS parameters (all p < .05). However, no statistically significant differences (all p > .05) were found in residual somatic symptoms and social functioning parameters between different education levels (≤12 years vs. >12 years) at baseline, 3 months, and 6 months, based on total scores on the scale. Repeated measures mixed model indicates that the QIDS-SR16 assessment indicates statistical differences among various marital statuses, income levels, medical histories, and antipsychotic medication use (p < .05). Furthermore, PHQ-15 and SDS assessments reveal statistical differences between single and married/cohabiting statuses, physical comorbidities, 3 and 6 months follow-ups compared to baseline (p < .05). CONCLUSION: This study indicates that compared to depressive patients >45 years old, those ≤45 years old often exhibit more residual depression, somatic symptoms, and severe social functional impairment; patients' education levels less influence this trend.

Factors influencing the tendency of residual symptoms in patients with depressive disorders: a longitudinal study.

BACKGROUND: Residual symptoms of depressive disorders are serious health problems. However, the progression process is hardly predictable due to high heterogeneity of the disease. This study aims to: (1) classify the patterns of changes in residual symptoms based on homogeneous data, and (2) identify potential predictors for these patterns. METHODS: In this study, we conducted a data-driven Latent Class Growth Analysis (LCGA) to identify distinct tendencies of changes in residual symptoms, which were longitudinally quantified using the QIDS-SR16 at baseline and 1/3/6 months post-baseline for depressed patients. The association between baseline characteristics (e.g. clinical features and cognitive functions) and different progression tendencies were also identified. RESULTS: The tendency of changes in residual symptoms was categorized into four classes: "light residual symptom decline (15.4%)", "residual symptom disappears (39.3%)", "steady residual symptom (6.3%)" and "severe residual symptom decline (39.0%)". We observed that the second class displayed more favorable recuperation outcomes than the rest of patients. The severity, recurrence, polypharmacy, and medication adherence of symptoms are intricately linked to the duration of residual symptoms' persistence. Additionally, clinical characteristics including sleep disturbances, depressive moods, alterations in appetite or weight, and difficulties with concentration have been identified as significant factors in the recovery process. CONCLUSIONS: Our research findings indicate that certain clinical characteristics in patients with depressive disorders are associated with poor recovery from residual symptoms following acute treatment. This revelation holds significant value in the targeted attention to specific patients and the development of early intervention strategies for residual symptoms accordingly.

Bidirectional, longitudinal associations between depressive symptoms and IADL/ADL disability in older adults in China: a national cohort study.

INTRODUCTION: Based on the data from the China Health and Retirement longitudinal study (CHARLS), we aimed to investigate the bidirectional relationship between depressive symptoms and functional disability. METHODS: Data were collected across 3 waves from 2013 to 2018. The activities of daily living (ADLs) and the instrumental activities of daily living (IADLs) scales were used to measure functional disability and the CESD-10 was used to measure depressive symptoms. Cross-lagged models were performed to examine cross effect between depressive symptoms and functional disability across three waves. RESULTS: Data on 10,092(mean [SD] age, 61.98[8.44] years; 3764 females [37.30%]) and 10,180 participants (mean [SD] age, 62.01[8.46] years; 3788 females [37.21%]) in IADL sample and ADL sample were included in the analyses. For IADL disability, the cross-lagged model shows a bidirectional association across three waves; the multivariable GEE model revealed that changes in CESD-10 score across waves were associated with worse IADL disability (ß ranges: 0.08-0.10) and vice versa, worsen of IADL disability ascending developing of CESD-10 score (ß ranges: 0.09-0.10). For ADL disability, the cross-lagged model shows a bidirectional association across three waves; the multivariable GEE model revealed that changes of CESD-10 score across waves were associated with worse IADL disability (ß ranges: 0.08-0.10) and vice versa, worsen of IADL disability ascending developing of CESD-10 score (ß ranges: 0.09-0.10). DISCUSSION: Study findings underscore a significant bidirectional between depressive symptoms and functional disability in older adults. Thus, simultaneous intervention should be taken to manage the mutual development of functional disability and depression.

Identifying influencing factors of metabolic syndrome in patients with major depressive disorder: A real-world study with Bayesian network modeling.

BACKGROUND: The bidirectional relationships between metabolic syndrome (MetS) and major depressive disorder (MDD) were discovered, but the influencing factors of the comorbidity were barely investigated. We aimed to fully explore the factors and their associations with MetS in MDD patients. METHODS: The data were retrieved from the electronic medical records of a tertiary psychiatric hospital in Beijing from 2016 to 2021. The influencing factors were firstly explored by univariate analysis and multivariate logistic regressions. The propensity score matching was used to reduce the selection bias of participants. Then, the Bayesian networks (BNs) with hill-climbing algorithm and maximum likelihood estimation were preformed to explore the relationships between influencing factors with MetS in MDD patients. RESULTS: Totally, 4126 eligible subjects were included in the data analysis. The proportion rate of MetS was 32.6 % (95 % CI: 31.2 %-34.1 %). The multivariate logistic regression suggested that recurrent depression, uric acid, duration of depression, marriage, education, number of hospitalizations were significantly associated with MetS. In the BNs, number of hospitalizations and uric acid were directly connected with MetS. Recurrent depression and family history psychiatric diseases were indirectly connected with MetS. The conditional probability of MetS in MDD patients with family history of psychiatric diseases, recurrent depression and two or more times of hospitalizations was 37.6 %. CONCLUSION: Using the BNs, we found that number of hospitalizations, recurrent depression and family history of psychiatric diseases contributed to the probability of MetS, which could help to make health strategies for specific MDD patients.

Increased antipsychotic drug concentration in hospitalized patients with mental disorders following COVID-19 infection: a call for attention.

Purpose: Examine the alterations in antipsychotic concentrations following coronavirus disease-2019 (COVID-19) infection among hospitalized patients with mental disorders and conduct an analysis of the factors influencing these changes. Methods: Data were collected from inpatients at Beijing Huilongguan Hospital between December 12, 2022, and January 11, 2023, pre- and post-COVID-19. Based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, 329 inpatients with mental disorders were included (3 with incomplete data excluded). Primary outcomes assessed changes in antipsychotic concentrations pre- and post-COVID-19, while secondary outcomes examined factors linked to concentration increases and antipsychotic dose adjustments. Results: Clozapine (P < 0.001), aripiprazole (P < 0.001), quetiapine (P = 0.005), olanzapine (P < 0.001), risperidone (P < 0.001), and paliperidone (P < 0.001) concentrations increased post-COVID-19 in patients with mental disorders. Notably, clozapine concentration surpassing pre-infection levels was highest. Clozapine users were more likely to adjust their dose (50.4%) compared to olanzapine (17.5%) and other antipsychotics. Moreover, traditional Chinese patent medicines and antibiotics during COVID-19 infection were associated with antipsychotic reduction or withdrawal (OR = 2.06, P = 0.0247; OR = 7.53, P = 0.0024, respectively). Conclusion: Antipsychotic concentrations in hospitalized patients with mental disorders increased after COVID-19 infection, that may be related not only to COVID-19, but also to the use of Chinese patent medicines during infection. The pre-infection concentration and types of antipsychotics, patient's gender, and combination of traditional Chinese medicine or antibiotics, were factors found to correlate with increased drug concentrations and necessitate dose adjustments.

Integrated Single-Cell RNA-seq and ATAC-seq Reveals Heterogeneous Differentiation of CD4+ Naive T Cell Subsets is Associated with Response to Antidepressant Treatment in Major Depressive Disorder.

The mechanism involved in major depressive disorder (MDD) is well-studied but the mechanistic origin of the heterogeneous antidepressant effect remains largely unknown. Single-cell RNA-sequencing (scRNA-seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) on peripheral blood mononuclear cells from 8 healthy individuals and 8 MDD patients before or after 12 weeks of antidepressant treatment is performed. scRNA-seq analysis reveals a lower proportion of naive T cells, particularly CD4+ naive T cells, in MDD patients compared to controls, and in nonresponders versus responders at the baseline. Flow cytometry data analysis of an independent cohort of 35 patients and 40 healthy individuals confirms the findings. Enrichment analysis of differentially expressed genes indicated obvious immune activation in responders. A specific activated CD4+ naive T population in responders characterized by enhanced mitogen-activated protein kinases (MAPK) pathway is identified. E-twenty six (ETS) is proposed as an upstream regulator of the MAPK pathway and heterogeneous differentiation in activated CD4+ naive T population is associated with the response to antidepressant treatment in MDD patients. A distinct immune feature manifested by CD4+ naive T cells during antidepressant treatment in MDD is identified. Collectively, this proposes the molecular mechanism that underlies the heterogeneous antidepressant outcomes for MDD.

Sociodemographic, clinical and treatment characteristics of current rapid-cycling bipolar disorder: a multicenter Chinese study.

BACKGROUND: Rapid cycling bipolar disorder (RCBD), characterized by four or more episodes per year, is a complex subtype of bipolar disorder (BD) with poorly understood characteristics. METHOD: This multicenter, observational, longitudinal cohort study enrolled 520 BD patients across seven psychiatric institutions in China from January 2013 to January 2014. Participants were divided into RCBD and non-RCBD (NRCBD) groups based on the frequency of mood episodes in the preceding year. Data collection utilized a standardized form, supplemented by a medical record review, focusing on sociodemographic, clinical, and treatment characteristics. Statistical analysis involved independent samples t-tests, Kruskal-Wallis H tests, Chi-square or Fisher's exact tests, with Bonferroni correction applied to account for multiple comparisons, and multivariable logistic regression to identify characteristics associated with RCBD. RESULTS: Among the BD cohort, 9.4% were identified as current RCBD. Compared to NRCBD, RCBD patients had a shorter duration from the first psychiatric consultation to the diagnosis of BD, a reduced duration of their longest period of euthymia, a lower proportion of lifetime hospitalization history due to BD, and less use of electroconvulsive therapy (ECT) within the last 12 months. Additionally, they presented higher baseline scores on the Mood Disorder Questionnaire (MDQ) and the Brief 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). However, after applying the Bonferroni correction, these differences were not statistically significant. Multivariable logistic regression analysis identified three factors that were independently associated with RCBD: time from first psychiatric consultation to BD diagnosis (Odds Ratio [OR] = 0.512, P = 0.0416), lifetime hospitalization history due to BD (OR = 0.516, P = 0.0476), and ECT treatment within the past 12 months (OR = 0.293, P = 0.0472). CONCLUSION: This study revealed that the duration from first psychiatric consultation to BD diagnosis, lifetime hospitalization history due to BD, and ECT treatment in the past year were associated with RCBD. Recognizing these factors could contribute to enhance the early identification and clinical outcomes of RCBD. Trial Registration Number Registry ClinicalTrials.gov NCT01770704. Date of Registration: First posted on January 18, 2013.

Mapping prodromal symptoms in patients with bipolar disorder: A network perspective.

Bipolar disorder (BD) is a major mental disorder that significantly impairs behavior and social functioning. This study assessed the network structure of prodromal symptoms in patients with BD prior to their index mood episode. Semi-structured interviews were conducted with the Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R) to examine patients' prodromal symptoms. Network analysis was conducted to elucidate inter-relations between prodromal symptoms. A total of 120 eligible patients participated in this study. Network analysis indicated that the observed model was stable. The edge Mania3-Depression9 ('Racing thoughts' - 'Thinking about suicide', edge weight = 14.919) showed the strongest positive connection in the model, followed by the edge Mania1-depression1 ('Extremely energetic/active' - 'Depressed mood', edge weight = 14.643). The only negative correlation in the model was for Mania7-depression2 ('Overly self-confident' - 'Tiredness or lack of energy', edge weight = -1.068). Nodes Mania3 ('Racing thoughts'), Depression9 ('Thinking about suicide'), Mania1 ('Extremely energetic/active'), and Depression1 ('Depressed mood') were the most central symptoms. Both depressive and manic or hypomanic symptoms appeared in the prodromal phase. Symptoms reflecting 'Racing thoughts', 'Thinking about suicide', 'Extremely energetic/active', and 'Depressed mood' should be thoroughly assessed and targeted as crucial prodromal symptoms in interventions to reduce the risk of BD episodes.

Discrepancy between objective and subjective cognition and its association with the trajectory of symptoms and functioning in depressive patients.

BACKGROUND: Discrepancy between objective and subjective cognitive deficit is common among patients with major depressive disorders (MDDs) and may play a key role in the mechanism linking cognition with recovery of symptom and psychosocial function. This study, therefore, explores the cognitive discrepancy, and its association with the trajectory of symptoms and functioning over a 6-month period. METHODS: We used data from the Prospective Research Observation to Assess Cognition in Treated patients with MDD (PROACT) study, from which 598 patients were included. Cognitive discrepancy scores were computed using a novel methodology, with positive values indicating more subjective than objective deficit (i.e. 'underestimation') and negative values indicating more objective than subjective difficulties (i.e. 'overestimation'). Linear growth curve models were employed to examine the association of the cognitive discrepancy with the trajectory of depressive symptoms, psychosocial function, and quality of life. RESULTS: About 68% of patients displayed disproportionately more objective than subjective cognitive deficit at baseline, and the mean cognitive discrepancy score was -1.4 (2.7). Overestimation was associated with a faster decrease of HDRS-17 (ß = -0.46, p = 0.002) and a faster decrease of psychosocial function in social life (ß = -0.13, p = 0.013) and family life (ß = -0.12, p = 0.026), and a greater improvement of EQ-5D utility score (ß = 0.01, p < 0.001). CONCLUSION: We found a lower sensitivity of cognitive deficit at baseline and its decrease was associated with better health outcomes. Our findings have clinical implications of the necessity to assess both subjective and objective cognition for identification and categorization and to incorporate cognitive and psychological therapies for optimized treatment outcomes.

Population pharmacokinetics of Amisulpride in Chinese patients with schizophrenia with external validation: the impact of renal function.

Introduction: Amisulpride is primarily eliminated via the kidneys. Given the clear influence of renal clearance on plasma concentration, we aimed to explicitly examine the impact of renal function on amisulpride pharmacokinetics (PK) via population PK modelling and Monte Carlo simulations. Method: Plasma concentrations from 921 patients (776 in development and 145 in validation) were utilized. Results: Amisulpride PK could be described by a one-compartment model with linear elimination where estimated glomerular filtration rate, eGFR, had a significant influence on clearance. All PK parameters (estimate, RSE%) were precisely estimated: apparent volume of distribution (645 L, 18%), apparent clearance (60.5 L/h, 2%), absorption rate constant (0.106 h-1, 12%) and coefficient of renal function on clearance (0.817, 10%). No other significant covariate was found. The predictive performance of the model was externally validated. Covariate analysis showed an inverse relationship between eGFR and exposure, where subjects with eGFR= 30 mL/min/1.73 m2 had more than 2-fold increase in AUC, trough and peak concentration. Simulation results further illustrated that, given a dose of 800 mg, plasma concentrations of all patients with renal impairment would exceed 640 ng/mL. Discussion: Our work demonstrated the importance of renal function in amisulpride dose adjustment and provided a quantitative framework to guide individualized dosing for Chinese patients with schizophrenia.

Poly-1,3-dioxolane anchoring graphitic carbon nitride to achieve high-energy-density solid-state Li metal batteries.

Solid-state Li metal batteries (SSLMBs) are promising solutions for the next-generation energy storage devices with high energy densities and safety. Accordingly, the advanced solid-state electrolytes are further needed to address the challenges-low ionic conductivity, poor interfacial compatibility and uncontrollably Li dendrites, boosting the electrochemical and safety performances of SSLMBs. Herein, a "flexible and rigid" strategy is proposed to enhance the electrochemical and mechanical properties of polyethylene oxide (PEO)-based electrolytes. Specifically, the flexible poly-1,3-dioxolane (poly-DOL) and rigid graphitic carbon nitride (g-C3N4) are coordinated by a coupling reaction to prepare g-C3N4-poly-DOL, which is further employed as the filler for the PEO matrix to fabricate a composite polymer electrolyte g-C3N4-pDOL-PEO. The flexible poly-DOL and rigid g-C3N4 together endow the PEO-based electrolyte with good interfacial stability, high ion-conductivity and strong mechanical strength. Consequently, the Li/g-C3N4-pDOL-PEO/LiFePO4 cell delivers high cyclability with a capacity retention ratio of 89.7 % after 150 cycles and an average Coulombic efficiency over 99.9 %, and, the Li/g-C3N4-pDOL-PEO/Li cell can stably cycle beyond 300 h at 0.2 mAh cm-2 with small polarization (13 mV). The "flexible and rigid" strategy coupling the polymer with the filler provides an effective electrolyte design for high-performance SSLMBs.

Esketamine vs Midazolam in Boosting the Efficacy of Oral Antidepressants for Major Depressive Disorder: A Pilot Randomized Clinical Trial.

Importance: Loss of a previously effective response while still using adequate antidepressant treatment occurs in a relatively high proportion of patients with major depressive disorder (MDD); therefore, there is a need to develop novel effective treatment strategies. Objective: To assess the efficacy and safety of a single subanesthetic dose of esketamine in boosting the efficacy of oral antidepressants for treating fluctuating antidepressant response in MDD. Design, Setting, and Participants: This single-center, double-blind, midazolam-controlled pilot randomized clinical trial was conducted at Beijing Anding Hospital, Capital Medical University in China. The study enrolled participants aged 18 years and older with fluctuating antidepressant response, defined as patients with MDD experiencing fluctuating symptoms after symptom relief and stabilization. Patient recruitment was conducted from August 2021 to January 2022, and participants were followed-up for 6 weeks. Data were analyzed as intention-to-treat from July to September 2022. Interventions: All participants in the esketamine-treated group received intravenous esketamine at 0.2 mg/kg in 40 minutes. Participants in the midazolam control group received intravenous midazolam at 0.045 mg/kg in 40 minutes. Main Outcomes and Measures: The primary outcome was the response rate at 2 weeks, defined as a 50% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary outcomes included response rate at 6 weeks, remission rates at 2 and 6 weeks, and change in MADRS and Clinical Global Impression-Severity score from baseline to 6 weeks; remission was defined by a MADRS score of 10 or lower. Results: A total of 30 patients (median [IQR] age, 28.0 [24.0-40.0] years; 17 [56.7%] female) were randomized, including 15 patients randomized to midazolam and 15 patients randomized to esketamine; 29 patients completed the study. Response rates at 2 weeks were significantly higher in the esketamine-treated group than in the midazolam control group (10 patients [66.7%] vs 1 patient [6.7%]; P < .001). Participants treated with esketamine experienced significantly greater reduction in MADRS score from baseline to 2 weeks compared with those treated with midazolam (mean [SD] reduction, 15.7 [1.5] vs 3.1 [1.3]; P < .001). No serious adverse events were observed in this trial, and no psychotogenic effects and clinically significant manic symptoms were reported. Conclusions and Relevance: This pilot randomized clinical trial found that a single subanesthetic dose of esketamine could boost the efficacy of oral antidepressants in treating fluctuating antidepressant response, with a good safety profile. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2100050335.

Gender specific sexual dysfunction in patients with depression.

Background: This study aims to investigate the factors associated with sexual dysfunction (SD), with a particular focus on the influence of sex on the occurrence and severity of this condition in patients with major depressive disorder (MDD). Method: Sociodemographic and clinical assessments were conducted on 273 patients with MDD (female = 174, male = 99), including the ASEX, QIDS-SR16, GAD-7, and PHQ-15. Univariate analyses, independent samples t-test, Chi-square test, and Fisher's exact test were used as appropriate, and logistic regression analysis was used to identify correlation factors for SD. Statistical analyses were performed using the Statistical Analysis System (SAS 9.4). Result: SD was reported in 61.9% of the participants (ASEX score = 19.6 ± 5.5), and the prevalence of it in females (75.3%, ASEX score = 21.1 ± 5.4) was significantly higher than that in males (38.4%, ASEX score = 17.1 ± 4.6). Factors associated with SD included being female, being aged 45 years or above, having a low monthly income (≤750 USD), feeling more sluggish than usual (a QIDS-SR16 Item 15 score of 1 or above), and having somatic symptoms (evaluated with the total score of PHQ15). Limitation: The use of antidepressants and antipsychotics might be a confounding factor affecting sexual function. Also, the lack of information in the clinical data regarding the number, duration, and time of onset of the episodes limits the richness of the results. Conclusion: Our findings reveal the sex differences in the prevalence and severity of SD in patients with MDD. Evaluated with the ASEX score, female patients showed significantly worse sexual function than male patients. Being female, having a low monthly income, being aged 45 years or above, feeling sluggish, and having somatic symptoms may increase the risk of SD in patients with MDD.

Factors associated with hospitalization times and length of stay in patients with bipolar disorder.

Aim: Appraise the clinical features and influencing factors of the hospitalization times and length of stay in bipolar disorder (BD) patients. Methods: This is a multicenter, observational, cohort study of patients diagnosed of type I or type II bipolar disorder. Five hundred twenty outpatients in seven hospitals from six cities in China were recruited from February 2013 to June 2014 and followed up using a continuous sampling pattern. The research included a retrospective period of 12 months and the prospective period of 9 months. The demographic and clinical features of the patients were collected. The influencing factors that could affect the length of stay (number of days spent in the hospital in the prospective period) were analyzed by poisson's regression and the hospitalization times (times of hospitalization in the prospective and retrospective period) was analyzed by general linear model. The selected variables included gender, age, years of education, occupational status, residence status, family history of mental disease, comorbid substance abuse, comorbid anxiety disorder, times of suicide (total suicide times that occurred in the retrospective and prospective period), polarity of the first mood episode, and BD type(I/II). Results: Poisson's regression analysis showed that suicide times [Incidence Rate Ratio (IRR) = 1.20, p < 0.001], use of antipsychotic (IRR = 0.62, p = 0.011), and use of antidepressant (IRR = 0.56, p < 0.001) were correlated to more hospitalization times. Linear regression analysis showed that BD type II (ß = 0.28, p = 0.005) and unemployment (ß = 0.16, p = 0.039) which might mean longer duration of depression and poor function were correlated to longer length of stay. However, patients who experienced more suicide times (ß = -0.21, p = 0.007) tended to have a shorter length of stay. Conclusion: Overall, better management of the depressive episode and functional rehabilitation may help to reduce the length of stay. BD patients with more hospitalization times were characterized by higher risk of suicide and complex polypharmacy. Patients at high risk of suicide tended to have inadequate therapy and poor compliance, which should be assessed and treated adequately during hospitalization. Clinical trial registration: www.ClinicalTrials.gov, Identifier: NCT01770704.

Clinicodemographic correlates of psychotic features in bipolar disorder - a multicenter study in China.

BACKGROUND: Psychotic symptoms are prevalent in patients with bipolar disorder (BD). However, nearly all previous studies on differences in sociodemographic and clinical factors between patients with (BD P +) and without (BD P-) psychotic symptoms were conducted in Western populations, and limited information is known in China. METHOD: A total of 555 patients with BD from seven centers across China were recruited. A standardized procedure was used to collect patients' sociodemographic and clinical characteristics. The patients were divided into BD P + or BD P- groups based on the presence of lifetime psychotic symptoms. Mann-Whitney U test or chi-square test was used to analyze differences in sociodemographic and clinical factors between patients with BD P + and BD P-. Multiple logistic regression analysis was conducted to explore factors that were independently correlated with psychotic symptoms in BD. All the above analyses were re-conducted after the patients were divided into BD I and BD II group according to their types of diagnosis. RESULTS: A total of 35 patients refused to participate, and the remaining 520 patients were included in the analyses. Compared with patients with BD P-, those with BD P + were more likely to be diagnosed with BD I and mania/hypomania/mixed polarity in the first mood episode. Moreover, they were more likely to be misdiagnosed as schizophrenia than major depressive disorder, were hospitalized more often, used antidepressants less frequently, and used more antipsychotics and mood stabilizers. Multivariate analyses revealed that diagnosis of BD I, more frequent misdiagnosis as schizophrenia and other mental disorders, less frequent misdiagnosis as major depressive disorder, more frequent lifetime suicidal behavior, more frequent hospitalizations, less frequent use of antidepressants, more frequent use of antipsychotics and mood stabilizers were independently correlated with psychotic symptoms in BD. After dividing the patients into BD I and BD II groups, we observed notable differences in sociodemographic and clinical factors, as well as clinicodemographic correlates of psychotic features between the two groups. CONCLUSIONS: Differences in clinical factors between patients with BD P + and BD P- showed cross-cultural consistency, but results on the clinicodemographic correlates of psychotic features were not. Notable differences between patients with BD I and BD II were found. Future work exploring the psychotic features of BD needs to take types of diagnosis and cultural differences into consideration. TRIAL REGISTRATION: This study was first registered on the website of the ClinicalTrials.gov ( https://clinicaltrials.gov/ ) on 18/01/2013. Its registration number is NCT01770704.

Group-Based Symptom Trajectory of Intramuscular Administration of Scopolamine Augmentation in Moderate to Severe Major Depressive Disorder: A Post-Hoc Analysis.

Objective: Developing new strategies for rapid and sustained relief of depressive symptom has been the focus of research in the field of major depressive disorder (MDD). Scopolamine exerts rapid antidepressant effect in recent years but is controversial. Therefore, we aimed to identify a sensitive patient who may respond to intramuscular injections of scopolamine added to antidepressants based on distinct trajectory patterns. Methods: We analyzed longitudinal post hoc data collected from 66 MDD patients at Beijing Anding Hospital, Capital Medical University, over a 4-week period. In addition to demographics, depressive symptoms were assessed using the 16-item Quick Inventory of Depressive Symptomatology and Self-Report (QIDS-SR16) Scale and 17-item Hamilton Rating Scale for Depression (HRSD-17) following an i.m. injection of scopolamine. We explored different longitudinal patterns of depressive symptoms using a group-based trajectory model (GBTM). We used multiple logistic regression models to help identify predictors of different depressive symptom trajectories. Results: A two-class GBTM was identified as optimal for classifying depressive symptoms: high/rapidly declining (39.4%) and moderate/gradually declining depression trajectories (60.6%) were distinguished based on the HRSD-17. The high/rapidly declining depression trajectory was characterized by high initial depression followed by a rapid decrease at the end of the study. The moderate/gradual decline trajectory was dominated by moderate depression and gradual decline over 4 weeks. There were no significant associations of age, gender, education, or age of onset with the two trajectory groups. Conclusion: Scopolamine added to antidepressants can effectively relieve the symptoms of patients with severe depression, and it decreases faster than patients with moderate depression.

Sex differences in residual somatic symptoms in patients with first-episode depression after acute-phase treatment.

BACKGROUND: Residual somatic symptoms (RSS) are common in depressed patients, predicting treatment effectiveness. However, sex differences in RSS have received little systematic study. This study was conducted to compare sex differences of RSS in patients with first-episode depression (FED). METHODS: Nine hundred eighty-two patients with FED were selected and treated for 8 to 12 weeks. We evaluated the subjects' socio-demographic characteristics and residual depressive symptoms. Using the Patient Health Questionnaire-15 (PHQ-15) scale to assess residual somatic symptoms, the Sheehan Disability Scale (SDS) for the assessment of patients' function, the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) for quality of life. RESULTS: The incidence of RSS with FED was 46.4%. For patients with residual symptoms, the age and age of onset in females were higher than males, but males had more years of education than females. The degree of "stomach pain" in females was more severe than in males, while "trouble sleeping" in males was more severe than that in females. Multiple regression analysis showed that the total Q-LES-Q-SF score was an independent influencing factor of RSS in both males and females, while the total SDS score only affected female RSS. CONCLUSIONS: The prevalence of RSS in FED after acute-phase treatment is high. The symptom of "stomachache" is more pronounced in females, while "trouble sleeping" is more severe in males. Quality of life plays an essential role in RSS in both genders. Thus, sex needs to be considered when assessing the relationship between RSS and therapeutic effect in depression.

A prospective cohort study of depression (PROUD) in China: rationale and design.

Background: Major depressive disorder (MDD) imposes a heavy global disease burden. However, current etiology, diagnosis and treatment remain unsatisfactory and no previous study has resolved this problem. Building on the strengths and limitations of previous cohort studies of MDD, the prospective cohort study of depression (PROUD) is a 3-year large-scale cohort study designed to collect multidimensional data with a flexible follow-up schedule and strategy. The goal is to establish a nationally representative, high-quality, standardized depression cohort to support precise diagnosis and treatment of MDD and address the gap in current research. Methods: PROUD is a patient-based, nationally representative multicenter prospective cohort study with baseline and 3-year follow-up assessments. It will be carried out from January 2022 to December 2026 in 52 qualified tertiary hospitals in China. A total of 14,000 patients diagnosed with MDD, according to the DSM-5 criteria, and aged ≥ 16 years, will be recruited to PROUD. Participants aged 18-65 years who have not received any treatment during a depressive episode will be included in the precision medicine cohort (PMC) of PROUD (n=4,000). Patients who meet the general eligibility criteria but not the PMC criteria will be included in the naturalistic observation cohort (NOC) of PROUD (n=10,000). A multiple follow-up strategy, including scheduled, remote, telephone, external visits and patient self-reports, will be implemented to collect comprehensive sociodemographic, clinical information, biospecimens, neuroimaging, cognitive function and electrophysiology data and digital phenotypes according to strict standard operating procedures implemented across centers. Trial registration: ChiCTR2200059053, registered on 23 April 2022, http://www.chictr.org.cn/showproj.aspx?proj=165790. Conclusions: PROUD is a prospective cohort study of MDD patients in China. It will provide a comprehensive database facilitating further analyses and aiding the development of homeostatic and precision medicine in China.

The effect of the time to remission on residual symptoms and functioning among depressive patients.

OBJECTIVES: To explore the effect of time to remission on residual symptoms, functioning and quality of life (QOL) of the patients with major depressive disorder (MDD). METHOD: A total of 434 patients were enrolled from 16 sites of China. The Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR) and self-rating scales were assessed at baseline, and months 1, 3 and 6. Baseline remitters were defined as those subjects with a QIDS-SR score ≤ 5 at baseline. Later remitters was defined as those reaching remission one month (Month 1 remitters) or three month (Month 3 remitters) after baseline. Persistent non-remitters were defined as those with QIDS-SR score > 5 at all 3 assessments. A follow-up assessment was done at month 6 to examine outcomes. Cross-lagged models indicated QIDS-SR predicted social functioning and QOL. RESULTS: Totally, 179 patients at baseline achieved remission. An additional 141 participants remitted at month 1 (n = 94) or month 3 (n = 47), and 63 patients were persistent non-remitters. There were significant differences between all groups on depression severity at baseline. QOL was similar for both late remitter groups, which was better than non-remitters, but lower than early-remitters. Late remitters and non-remitters showed significant differences on change of functioning and QOL (P < 0.001) at each visit. By 6 months, all remitting groups showed lower depression severity and better social functioning and QOL than persistent non-remitters. Cross-lagged models indicated QIDS-SR predicted social functioning and QOL. CONCLUSION: We confirmed the association of earlier remission with a better quality of remission at early stage; but the time to remission does not affect future functioning and QOL.