The unique biodegradation pathway of benzo[a]pyrene in moderately halophilic Pontibacillus chungwhensis HN14.

Benzo[a]pyrene (BaP), as the typical representative of polycyclic aromatic hydrocarbons (PAHs), is a serious hazard to human health and natural environments. Though the study of microbial degradation of PAHs has persisted for decades, the degradation pathway of BaP is still unclear. Previously, Pontibacillus chungwhensis HN14 was isolated from high salinity environment exhibiting a high BaP degradation ability. Here, based on the intermediates identified, BaP was found to be transformed to 4,5-epoxide-BaP, BaP-trans-4,5-dihydrodiol, 1,2-dihydroxy-phenanthrene, 2-carboxy-1-naphthol, and 4,5-dimethoxybenzo[a]pyrene by the strain HN14. Furthermore, functional genes involved in degradation of BaP were identified using genome and transcriptome data. Heterogeneous co-expression of monooxygenase CYP102(HN14) and epoxide hydrolase EH(HN14) suggested that CYP102(HN14) could transform BaP to 4,5-epoxide-BaP, which was further transformed to BaP-trans-4,5-dihydrodiol by EH(HN14). Moreover, gene cyp102(HN14) knockout was performed using CRISPR/Cas9 gene-editing system which confirmed that CYP102(HN14) play a key role in the initial conversion of BaP. Finally, a novel BaP degradation pathway was constructed in bacteria, which showed BaP could be converted into chrysene, phenanthrene, naphthalene pathways for the first time. These findings enhanced our understanding of microbial degradation process for BaP and suggested the potential of using P. chungwhensis HN14 for bioremediation in PAH-contaminated environments.

The prevalence and clinical correlates of suicide attempts in patients with bipolar disorder misdiagnosed with major depressive disorder: Results from a national survey in China.

BACKGROUND AND AIM: Suicide is nearly always associated with underlying mental disorders. Risk factors for suicide attempts (SAs) in patients with bipolar disorder (BD) misdiagnosed with major depressive disorder (MDD) remain unelucidated. This study was to evaluate the prevalence and clinical risk factors of SAs in Chinese patients with BD misdiagnosed with MDD. METHODS: A total of 1487 patients with MDD from 13 mental health institutions in China were enrolled. Mini International Neuropsychiatric Interview (MINI) was used to identify patients with BD who are misdiagnosed as MDD. The general sociodemographic and clinical data of the patients were collected and MINI suicide module was used to identify patients with SAs in these misdiagnosed patients. RESULTS: In China, 20.6% of patients with BD were incorrectly diagnosed as having MDD. Among these misdiagnosed patients, 26.5% had attempted suicide. These patients tended to be older, had a higher number of hospitalizations, and were more likely to experience frequent and seasonal depressive episodes with atypical features, psychotic symptoms, and suicidal thoughts. Frequent depressive episodes and suicidal thoughts during depression were identified as independent risk factors for SAs. Additionally, significant sociodemographic and clinical differences were found between individuals misdiagnosed with MDD in BD and patients with MDD who have attempted suicide. CONCLUSIONS: This study highlights the importance of accurate diagnosis in individuals with BD and provide valuable insights for the targeted identification and intervention of individuals with BD misdiagnosed as having MDD and those with genuine MDD, particularly in relation to suicidal behavior.

Cytochrome P450 for environmental remediation: catalytic mechanism, engineering strategies and future prospects.

Environmental pollution is a global concern. Various organic compounds are released into the environment through wastewater, waste gas, and waste residue, ultimately accumulating in the environment and the food chain. This poses a significant threat to both human health and ecology. Currently, a growing body of research has demonstrated that microorganisms employ their Cytochrome P450 (CYP450) system for biodegradation, offering a crucial approach for eliminating these pollutants in environmental remediation. CYP450, a ubiquitous catalyst in nature, includes a vast array of family members distributed widely across various organisms, including bacteria, fungi, and mammals. These enzymes participate in the metabolism of diverse organic compounds. Furthermore, the rapid advancements in enzyme and protein engineering have led to increased utilization of engineered CYP450s in environmental remediation, enhancing their efficiency in pollutant removal. This article presents an overview of the current understanding of various members of the CYP450 superfamily involved in transforming organic pollutants and the engineering of biodegrading CYP450s. Additionally, it explores the catalytic mechanisms, current practical applications of CYP450-based systems, their potential applications, and the prospects in bioremediation.

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.

Efficacy and safety profiles of mood stabilizers and antipsychotics for bipolar depression: a systematic review.

The whole picture of psychotropics for bipolar depression (BPD) remains unclear. This review compares the differences in efficacy and safety profiles among common psychotropics for BPD. MEDLINE, EMBASE, and PsycINFO were searched for proper studies. The changes in the depressive rating scale, remission/response rates, nervous system adverse events (NSAEs), gastrointestinal adverse events (GIAEs), metabolic parameters, and prolactin were compared between medication and placebo or among medications with the Cohen's d or number needed to treat/harm. The search provided 10 psychotropics for comparison. Atypical antipsychotics (AAPs) were superior to lithium and lamotrigine at alleviating acute depressive symptoms. Lithium was more likely to induce dry mouth and nausea. Cariprazine and aripiprazole seemed to be associated with an increased risk of akathisia and upper GIAEs. Lurasidone was associated with an increased risk of developing akathisia and hyperprolactinemia. Olanzapine, olanzapine-fluoxetine combination (OFC), and quetiapine were associated with an increased risk of NSAEs, metabolic risk, dry mouth, and constipation. Cariprazine, lurasidone, OFC, or quetiapine was optimal monotherapy for BPD. Further studies are needed to assess the efficacy and safety of lamotrigine for treating BPD. Adverse events varied widely across different drug types due to variations in psychopharmacological mechanisms, dosages, titration, and ethnicities.

Age of onset for major depressive disorder and its association with symptomatology.

BACKGROUND: The age of onset (AOO) is a key factor for heterogeneity in major depressive disorder (MDD). Looking at the effect of AOO on symptomatology may improve clinical outcomes. This study aims to examine whether and how AOO affects symptomatology using a machine learning approach and latent profile analysis (LPA). METHODS: The study enrolled 915 participants diagnosed with MDD from eight hospitals across China. Depressive symptoms were assessed using the 17-item Hamilton Depression Rating Scale. The relationship between symptom profiles and AOO was explored using Random Forest. The effect of AOO on symptom clusters and subtypes was investigated using multiple linear regression and LPA. A continuous AOO indicator was used to conduct the analyses. RESULTS: Based on the Random Forest, symptom profiles were closely associated with AOO. The regression model showed that the severity of neurovegetative symptoms was positively associated with AOO (ß = 0.18, p < 0.001), and the severity of cognitive-behavioral symptoms was negatively associated with AOO (ß = -0.12, p < 0.001). LPA demonstrated that the subgroups characterized by suicide and guilt had earlier onset of depression. The subgroup with the lowest global severity of depression had the latest onset. LIMITATIONS: AOO was recalled retrospectively. The relative scarcity of participants with childhood and adolescence onset depression. CONCLUSIONS: AOO has an important impact on symptomatology. The findings may enhance clinical evaluations for MDD and assist clinicians in promoting earlier detection and individualized care in vulnerable individuals.

Early Diagnosis of Bipolar Disorder Coming Soon: Application of an Oxidative Stress Injury Biomarker (BIOS) Model.

Early distinction of bipolar disorder (BD) from major depressive disorder (MDD) is difficult since no tools are available to estimate the risk of BD. In this study, we aimed to develop and validate a model of oxidative stress injury for predicting BD. Data were collected from 1252 BD and 1359 MDD patients, including 64 MDD patients identified as converting to BD from 2009 through 2018. 30 variables from a randomly-selected subsample of 1827 (70%) patients were used to develop the model, including age, sex, oxidative stress markers (uric acid, bilirubin, albumin, and prealbumin), sex hormones, cytokines, thyroid and liver function, and glycolipid metabolism. Univariate analyses and the Least Absolute Shrinkage and Selection Operator were applied for data dimension reduction and variable selection. Multivariable logistic regression was used to construct a model for predicting bipolar disorder by oxidative stress biomarkers (BIOS) on a nomogram. Internal validation was assessed in the remaining 784 patients (30%), and independent external validation was done with data from 3797 matched patients from five other hospitals in China. 10 predictors, mainly oxidative stress markers, were shown on the nomogram. The BIOS model showed good discrimination in the training sample, with an AUC of 75.1% (95% CI: 72.9%-77.3%), sensitivity of 0.66, and specificity of 0.73. The discrimination was good both in internal validation (AUC 72.1%, 68.6%-75.6%) and external validation (AUC 65.7%, 63.9%-67.5%). In this study, we developed a nomogram centered on oxidative stress injury, which could help in the individualized prediction of BD. For better real-world practice, a set of measurements, especially on oxidative stress markers, should be emphasized using big data in psychiatry.

Prevalence, clinical features and prescription patterns of psychotropic medications for patients with psychotic depression in China.

OBJECTIVE: To investigate the prevalence of psychotic depression and the differences in sociodemographic and clinical characteristics and prescription patterns of psychotropic medications between patients with psychotic depression (PD) and patients with nonpsychotic depression (NPD) in China. METHODS: We conducted a cross-sectional study in 13 major psychiatric hospitals or the psychiatric units of general hospitals in China from September 1, 2010, to February 28, 2011. PD was defined according to the psychotic disorder section of the Mini International Neuropsychiatric Interview (MINI). The sociodemographic and clinical characteristics and the prescription patterns of psychotropic medications were compared between the PD and NPD groups. Multivariate logistic regression analysis was used to investigate factors associated with an increased likelihood of PD. RESULTS: Among 1172 MDD patients, the prevalence of psychotic features was 9.2% in the present study. The logistic regression analysis indicated that unmarried (OR = 2.08, p < 0.001), frequent depressive episodes (OR = 2.10, p = 0.020), depressive episodes with suicidal ideation and attempts (OR = 1.91, p = 0.004), and patients who were prescribed any antipsychotics (OR = 2.94, p < 0.001) were associated with psychotic features in patients with MDD. LIMITATIONS: Cross-sectional design, retrospective recall of some data CONCLUSION: The prevalence of PD is high in China, and there were some differences in demographic and clinical characteristics between patients with PD and patients with NPD. Clinicians should regularly assess psychotic symptoms and consider intensive treatment and close monitoring when treating subjects with PD.

Altered task-modulated functional connectivity during emotional face processing in euthymic bipolar patients: A whole-brain psychophysiological interaction study.

BACKGROUND: Patients with bipolar disorder (BD) show deficits of facial emotion processing even in the euthymic phase. However, the large-scale functional brain network mechanism underlying the emotional deficit of BD remains unclear. Specifically, it is of importance to understand how the task-modulated functional connectivity (FC) was alternated over distributed brain networks in BD. METHODS: In this study, we analyzed functional MRI data of a face-matching task from 29 euthymic BD patients and 29 healthy controls (HC), and performed whole-brain psychophysiological interaction (PPI) analysis to obtain task-modulated FC. Abnormal FC patterns were identified through support vector machine-based classification. The topological organization of task-modulated FC networks was estimated by the graph theoretical analysis and compared between BD and HC. RESULTS: BD exhibited widely distributed aberrant task-modulated FC patterns not only in core neurocognitive intrinsic brain networks (the fronto-parietal, cingulo-opercular, and default mode networks), but also in the cerebellum and primary processing networks (sensorimotor and visual). Furthermore, the local efficiency of the frontal-parietal network was significantly increased in BD. LIMITATIONS: The modest sample size. Only face pictures with negative emotion were used. Only unidirectional task-modulated FC was investigated. CONCLUSIONS: BD patients showed a widely distributed aberrant task-modulated FC pattern. Particularly, the fronto-parietal network, as one of the core neurocognitive intrinsic brain networks, was the primary network that demonstrated changes of both FC strength and local efficiency in BD. These findings on the task-modulated FC between these intrinsic brain networks might be considered an endophenotype of the BD condition persistent in the euthymic state.

Derivation and validation of the CANP scoring model for predicting the neurological outcome in post-cardiac arrest patients.

OBJECTIVES: To establish and validate a prognostic scoring model in a Chinese population to predict the neurological outcome among comatose survivors of cardiac arrest (CA). METHODS: 159 CA patients between January 2016 and November 2020 were recruited in this retrospective study. In the derivation cohort, prognostic factors available from arrest circumstances and early in-hospital indicators were measured. The Cardiac Arrest Neurological Prognosis (CANP) score was then constructed to predict unfavorable outcomes at 30 days after CA. The assessment of predictive effectiveness of this scoring model was conducted in both derivation and validation cohorts. RESULTS: Witnessed status, bystander cardiopulmonary resuscitation, initial rhythm, duration of resuscitation, Glasgow Coma Scale motor score, pupillary/corneal reflex, gray-white matter ratio and neuron-specific enolase exhibit strong correlations with the neurological outcomes in the derivation cohort (all p<0.05), and a risk scoring model for the prediction of an unfavorable outcome was created using these factors. In the validation cohort, significantly higher CANP scores were noted in the unfavorable outcome group. A CANP score ≥5 was associated with unfavorable neurological outcomes (sensitivity 68.8%, specificity 100%). CONCLUSION: The CANP score was established and validated for predicting the possible neurological prognosis in comatose post-CA survivors.

Reliability and validity of the Chinese version of the CUDOS-M in patients with mood disorders: A multicenter study across China.

BACKGROUND: A useful scale for identification of mixed features in major depressive episodes (MDE) patients is urgent in China. This study aimed to evaluate the reliability and validity of the Chinese version of the Clinically Useful Depression Outcome Scale supplemented with questions for the DSM-5 mixed features specifier (Chinese-CUDOS-M) in MDE patients. METHODS: A total of 152 MDE patients were recruited and assessed using Chinese-CUDOS-M, Patient Health Questionnaire-9 (PHQ-9) and 32-item Hypomania Checklist (HCL-32). Principal component analysis (PCA) and exploratory factor analysis (EFA) were conducted. The predictive validity was calculated by the area under the receiver operating characteristic curve (AUROC). RESULTS: The Cronbach's alpha of Chinese-CUDOS-M was 0.85. PCA showed three common factors with eigenvalue greater than 1; the eigenvalue of factor I was 4.96, with 38.1% of variance explanation. Chinese-CUDOS-M depression subscale was associated with PHQ-9 (r = 0.83, p<0.01), and manic subscale was associated with HCL-32 (r = 0.73, p< 0.01). AUROC of the Chinese-CUDOS-M for patients with mixed depression was 0.90 (95%CI: 0.85-0.95), with a cut-off value of 7, sensitivity of 0.95, and specificity of 0.73. Furthermore, AUROC was 0.88 in patients with major depressive disorder (MDD), with a cut-off value of 7, sensitivity of 0.96, and specificity of 0.71. AUROC was 0.92 in bipolar disorder (BD) depression patients, with a cut-off value of 9, sensitivity of 0.89, and specificity of 0.87. CONCLUSION: Our study shows that the Chinese-CUDOS-M can identify mixed features in both MDD and BD depression with satisfactory reliability and validity.

Reliability and validity of clinically useful depression outcome scale identifying mixed features in patients with manic episode.

OBJECTIVES: This study aims to explore the reliability, validity, and feasibility of Clinically Useful Depression Outcome Scale (CUDOS) in screening mixed features in patients diagnosed with mania. METHODS: A total of 109 patients with (hypo-) manic episode were recruited. The reliability of Chinese version of CUDOS (CUDOS-C) were analyzed with Cronbach's alpha and intraclass correlation coefficient (ICC). Spearman correlation coefficient was used to analyze the validity by comparing the correlation between CUDOS-C and Patient Health Questionnaire-9 (PHQ-9), 32-item Hypomania Checklist (HCL-32). The score of MINI (hypo-) manic episode with mixed features-DSM-5 Module-Chinese version(MINI-M-C) ≥ 2 was considered as the gold standard of mixed features, and the receiver operating characteristic (ROC) curve analysis was used to calculate the optimal cut-off values of CUDOS-C score. RESULTS: The Cronbach's alpha value of CUDOS-C was 0.898, and the ICC of CUDOS-C test-retest was 0.880 (95% CI: 0.812-0.923, p < .05).The CUDOS-C score was significantly correlated with PHQ-9 score (r = 0.893, p = .000), but not with HCL-32 score(r = 0.088, p = .364).The area under ROC curve was 0.909 (95% CI: 0.855 to 0.963, p < .001) for CUDOS-C identifying mixed features in mania. The optimal cut-off value was 11 with a sensitivity of 0.854 and a specificity of 0.868. The CUDOS-C (score ≥ 12) identified 40.4% of the patients with mixed features, which was higher than those diagnosed by clinicians (18.3%) and screened using MINI-M-C (37.6%). CONCLUSIONS: The results indicate the CUDOS-C is a reliable and valid self-administered questionnaire for assessing depressive symptoms and screening patients with mixed mania.

Abnormal transitions of dynamic functional connectivity states in bipolar disorder: A whole-brain resting-state fMRI study.

BACKGROUND: Dynamic functional connectivity (dFC) based on resting-state fMRI has attracted interest in the field of bipolar disorder (BD), because dFC can better capture the evolving processes of emotion and cognition, which are typically impaired in BD. However, previous dFC studies of BD have typically focused on specific seed brain regions or specific functional brain networks, and they have ignored global dynamic information interaction in the whole brain. This study is aimed to reveal aberrant and interpretable whole-brain dFC patterns of BD. METHODS: The resting-state fMRI data collected from 35 euthymic BD patients and 30 healthy people. We developed a new dFC inference pipeline, including the sliding-window method, k-means clustering, a new permutation with zero-inflated Poisson regression method, and a similarity analysis for interpretable states, to examine the different patterns of dFC states between BD patients and healthy participants. RESULTS: BD patients had significantly more frequent transitions between two specific dFC states, which were respectively close to high-level cognitive networks and low-level sensory networks, than healthy controls (p < 0.05, FDR). LIMITATIONS: The size of samples and other BD types need to be expanded to validate the results of this study. Possible confounding effect of medication. CONCLUSIONS: This study detected aberrant dFC pattern of BD, which indicated the increased lability of the processes of cognition and emotion in BD, and this finding could improve our understanding of the neuropathological mechanism of BD.

MiR-324-3p Regulates Fibroblast Proliferation via Targeting TGF-ß1 in Atrial Fibrillation.

Atrial fibrillation (AF), one of the common clinical arrhythmias, lacks effective treatment manners. Cardiac fibroblasts play an essential role in myocardial fibrosis and cardiac remodeling, which are involved in AF progression. Reportedly, MicroRNAs (miRNAs) regulate the myocardial fibrosis in AF. However, whether miR-324-3p involves myocardial fibrosis in AF and the tentative molecular mechanisms of miR-324-3p regulating cardiac fibroblasts during AF remains unknown. In the present study, miR-324-3p was found to be decreased in patients with AF and AF rat model. Next, we investigated the effect of miR-324-3p on myocardial fibroblast proliferation through miR-324-3p overexpression and found that miR-324-3p inhibited fibroblast proliferation in vitro. Furthermore, we found that miR-324-3p directly targeted transforming growth factor ß1 in fibroblast, which may be involved in the development of myocardial fibrosis during AF. Meanwhile, miR-324-3p mimics treatment suppressed the PI3K/AKT signaling pathway in fibroblast. These results demonstrated a molecular mechanism of miR-324-3p regulating fibroblast proliferation in vitro, which might provide a novel potential treatment manner in AF in clinic.

Acceptability of Acute and Maintenance Pharmacotherapy of Bipolar Disorder: A Systematic Review of Randomized, Double-Blind, Placebo-Controlled Clinical Trials.

PURPOSE/BACKGROUND: The aim of the study was to estimate and rank the risk for the discontinuation due to adverse events (DAEs), 7% or more weight gain (WG), and somnolence during the acute and maintenance treatment of bipolar disorder with a mood stabilizer or an antipsychotic monotherapy. METHODS/PROCEDURES: The search of MEDLINE, EMBASE, PsycINFO, and clinicaltrials.gov from the inception to December 31, 2018, provided 32 studies in mania, 16 in bipolar depression, and 13 in maintenance. Data of DAEs, WG, and somnolence from each study were extracted. The risk for these variables of an active treatment relative to placebo was estimated with a number needed to harm (NNH) as a single study and pooled sample. FINDINGS/RESULTS: For DAEs, pooled NNH ranged from 19 with carbamazepine to -21 with quetiapine-XR in mania, 11 with quetiapine-IR 600 mg/d to -37 with olanzapine/fluoxetine combination in bipolar depression, and 5 with lithium to -8 with asenapine in maintenance. For WG, pooled NNH ranged from 9 with olanzapine to -78 with aripiprazole in mania, 5 with olanzapine to -112 with lithium in bipolar depression, and 4 with olanzapine to 126 with asenapine in maintenance. For somnolence, pooled NNH was from 5 with carbamazepine to 23 with cariprazine in mania, 3 with quetiapine-XR 300 mg/d to 79 with lurasidone in bipolar depression, and 11 with olanzapine to -49 with aripiprazole in maintenance. IMPLICATIONS/CONCLUSIONS: All medications studied in bipolar disorder were relatively well tolerated during different phases of treatment; however, the risk for short- and long-term WG and somnolence varied widely among included psychotropics.

Symptomatology differences of major depression in psychiatric versus general hospitals: A machine learning approach.

BACKGROUND: Symptomatology differences of major depressive disorder (MDD) in psychiatric and general hospitals in China leads to possible misdiagnosis. Looking at the symptomatology of first-visit patients with MDD in different mental health services, and identifying predictors of health-seeking behavior using machine learning may help to improve diagnostic accuracy. METHODS: 1500 patients first diagnosed with MDD were recruited from 16 psychiatric hospitals and 16 general hospitals across China. Socio-demographic characteristics, causal attribution, symptoms of depression within and outside Diagnostic and Statistical Manual of Mental Disorders (DSM) framework were collected using a self-made questionnaire. A predictive model of 62 variables was established using Random forest, symptom frequencies of patients in general hospitals and psychiatric hospitals were compared. RESULTS: The machine learning approach revealed that symptoms were strong predictors of health-seeking behavior among patients with MDD. General hospitals patients had higher frequencies of suicidal ideation (χ2=15.230, p<0.001), psychosis (χ2=14.264, p<0.001), weight change (all p<0.001), hypersomnia (χ2=25.940, p<0.001), and a tendency of denying emotional/cognitive symptoms compared with psychiatric hospitals patients. LIMITATIONS: Stigma and preference bias were not measured. Severity of current depressive episodes was not assessed. Data of previous episode(s) was not presented. CONCLUSIONS: Symptom evaluation targeting specific patient population in different hospitals is crucial for diagnostic accuracy. Suicide prevention reliant on collaboration between general hospitals and psychiatric hospitals is required in the future construction of Chinese mental health system.

Do Asian and North American patients with bipolar disorder have similar efficacy, tolerability, and safety profile during clinical trials with atypical antipsychotics?

BACKGROUND: The approvals of psychotropics for bipolar disorder (BD) are mainly based on randomized, double-blind, placebo-controlled trials (RCTs) from North America. It remains unknown whether approved psychotropics have similar efficacy, tolerability, and safety for Asians with BD. The aim of this systematic review was to compare those differences of psychotropics between Asians and North Americans with BD. METHODS: MEDLINE, EMBASE, and PsycINFO were searched for RCTs studied in two regions. The effect size, remission/response rate, and risk for discontinuation due to adverse events (AEs), weight gain (WG), nervous systems and gastrointestinal AEs were assessed and compared between two regions with Cohen's d or number needed to treat/harm. RESULTS: Eleven studies of aripiprazole, olanzapine, risperidone, and quetiapine in BD were included. Similar efficacy and relatively benign tolerability of atypical antipsychotics (AAPs) between Asians and Americans with BD were observed in most studies. The risk for AAP-related WG was similar between two regions. Asians with mania or bipolar depression were more vulnerable to akathisia/tremor or constipation. Japanese and Chinese with bipolar depression were more sensitive to somnolence and dizziness, respectively. Americans were more likely to have dry mouth, nausea, and vomiting. LIMITATIONS: The number of included psychotropics and papers was small. CONCLUSIONS: Differences in AAP-related efficacy and tolerability were minimal between the two regions, but some AEs appeared to be different. Clinicians should pay attention to these differences to optimize treatment strategies in different races/ethnicities with BD.

Fusion analysis of gray matter and white matter in bipolar disorder by multimodal CCA-joint ICA.

BACKGROUND: Bipolar disorder (BD) patients show morphological abnormalities in gray matter (GM) and white matter (WM), which can be revealed by structure MRI (sMRI) and diffusion tensor imaging (DTI) respectively. However, previous studies on BD mainly relied on separated analysis of single neuroimaging modality, and it remains unclear how GM and WM covary to the abnormal brain structures of BD patients. METHODS: We recorded multimodal sMRI-DTI data of 35 BD patients and 30 healthy controls (HC) and used multimodal canonical component analysis and joint independent component analysis (mCCA-jICA) to identify altered covariant structures in GM and WM of BD. Group-discriminative and joint group-discriminative independent components (ICs) were identified between BD and HC. Correlation analysis was performed between the mixing coefficients and behavioral index. RESULTS: For BD patients, experiments results revealed that the GM atrophy in inferior frontal gyrus, right anterior cingulate gyrus and left superior frontal gyrus are associated with the WM integrity reduction in corticospinal tract and superior longitudinal fasciculus. Further, compared with HC, different correlation between mixing coefficients of ICs and age was observed for BD patients. LIMITATIONS: The number of participants needs to be increased to more rigorously validate the results of this study, ideally from multiple sites. Functional imaging data could be utilized to explore structural-functional covariant pattern in BD. Possible confounding effect of medication. CONCLUSIONS: We performed fusion analysis of sMRI and DTI and revealed covariant (GM-WM) structural patterns of BD patients. This study could be useful for developing more reliable neural biomarkers of BD.

Causes of drug discontinuation in patients with major depressive disorder in China.

BACKGROUND: This research was designed to investigate patient-reported and doctor-reported reasons for the discontinuation of pharmacological treatment in Chinese patients with major depressive disorder (MDD), which was part of the National Survey on Symptomatology of Depression (NSSD) from 2014 to 2015. METHODS: This cross-sectional study included 649 patients who had discontinued antidepressant medications and 711 patients who had remained on them, selected from a group of 3516 candidates who have had at least one depressive episode. Differences in the two groups' sociodemographic factors, clinical characteristics, medication use, and self-reported reasons for drug discontinuation were compared via Student's t-test or chi-square test. Logistic regression analysis was then used to determine the association of all non-subjective dichotomous and ordinal categorical variables, including the additional 63 items of our physician-evaluated symptomatic assessment, with drug compliance. RESULTS: Compared to the spontaneous drug discontinuation (SDD) group, the drug adherence (DA) group had significantly lower rates of the following: family history of mental disease (9.0% vs 13.6%), highest level of education achieved being post-graduate or above (1.6% vs 4.7%), smoking (5.8% vs 9.7%), and other health problems (33.9% vs 42.4%) (p's < 0.05). On the other hand, first-episode depression (48.5% vs 21.9%) and taking of mood stabilizer(s) (8.3% vs 5.6%) were higher in the former group than in the latter (p's < 0.05). Logistic Regression Analysis showed that five symptoms, such as depressed mood, were correlated positively with SDD, while another six symptoms, such as psychomotor retardation, were correlated negatively with it. The receiver operating characteristic (ROC) curve of this model yielded an area under the curve (AUC) of 0.701 (95% CI, 0.673-0.729). Notably, there were three main reasons given by patients in the DA group as to why they discontinued their medication(s): (1) concern about long-term side effects (36.1%), (2) no perceived need for taking said medication(s) long-term (34.2%), and (3) believing oneself to have been cured completely (30.0%). CONCLUSIONS: The aforementioned factors may affect patient compliance and elicit maladaptive thinking even from patients with good educational backgrounds, increasing the risk of drug discontinuation. Compliance of pharmacological treatment might be improved by increasing clarification and elucidation of different symptom clusters to the patient and combating the main reasons for drug discontinuation.