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Deep brain stimulation (DBS) of structures in the brain’s reward system is a promising therapeutic option for patients with treatment-resistant depression (TRD). Recently, DBS of the habenula (HB) in the brain’s anti-reward system has also been reported to alleviate depressive symptoms in patients with TRD or bipolar disorder (BD). In this pilot open-label prospective study, we explored the safety and clinical effectiveness of HB–DBS treatment in seven patients with TRD or BD. Also, local field potentials (LFPs) were recorded from the patients’ left and right HB to explore the power and asymmetry of oscillatory activities as putative biomarkers of the underlying disease state. At 1-month follow-up (FU), depression and anxiety symptoms were both reduced by 49% ( n  = 7) along with substantial improvements in patients’ health status, functional impairment, and quality of life. Although the dropout rate was high and large variability in clinical response existed, clinical improvements were generally maintained throughout the study [56%, 46%, and 64% reduction for depression and 61%, 48%, and 70% reduction for anxiety at 3-month FU ( n  = 5), 6-month FU ( n  = 5), and 12-month FU ( n  = 3), respectively]. After HB–DBS surgery, sustained improvements in mania symptoms were found in two patients who presented with mild hypomania at baseline. Another patient, however, experienced an acute manic episode 2 months after surgery that required hospitalization. Additionally, weaker and more symmetrical HB LFP oscillatory activities were associated with more severe depression and anxiety symptoms at baseline, in keeping with the hypothesis that HB dysfunction contributes to MDD pathophysiology. These preliminary findings indicate that HB–DBS may offer a valuable treatment option for depressive symptoms in patients who suffer from TRD or BD. Larger and well-controlled studies are warranted to examine the safety and efficacy of HB–DBS for treatment-refractory mood disorders in a more rigorous fashion.

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.

The nucleus accumbens (NAc) is considered a hub of reward processing and a growing body of evidence has suggested its crucial role in the pathophysiology of major depressive disorder (MDD). However, inconsistent results have been reported by studies on reward network-focused resting-state functional MRI (rs-fMRI). In this study, we examined functional alterations of the NAc-based reward circuits in patients with MDD via meta- and mega-analysis. First, we performed a coordinated-based meta-analysis with a new SDM-PSI method for all up-to-date rs-fMRI studies that focused on the reward circuits of patients with MDD. Then, we tested the meta-analysis results in the REST-meta-MDD database which provided anonymous rs-fMRI data from 186 recurrent MDDs and 465 healthy controls. Decreased functional connectivity (FC) within the reward system in patients with recurrent MDD was the most robust finding in this study. We also found disrupted NAc FCs in the DMN in patients with recurrent MDD compared with healthy controls. Specifically, the combination of disrupted NAc FCs within the reward network could discriminate patients with recurrent MDD from healthy controls with an optimal accuracy of 74.7%. This study confirmed the critical role of decreased FC in the reward network in the neuropathology of MDD. Disrupted inter-network connectivity between the reward network and DMN may also have contributed to the neural mechanisms of MDD. These abnormalities have potential to serve as brain-based biomarkers for individual diagnosis to differentiate patients with recurrent MDD from healthy controls.

Summary Aims Nonadherence is one of the leading challenges to treatment of the major depressive disorder (MDD). Few studies have systematically analyzed the relationship between clinical characteristics, especially symptoms of depressive patients and their therapeutic nonadherence over a relatively large sample. This study aimed to investigate factors of nonadherence in a nationwide survey in China. Methods Participants with MDD who met the criteria of Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM‐IV) were recruited from 32 sites throughout China. Patients were all over 16 years old. A doctor‐rating questionnaire with 64 symptoms based on DSM‐IV was constructed to evaluate depression‐related feeling and behavior. Single‐factor logistic regression was utilized to screen variables, and multifactor logistic regressive analysis was used to identify which factors were risk or protective for nonadherence. We included 882 patients of poor adherence and 857 patients of good adherence. Results Recurrence, untreated first episode, tricyclic antidepressant (TCA)‐treated first episode, antidepressant‐only‐treated current episode, decrease or loss of interest, more somatic symptoms, and “atypical” symptoms were risk factors for nonadherence, whereas selective noradrenaline reuptake inhibitor (SNRI)‐treated first episode was a protecting factor. Conclusion Clinical characteristics may play an important role in predicting nonadherence. Doctors may have to pay much attention on patients with these factors and should keep on discussing them with patients.

Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.

The aim of this study was to test the ability of the Chinese version of the Mood Disorder Questionnaire (MDQ) to identify Bipolar Disorders (BD) in patients diagnosed with Major Depressive Disorder (MDD) or Unipolar Disorder (UD) in the clinical setting. 1,487 being treated for MDD or UD at 12 mental health centers across China, completed the MDQ and subsequently examined by the Mini International Neuropsychiatric Interview (MINI). Receiver Operating Characteristic(ROC) curves were used to determine the ability of the MDQ to differentiate between BD (BD, BD-I and BD-II) and MDD or UD and patients with BD-I from patients with BD-II. Of the 1,487 patients, 309 (20.8%) satisfied the DSM-IV criteria for BD: 118 (7.9%) for BD-I and 191 (12.8%) for BD-II. When only part one of the MDQ was used, the best cutoff was 7 between BD and UD (sensitivity 0.66, specificity 0.88, positive predictive value 0.59, negative predictive value 0.91), 6 between BD-II and UD, and 10 between BD-I and BD-II. If all three parts of the MDQ were used, the MDQ could not distinguish between BD and UD at a cutoff of 7 (or 6), and the sensitivity was only 0.22 (or 0.24). The Chinese version of the MDQ had good psychometric features in screening bipolar disorders from depressive patients with mood disorders when part two and part three of the MDQ were ignored.

The application of all-solid-state Li-metal batteries with solid oxide electrolytes is hindered by interfacial issues, especially the solid electrolyte/Li-metal interface. This work introduced a uniform indium film layer on the surface of Na + super ionic conductor (NASICON) solid electrolyte Li 1.5 Al 0.5 Ge 1.5 P 3 O 12 (LAGP), which promotes the intimate contact between Li metal and solid electrolyte and hinders the side reactions at the interface. Electrochemical impedance spectra show that the battery with coated solid electrolyte presents a smaller interfacial resistance and maintains stability after a long cycling time. By contrast, the baseline battery with a pure LAGP pellet shows a contact loss after cycling with the vibration of interfacial impedance. The Li symmetric cells with indium-modified solid electrolyte present stable cycling behavior over 400 h at 0.1 and 0.2 mA·cm −2 . The all-solid-state Li-metal batteries with a Li anode, indium coating LAGP and two kinds of cathodes, namely carbon nanotubes (CNTs) and LiNi 0.8 Co 0.1 Mn 0.1 O 2 (NCM811), are prepared and tested. The CNTs cathode for Li–O 2 and Li–air batteries has a higher specific capacity than traditional Li-ion battery cathodes. The Li-NCM811 batteries deliver an initial Coulombic efficiency of about 75%, with 82% capacity retention after 20 cycles.

Background The 32-item Hypomania Checklist (HCL-32), a questionnaire for screening bipolar disorders, has been utilised in several countries, but it unclear if the Chinese version of the HCL-32 is valid. Methods Consecutive patients with bipolar disorders (BP, N = 300) and unipolar major depression (UP, N = 156) completed the Chinese version of the HCL-32. The subjects underwent a structured clinical interview for DSM-IV Axis-I disorders (SCID). Results The eigenvalues for the first three factors in the HCL-32 were calculated as 5.16 (active/elated), 2.72 (risk-taking) and 2.48 (irritable) using factor analysis. Cronbach's alpha for the HCL-32 was calculated to be 0.88. Positive responses to twenty-eight items were significantly more frequent by patients with BP than those with UP, and the other four items (7th, 21st, 25th and 32nd) showed no such trend. Fourteen was the optimal cut-off for discriminating between BP and UP. The HCL-32 distinguished between BP-II and UP, with 13 being the optimal cut-off. A cut-off of 13 yielded a sensitivity of 0.77 and a specificity of 0.62 between BP and UP. Conclusions This study demonstrated that the simplified Chinese version of HCL-32 was valid for patients with mood disorders. The optimal cut-off of 13 for distinguishing between BP-II and UP was valid and could be used to improve the sensitivity of screening BP-II patients when the HCL-32 is used in psychiatric settings in China.

Little has been known about the demographic and clinical features of the melancholic subtype of major depressive disorder (MDD) in Chinese patients. This study examined the frequency of melancholia in Chinese MDD patients and explored its demographic and clinical correlates and prescribing patterns of psychotropic drugs. A consecutively collected sample of 1,178 patients with MDD were examined in 13 psychiatric hospitals or psychiatric units of general hospitals in China nationwide. The cross-sectional data of patients' demographic and clinical characteristics and prescriptions of psychotropic drugs were recorded using a standardized protocol and data collection procedure. The diagnosis of the melancholic subtype was established using the Mini International Neuropsychiatric Interview (MINI). Medications ascertained included antidepressants, mood stabilizers, antipsychotics and benzodiazepines. Six hundred and twenty nine (53.4%) of the 1,178 patients fulfilled criteria for melancholia. In multiple logistic regression analyses, compared to non-melancholic counterparts, melancholic MDD patients were more likely to be male and receive benzodiazepines, had more frequent suicide ideations and attempts and seasonal depressive episodes, while they were less likely to be employed and receive antidepressants and had less family history of psychiatric disorders and lifetime depressive episodes. The demographic and clinical features of melancholic MDD in Chinese patients were not entirely consistent with those found in Western populations. Compared to non-melancholic MDD patients, melancholic patients presented with different demographic and clinical features, which have implications for treatment decisions.

Background: Early-onset major depressive disorder (MDD) (EOD) is often particularly malignant due to its special clinical features, accompanying impaired social function, protracted recovery time, and frequent recurrence. This study aimed to observe the effects of age onset on clinical characteristics and social function in MDD patients in Asia. Methods: In total, 547 out-patients aged 18-65 years who were from 13 study sites in five Asian countries were included. These patients had MDD diagnose according to the Diagnostic and Statistical Manual of Mental Disorders, 4 th Edition criteria. Clinical features and social function were assessed using Symptom Checklist-90-revised (SCL-90-R) and Sheehan Disability Scale (SDS). Quality of life was assessed by a 36-item Short-form Health Survey (SF-36). Analyses were performed using a continuous or dichotomous (cut-off: 30 years) age-of-onset indicator. Results: Early-onset MDD (EOD, <30 years) was associated with longer illness (P = 0.003), unmarried status (P < 0.001), higher neuroticism (P ≤ 0.002) based on the SCL-90-R, and more limited social function and mental health (P = 0.006, P = 0.007) based on the SF-36 and SDS. The impairment of social function and clinical severity were more prominent at in-patients with younger onset ages. Special clinical features and more impaired social function and quality of life were associated with EOD, as in western studies. Conclusions: EOD often follows higher levels of neuroticism. Age of onset of MDD may be a predictor of clinical features and impaired social function, allowing earlier diagnosis and treatment.