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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.

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.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.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.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.

Highlights • Two subtypes with distinct default mode network profiles exist in major depression. • Subtypes of major depression are robust in validation datasets across brain atlases. • Hyper- & hypo-connectivity DMN subgroups have comparable clinical symptom variables. • Future studies should examine whether two subtypes have differing treatment response., Background Major depressive disorder (MDD) is heterogeneous disorder associated with aberrant functional connectivity within the default mode network (DMN). This study focused on data-driven identification and validation of potential DMN-pattern-based MDD subtypes to parse heterogeneity of the disorder. Methods The sample comprised 1397 participants including 690 patients with MDD and 707 healthy controls (HC) registered from multiple sites based on the REST-meta-MDD Project in China. Baseline resting-state functional magnetic resonance imaging (rs-fMRI) data was recorded for each participant. Discriminative features were selected from DMN between patients and HC. Patient subgroups were defined by K-means and principle component analysis in the multi-site datasets and validated in an independent single-site dataset. Statistical significance of resultant clustering were confirmed. Demographic and clinical variables were compared between identified patient subgroups. Results Two MDD subgroups with differing functional connectivity profiles of DMN were identified in the multi-site datasets, and relatively stable in different validation samples. The predominant dysfunctional connectivity profiles were detected among superior frontal cortex, ventral medial prefrontal cortex, posterior cingulate cortex and precuneus, whereas one subgroup exhibited increases of connectivity (hyperDMN MDD) and another subgroup showed decreases of connectivity (hypoDMN MDD). The hyperDMN subgroup in the discovery dataset had age-related severity of depressive symptoms. Patient subgroups had comparable demographic and clinical symptom variables. Conclusions Findings suggest the existence of two neural subtypes of MDD associated with different dysfunctional DMN connectivity patterns, which may provide useful evidence for parsing heterogeneity of depression and be valuable to inform the search for personalized treatment strategies.

Background: Bipolar disorder (BD) is a kind of mental disorder with the greatest risk of suicide, but it is often misdiagnosed as major depressive disorder (MDD) clinically. This study aimed to analyze the sociodemographic factors and clinical characteristics associated with suicide attempts (SA) in patients with BD misdiagnosed with MDD in China. Methods: A total of 1487 MDD patients were consecutively enrolled in 13 mental health centers in China. Data on patients’ sociodemographic and clinical characteristics were collected using a standardized protocol. Of these, 306 BD patients were misdiagnosed with MDD according to the Mini International Neuropsychiatric Interview (MINI). Suicide attempters and non-attempters were classified by the suicidality module of the MINI. Multiple logistic regression analyses were performed to assess the association between the independent variables of interest and SA in BD patients misdiagnosed with MDD. Results: Of the 306 BD patients misdiagnosed with MDD, 225 (73.5%) were non-attempters and 81 (26.5%) were attempters. Compared to non-attempters, attempters were older (Z =2.2, p = 0.03) and had more admissions(χ2 =6.1, p = 0.013), more frequent depressive episodes, more atypical characteristics (e.g. increased appetite, weight gain, and more sleep time)(χ2 = 5.8, p = 0.016), more suicidal ideation (χ2 = 27.3, p < 0.001), more psychotic symptoms (χ2 = 7.4, p = 0.006) and more seasonal depressive episodes (χ2 = 5.6, p = 0.018). Multiple logistic regression analyses revealed that attempters were characterized by more suicidal ideation (OR = 5.7, 95% CI: 2.6–12.5) and frequent depressive episodes (OR = 2.4, 95% CI: 1.3–4.6). The limitations of this study include its cross-sectional design and data collection by suicide attempters’ retrospective recall. Conclusions: The findings of this study suggest that BD patients misdiagnosed with MDD are at a higher risk of suicide, and more frequent depressive episodes and suicidal ideation are risk factors for attempted suicide. Early identification of and interventions for these risk factors might reduce the risk of suicide in BD patients misdiagnosed with MDD.

Background: Major depressive disorder (MDD) is known to be characterized by altered brain functional connectivity (FC) patterns. However, whether and how the features of dynamic FC would change in patients with MDD are unclear. In this study, we aimed to characterize dynamic FC in MDD using a large multi-site sample and a novel dynamic network-based approach. Methods: Resting-state functional magnetic resonance imaging (fMRI) data were acquired from a total of 460 MDD patients and 473 healthy controls, as a part of the REST-meta-MDD consortium. Resting-state dynamic functional brain networks were constructed for each subject by a sliding-window approach. Multiple spatio-temporal features of dynamic brain networks, including temporal variability, temporal clustering and temporal efficiency, were then compared between patients and healthy subjects at both global and local levels. Results: The group of MDD patients showed significantly higher temporal variability, lower temporal correlation coefficient (indicating decreased temporal clustering) and shorter characteristic temporal path length (indicating increased temporal efficiency) compared with healthy controls (corrected p < 3.14×10−3). Corresponding local changes in MDD were mainly found in the default-mode, sensorimotor and subcortical areas. Measures of temporal variability and characteristic temporal path length were significantly correlated with depression severity in patients (corrected p < 0.05). Moreover, the observed between-group differences were robustly present in both first-episode, drug-naïve (FEDN) and non-FEDN patients. Conclusions: Our findings suggest that excessive temporal variations of brain FC, reflecting abnormal communications between large-scale bran networks over time, may underlie the neuropathology of MDD.

Stigma of major depressive disorder (MDD) is an important public health problem. This study aimed to examine the level of perceived stigma and its associated factors in MDD patients in five Asian countries, including China, Korea, Malaysia, Singapore, and Thailand. A total of 547 outpatients with MDD were included from Asian countries. We used the stigma scale of the Explanatory Model Interview Catalogue (EMIC) to assess stigma. The Montgomery–Asberg Depression Rating Scale (MADRS), Symptoms Checklist 90-Revised (SCL-90-R), Fatigue Severity Scale (FSS), Sheehan Disability Scale (SDS), 36-Item Short-Form Health Survey (SF-36), and Multidimensional Scale of Perceived Social Support (MSPSS) were used to assess symptoms, clinical features, functional impairment, health status, and social support. The stigma scores of patients under 55 years old were significantly higher than those equal to or greater than 55 years old (P < 0.001). The stigma scores exhibited significant negative correlation with age; MSPSS scores of family, friends, and others; and SF-36 subscale of mental health, but significant positive correlation with MADRS, FSS, SDS, and SCL-90-R subscale scores of depression, interpersonal sensitivity, obsession–compulsion, psychoticism, and somatization. Multivariate regression analysis revealed that age, SCL-90-R interpersonal sensitivity, obsession–compulsion, psychoticism, MSPSS scores of friends and others, and SF-36 of mental health were significantly associated with the level of perceived stigma. These findings suggest that MDD patients who are young, have a high degree of interpersonal sensitivity and psychoticism, have low health-related quality of life, and have low social support are the target population for stigma interventions in Asia.

Background: With attention to misdiagnosis of bipolar disorder (BP), long duration of undiagnosed bipolar disorder (DUBP) had been reported recently in years. This study aims to investigate the contributions of long DUBP to the frequency of relapse in bipolar patients, and explore affect factors of DUBP. Method: From 26 hospitals throughout China, 3896 participants diagnosed with BP according to International Classification of Diseases 10th criteria were enrolled in this study. Socio-demographic and clinical data were collected from medical records and specific questionnaires through clinical interviews with patients and their relatives. Results: (1) Our results showed that the mean of DUBP was 40.52 months. In total, 779 patients (19.995%) reported DUBP greater than 5 years, and 1931 patients (49.564%) reported their DUBP greater than 2 years. The number of mood episodes was averaged 5.44, and the frequency ratio of (hypo) mania to depressive episodes was 1.49 (3.27/2.19). (2) Multiple linear regression analysis revealed that DUBP was significantly contributed to the number of relapse (Beta = 0.072, p

Objective: To analyze the factors associated with recent suicide attempts including socio-demographic and clinical characteristics in major depressive disorder (MDD) patients in China.Methods: The data were from a nationwide sample from 13 major psychiatric hospitals or the psychiatric units of general hospitals in China, from September 1, 2010 to February 28, 2011. Melancholic features and suicide attempts in the past month were defined according to the melancholic feature module and the suicide module of the Mini International Neuropsychiatric Interview (MINI). Socio-demographic and clinical characteristics were compared between MDD patients with and without recent suicide attempts. Further analyses regarding the factors associated with recent suicide attempts in MDD patients were performed via multivariate logistic regression analysis.Results: Among 1,172 MDD patients, 57 (4.9%) were reported to have made a suicide attempt in the past month. Compared to the MDD patients without recent suicide attempt, significantly higher percentage of patients in the recent suicide attempters group had previous suicide attempts (χ2 = 171.861, p < 0.001) and depressive episodes with melancholic features (χ2 = 22.837, p < 0.001). Logistic regression analysis indicated that previous suicide attempts (OR = 20.81, 95% CI: 11.12–38.94, p < 0.001) and depressive episodes with melancholic features (OR = 4.43, 95% CI: 2.09–9.43, p < 0.001) were independently associated with recent suicide attempts in MDD patients.Limitations: Cross-sectional design, retrospective recall of suicide attempt data.Conclusion: Recent suicide attempts are associated with melancholic features and previous suicide attempts in MDD patients in China. These data may help clinicians to identify MDD patients at high risk of suicide attempt behavior.

The objective of this study was to evaluate morphological changes at the articular disc of the temporomandibular joint and capillary of the retrodiscal tissue in a rat model for type 2 spontaneous diabetes mellitus (DM) (i.e., Goto-Kakizaki [GK] rats) compared to normal Wistar rats. A total of 20 experimental rats were used in this study; the rats were categorized into the normal (n = 10 male 8-week-old Wistar rats) and DM (n = 10 male 8-week-old GK rats) groups. Hematoxylin-eosin stained specimens were obtained from 5 rats from each group. Image analyses of the hematoxylin-eosin stained specimens were conducted using light micrographs, which allowed comparisons of the thickness of the anterior, central, and posterior parts of the articular disc. Afterwards, the microvascular corrosion cast specimens were obtained from 5 rats from each group. The diameter of the capillary of the retrodiscal tissue was determined by analyzing scanning electron micrographs of the microvascular corrosion cast specimens. Student's t-test was used to test for statistical significant differences between the 2 groups. Differences were considered significant when p < 0.01. We found that the thickness of the anterior, central, and posterior parts of the articular disc, and the diameter of the capillary of the retrodiscal tissue was significantly lower in the DM vs. normal group. Therefore, we consider that DM-associated the hyperglycemia causes atrophy of the articular disc and microangiopathy of the capillary of the retrodiscal tissue in GK rats.

OBJECTIVE To analyze the sociodemographic and clinical factors related to anxiety in patients with major depressive disorder (MDD). METHODS This study involved a secondary analysis of data obtained from the Diagnostic Assessment Service for People with Bipolar Disorders in China (DASP), which was initiated by the Chinese Society of Psychiatry (CSP) and conducted from September 1, 2010 to February 28, 2011. Based on the presence or absence of anxiety-related characteristics, 1,178 MDD patients were classified as suffering from anxious depression (n=915) or non-anxious depression (n=263), respectively. RESULTS Compared with the non-anxious group, the anxious-depression group had an older age at onset (t=-4.39, p

Background: Major Depressive Disorder (MDD) is common and disabling, but its neural pathophysiology remains unclear. Functional brain network studies in MDD have largely 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. Methods: The 25 research groups in China composing the REST-meta-MDD Project contributed R-fMRI data of 1,300 patients with MDD and 1,128 normal controls (NCs). The data were preprocessed locally with a standardized protocol prior to aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to show increased FC in MDD. Outcomes: We found decreased instead of increased DMN FC in MDD compared to NCs. We found FC reduction only in recurrent MDD, not in first-episode drug-naive MDD. Decreased DMN FC was associated with medication usage but not with MDD duration or severity. Exploratory analyses also revealed alterations of local intrinsic activity in MDD. Interpretation: 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 treatment response. All the R-fMRI indices have been made publicly available via the R-fMRI Maps Project. The REST-meta-MDD model can be generalized to longitudinal MDD studies and to other psychiatric disorders. Funding Statement: This work was supported by the National Key R&D Program of China (2017YFC1309902), the National Natural Science Foundation of China (81671774, 81630031 and 81371488), the Hundred Talents Program of the Chinese Academy of Sciences, Beijing Municipal Science & Technology Commission (Z161100000216152 and Z171100000117016), Department of Science and Technology, Zhejiang Province (2015C03037). Declaration of Interests: All the authors declare no competing financial interests. Ethics Approval Statement: All contributed data were from studies approved by local Institutional Review Boards. Data submitted to the consortium were fully deidentified and anonymized.

There is evidence that bipolar disorder (BD) patients with an unhealthy lifestyle have a worse course of illness. This study was designed to examine the extent to which lifestyle could influence the severity of clinical symptoms associated with BD. A total of 113 BD patients were recruited in this study. The lifestyle information including data on dietary patterns, physical activity, and sleep quality were collected using a self-rated questionnaire. The results showed that the consumption of whole grain, seafood, and dairy products were significantly negatively correlated with the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score. The consumption of sugar, soft drinks, and alcohol as well as being a current smoker were positively correlated with the severity of clinical symptoms. Multiple linear regression and binary logistic regression analyses demonstrated an independent negative correlation between both whole grain and dairy product consumption with the HAMD-17 score. The results from the current study suggested that lifestyle factors, especially dietary patterns, might be associated with clinical symptoms of BD. The association between the consumption of specific foods and severity of depressive symptoms may offer some useful information and further understanding of the role of lifestyle factors in the development of BD.

Objectives Bipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD), which may lead to inappropriate treatment and poor outcomes. This study aimed to compare demographic and clinical features between patients with MDD and those with BD, but being misdiagnosed as MDD, in China. Methods A total of 1487 patients diagnosed with MDD were consecutively evaluated in 13 psychiatric hospitals or psychiatric units of general hospitals nationwide in China. The patients' sociodemographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. The Mini-International Neuropsychiatric Interview (MINI) was used to establish DSM-IV diagnoses, and identify patients with MDD and those with BD, but being misdiagnosed with MDD. Results The proportions of BD (all types), bipolar I disorder (BD-I), and bipolar II disorder (BD-II) misdiagnosed as MDD in clinical practice were 20.8%, 7.9%, and 12.8%, respectively. Multiple logistic regression analyses revealed that compared to MDD patients, BD-I was characterized by more atypical depressive features (increased appetite, increased sleep, and weight gain) [odds ratio (OR) = 2.0, 95% confidence interval (CI): 1.2–3.2], more psychotic symptoms (OR = 2.1, 95% CI: 1.3–3.5), more lifetime depressive episodes (OR = 1.1, 95% CI: 1.1–1.2), and earlier age of onset (OR = 0.97, 95% CI: 0.9–0.99); BD-II was characterized by more psychotic symptoms (OR = 2.1, 95% CI: 1.4–3.1) and earlier age of onset (OR = 0.96, 95% CI: 0.9–0.97). In addition, compared to BD-II patients, BD-I patients were characterized by more frequent depressive episodes per year (OR = 3.1, 95% CI: 1.5–6.6). Conclusions Depressive episodes in the context of BD-I and BD-II, among those who were misclassified as MDD, present some different clinical features compared to MDD. This finding should be taken into account in guiding diagnostic practices in China.

The injection of acrylic resin into vessels is an excellent method for macroscopically and microscopically observing their three-dimensional features. Conventional methods can be enhanced by removal of the polymerization inhibitor (hydroquinone) without requiring distillation, a consistent viscosity of polymerized resin, and a constant injection pressure and speed. As microvascular corrosion cast specimens are influenced by viscosity, pressure, and speed changes, injection into different specimens yields varying results. We devised a method to reduce those problems. Sodium hydroxide was used to remove hydroquinone from commercial methylmethacrylate. The solid polymer and the liquid monomer were mixed using a 1 : 9 ratio (low-viscosity acrylic resin, 9.07 ± 0.52 mPa•s) or a 3:7 ratio (high-viscosity resin, 1036.33 ± 144.02 mPa•s). To polymerize the acrylic resin for injection, a polymerization promoter (1.0% benzoyl peroxide) was mixed with a polymerization initiator (0.5%, N, N-dimethylaniline). The acrylic resins were injected using a precise syringe pump, with a 5-mL/min injection speed and 11.17 ± 1.60 mPa injection pressure (low-viscosity resin) and a 1-mL/min injection speed and 58.50 ± 5.75 mPa injection pressure (high-viscosity resin). Using the aforementioned conditions, scanning electron microscopy indicated that sufficient resin could be injected into the capillaries of the microvascular corrosion cast specimens.

To explore the correlation between the interleukin-17 (IL-17) level of peripheral blood and aggression of bipolar mania.Thirty-six patients of bipolar mania were selected as experimental group by DSM-IV-TR and received treatment with quetiapine and lithium. Thirty-six healthy volunteers with similar age and gender were selected as control group. The level of IL-17 at baseline in each group and the level of IL-17 in the experimental group after treatment for 2, 4 and 8 weeks were detected by ELISA.The level of IL-17 in experimental group at baseline, after treatment for 2 and 4 weeks were all significantly higher than that in control group. After 8 weeks treatment, there was no significant difference between the two groups (P0.05). After 2, 4 and 8 weeks treatment, the total score and aggression score of Young Mania Rating Score (YMRS) were significantly lower than the baseline level (P0.05). In experimental group, the level of IL-17 was positively correlated with the two scores of YMRS at baseline (P0.05).Bipolar mania may be related to the up-regulation of IL-17. The level of IL-17 is related to the severity of manic symptoms at baseline, especially aggression symptom.

Background Bipolar disorder (BD) is often misdiagnosed as a major depressive disorder (MDD). This study aimed to test the usefulness of the screening tool, the Mood Disorders Questionnaire (MDQ), to identify BD patients misdiagnosed as MDD in Chinese clinical settings. Methods A total of 1487 patients treated for MDD were consecutively examined in 13 mental health centers in China. The patients’ socio-demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. The MDQ was completed by patients to identify symptoms characteristic of BD. DSM-IV diagnoses were established using the Mini International Neuropsychiatric Interview (MINI). Results Three hundred-nine of the 1487 patients (20.8%) satisfied DSM-IV criteria for BD; 118 (7.9%) for BD-I and 191 (12.8%) for BD-II on the MINI. The optimal cut-off point on the MDQ to differentiate BD from MDD was 3, while cut-off points of 5 and 3 differentiated BD-I and BD-II from MDD, respectively. The maximum sensitivity was 0.31, 0.45 and 0.22 for differentiating BD, BD-I and BD-II from MDD, respectively. Conclusions The optimal cutoff points of the MDQ for screening BD in Chinese patients originally diagnosed as MDD were considerably lower than those in earlier studies. The routine clinical use of the MDQ as a screening scale for BD in Chinese patients treated for MDD does not seem to be justified.

BackgroundAtypical antipsychotics are widely used in bipolar mania. However, the efficacy of atypical antipsychotics in bipolar depression has not been comprehensively explored.AimsTo evaluate olanzapine monotherapy in patients with bipolar depression.MethodPatients with bipolar depression received olanzapine (5–20mg/day, n = 343) or placebo (n = l71) for 6 weeks. The primary outcome was change from baseline to end-point in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Secondary outcomes included: Clinical Global impression - Bipolar Version (CGI-BP) scale, 17-item Hamilton Rating Scale for Depression (HRSD-17) and Young Mania Rating Scale (YMRS) scores, and the rate of response (≥50% reduction in MADRS at end-point), recovery (MADRS ≤12 for ≥4 weeks plus treatment completion) and remission (MADRS ≤8). The trial was registered with ClinicalTrials.gov (NCT00510146).ResultsOlanzapine demonstrated: significantly greater (Pv. -11.67), HRSD-17 and YMRS total scores and all CGI-BP subscale scores v. placebo; significantly (P≤0.05) more response and remission, but not recovery; significantly (PPConclusionsOlanzapine monotherapy appears to be efficacious in bipolar depression. Additional long-term studies are warranted to confirm these results. Safety findings were consistent with the known safety profile of olanzapine.

Background Bipolar disorder (BD) is a recurrent, complex illness and often misdiagnosed and treated as a major depressive disorder (MDD). This study set out (1) to investigate the proportion of BD in patients treated for MDD using DSM-IV diagnostic criteria; (2) to test the usefulness of the screening tool — the 32-item Hypomania Checklist (HCL-32) in Chinese patients; and (3) to assess whether MDD patients with subthreshold manic features (patients who screened positive for BD on the HCL-32, but did not meet the diagnostic criteria for DSM-IV BD as measured by Mini International Neuropsychiatric Interview (MINI)) differ from those with BD, and from those suffering from MDD without manic features in terms of basic demographic and clinical variables. Methods A total of 1487 patients treated for MDD were consecutively examined in 13 mental health centers in China. The patients' socio-demographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. The HCL-32 was self-completed by patients to identify hypomanic symptoms, and the MINI was used by clinicians to establish DSM-IV diagnoses. Results The proportions of undiagnosed BD (all types), BD-I and BD-II were 20.8%, 7.9% and 12.8%, respectively. The HCL-32 had low positive predictive value (0.43). Compared to MDD patients without subthreshold manic features, MDD patients with subthreshold manic features were younger at onset, less likely to be married and had more depressive episodes on a seasonal basis, and more frequent depressive episodes overall. Compared to BD patients, MDD patients with subthreshold manic features had an older age at onset and less frequent depressive episodes and less family history of psychiatric disorders, appetite, weight gain and time spent sleeping, suicide ideation and attempts and psychotic symptoms. Conclusions At least one fifth of Chinese patients treated for MDD may have an undiagnosed BD. The HCL-32 is useful to identify broader subthreshold bipolar features. The findings need to be confirmed by longitudinal studies using more comprehensive, standardized instruments.

Periodontal infections can increase patients' serum C-reactive protein (CRP) level, which is a predictive marker of future cardiovascular events. Serum CRP may be a key mediator associating periodontitis with cardiovascular disease. It is not yet clarified whether the chemotactic activity of monocytes changes with increased serum CRP. This study investigated the influence of CRP on monocyte chemotaxis and the effects of CRP on CC chemokine receptor 2 (CCR2) expression by monocytes in vitro. Monocyte cell line THP-1 was cultured with human recombinant CRP of different final concentrations, which were 2, 4, 6, 8, and 10 mg/L, respectively. After 24 h incubation, Transwell chambers were applied to analyze the chemotactic activity of pretreated monocytes. Flow cytometry analysis and real-time reverse transcription-polymerase chain reaction (RT-PCR) were applied to detect the CCR2 protein and gene expression levels. In Transwell chambers, more cells were attracted in CRP-pretreated groups than that of blank control with no CRP (p

To investigate the validity of the Chinese version of Mood Disorder Questionnaire (C-MDQ) in China. Patients with bipolar disorders (BP, N=284) and patients with unipolar depressive disorder (UP, N=134) were assessed with the C-MDQ. The Eigenvalues of the first two factors were 3.15 and 2.09, respectively. The Cronbach's alpha of the C-MDQ was 0.79. The frequency of positive responses of UP patients was significantly lower than those of BP patients for 12 items except the seventh item. A C-MDQ screening score of seven or more was the best cutoff between BP and UP. The C-MDQ could distinguish between bipolar II disorder (BP-II) and UP, and the best cutoff was five. A cutoff of five had a sensitivity of 0.80 and a specificity of 0.54 between BP and UP. This study demonstrated the good validity of C-MDQ in China. The best cutoff between BP-II and UP can be regarded as the optimal cutoff between BP and UP to improve the sensitivity of screening for BP-II. Five should be the optimal cutoff between the BP and UP when only the 13 items of the questionnaire are used in China.

Little has been reported about the demographic and clinical features of major depressive disorder (MDD) with comorbid dysthymia in Chinese patients. This study examined the frequency of comorbid dysthymia in Chinese MDD patients together with the demographic and clinical correlates and prescribing patterns of psychotropic drugs.Consecutively collected sample of 1178 patients with MDD were examined in 13 major psychiatric hospitals in China. Patients' demographic and clinical characteristics and psychotropic drugs prescriptions were recorded using a standardized protocol and data collection procedure. The diagnosis of dysthymia was established using the Mini International Neuropsychiatric Interview. Medications ascertained included antidepressants, antipsychotics, benzodiazepines, and mood stabilizers.One hundred and three (8.7%) patients fulfilled criteria for dysthymia. In multiple logistic regression analyses, compared to non-dysthymia counterparts, MDD patients with dysthymia had more depressive episodes with atypical features including increased appetite, sleep, and weight gain, more frequent lifetime depressive episodes, and less likelihood of family history of psychiatric disorders. There was no significant difference in the pattern of psychotropic prescription between the 2 groups.There are important differences in the demographic and clinical features of comorbid dysthymia in Chinese MDD patients compared with previous reports. The clinical profile found in this study has implications for treatment decisions.

The expression pattern of cytokeratins (CKs) varies with epithelial cell type. However, the expression of many different CKs has not been clearly defined in ameloblastomas. We used cytokeratins (CK) 1, 4, 6, 7, 10, 10/13, 15, 16, 17, 19, 20 and AE1/AE3 monoclonal antibodies and polyclonal keratin (PK) antibody to elucidate the localization of these CKs in ameloblastomas by immunohistochemistry. Biopsy and operative specimens of 31 ameloblastomas, of which 13 were follicular and 18 plexiform, were used in the present study. CK8, CK19, AE1/AE3 and PK were positive in all follicular (100%) and plexiform (100%) patterns of ameloblastomas. Although CK8 and CK19 are present in simple epithelium, they were observed in the inner cells of tumor nests of ameloblastomas. CK13 was also positive in all metaplastic epithelium of follicular patterns (100%) and was positive in plexiform patterns (56%). CK6, CK7, CK15, CK16 and CK17 positive rates were 54%, 8%, 23%, 46% and 54% in follicular patterns, and 22%, 17%, 0%, 0% and 11% in plexiform patterns, respectively. CK1, 4, 10 and 20 were negative in all both follicular and plexiform patterns. These results indicate that CK15 and CK16 tend to be more specific positive in follicular than in plexiform ameloblastomas.

Transection of the rat facial nerve (FN) leads to a series of retrograde changes within the facial nuclei, which has been called the axon reaction. This reaction includes the rapid activation of both astrocytes and microglia and a change in the gene expression in axotomized motoneurons. In the present study, we investigated the expression of the transforming growth factor-β (TGF-β) superfamily member [bone morphogenetic protein (BMP)-2, 4, 6 and TGF-β1] in the axotomized facial nuclei using in situ hybridization. The aim of the present study was to clarify whether the BMP-2, 4, 6 and TGF-β1 are related to the regenerative and degenerative processes in the axotomized facial nuclei. The results showed that BMP-2 and TGF-β1 mRNA increased gradually after axotomy, and reached the maximal values on day 7 post injury. BMP-6 was expressed abundantly in the facial motoneurons, and no obvious differences were shown in the gene expression after transection of FN. However, no significant signals for BMP-4 in motoneuron were detected at any time point. These results revealed that some members of the TGF-β superfamily such as BMP-2 and TGF-β1, might be involved in glial activation and motoneuron survival, and might be potential neurotrophic factors of FN.

Despite the numerous flaps for facial reconstruction that have been described, the search for the ideal flap with good color matching and minimal donor-site morbidity continues. In the past 3 years we have repaired 13 facial defects with success using the lateral genicervical flap – a type of facial subdermal vascular network flap (SVNF) – with a pedicle located on the preauricular region. An anatomic study of the facial SVNF, including blood supply and vascular distribution of the face and anatomic characteristics of facial vessels, based on 14 cadaver dissections, was carried out. The blood supply of the facial skin basically originated from the branches of the facial, superficial temporal and infraorbital arteries. The lateral genicervical skin was supplied basically by the branches of the facial, superficial temporal and occipital arteries, but also by the terminal branches of the superior thyroid artery. The branches diverging from these arteries became superficial and formed a subcutaneous arterial network. The arterioles from the network went to the corium layer and formed a subdermal arterial network whose arterioles anastomosed with each other in a honeycomb-like structure. The vascular distribution presented certain directivity on different areas. The blood supply of the pedicle originated from the subdermal vascular network formed by the perforator branches of these arteries. The arterioles from the facial and superficial temporal arteries anastomosed in the lateral genicervical region. From the anatomic study, we think that the viability of the facial SVNF depends basically on the subdermal vascular network formed by the perforator branches of the pedicle, and that the anastomoses between the facial and superficial temporal arteries provide a solid anatomic basis to the lateral genicervical flap. The clinical data also indicated that this flap is a useful alternative for facial, especially superficial temporal, defects. But the directivity must be taken into account in its clinical application. The French version of this article is available in the form of electronic supplementary material and can be obtained by using the Springer Link server located at http://dx.doi.org/10.1007/s00276-002-0061-2.

Human papillomavirus (HPV) is established as the cause of almost 100% of cervical carcinomas. However, the association of HPV with oral squamous cell carcinomas (SCCs) is less well understood. We examined the prevalence of HPV in oral SCCs in samples of Japanese and Chinese populations. Using in situ polymerase chain reaction (PCR) analysis (MY09 and MY11 consensus primers), HPV was detected in the nucleus of epithelia and tumor cells in oral lesions. Analysis revealed the specific presence of HPV DNA in all cases of SCC in our Japanese (10/10) and Chinese (10/10) population samples. These results suggest that HPV infection could be one of several risk factors contributing to oral SCC in Japanese and Chinese.

It has been shown that apoptosis is involved in normal embryonic development. The aim of the present study was to elucidate the role and alteration of apoptosis in the pathogenesis of cleft palate induced by retinoic acid (RA) and the ectomesenchymal stem (EMS) cells influenced by RA. RA was administered by gavage to pregnant C57BL/6N strain mice in the experimental group, and the control group received oil alone. Pregnant mice were killed at set periods of time thereafter and histologically analyzed. EMS cells explanted from the palatal shelves of embryonic mice were cultured and characterized by immunohistochemistry, growth curves and population-doubling time. The alterations of apoptosis of EMS cells and developing palatal shelves influenced by RA were evaluated by the terminal deoxynucleotidyl transferase-mediated UTP-biotin nick end-labeling (TUNEL) method. RA-treated mice showed formation of cleft palates resulted from the small size of the palatal shelves and their failure to lift. TUNEL staining showed that the number of apoptotic mesenchymal cells in palatal shelves in the RA-treated mice was increased significantly when compared with the control group. The primary culture of EMS cells proceeded successfully. The population-doubling time of RA-treated cells was much longer compared with non-treated EMS cells. RA also dramatically increased the number of apoptotic cells in EMS cells in vitro. We concluded that EMS cells are the crucial cells in palate development. RA could inhibit the proliferation and induced the apoptosis of EMS cells. The inhibition of growth and excess apoptosis of EMS cells may contribute to the formation of cleft palate and other orofacial congenital malformations.

Background 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. Methods 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. Results 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). Conclusion 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.

Few characteristic changes of linear electroencephalograph (EEG) have been reported in schizophrenia. The aim of the present study was to investigate the changes in temporal-spatial dimensional properties of EEG under different cognitive tasks in patients with schizophrenia.EEG was recorded by using EEG-1518K system and mapping system (Nihon Kohden Tomioka Corporation, Japan) in 45 schizophrenic patients and 47 healthy adults (normal control, NC) under five states: eyes closed, eyes open, mental arithmetic test with eyes closed, memory test with eyes open, and number cancellation test. Correlation dimension (D2) and point-wise correlation dimension (PD2) were calculated for all EEG analyses.(1) There were no significant differences of D2 and PD2 between NC and schizophrenic patients under states of eyes open and closed. (2) Compared with NC, schizophrenic patients showed decreased performance of D2 in mental arithmetic test with eyes closed and number cancellation test (mental arithmetic test with eyes closed: Nc 5.9 ± 0.6, Sch 3.0 ± 0.8; number cancellation test: Nc 6.0 ± 0.6, Sch 4.4 ± 0.7; P0.05 or P0.01). (3) Schizophrenic patients also showed decrease performance of PD2 in mental arithmetic test with eyes closed, memory test with eyes open, and number cancellation test (mental arithmetic test with eyes closed: Nc 6.9 ± 0.7, Sch 4.0 ± 0.8; memory test with eyes open: Nc 6.6 ± 0.8, Sch 5.0 ± 0.9; number cancellation test: Nc 7.1 ± 0.7, Sch 4.8 ± 0.9; P0.05 or P0.01).Nonlinear dynamic analysis provided a new approach in clinical investigation of EEG signals. It was helpful to further understand the cerebral mechanism in schizophrenic cognitive process.

Metabolic syndrome (MetS) has consistently been identified as an adverse effect of long-term treatment with atypical antipsychotics (AAPs) such as clozapine. Elevated serum homocysteine concentration has been found to act as an independent risk factor for MetS, and catechol-O-methyltransferase (COMT) catalyzes the homocysteine metabolism. We accordingly hypothesized that COMT dysregulation may confer the susceptibility to MetS induced by AAPs, potentially in a gender-specific manner, because the interaction effects of COMT and gender have been consistently reported. This study aimed at determining the prevalence and influence of COMT on MetS among a population undergoing long-term clozapine treatment. A total of 468 schizophrenia patients taking clozapine were divided into two groups, those experiencing MetS and non-MetS. We genotyped three functional variants (rs4633, rs4680, and rs4818) in COMT and measured the serum levels of fasting homocysteine, glucose, triglyceride (TG), and high-density lipoprotein cholesterol. MetS was found in 202/468 (43.2 %) of all the patients, with 40.2 % prevalence (138/343) in males and 51.2 % (64/125) in females. Patients with MetS had notably higher metabolic parameters than those without MetS. The mean levels of homocysteine in patients with MetS were significantly higher than those without MetS. We found a positive association between the rs4680 polymorphism and the serum triglyceride levels (corrected P = 0.024). Further analysis revealed that the rs4680 Met allele was significantly associated with increased triglyceride levels among female patients (P = 0.009), but not among males (P = 0.07). Our findings suggest a potential association between rs4680 in COMT and elevated TG levels, particularly among female patients.

Many types of skin substitutes have been constructed using exogenous materials. Angiogenesis is an important factor for tissue-engineered skin constructs. In this study, we constructed a scaffold-free bilayered tissue-engineered skin containing a capillary network. First, we cocultured dermal fibroblasts with dermal microvascular endothelial cells at a ratio of 2 : 1. A fibrous sheet was formed by the interactions between the fibroblasts and the endothelial cells, and capillary-like structures were observed after 20 days of coculture. Epithelial cells were then seeded on the fibrous sheet to assemble the bilayered tissue. HE staining showed that tissue-engineered skin exhibited a stratified epidermis after 7 days. Immunostaining showed that the epithelium promoted the formation of capillary-like structures. Transmission electron microscopy (TEM) analysis showed that the capillary-like structures were typical microblood vessels. ELISA demonstrated that vascularization was promoted by significant upregulation of vascularization associated growth factors due to interactions among the 3 types of cells in the bilayer, as compared to cocultures of fibroblast and endothelial cells and monocultures.

Introduction Little has been reported about the demographic and clinical features of major depressive disorder (MDD) with comorbid dysthymia in Chinese patients. This study examined the frequency of comorbid dysthymia in Chinese MDD patients together with the demographic and clinical correlates and prescribing patterns of psychotropic drugs. Methods Consecutively collected sample of 1178 patients with MDD were examined in 13 major psychiatric hospitals in China. Patients' demographic and clinical characteristics and psychotropic drugs prescriptions were recorded using a standardized protocol and data collection procedure. The diagnosis of dysthymia was established using the Mini International Neuropsychiatric Interview. Medications ascertained included antidepressants, antipsychotics, benzodiazepines, and mood stabilizers. Results One hundred and three (8.7%) patients fulfilled criteria for dysthymia. In multiple logistic regression analyses, compared to non-dysthymia counterparts, MDD patients with dysthymia had more depressive episodes with atypical features including increased appetite, sleep, and weight gain, more frequent lifetime depressive episodes, and less likelihood of family history of psychiatric disorders. There was no significant difference in the pattern of psychotropic prescription between the 2 groups. Conclusions There are important differences in the demographic and clinical features of comorbid dysthymia in Chinese MDD patients compared with previous reports. The clinical profile found in this study has implications for treatment decisions.

To explore the features of events-related potentials (ERP) component N400 in generalized anxiety disorder (GAD) versus obsessive compulsive disorder (OCD) patients and understand the cognitive pattern and processing characteristic for Chinese characters.ERP component N400 was recorded by Guangzhou Runjie WJ-1 ERP apparatus. And 41 GAD patients, 69 OCD patients and 58 normal controls (NC) were tested by the Chinese idioms ending with matching (congruent) or mismatching (incongruent) words.(1) Latencies: Significant differences were found of N400 latencies in ending words with the same pronunciation but different forms and meanings (NC: (377 ± 40) ms, OCD: (395 ± 43) ms, GAD: (396 ± 43) ms, congruent; NC: (415 ± 32) ms, OCD: (429 ± 35) ms, GAD: (430 ± 36) ms, incongruent), ending words with the same meaning but different pronunciations and forms (NC: (411 ± 32) ms, OCD: (424 ± 40) ms, GAD: (433 ± 39) ms, incongruent), ending words with different pronunciations, forms and meanings (NC: (399 ± 47) ms, OCD: (427 ± 53) ms, GAD: (434 ± 42) ms, congruent; NC: (442 ± 36) ms, OCD: (465 ± 35) ms, GAD: (474 ± 35) ms, incongruent) (P0.05 - 0.01). Compared with NC, the N400 latencies were prolonged in GAD and OCD patients. Compared with OCD patients, the GAD patients also showed prolonged N400 latencies in ending words with different pronunciations, forms and meanings (incongruent situation). (2) Significant differences were found of N400 amplitudes in ending words with the same pronunciation but different forms and meanings (NC: (9 ± 5) µV, OCD: (6 ± 5) µV, GAD: (6 ± 5) µV, congruent; NC: (11 ± 6) µV, OCD: (5 ± 4) µV, GAD: (6 ± 4) µV, incongruent), ending words with similar forms but different pronunciations and meanings (NC: (9 ± 5) µV, OCD: (5 ± 4) µV, GAD: (7 ± 5) µV, congruent; NC: (14 ± 6) µV, OCD: (6 ± 5) µV, GAD: (9 ± 7) µV, incongruent), ending words with different pronunciations, forms and meanings (NC: (9 ± 5) µV, OCD: (5 ± 4) µV, GAD: (5 ± 3) µV, congruent; NC: (14 ± 6) µV, OCD: (9 ± 7) µV, GAD: (9 ± 7) µV, incongruent) (P0.05 - 0.01). Compared with NC, N400 amplitudes decreased in GAD and OCD patients respectively. Compared with OCD patients, the GAD patients also showed elevated N400 amplitudes in ending words with similar forms but different pronunciations and meanings (congruent).The cognitive and emotional problems in GAD and OCD may be measured by N400 elicited by Chinese idioms. Notable N400 priming effects can be found in Chinese idioms.

Reports on mood regulating circuit (MRC) indicated different activities between depressed patients and healthy controls. The functional networks based on MRC have not been described in major depression disorder (MDD). Both the anterior cingulate cortex (ACC) and thalamus are all the key regions of MRC. This study was to investigate the two functional networks related to ACC and thalamus in MDD.Sixteen patients with MDD on first episode which never got any medication and sixteen matched health controls were scanned by 3.0 T functional magnetic resonance imaging (fMRI) during resting-state. The pregenual anterior cingulate cortex (pgACC) was used as seed region to construct the functional network by cortex section. The thalamus was used as seed region to construct the functional network by limbic section. Paired-t tests between-groups were performed for the seed-target correlations based on the individual fisher z-transformed correlation maps by SPM2.Depressed subjects exhibited significantly great functional connectivity (FC) between pgACC and the parahippocampus gyrus in one cluster (size 923) including left parahippocampus gyrus (-21, -49, 7), left parietal lobe (-3, -46, 52) and left frontal lobe (-27, -46, 28). The one cluster (size 962) of increased FC on thalamus network overlapped the precuneus near to right parietal lobe (9, -52, 46) and right cingulate gyrus (15, -43, 43) in health controls.Abnormal functional networks exist in earlier manifestation of MDD related to MRC by both cortex and limbic sections. The increased functional connectivity of pgACC and decreased functional connectivity of thalamus is mainly involved in bias mood processing and cognition.

Bipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD), which may lead to inappropriate treatment and poor outcomes. This study aimed to examine prescribing patterns of antidepressants, antipsychotics and mood stabilizers in BD patients misdiagnosed with MDD in China.A total of 1487 patients originally diagnosed with MDD were consecutively screened for diagnostic revision in 13 psychiatric hospitals or psychiatric units of general hospitals in China nationwide. The patients' sociodemographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. The Mini International Neuropsychiatric Interview (MINI) was used to establish DSM-IV diagnoses. Data on psychotropic prescriptions were collected by a review of medical records.Three hundred and nine of the 1487 patients (20.8%) fulfilled DSM-IV criteria for BD; 118 (7.9%) for BD-I and 191 (12.8%) for BD-II on the MINI. Of the BD patients (n = 309), 227 (73.5%) received any use of antidepressants, 73 (23.6%) antipsychotics and 33 (10.7%) mood stabilizers. In multiple logistic regression analyses, compared with those with MDD, patients with BD-I were more likely to receive antidepressants (OR 1.7, 95% CI 1.1-2.8, p = 0.02), antipsychotics (OR 1.6, 95% CI 1.04-2.5, p = 0.04) and mood stabilizers (OR 3.9, 95% CI 2.1-7.2, p0.001), whereas patients with BD-II were more likely to receive mood stabilizers (OR 2.4, 95% CI 1.3-4.4, p = 0.003). There was no difference in the use of antidepressants (OR 1.1, 95% CI 0.8-1.5, p = 0.7) and antipsychotics (OR 1.3, 95% CI 0.9-1.9, p = 0.2) between BD-II and MDD. In addition, there was no difference between BD-I and BD-II in any use of antidepressants, antipsychotics and mood stabilizers.The prescription of antidepressants for BD patients misdiagnosed with MDD is very common, and only a very small proportion of patients received guideline-concordant treatment. Considering the potentially hazardous effects of inappropriate pharmacotherapy in this population, continuing education and training addressing the correct diagnosis of BD and rational use of psychotropic medications are needed in China.

To explore the relationship between dopamine D1 receptor gene (DRD1) and symptom quantitative trait of schizophrenia.Peripheral blood samples were collected from 211 schizophrenics and 247 healthy controls at our center. Five tag SNPs (single nucleotide polymorphisms) (rs4532, rs5326, rs2168631, rs6882300rs267418) within DRD1 gene were genotyped by TaqMan SNP genotyping assay. The positive and negative syndrome scale (PANSS) was used to quantify the phenotypes of schizophrenia.No significant differences existed in the frequencies of genotypes and alleles of DRD1 gene between the schizophrenics and normal controls (Ps0.05); strong linkage disequilibrium was observed between rs4532 and rs5326 (D' = 0.84); no significant difference of haplotypic distribution was identified between the patients and controls (Ps0.05); the patients with rs4532G allele had a higher negative subscale score than those without G allele (20.3 ± 3.3 vs 18.2 ± 3.9, P0.01).The rs4532 within DRD1 gene may be associated with negative symptom quantitative trait in schizophrenia.

Understanding the reasons for the delayed action of antidepressants in patients with depression is an important step in the effort to understand the etiology and course of this disabling condition. Researches using animal models of depression find that depression is associated with impaired neurogenesis and structural plasticity in specific regions of the brain. Chronic treatment with antidepressants increases neurogenesis and reduces animal behaviors that are associated with depression. Other studies suggests that neurogenesis is an important component of the mechanism of action of both antidepressants and mood stabilizers. Moreover, the time course of increased neurogenesis is parallel to that of the behavioral effects, and animals with higher baseline hippocampus neurogenesis have a more rapid response to antidepressants. However, the molecular mechanisms that link antidepressants, neurogenesis and behavioral changes remain unknown. Previous research has shown that the extracellular signal-regulated kinase (ERK) signaling pathway plays an important role in regulating neurogenesis and synaptic plasticity in the brain and is activated by antidepressants and mood stabilizers. We hypothesize that the ERK pathway is the mechanism by which antidepressants regulate neurogenesis in the hippocampus and, thus, should be considered a potential target for the development of new antidepressants.

to identify the impact of gene-gene interaction between DNMT3B and DRD1 on the risk of schizophrenia.two SNPs (rs2424908 and rs6119954) within DNMT3B and five SNPs (rs4532, rs5326, rs2168631, rs6882300 and rs267418) within DRD1 were genotyped in 365 schizophrenic patients and 365 healthy controls. The gene-gene interaction between DNMT3B and DRD1 was analyzed by Multifactor Dimensionality Reduction (MDR) software.the frequency of genotypes of rs6119954 within DNMT3B was significantly higher in patients than that in controls (χ(2) = 8.06, P = 0.018). MDR revealed that the significance were shown in patterns with 2 SNPs (rs6119954-rs267418) (OR = 1.79, 95%CI: 1.29 - 2.47; χ(2) = 12.51, P = 0.0004), 3 SNPs (rs6119954-rs5326-rs267418) (OR = 2.36, 95%CI: 1.73 - 3.22; χ(2) = 29.33, P0.0001) and 4 SNPs (rs2424908-rs6119954-rs5326-rs267418) (OR = 3.08, 95%CI: 2.24 - 4.24;χ(2) = 48.88, P0.0001).the gene-gene interaction between DNMT3B and DRD1 may exist and increase the risk for schizophrenia.

This histological investigation examined the formation and differentiation of pulp cells under the influence of HAP/BMP complex. HAP/BMP complex was implanted in exposed pulp of the mandibular premolars and alveolar bone defect in the dog. Sequential changes in these areas were examined mainly under a light microscope and partly under a scanning electron microscope. Two weeks after the operation, fibroblast-like cells proliferated right beneath the implanted complex, and after 3 weeks, dentin including dentin tubules grew in the pulp. After four weeks a dentin bridge composed of osteoid dentin was found, and after 8 weeks this dentin calcified and covered the defective surface of the root and adhered to new bone surrounding the HAP granules. The results indicated that the dentin induced by HAP/BMP complex may be of two types: tubular dentin and osteodentin. This complex exhibited outstanding ability to induce dentinogenesis and osteogenesis.

本研究はラットの舌背粘膜に実験的熱傷 (皮膚熱傷第II度相当) を与え, 微細血管鋳型によって組織ならびに微細血管構築について実験直後から治癒までの修復過程を経時的に走査電顕観察を行った。熱傷の治癒過程は, 1) 水泡形成期, 2) 同退縮期, 3) 潰瘍期, 4) 上皮修復前および5) 後期の5期に区分することができた。水泡形成期では固有層毛細血管は拡張し, 筋線維の横紋が消失していた。糸状乳頭の配列は不規則となり, 乳頭間距離は広がっていた。毛細血管ループの両脚間と細静脈網の網目が拡大していた。水泡退縮期では固有層乳頭と毛細血管は消失していた。糸状乳頭の毛細血管ループと細静脈網の網目は断裂, 消失し, 細動静脈のみが直接認められた。潰瘍期では創縁粘膜上皮の隆起, 創面の放射状の溝と創中心部の陥凹とともに糸状乳頭の毛細血管ループは創中心へ傾斜していた。上皮修復前期では創周囲粘膜上皮の創面全体への伸展とともに糸状乳頭が新生し, 創縁の既存毛細血管や創底からの新生洞様血管が吻合して血管網が形成されていた。その後, 創部はすべて新生糸状乳頭となり, 非実験群と同じ像を呈していた。現在のところ, 熱傷第II度で損傷した口腔粘膜組織と微細血管構築が治癒状態をとるには約6週を要することが明らかになった。

Treatment-resistant depression (TRD) is a therapeutic challenge for clinicians. Despite a growing interest in this area, an understanding of the pathophysiology of depression, particularly TRD, remains lacking. This study aims to detect the white matter abnormalities of whole brain fractional anisotropy (FA) in patients with TRD compared with major depressive disorder (MDD) before treatment by voxel-based analysis using diffusion tensor imaging. A total of 100 patients first diagnosed with untreated MDD underwent diffusion tensor imaging scans. 8 weeks after the first treatment, 54 patients showed response to the medication, whereas 46 did not. Finally, 20 patients were diagnosed with TRD after undergoing another treatment. A total of 20 patients with TRD and another 20 with MDD before treatment matched in gender, age, and education was enrolled in the research. For every subject, an FA map was generated and analyzed using SPM5. Subsequently, t-test was conducted to compare the FA values voxel to voxel between the two groups (p0.001 [FDR corrected], t7.57, voxel size30). Voxel-based morphometric (VBM) analysis was performed using T1W images. Significant reductions in FA were found in the white matter located in the bilateral of the hippocampus (left hippocampus: t=7.63, voxel size=50; right hippocampus: t=7.82, voxel size=48). VBM analysis revealed no morphological abnormalities between the two groups. Investigation of brain anisotropy revealed significantly decreased FA in both sides of the hippocampus. Although preliminary, our findings suggest that microstructural abnormalities in the hippocampus indicate vulnerability to treatment resistance.

Depressive disorder is a well-known chronic, recurrent and disabling mental disease with high direct and indirect costs to society in both western and eastern cultures. Approximately 40% of depressed patients show only partial or no response to initial or even multiple antidepressant medications and are usually called treatment-resistant depression (TRD) patients. The present work was to measure the features of sensory gating (SG) P50 in TRD patients with the intent of understanding the characteristics of this disease.In 50 TRD patients, 39 non-treatment-resistant depression (NTRD) patients and 51 healthy controls (HC), auditory evoked potential P50 was measured using the conditioning/testing paradigm presented with auditory double clicks stimuli, and 36 TRD patients had repeated measurements after an 8-week venlafaxine treatment course.All the depressive disorder patients, including the TRD and NTRD groups, showed an increased testing stimulus wave (S2-P50) amplitude compared to controls (P0.01 and P0.05), but there was no significant difference between the TRD and NTRD groups (P0.05). There were significant differences in the ratio of testing stimulus (S2) and conditioning stimulus (S1) (S2/S1) and in the value of 100 x (1 - S2/S1) among the three groups. Compared to the baseline, TRD patients had no significant changes of features and different expression of P50 after acute treatment (P0.05). Meanwhile, a statistically significant positive correlation of S2/S1 with the scores of the 17-item Hamilton Rating Scale for Depression (HAMD-17) (P0.01), and a significantly negative correlation of S1 - S2, 100 x (1 - S2/S1) with the scores of HAMD-17 (P0.01) were observed in the TRD patients' baseline measurement, but there was no correlation after venlafaxine treatment (P0.05).Both the TRD and NTRD patients had obvious SG deficits, with a more severe deficit in TRD patients. Although, with a correlated relationship to the severity of depressive symptoms, SG P50 deficit might be suggested as a trait marker for TRD, and a combination of S2/S1 ratio, S1 - S2 and 100 x (1 - S2/S1), was recommended for electrophysiological measurement in TRD patients.

Backgrounds: The postmortem and magnetic resonance imaging studies for schizophrenic patients showed neuropathological abnormalities including neuron loss and volume reduction in ventral hippocampus (VH), some longitudinal studies suggest these changes may be a neurodegenerative process. Objectives: The present study examined the effects of adult bilateral VH lesions on a dopaminergic stimulant, methamphetamine (METH)-induced and an N-methyl-Daspartate (NMDA) receptor antagonist, dizocilpine (MK-801)-induced behavioral and neurochemical changes in rats, in order to evaluate a potential of adult VH lesion animals for a model of schizophrenia. Methods: To study the behavioral effects after bilateral VH lesions in adult rats, locomotor activity was measured individually by an infra-red sensor. Extracellular concentrations of dopamine in the nucleus accumbens (NAc) were measured using in vivo brain microdialysis. Results: The bilateral adult VH lesion rats showed a significant enhanced hyperlocomotion in response to METH but no changes to MK-801 and phencyclidine; while bilateral adult VH lesion enhanced METH-induced increasing dopamine levels in the NAc. Conclusions: The bilateral adult VH lesions enhanced locomotor activity, which related to increased dopamine releases in the NAc, induced by a dopaminergic stimulant; these findings may suggest a potential of adult VH lesion animal for a model reflecting dopamine D2 receptor antagonist-responsive pathophysiology of schizophrenia by way of neurodegenerative processes.

The objective of this study was to establish a new method for reconstruction of a tissue-engineered skin containing melanocytes by employing tissue engineering. The keratinocytes, melanocytes and dermal fibroblasts were isolated and purified from human foreskin biopsies. Then the cells were used to construct a tissue-engineered skin containing melanocytes. The localization of melanocytes in the tissue-engineered skin was detected by DOPA staining, S-100 immunohistochemical staining and transmission electron microscope (TEM). The results showed that the melanocytes could be detected in the basal layer of the constructed skin and the melanocytes showed dendritic morphology. Moreover the constructed skins were used to repair the athymic mice skin defects. Animal experiment results indicated that the skin equivalents could successfully repair full thickness skin defects in athymic mice and generated black skins by 6 weeks after grafting. Melanocytes located in the basal layer of the athymic mice skin could also be detected by using the S-100 immunohistochemical staining. Our established method is useful to repair the full-thickness skin defects.

To investigate the association between G72 gene polymorphisms and depression,and to probe the difference of G72 gene polymorphisms between depression with and without mixed family history.The polymorphisms of G72 gene (rs947267 and rs2181953) were detected by PCR technique in 100 depressive patients without mixed family history, 50 depressive patients with mixed family history and 86 normal controls.(1) The frequencies of rs947267 genotypes and alleles in female depressive patients without mixed family history were significant different to the controls (P=0.017 and P=0.008), the OR scores were 0.300 (A/A, P=0.010), 0.456(A, P=0.008) and 2.195(C, P=0.008) respectively; but in male patients there were no significant differences to the controls (P0.05). (2) The frequencies of rs2181953 genotypes and alleles in the depressive patients without mixed family history were not significantly different to the controls regardless of sex (P0.05). (3) The frequencies of rs947267 and rs2181953 genotypes and alleles in the depressive patients with mixed family history were not significantly different to the controls regardless of sex (P0.05).The G72 gene polymorphism may be associated with female depressive patients without mixed family history,C allele of rs947267 may be the risk factor.

We investigated the effects of bone morphogenetic protein-2 (BMP-2) and some other BMPs on regeneration of peripheral motor nerves in vivo. The facial nerves of 24 New Zealand rabbits were crushed to examine a series of retrograde changes in the facial nuclei and axons, in what has been called the “axon reaction”. The facial nerves of the experimental group were treated with epineurial coaptation and BMP-2 after the injury. Nerves not treated with BMP-2 were regarded as controls. The expression of BMP-2 was investigated by in situ hybridisation in the neurons of facial nuclei. The electrophysiology, image analysis and transmission electron microscopy were used to evaluate the level of the recovery of facial nerves. The results showed that the axons in the experimental group were thicker and denser than those in the control group four weeks later. The expression of BMP-2 in the neurons of facial nuclei increased after injury. The electron microscopic observations showed that the axons’ degeneration in the experimental group was less than that in the control group. Despite the morphological difference between the two groups, there was no apparent difference between them in nerve conduction velocity. These findings suggest that BMP-2 might be involved in the regeneration of facial nerves, and might function as a potential neurotrophic factor.

This study was to explore the relationships between NOTCH4 gene and schizophrenia (SP) and mood disorders (MD), and to search for a common susceptible gene for SP and MD in Chinese Han population. We collected 61 mixed pedigrees of SP and MD in Chinese Han population. NOTCH4 polymorphisms -1725T/G and-25T/C were genotyped by applying PCR-RLFP technique, then transmission disequilibrium test (TDT) and haplotype-based haplotype relative risk analysis(HHRR) were performed. The results showed that -1725T/G was not associated with SP or MD (P0.05), -25T/C was not associated with SP (P0.05), but associated significantly with MD for female or early-onset (age of onsetor=25 years) group (P0.05), and - 1725G/-25T haplotype was significantly associated with SP (P0.05), but not associated with MD (P0.05). Our results suggested NOTCH4 or neighboring gene might be a common susceptible gene for SP and MD in the pedigrees studied.