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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.