Mapping the global, regional and national burden of bipolar disorder from 1990 to 2019: trend analysis on the Global Burden of Disease Study 2019.

BACKGROUND: Data on trends in the epidemiological burden of bipolar disorder are scarce. AIMS: To provide an overview of trends in bipolar disorder burden from 1990 to 2019. METHOD: Revisiting the Global Burden of Disease Study 2019, we analysed the number of cases, calculated the age-standardised rate (per 100 000 population) and estimated annual percentage change (EAPC) of incidence, prevalence and years lived with disability (YLDs) for bipolar disorder from 1990 to 2019. The independent effects of age, period and cohort were estimated by the age-period-cohort modelling. RESULTS: Globally, the bipolar disorder-related prevalent cases, incident cases and number of YLDs all increased from 1990 to 2019. Regionally, the World Health Organization Region of the Americas accounted for the highest estimated YLD number and rate, with the highest age-standardised prevalence rate in 1990 and 2019 and highest EAPC of prevalence. By sociodemographic index (SDI) quintiles, all five SDI regions saw an increase in estimated incident cases. Nationally, New Zealand reported the highest age-standardised rate of incidence, prevalence and YLDs in 1990 and 2019. The most prominent age effect on incidence rate was in those aged 15-19 years. Decreased effects of period on incidence, prevalence and YLD rates was observed overall and in females, not in males. The incidence, prevalence and YLD rates showed an unfavourable trend in the younger cohorts born after 1990, with males reporting a higher cohort risk than females. CONCLUSIONS: From 1990 to 2019, the overall trend of bipolar disorder burden presents regional and national variations and differs by age, sex, period and cohort.

Clinical distinctions in symptomatology and psychiatric comorbidities between misdiagnosed bipolar I and bipolar II disorder versus major depressive disorder.

BACKGROUND: To explore the demographic and clinical features of current depressive episode that discriminate patients diagnosed with major depressive disorder (MDD) from those with bipolar I (BP-I) and bipolar II (BP-II) disorder who were misdiagnosed as having MDD . METHODS: The Mini-International Neuropsychiatric Interview (MINI) assessment was performed to establish DSM-IV diagnoses of MDD, and BP-I and BP-II, previously being misdiagnosed as MDD. Demographics, depressive symptoms and psychiatric comorbidities were compared between 1463 patients with BP-I, BP-II and MDD from 8 psychiatric settings in mainland China. A multinomial logistic regression model was performed to assess clinical correlates of diagnoses. RESULTS: A total of 14.5% of the enrolled patients initially diagnosed with MDD were eventually diagnosed with BP. Broad illness characteristics including younger age, higher prevalence of recurrence, concurrent dysthymia, suicidal attempts, agitation, psychotic features and psychiatric comorbidities, as well as lower prevalence of insomnia, weight loss and somatic symptoms were featured by patients with BP-I and/or BP-I, compared to those with MDD. Comparisons between BP-I and BP-II versus MDD indicated distinct symptom profiles and comorbidity patterns with more differences being observed between BP-II and MDD, than between BP-I and MDD . CONCLUSION: The results provide evidence of clinically distinguishing characteristics between misdiagnosed BP-I and BP- II versus MDD. The findings have implications for guiding more accurate diagnoses of bipolar disorders.

Identifying causal associations between women's reproductive traits and risk of schizophrenia: a multivariate validated two-sample Mendelian randomization analysis.

BACKGROUND: A significant association between women's reproductive traits and the risk of schizophrenia (SCZ) has been discovered, but the causalities remain unclear. We designed a two-sample univariate Mendelian randomization (MR) study using female-specific SNPs collected from a large-scale genome-wide association study as a genetic tool to explore the causal effect of female reproductive traits on the risk of SCZ, and conducted a multivariate MR study to re-validate the above findings. METHODS: From extensive genome-wide association studies (GWAS) of people with European ancestry (n = 176,881 to 418,758 individuals), summary-level data on five female reproductive variables were extracted. Summary-level information on SCZ was taken from a GWAS meta-analysis involving 320,404 people with European ancestry. The inverse variance weighting estimations for both univariable MR (UVMR) and multivariable MR (MVMR) were presented as the primary results. MR-Egger, weighted median, simple mode, and weighted mode regression methods for UVMR, and MVMR-Egger, MVMR-Lasso, and MVMR-median methods for MVMR were used for sensitivity analyses. RESULTS: The UVMR produced compelling proof for a connection between genetically predicted later age at first sexual intercourse (AFS) (OR, 0.632; 95% CI, 0.512-0.777; P < 0.01) and decreased SCZ risk. Pleiotropy analysis of the AFS-SCZ association confirmed the robustness of the MR results (P > 0.05). Consistent, substantial causal effects of AFS (OR, 0.592; 95%CI, 0.407-0.862; P < 0.01) on the risk of SCZ were demonstrated after adjusting for body mass index, years of schooling, and smoking initiation using MVMR. CONCLUSIONS: Our findings provide convincing evidence that early AFS is a risk factor for SCZ. SCZ risk may be decreased by raising awareness of reproductive healthcare for women.

Gender differences in prevalence and associations between cognitive symptoms and suicidal ideation in patients with recurrent major depressive disorder: findings from the Chinese NSSD study.

BACKGROUND: This study aimed to explore gender differences in associations between cognitive symptoms and suicidal ideation (SI) among patients with recurrent major depressive disorder (MDD). METHODS: We recruited 1222 patients with recurrent MDD from the National Survey on Symptomatology of Depression (NSSD), a survey designed to investigate the symptoms experienced during current major depressive episodes in China. A four-point Likert questionnaire was used to assess the frequency of cognitive symptoms and SI in the past two weeks. RESULTS: Gender differences in clinical features and cognitive symptoms of participants with recurrent MDD were found. Specifically, male patients had a higher prevalence of memory loss, decreased verbal output, indecisiveness, and impaired interpersonal relationships, while female patients exhibited a higher prevalence of impaired social and occupational functioning (all P < 0.05). No significant difference in SI prevalence was found between male and female patients. The logistic regression analysis revealed that in male patients, SI was associated with indecisiveness and impaired interpersonal relationships. In female patients, reduced verbal output and impaired social and professional functions were also associated with SI in addition to the above-mentioned variables. CONCLUSION: The findings of gender differences in associations between cognitive symptoms and SI highlight the need to carefully assess gender-specific cognitive predictors of SI in patients with recurrent MDD. This has further implications for more targeted prevention and treatment strategies for SI based on gender.

Structural and functional correlates of the response to deep brain stimulation at ventral capsule/ventral striatum region for treatment-resistant depression.

BACKGROUND: Though deep brain stimulation (DBS) shows increasing potential in treatment-resistant depression (TRD), the underlying neural mechanisms remain unclear. Here, we investigated functional and structural connectivities related to and predictive of clinical effectiveness of DBS at ventral capsule/ventral striatum region for TRD. METHODS: Stimulation effects of 71 stimulation settings in 10 TRD patients were assessed. The electric fields were estimated and combined with normative functional and structural connectomes to identify connections as well as fibre tracts beneficial for outcome. We calculated stimulation-dependent optimal connectivity and constructed models to predict outcome. Leave-one-out cross-validation was used to validate the prediction value. RESULTS: Successful prediction of antidepressant effectiveness in out-of-sample patients was achieved by the optimal connectivity profiles constructed with both the functional connectivity (R=0.49 at p<10-4; deviated by 14.4±10.9% from actual, p<0.001) and structural connectivity (R=0.51 at p<10-5; deviated by 15.2±11.5% from actual, p<10-5). Frontothalamic pathways and cortical projections were delineated for optimal clinical outcome. Similarity estimates between optimal connectivity profile from one modality (functional/structural) and individual brain connectivity in the other modality (structural/functional) significantly cross-predicted the outcome of DBS. The optimal structural and functional connectivity mainly converged at the ventral and dorsal lateral prefrontal cortex and orbitofrontal cortex. CONCLUSIONS: Connectivity profiles and fibre tracts following frontothalamic streamlines appear to predict outcome of DBS for TRD. The findings shed light on the neural pathways in depression and may be used to guide both presurgical planning and postsurgical programming after further validation.

Phenotypes, mechanisms and therapeutics: insights from bipolar disorder GWAS findings.

Genome-wide association studies (GWAS) have reported substantial genomic loci significantly associated with clinical risk of bipolar disorder (BD), and studies combining techniques of genetics, neuroscience, neuroimaging, and pharmacology are believed to help tackle clinical problems (e.g., identifying novel therapeutic targets). However, translating findings of psychiatric genetics into biological mechanisms underlying BD pathogenesis remains less successful. Biological impacts of majority of BD GWAS risk loci are obscure, and the involvement of many GWAS risk genes in this illness is yet to be investigated. It is thus necessary to review the progress of applying BD GWAS risk genes in the research and intervention of the disorder. A comprehensive literature search found that a number of such risk genes had been investigated in cellular or animal models, even before they were highlighted in BD GWAS. Intriguingly, manipulation of many BD risk genes (e.g., ANK3, CACNA1C, CACNA1B, HOMER1, KCNB1, MCHR1, NCAN, SHANK2 etc.) resulted in altered murine behaviors largely restoring BD clinical manifestations, including mania-like symptoms such as hyperactivity, anxiolytic-like behavior, as well as antidepressant-like behavior, and these abnormalities could be attenuated by mood stabilizers. In addition to recapitulating phenotypic characteristics of BD, some GWAS risk genes further provided clues for the neurobiology of this illness, such as aberrant activation and functional connectivity of brain areas in the limbic system, and modulated dendritic spine morphogenesis as well as synaptic plasticity and transmission. Therefore, BD GWAS risk genes are undoubtedly pivotal resources for modeling this illness, and might be translational therapeutic targets in the future clinical management of BD. We discuss both promising prospects and cautions in utilizing the bulk of useful resources generated by GWAS studies. Systematic integrations of findings from genetic and neuroscience studies are called for to promote our understanding and intervention of BD.

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

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

Disrupted intrinsic functional brain topology in patients with major depressive disorder.

Aberrant topological organization of whole-brain networks has been inconsistently reported in studies of patients with major depressive disorder (MDD), reflecting limited sample sizes. To address this issue, we utilized a big data sample of MDD patients from the REST-meta-MDD Project, including 821 MDD patients and 765 normal controls (NCs) from 16 sites. Using the Dosenbach 160 node atlas, we examined whole-brain functional networks and extracted topological features (e.g., global and local efficiency, nodal efficiency, and degree) using graph theory-based methods. Linear mixed-effect models were used for group comparisons to control for site variability; robustness of results was confirmed (e.g., multiple topological parameters, different node definitions, and several head motion control strategies were applied). We found decreased global and local efficiency in patients with MDD compared to NCs. At the nodal level, patients with MDD were characterized by decreased nodal degrees in the somatomotor network (SMN), dorsal attention network (DAN) and visual network (VN) and decreased nodal efficiency in the default mode network (DMN), SMN, DAN, and VN. These topological differences were mostly driven by recurrent MDD patients, rather than first-episode drug naive (FEDN) patients with MDD. In this highly powered multisite study, we observed disrupted topological architecture of functional brain networks in MDD, suggesting both locally and globally decreased efficiency in brain networks.

Impaired robust interhemispheric function integration of depressive brain from REST-meta-MDD database in China.

BACKGROUND: Recently, functional homotopy (FH) architecture, defined as robust functional connectivity (FC) between homotopic regions, has been frequently reported to be altered in MDD patients (MDDs) but with divergent locations. METHODS: In this study, we obtained resting-state functional magnetic resonance imaging (R-fMRI) data from 1004 MDDs (mean age, 33.88 years; age range, 18-60 years) and 898 matched healthy controls (HCs) from an aggregated dataset from 20 centers in China. We focused on interhemispheric function integration in MDDs and its correlation with clinical characteristics using voxel-mirrored homotopic connectivity (VMHC) devised to inquire about FH patterns. RESULTS: As compared with HCs, MDDs showed decreased VMHC in visual, motor, somatosensory, limbic, angular gyrus, and cerebellum, particularly in posterior cingulate gyrus/precuneus (PCC/PCu) (false discovery rate [FDR] q < 0.002, z = -7.07). Further analysis observed that the reduction in SMG and insula was more prominent with age, of which SMG reflected such age-related change in males instead of females. Besides, the reduction in MTG was found to be a male-special abnormal pattern in MDDs. VMHC alterations were markedly related to episode type and illness severity. The higher Hamilton Depression Rating Scale score, the more apparent VMHC reduction in the primary visual cortex. First-episode MDDs revealed stronger VMHC reduction in PCu relative to recurrent MDDs. CONCLUSIONS: We confirmed a significant VMHC reduction in MDDs in broad areas, especially in PCC/PCu. This reduction was affected by gender, age, episode type, and illness severity. These findings suggest that the depressive brain tends to disconnect information exchange across hemispheres.

Peripheral biomarkers to predict the diagnosis of bipolar disorder from major depressive disorder in adolescents.

The onset of bipolar disorder (BD) occurs in childhood or adolescence in half of the patients. Early stages of BD usually present depressive episodes, which makes it difficult to be distinguished from major depressive disorder (MDD). Objective biomarkers for discriminating BD from MDD in adolescent patients are limited. We collected basic demographic data and the information of the first blood examination performed after the admission to psychiatry unit of BD and MDD inpatients during 2009-2018. We recruited 261 adolescents (aged from 10 to 18), including 160 MDD and 101 BD. Forward-Stepwise Selection of binary logistic regression was used to construct predictive models for the total sample and subgroups by gender. Independent external validation was made by 255 matched patients from another hospital in China. Regression models of total adolescents, male and female subgroups showed accuracy of 73.3%, 70.6% and 75.2%, with area under curves (AUC) as 0.785, 0.816 and 0.793, respectively. Age, direct bilirubin (DBIL), lactic dehydrogenase (LDH), free triiodothyronine (FT3) and C-reactive protein (CRP) were final factors included into the models. The discrimination was well at external validation (AUC = 0.714). This study offers the evidence that accessible information of common clinical laboratory examination might be valuable in distinguishing BD form MDD in adolescents. With good diagnostic accuracies and external validation, the total regression equation might potentially be applied to individualized clinical inferences on adolescent BD patients.

Efficacy of adjunctive intensive transcranial direct current stimulation of different cortices in treatment-resistant depression: a study protocol for a randomized double-blinded sham-controlled trial.

BACKGROUND: Treatment-resistant depression (TRD) carries a high economic burden worldwide. Transcranial direct current stimulation (tDCS) is advantageous for improving cognition and can be safely used in the treatment of depression. The effectiveness of tDCS of the left and right orbitofrontal cortex (OFC) as adjuvant treatment in patients with TRD has rarely been explored. Therefore, the objective of this trial is to evaluate the effectiveness there of when administering left dorsolateral prefrontal cortex (DLPFC) positive stimulation or OFC negative stimulation in patients with TRD. METHODS: Ninety eligible participants will be recruited to receive intervention at Shanghai Mental Health Center. Treatment will be randomly assigned in a double-blind fashion. Participants will receive either DLPFC (n = 30), OFC (n = 30), or sham (n = 30) tDCS, while continuing their usual pharmacotherapy at a stable dosage for at least 2 weeks before enrollment and throughout the stimulation period. All participants will receive 20 weekday stimulation sessions of 60 minutes duration each. Participants in the active group will be stimulated at 2 mA throughout the session, whereas the sham group will receive only a brief period of stimulation to mimic the sensation. After 20 stimulation sessions, no further treatment will be administered. Measurements will be conducted at regular points throughout and at 8 weeks after trial completion. The primary outcome is the change in the 17-item Hamilton Depression Rating Scale (HAMD-17) score after 20 sessions. Secondary outcomes were defined as changes in other measurement scales, cognitive function, resting-state functional magnetic resonance imaging (rs-fMRI), and serum biomarkers. DISCUSSION: We hypothesize that, in contrast to the sham group, both the active DLPFC and OFC tDCS groups will show superiority in HAMD-17 score reduction after 5, 10, and 20 sessions. Moreover, associations of the improvement of depressive symptoms with variations in rs-fMRI and TRD-related biomarkers will be evaluated. Our study may suggest that adjunctive intensive tDCS with left DLPFC positive stimulation or right OFC negative stimulation may be effective as a novel method to relieve depressive symptoms in patients with TRD. The variation of rs-fMRI, biomarkers could be used as a potential prediction model of treatment efficacy in TRD. TRIAL REGISTRATION: The trial protocol is registered with www.chictr.org.cn under protocol registration number ChiCTR2200058030. Date of registration: March 27, 2022. Recruitment started in September 2022 and is ongoing.

Reduced default mode network functional connectivity in patients with recurrent major depressive disorder.

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

Cognitive control and emotional response in attention-deficit/ hyperactivity disorder comorbidity with disruptive, impulse-control, and conduct disorders.

BACKGROUND: This study investigated cognitive and emotional functioning in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and disruptive, impulse-control, and conduct disorders (DICCD). METHODS: Thirty patients with ADHD, 26 with DICCD, 22 with ADHD+DICCD were recruited from the outpatient department of Shanghai Changning Mental Health Center, plus 20 healthy controls (HC). Differences between the groups in cognitive and emotional functioning were examined using Golden's Stroop and Emotional Stroop tests. For Emotional Stroop Mean reaction time (RT) of positive word (POS) and negative word (NEG) with color congruence (C) or incongruence (I) were recorded as POS-C, POS-I, NEG-C and NEG-I, respectively. RESULTS: For Golden's interference scores (IGs), both errors and RTs in the ADHD group were higher than in the other groups. Longer mean RTs of POS-C, POS-I, NEG-C and neural word (NEU) of the ADHD group, and NEG-I of ADHD+DICCD and DICCD groups were observed compared to HC. After 12 weeks of methylphenidate treatment, differences between ADHD subgroups and HC on Golden's Stroop RT disappeared, but differences in Golden's Stroop errors and Emotional Stroop mean RTs remained. The ADHD+DICCD group showed longer mean RTs in NEG-C, NEG-I and NEU of the Emotional Stroop test than the ADHD group. CONCLUSIONS: Our study shows that regardless of emotional responding, deficit in cognitive control is the core symptom of ADHD. However, emotionally biased stimuli may cause response inhibitory dysfunction among DICCD with callous-unemotional traits, and the comorbidity of ADHD and DICCD tends to account for the negative emotional response characteristic of DICCD. These deficits may be eliminated by medication treatment in ADHD, but not the ADHD with comorbid DICCD. Our results support the notion that ADHD with comorbid DICCD is more closely related to DICCD than to ADHD.

Barriers and facilitators to implementing measurement-based care for depression in Shanghai, China: a situational analysis.

BACKGROUND: Measurement-based care (MBC) is an evidence-based practice for depression, but its use by clinicians remains low. Enhanced MBC (eMBC), which uses digital technologies, can help to facilitate the use of MBC by clinicians and patients. Understanding factors that act as barriers and drivers to the implementation of MBC and eMBC is important to support the design of implementation strategies, promoting uptake by clinicians and patients. OBJECTIVE: This situational analysis identifies barriers and facilitators to the implementation of standard and eMBC at mental health centers in Shanghai, China. METHODS: We used mixed methods to develop a comprehensive understanding of the factors influencing MBC and eMBC implementation in Shanghai. This study took place across three mental health centers in Shanghai. We used situational analysis tools to collect contextual information about the three centers, conducted surveys with n = 116 clinicians and n = 301 patients, conducted semi-structured interviews with n = 30 clinicians and six focus groups with a total of n = 19 patients. Surveys were analysed using descriptive statistics, and semi-structured interviews and focus groups were analysed using framework analysis. RESULTS: Several potential barriers and facilitators to MBC and eMBC implementation were identified. Infrastructure, cost, attitudes and beliefs, and perceptions about feasibility and efficacy emerged as both challenges and drivers to MBC and eMBC implementation in Shanghai. CONCLUSIONS: The results of this study will directly inform the design of an implementation strategy for MBC and eMBC in Shanghai, that will be tested via a randomized controlled trial. This study contributes to the emerging body of literature on MBC implementation and, to the best of our knowledge, is the first such study to take place in Asia. This study identifies several factors that are relevant to the equitable delivery of MBC, recognizing the need to explicitly address equity concerns in global mental health implementation research.

Association between residual symptoms and social functioning in patients with depression.

OBJECTIVE: There is a lack of data about residual symptoms in Chinese patients with depression. The aim of this study was to evaluate the association of residual symptoms with social functional impairment in these patients. METHODS: This was a multicenter cross-sectional study conducted in 11 hospitals in eight cities of China from September 2014 to April 2015. Residual symptoms and social functioning were assessed using the SDS, QIDS-SR16, Q-LES-Q-SF, and PHQ-15 scales. Logistic regression analysis was used to determine the factors associated with social functional impairment. RESULTS: Among the 1503 patients, 915 (60.9%) had no functional impairment (SDS ≤6) and 588 (39.1%) showed functional impairment (SDS >6). Those with impairment had higher PHQ-15 scores (7.4 ± 4.8 vs. 4.0 ± 3.4, P < 0.0001), lower Q-LES-Q-SF scores (all items P < 0.0001), higher SDS scores (13.9 ± 5.7 vs. 2.8 ± 2.2, P < 0.0001), and higher scores for all QIDS dimensions (all P < .0001). The factors related to functional impairment included QIDS dimension 7 (loss of interest) (OR = 2.137, 95%CI 1.600-2.853, P < 0.0001), QIDS dimension 9 (mental anxiety) (OR = 1.627, 95%CI 1.215-2.180, P = 0.0011), QIDS dimension 3 (appetite) (OR = 1.502, 95%CI 1.141-1.977, P = 0.0037), QIDS dimension 8 (energy) (OR = 1.468, 95%CI 1.092-1.973, P = 0.0110), age (OR = 0.982, 95%CI 0.971-0.993, P = 0.0013), disease course (OR = -1.004, 95%CI 1.002-1.006, P = 0.0004), and QIDS dimension 1 (sleep disorders) (OR = 1.622, 95%CI 1.068-2.463, P = 0.0232). CONCLUSION: Compared with patients with normal social function, cases with impaired social function have more physical symptoms, more residual symptoms of depression, and less satisfaction with the quality of life. Residual symptoms are associated with social functional impairment in patients with depression.

Introduction.

Depressive disorder is one of the most widespread forms of mental disorders which lead to a significant public health concern, such as disability, suicide, and so on. Its etiology remains vague but it is believed that depressive disorder is a multifactorial disease which is induced by the interaction of social, psychological, and biological factors. Thus, there is no clear and definite pathological theory could illustrate its mechanism independently until now, involving genetics, neuroimaging, neuroinflammation, neuroendocrine, and others. Comprehensive assessment to patients with depression is the starting point for a right diagnosis. History-taking of physical condition is as important as psychiatric interview and rational usage of scales would be beneficial for screening. There are many kinds of therapeutic measures for depressive patients nowadays, including general intervention, pharmacotherapy, psychotherapy, and physical therapy. For now, anti-depressants used in clinical practice is almost monoamine-based drugs while much more progress have been made in developing new antidepressant medications, like prototypical N-methyl-D-aspartate (NMDA) receptor antagonists, opioid agonists, gamma-aminobutyric acid (GABAA) receptors, and psychedelics. Once these novel drugs are proved to be practicable, it will create a historical evolution in the field of psychiatry. In addition, we advocate that measurement-based care (MBC) should run through the whole duration of treatment and goals of MBC in every stage are different. As brain projects in many countries are conducting in inspiring ways, we believe that our understanding about depressive disorder, of course, and other neuropsychiatric disorders will be better in the future.

Advance in Diagnosis of Depressive Disorder.

Diagnosis for MDD in modern psychiatry has developed for decades based on long traceable historic efforts on conceptualizing the illness. This article reviews the historical background of current diagnostic framework for MDD, diagnostic criteria and two newly added specifiers ("with anxious distress" and "with mixed features" specifiers) of MDD in the DSM-5, the most influential diagnostic instrument in the world, as well as problems and limitations of symptom-based diagnosis for sake of better understanding about the inter-relationship between diagnostic criteria and MDD.

Association of DNA methylation in BDNF with escitalopram treatment response in depressed Chinese Han patients.

PURPOSE: The neurotrophin brain-derived neurotrophic factor (BDNF) has been found to be associated with both the pathophysiology of depression and antidepressants response. Gene expression differences were partly mediated by SNP, which might be identified as a predictor of antidepressant response. In the present study, we attempt to identify whether DNA methylation, another factor known to affect gene transcription, might also predict antidepressant response. METHODS: A total of 85 depressed Chinese Han patients were followed-up 8 weeks after initiating escitalopram treatment. Treatment response was assessed by changes in the Hamilton Depression Rating Scale-17 (HAMD-17) score. The Life Events Scale (LES) and the Childhood Trauma Questionnaire (CTQ) were utilized as the assessment of previous life stress. The bisulfate sequencing was used to assess DNA methylation. Four single nucleotide polymorphisms (SNPs) in the BDNF gene were genotyped using PCR-RFLP or PCR sequencing. RESULTS: We identified a DNA methylation predictor (P = 0.006-0.036) and a DNA methylation by LES interaction predictor (OR = 1.442 [1.057-1.968], P = 0.021) of general antidepressant treatment response. Lower mean BDNF DNA methylation was associated with impaired antidepressant response. Furthermore, the present data indicated that age, life stress, and SNPs genotype might be likely related to DNA methylation status. Average DNA methylation of BDNF at baseline was significantly lower than that at endpoint after 8 weeks of escitalopram treatment, which was based only on a subset of cases (n = 44). CONCLUSIONS: Our results suggest that BDNF DNA hypomethylation and its interaction with lower LES score might result in impaired antidepressant treatment response. The pharmacoepigenetic study could eventually help in finding epigenetic biomarkers of antidepressant response.

Somatic symptoms vary in major depressive disorder in China.

PURPOSE: This study aimed to investigate the clinical characteristics of somatic symptoms of patients in China who suffer from major depressive disorder (MDD). METHOD: 3273 patients who met the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) MDD were recruited from 16 general hospitals and 16 mental health centers in China. Physicians and patients completed complementary customized depression disorder symptomatology questionnaires assessing the clinical characteristics of patients with MDD. RESULT: 1. In this study we analyzed physician-recorded data. The major somatic symptoms in patients with MDD in China were insomnia (64.6%), pre-verbal physical complaints (46.9%), weight loss (38.5%), low appetite (37.6%), circulatory system complaints (31.3%), headache (31.3%), hyposexuality (31.0%), gastrointestinal symptom complaints (29.6%), and respiratory system complaints (29.6%). 2. Compared with MDD patients who sought medical help from mental health centers, MDD patients who sought medical help from general hospitals were more likely to suffer from urinary system complaints, headache, sensory system complaints, trunk pain, and nervous system complaints. A lower prevalence rate of insomnia and hyposexuality was also observed among MDD patients who visited general hospitals (p < .05). 3. Patients aged from 40 to 54 had the highest probability of pre-verbal physical complaints, respiratory system complaints, trunk pain, hyposexuality, limb pain and other pain conditions, while patients over 55 years of age had the lowest prevalence respiratory system complaints, hyposexuality, and other pain conditions, and they also had the highest rate of low appetite and insomnia. 4. Female patients appeared to exhibit higher rates of pre-verbal physical complaints, low appetite, and insomnia than male patients, but had fewer urinary systems complaints than male patients (p < .05). CONCLUSION: The major somatic symptoms in patients with MDD in China are insomnia, pre-verbal physical complaints, weight loss, low appetite, circulatory system complaints, headache, hyposexuality, gastrointestinal system complaints, and respiratory system complaints. These symptoms vary by the type of medical setting to which patients present, and well as by age, and gender.

Blood-based dynamic genomic signature for obsessive-compulsive disorder.

No biologically based diagnostic criteria are in clinical use today for obsessive-compulsive disorder (OCD), schizophrenia, and major depressive disorder (MDD), which are defined with reference to Diagnostic and Statistical Manual clinical symptoms alone. However, these disorders cannot always be well distinguished on clinical grounds and may also be comorbid. A biological blood-based dynamic genomic signature that can differentiate among OCD, MDD, and schizophrenia would therefore be of great utility. This study enrolled 77 patients with OCD, 67 controls with no psychiatric illness, 39 patients with MDD, and 40 with schizophrenia. An OCD-specific gene signature was identified using blood gene expression analysis to construct a predictive model of OCD that can differentiate this disorder from healthy controls, MDD, and schizophrenia using a logistic regression algorithm. To verify that the genes selected were not derived as a result of chance, the algorithm was tested twice. First, the algorithm was used to predict the cohort with true disease/control status and second, the algorithm predicted the cohort with disease/control status randomly reassigned (null set). A six-gene panel (COPS7A, FKBP1A, FIBP, TP73-AS1, SDF4, and GOLGA8A) discriminated patients with OCD from healthy controls, MDD, and schizophrenia in the training set (with an area under the receiver-operating-characteristic curve of 0.938; accuracy, 86%; sensitivity, 88%; and specificity, 85%). Our findings indicate that a blood transcriptomic signature can distinguish OCD from healthy controls, MDD, and schizophrenia. This finding further confirms the feasibility of using dynamic blood-based genomic signatures in psychiatric disorders and may provide a useful tool for clinical staff engaged in OCD diagnosis and decision making.