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Yuncheng Zhu,1– 3,* Zhiguo Wu,4,* Dongmei Zhao,5 Xiaohui Wu,2 Ruoqiao He,6 Zuowei Wang,1,3 Daihui Peng,2 Yiru Fang2,7– 9 1Division of Mood Disorders, Shanghai Hongkou Mental Health Center, Shanghai, People’s Republic of China; 2Clinical Research Center & Division of Mood Disorders, Shanghai Mental Health Center, Shanghai JiaoTong University School of Medicine, Shanghai, People’s Republic of China; 3Clinical Research Center for Mental Health, School of Medicine, Shanghai University, Shanghai, People’s Republic of China; 4Clinical Research Center in Mental Health, Shanghai Yangpu District Mental Health Center, Shanghai University of Medicine & Health Sciences, Shanghai, People’s Republic of China; 5Division of Psychiatry, Shanghai Changning Mental Health Center, Shanghai, People’s Republic of China; 6New York University, New York, NY, USA; 7Department of Psychiatry & Affective Disorders Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 8CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, People’s Republic of China; 9Shanghai Key Laboratory of Psychotic Disorders, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yiru Fang, Email yirufang@aliyun.comObjective: This survey aims to explore the current medical treatment of major depressive disorder (MDD) in China and match its degree with Canadian Network for Mood and Anxiety Treatments (CANMAT).Methods: A total of 3275 patients were recruited from 16 mental health centers and 16 general hospitals in China. Descriptive statistics presented the total number and percentage of drugs, as well as all kinds of treatments.Results: Selective serotonin reuptake inhibitors (SSRIs) accounted for the largest proportion (57.2%), followed by serotonin-noradrenaline reuptake inhibitors (SNRIs) (22.8%) and mirtazapine (7.0%) in the first therapy, while that of SNRIs (53.9%) followed by SSRIs (39.2%) and mirtazapine (9.8%) in the follow-up therapy. An average of 1.85 medications was administered to each MDD patient.Conclusion: SSRIs were the first choice in the first therapy, while the proportion of those drugs decreased during the follow-up therapy and were replaced by SNRIs. Plenty of combined pharmacotherapies were directly selected as the first trial of patients, which was inconsistent with guideline recommendations.Keywords: major depressive disorder, Chinese, guideline, antidepressants

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

Major depression is the largest single contributor to suicide, and anxiety symptoms are associated with the severity of depression and suicidality. It is important to explore biomarkers of anxiety and suicidal ideation in major depression. In this study we hypothesized that the volume of subregions of the amygdala might be indicators of anxiety and suicidal ideation in patients with major depression.We recruited 59 drug-naïve patients with first-episode depression who scored17 on the Hamilton Rating Scale for depression, and 30 healthy controls to participate in a magnetic resonance imaging study. We examined the volume of sub-regions of the amygdala thought to be involved in processing anxious emotion in the depression and healthy control groups. We performed pair-wise comparisons of amygdala subfield volumes in patients with depression and healthy controls with an analysis of variance. We used logistic regression to test the relationship between suicidal ideation and anxious character with the volume of subregions of the amygdala.1) We found a significant difference in the volumes of the left amygdala (P = 0.003) and right amygdala (P = 0.001) between the two groups. There are significant differences in the volumes of the sub-region of the left amygdala. 2) The volume of the left lateral nucleus (P0.001), basal nucleus (P0.001), accessory basal nucleus (P0.05), left Paralaminar-nucleus (P0.001), right lateral-nucleus (P0.05), right basal-nucleus (P0.05), right anterior-amygdaloid area AAA (P0.05), right paralaminar-nucleus (P0.001) in the depression group are larger than healthy controls, however the volumes of the central-nucleus (P0.05), medial-nucleus (P0.001) in both sides are decreased in the major depression group. 3) There is a significantly larger volume of right medial nucleus in the suicidal ideation group comparing the hopelessness (P = 0.026), and the depressive patients without hopeless thoughts (P = 0.004). 4) We found a negative relation between the left basal nucleus and anxiety (OR: 0.940, 95%CI: 0.891-0.991), and a positive relation between the accessory basal nucleus on the left side and anxiety (OR: 1.007, 95%CI: 1.002-1.158).We were not able to examine the effects of gender or age. The changes of amygdala volume in patients with depression were not followed up. Our sample size was such that independent replication is needed to confirm the robustness of our results.The volumes of the basal nucleus in both sides are increased in depressed patients while the volumes of the central-nucleus, medial-nucleus bilaterally are reduced in the major depression group. Among the subregions, the volume of right medial nucleus might be the biomarkers for suicidal ideation in depressive patients.

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.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.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.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.

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.

Background Major depressive disorder (MDD) with atypical features, namely depression with atypical features (AFD), is one of the most common clinical specifiers of MDD, characterized by high risk of converting to bipolar disorder (BD). However, there is still lack of clinical guidelines for the diagnosis, treatment, and prognosis of AFD. Our study mainly focuses on three issues about what’s the objective endophenotype of AFD, how to select appropriate personalized treatment for AFD, what’s the predictive biomarkers of conversion to BD.Methods The Study of Individualized Diagnosis and Treatment for Depression with Atypical Features (iDoT-AFD) is a multicenter, prospective study consisting of a 12-week randomized-intervention trial followed by a real-world follow-up until 4 years or reaching the study endpoint. It is enrolling 480 patients with AFD (120 per treatment arm), 100 patients with BD, and 100 healthy controls (HC). Multivariate-dimension information is collected including clinical features, cognitive function, kynurenine pathway metabolomics, and multimodal magnetic resonance imaging (MRI) data. The iDoT-AFD study can be classified into three parts including the cross-sectional part and the prospective part. Firstly, multivariate informatics analyzes are performed to recognize patients with AFD from participants including the first-episode and recurrent atypical depression, patients with BD and HC. Secondly, patients with atypical depression are randomly allocated to one of the four treatment groups including ‘single application of selective serotonin reuptake inhibitor (SSRI) or serotonin-noradrenaline reuptake inhibitor (SNRI)’, ‘SSRI/SNRI combined with mood stabilizer’, ‘SSRI/SNRI combined with quetiapine (≥ 150mg/d)’, or ‘treatment as usual (TAU)’, and then followed up 12 weeks to find out the optimized treatment strategies. Thirdly, patients with atypical depression are followed up in the real world until 4 years or switching to BD to explore risk factors of conversion from atypical depression to BD and build the conversion risk early-warning model eventually.Discussion First enrolment was in August 2019, and the recruitment is ongoing. The iDoT-AFD study explores clinical and biological markers for the diagnosis, treatment, and prognosis of AFD, and further provide evidence for clinical guidelines of this depressive specifier which has high risk switching to BD.Trial registration Clinical Trials.gov ID: NCT04209166. Registered on December 19, 2019.

Effective and targeted interventions for improving quality of life (QOL) in addition to achieving 'clinical remission' are imperatives for patients with major depressive disorder (MDD). This study aimed to examine potential predictors and moderators of QOL in depression. Data were obtained from the Algorithm Guided Treatment Strategies for Major Depressive Disorder (AGTs-MDD) study, a multisite, randomized controlled trial composed of 980 depressed patients. Mixed Model Repeated Measures (MMRM) analyses were conducted to identify baseline characteristics associated with QOL overall (predictors) and their interaction effects (moderators). Severe core depressive, anxiety and pain symptoms were found to be independently associated with poor QOL over the 12-week acute phase treatment. Severe depression, severe anxiety or pain symptoms, or severe suicidal ideation predicted a larger improvement of QOL during acute phase treatment, whereas males showed less improvement. None of the putative moderators were identified except for the educational level. Patients with lower educational level showed a larger improvement of QOL in the AGT started with escitalopram (AGT-E) group and AGT started with mirtazapine (AGT-M) group compared to the treatment as usual (TAU) group. These findings may help to instruct informed decision-making for heterogeneous patients with MDD in the view of full recovery.

Little is known how often depressive episodes are accompanied by gastrointestinal symptoms in major depressive disorders (MDD). The authors sought to determine the frequency and clinical correlates of gastrointestinal symptoms during episodes of depressive disorder.3,256 MDD patients from the National Survey on Symptomatology of Depression (NSSD), which was designed to investigate the magnitude of symptoms of current major depressive episodes in China, were enrolled and assessed for gastrointestinal symptoms in this study. Illness characteristics were compared in patients with a different frequency of gastrointestinal symptoms. Pearson correlation analysis and multiple linear regression analysis were employed to investigate the associations between gastrointestinal symptoms and psychological characteristics in the patients.More than 70% of the subjects with depressive episodes had concomitant gastrointestinal symptoms. A higher frequency of gastrointestinal symptoms was associated with an increased risk of suicide ideation, suicide attempts, anxious mood, depressed mood, insomnia, feeling a failure, poor concentration, body pain, hopelessness, anger, and irritability. Pearson correlation analysis indicated moderate but significant associations between gastrointestinal symptoms and psychological characteristics (p0.001). Multiple linear regression analysis showed that suicide ideation (β=0.161, p0.001), anxiety mood (β=0.166, p = 0.006), insomnia (β =0.262, p0.001), anger (β=0.144, p0.001), feeling a failure (β =0.365, p0.001), and body pain (β=0.581 p0.001) were independently associated with gastrointestinal symptoms in MDD patients.Gastrointestinal symptoms were one of the most prevalent clinical presentations of MDD. The associations between gastrointestinal symptoms and psychological characteristics may prove useful in expanding our understanding of how gastrointestinal symptoms contributes to MDD.

Background The co-occurrence of insomnia and hypersomnia symptoms in patients with major depressive disorder (MDD) is associated with suicidal ideation and functional impairment. The relationship between sleep disturbances and clinical features and outcomes may not be adequately studied. In this study, we measured the functional impairments and clinical features of co-occurring insomnia and hypersomnia symptoms in Chinese patients with MDD. Methods A post-hoc analysis was performed on data from the National Survey on Symptomatology of Depression (NSSD), which assessed the MDD patients in 32 hospitals by a clinician-rating questionnaire. The clinical features and outcomes were compared among the following four groups: insomnia symptom only, hypersomnia symptom only, both insomnia and hypersomnia symptoms, no sleep disturbance, respectively. Results Totally, 234 (7.15%) of 3275 participants with MDD co-occurred insomnia and hypersomnia symptoms. They had more depressive symptoms (27.41 ± 9.123), higher rate of suicide ideation (39.7%), more severe impairment in physical (58.1%), economic (32.9%), work (55.1%), and relationship with families (29.5%). Patients with both sleep disturbances were more likely to excessive worry about sleep, have suicidal ideation, the distress of social disharmony, more somatic symptoms, lack of energy, hyperphagia, loss of mood reactivity, and diurnal change, whereas less likely to have anxious mood. Limitations Sleep disorders were not diagnosed by current standard diagnostic criteria. Conclusions Patients co-occurring with both sleep disturbances are associated with a higher rate of suicide risk and poorer social function. Our study could provide implications for suicidal risk evaluation and the development of therapeutic strategies for depression.

Background : Functional specialization is a feature of human brain for understanding the pathophysiology of major depressive disorder (MDD). The degree of human specialization refers to within and cross hemispheric interactions. However, most previous studies only focused on interhemispheric connectivity in MDD, and the results varied across studies. Hence, brain functional connectivity asymmetry in MDD should be further studied. Methods : Resting-state fMRI data of 753 patients with MDD and 451 healthy controls were provided by REST-meta-MDD Project. Twenty-five project contributors preprocessed their data locally with the Data Processing Assistant State fMRI software and shared final indices. The parameter of asymmetry (PAS), a novel voxel-based whole-brain quantitative measure that reflects inter- and intrahemispheric asymmetry, was reported. We also examined the effects of age, sex and clinical variables (including symptom severity, illness duration and three depressive phenotypes). Results : Compared with healthy controls, patients with MDD showed increased PAS scores (decreased hemispheric specialization) in most of the areas of default mode network, control network, attention network and some regions in the cerebellum and visual cortex. Demographic characteristics and clinical variables have significant effects on these abnormalities. Limitations : Although a large sample size could improve statistical power, future independent efforts are needed to confirm our results. Conclusions : Our results highlight the idea that many brain networks contribute to broad clinical pathophysiology of MDD, and indicate that a lateralized, efficient and economical brain information processing system is disrupted in MDD. These findings may help comprehensively clarify the pathophysiology of MDD in a new hemispheric specialization perspective.

Anhedonia and cognitive impairment are core features of major depressive disorder (MDD), and are essential to the treatment and prognosis. Here, we aimed to investigate anhedonia and its cognitive correlates between first episode of depression (FED) and recurrent depression (RD), which was part of the National Survey on Symptomatology of Depression.In this study, 1400 drug naïve FED patients and 487 on medicine RD patients were included. Differences of anhedonia, cognitive symptoms and other clinical characteristics between groups were compared via Student's t-test, or the chi-square test as appropriate. Partial correlation analysis was used to analyze the correlations between anhedonia and cognitive symptoms after adjusting for potential confounders. A stepwise logistic regression analysis was performed to identify relapse risk factors among symptomatic variables, demographic factors, clinical characteristics and medication use.Compared to FED, RD patients displayed more comprehensive depressive, impaired cognitive and anhedonia symptoms. Cognitive symptoms were significantly related with the anhedonia symptoms with varying aspects. Patients taking emotional stabilizers displayed more abnormal cognitive symptoms, followed by benzodiazepines, and finally SSRIs, SNRIs and TCAs. The effect of drug use on anhedonia is not as extensive as that of cognitive symptoms.Collectively, the results of this investigation advance the knowledge on changes in anhedonia and cognitive symptoms in MDD.As this is a cross sectional study, it is difficult to draw any causal conclusions between cognitive impairment and anhedonia in MDD, and to ascertain the worse cognitive performances identified here were induced by current drug use.

Background This study aims to explore the changes in functional neuroimaging in bipolar depression patients with anxiety symptoms (BDP-A). Methods Forty-five BDP-A patients, 22 bipolar depression patients without anxiety symptoms (BDP-NA), and 48 healthy controls (HC) were finally involved. The low-frequency oscillation characteristics, functional connectivity (FC), and network properties among the three groups of participants were analyzed. Results Compared with the BDP-NA group, BDP-A patients exhibited significantly decreased amplitude of low-frequency fluctuation (ALFF) in the left middle frontal gyrus (MFG), superior occipital gyrus, and inferior parietal, but supramarginal and angular gyri (IPL). Enhanced FC from left IPL to middle temporal gyrus, from left precentral gyrus (PreCG) to bilateral angular gyri, medial superior frontal gyrus, and left superior frontal gyrus (SFG)/MFG were also revealed. Compared with HC, the BDP-A group showed remarkably increased ALFF in the left MFG/PreCG, right superior parietal gyrus, while decreased ALFF in the left inferior frontal gyrus, opercular part, and SFG. In addition, higher regional homogeneity in the left MFG/PreCG was found. Limitations The limitations are as follows: (1) relatively small sample size; (2) not all the patients were drug-naive; (3) lack of pure anxiety disorder patients as a controlled group; (4) mental health conditions of HC were not systemic evaluated. Conclusions BDP-A patients showed significant differences in resting-state fMRI properties when compared with BDP-NA or HC group. These results may infer the dysfunction of the dorsal attention network, the default network, and the fronto-limbic system as well as disrupted brain network efficiency in BDP-A patients.

Background Since the novel coronavirus disease (COVID-19) outbreak in Wuhan, thousands of medical workers have been dispatched to support Wuhan against the virus. The purpose of this study was to identify the independent risk factors for psychological distress in order to develop a more effective strategy and precise evidence-based psychological intervention for medical workers. Methods This multisite cross-sectional survey recruited doctors and nurses from local and nonlocal medical teams working at 16 hospitals in Wuhan to complete this online survey from February to March, 2020. Psychological status was evaluated through Perceived Stress Scales (PSS), Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder Scale (GAD-7) and Acute Stress Disorder Scale (ASDS). Results Of 966 participants, the prevalence of stress (95.9%), depression (46.0%) and anxiety (39.3%) were high. Local medical workers exhibited even higher scores of PSS, PHQ-9, GAD-7 and ASDS than those from outside Hubei (P

Yun Wang,1 Xiaohua Liu,2,3 Daihui Peng,2 Yan Wu,2 Yun’ai Su,4 Jia Xu,5 Xiancang Ma,6 Yi Li,7 Jianfei Shi,8 Xiaojing Cheng,9 Han Rong,10 Yiru Fang1,3,11 1Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Psychiatry, Peking University Sixth Hospital, Peking, People’s Republic of China; 5Department of Psychiatry, Harbin First Specific Hospital, Harbin, People’s Republic of China; 6Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an, People’s Republic of China; 7Department of Psychiatry, Wuhan Mental Health Center, Wuhan, People’s Republic of China; 8Department of Psychiatry, Hangzhou Seventh People’s Hospital, Hangzhou, People’s Republic of China; 9Department of Psychiatry, Shandong Mental Health Center, Shandong, People’s Republic of China; 10Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen, People’s Republic of China; 11CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, People’s Republic of ChinaCorrespondence: Daihui Peng; Yiru Fang Email pdhsh@126.com; yirufang@aliyun.comBackground: Despite the best treatments, about 20% of patients with major depressive disorder (MDD) receiving drugs and psychological intervention show little or no improvement. There is no trial comparing different treatment methods in patients with anxiety/somatic subtype MDD.Aim: To compare the efficacy and safety of various treatments in patients with anxiety/somatic subtype MDD.Methods: This was a preliminary multicenter randomized controlled trial at eight participating hospitals in China (09/2016-06/2019) (ClinicalTrials.gov #NCT03219008). The patients were randomized to mirtazapine/SNRIs, mirtazapine/SNRIs+cognitive behavioral therapy (CBT), mirtazapine+SNRIs, or mirtazapine+SNRIs+physical therapies (modified electroconvulsive treatment or repetitive transcranial magnetic stimulation). The primary endpoint was the 17-item Hamilton Depression Scale (HAMD-17). The Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) and Quality of Life (QOL)-6 were the secondary endpoints. The adverse events (AEs) were monitored. The patients were assessed at baseline (0 weeks), and at the end of the 2nd, 4th, 6th, 8th, and 12th week during treatment.Results: Finally, 107 patients were included: mirtazapine/SNRIs (n=36), mirtazapine/SNRIs+CBT (n=28), mirtazapine+SNRIs (n=29), and mirtazapine+SNRIs+physical therapies (n=14). The 17-HDRS and QIDS-SR scores decreased in all four groups, and the QOL-6 scores increased. There were no differences in the 17-HDRS (P=0.099), QIDS-SR (P=0.407), and QOL-6 (P=0.485) scores among the four groups. There were no differences in the occurrence of AEs among the four groups (P=0.942).Conclusion: This preliminary trial suggests that all four interventions (mirtazapine/SNRIs, mirtazapine/SNRIs+CBT, mirtazapine+SNRIs, or mirtazapine+SNRIs+physical therapies) achieved similar response and remission rates in patients with anxiety/somatic subtype MDD. The safety profile was manageable.Keywords: major depressive disorder, anxiety, mirtazapine, serotonin-norepinephrine reuptake inhibitor, cognitive behavioral therapy, Hamilton Depression Scale

Background: Most patients with the major depressive disorder (MDD) have varying degrees of impaired social functioning, and functional improvement often lags behind symptomatic improvement. However, it is still unclear if certain neurobiological factors underlie the deficits of social function in MDD. The aim of this study was to investigate the biomarkers of social function in MDD using structural magnetic resonance imaging (MRI). Methods: 3T anatomical MRI was obtained from 272 subjects including 46 high-functioning (high-SF, Sheehan Disability Scale (SDS) rating < 18) and 63 low-functioning (low-SF, SDS score ≥ 18) patients with MDD and 163 healthy controls (HC). Voxel-based morphometry (VBM) was employed to locate brain regions with grey matter (GM) volume differences in relation to social function in MDD. Regions showing GM differences in relation to social function at baseline were followed up longitudinally in a subset of 38 patients scanned after 12-week treatment. Results: Volume of right parahippocampal gyrus (rPHG) was significantly reduced in low-SF patients with MDD when compared to high-SF ones (FDR-corrected p < 0.05). Over 12 weeks of follow-up, though SF improved overall, the high and low-SF subgroups continued to differ in their SF, but had no progressive changes in PHG volume. Limitations: Limited functional assessment, high drop-out rate and median-based grouping method. Conclusions: Greater GM volume (GMV) of the rPHG may mark better social function in patients with MDD.

The hippocampus is a core region of interest for all major mental disorders, and its subfields implement distinctive functions. It is unclear whether the mental disorders exhibit common patterns of hippocampal impairments, and we lack knowledge on whether and how hippocampal subfields represent deficit spectra across mental disorders.Using brain images of 1123 individuals scanned on a single magnetic resonance imaging scanner, we examined the commonality, specificity, and symptom associations of the volume of hippocampal subfields across patients with schizophrenia, patients with obsessive-compulsive disorder, patients with bipolar disorder, patients with major depressive disorder, and healthy control subjects. We further performed a transdiagnostic analysis of the individual variability of the volume of hippocampal subfields to reflect cross-disease gradients in the hippocampus.We found common and disease-specific abnormalities in a few hippocampal fields and identified 2 reliable transdiagnostic factors in the hippocampal subfields, each reflecting a spectrum of mental disorders. The plane spanned by the 2 most reliable factors provided a clearer view of hippocampal volume abnormality spectra among the major mental disorders. In addition, functional and genetic enrichment analyses supported the different roles of the 2 hippocampal factors in mental disorders.The volume of hippocampal subfields reflected some commonality and specificity among the 3 major mental disorders. We propose a new pathophysiological dimensional view of the hippocampus, reflecting at least 2 spectra of mental disorders, suggesting multivariate links among the diseases. This work highlights the value of the complementary categorical and dimensional views of the hippocampal deficits in mental disorders.

Background In spite of numerous options, the most efficacious treatment for major depressive disorder (MDD) remains elusive. Algorithm-guided treatments (AGTs) are proposed to address inadequate remission and optimize treatment delivery. This study aimed to evaluate the clinical benefit of AGTs for MDD, and to explore specific moderators of treatment outcomes for individual patients. Methods The study recruited 987 patients with MDD across eight hospitals who were randomly assigned to AGT with escitalopram (AGT-E), AGT with mirtazapine (AGT-M), or treatment-as-usual (TAU). The outcomes were symptom remission, response rate, early improvement rate, subsymptom clusters improvement over time, the mean time to first remission, relapse rate at 6-months posttreatment follow-up, quality of life (QOL), and adverse events. Resutls No significant differences were observed across groups in outcome, except that TAU showed significantly poorer QOL, higher relapse rates at 6-months posttreatment follow-up, and marginally significantly worse maximal burden of adverse events than the AGT groups. After 6 weeks of treatment initiation, remission rate did not significantly increase with extended treatment. AGT-M outperformed the TAU and AGT-E in treating sleep symptoms. AGT-E was less effective than AGT-M and TAU in patients with severe depression and somatic symptoms (DSSS). The superiority of TAU over AGTs was observed in recurrent MDD patients. Conclusion Although the superiority of AGTs over TAU was limited by failure of alternative subsequent treatment, AGTs outperformed in QOL and relapse rate. Types of disease episode and DSSS were regarded as specific moderators in treatment of depression. These findings might contribute to future research on targeted antidepressant treatment.

BackgroundTwo-thirds of major depressive disorder (MDD) patients initially present with somatic symptoms, yet no study has used approaches based on somatic symptoms to subtype MDD. This study aimed to classify MDD via somatic symptoms and tracked the prognosis of each subtype.MethodsData were obtained from the study of Algorithm Guided Treatment Strategies for Major Depressive Disorder (AGTs-MDD). We recruited 395 subjects who received monotherapy of mirtazapine or escitalopram and conducted 2-, 4-, 6-, 8-, and 12-week follow-up assessments (n = 311, 278, 251, 199, and 178, respectively). Latent profile analysis (LPA) was performed on somatic symptom items of the depression and somatic symptoms scale (DSSS). Generalized linear mixed models (GLMM) were used to study the longitudinal prognosis of the subtypes classed by LPA. Primary outcome measures were the Hamilton Depression Rating Scale (HAMD), HAMD score reduction rate, as well as somatic and depressive items of DSSS.ResultsThree subtypes of MDD were found, namely, depression with mild somatic symptoms (68.9%), depression with moderate somatic symptoms (19.2%), and depression with severe somatic symptoms (11.9%). Scores of HAMD (F = 3.175, p = 0.001), somatic (F = 23.594, p < 0.001), and depressive (F = 4.163, p < 0.001) DSSS items throughout the 12-week follow-up showed statistical difference among the three subtypes. The moderate group displayed a higher HAMD-17 score and a lower reduction rate at the 6th week, and more severe depressive symptoms both at the 4th and 6th weeks.ConclusionThe results indicate that somatic symptoms should be emphasized in patients with MDD, and more attention is needed for those with moderate somatic symptoms, which may be relevant to a worse prognosis.

Yun Wang,1 Xiaohua Liu,2,3 Daihui Peng,2 Yan Wu,2 Yun’ai Su,4 Jia Xu,5 Xiancang Ma,6 Yi Li,7 Jianfei Shi,8 Xiaojing Cheng,9 Han Rong,10 Yiru Fang1,3,11 1Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Psychiatry, Peking University Sixth Hospital, Peking, People’s Republic of China; 5Department of Psychiatry, Harbin First Specific Hospital, Harbin, People’s Republic of China; 6Department of Psychiatry, The First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an, People’s Republic of China; 7Department of Psychiatry, Wuhan Mental Health Center, Wuhan, People’s Republic of China; 8Department of Psychiatry, Hangzhou Seventh People’s Hospital, Hangzhou, People’s Republic of China; 9Department of Psychiatry, Shandong Mental Health Center, Shandong, People’s Republic of China; 10Department of Psychiatry, Shenzhen Kangning Hospital, Shenzhen, People’s Republic of China; 11CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, People’s Republic of ChinaCorrespondence: Daihui Peng; Yiru Fang Email pdhsh@126.com; yirufang@aliyun.comBackground: Fluoxetine, bupropion, cognitive behavioral therapy (CBT), and physical therapies (modified electroconvulsive treatment or repetitive transcranial magnetic stimulation) can be used to manage melancholic depression.Objective: To compare the efficacy and safety of various treatments in patients with melancholic depression.Methods: This was a preliminary multicenter randomized controlled trial that included patients with depression in their first or recurrent acute episode between September 2016 and June 2019, and randomized to fluoxetine, fluoxetine+CBT, fluoxetine+bupropion, and fluoxetine+bupropion+brain stimulation. The primary endpoint was the decrease in the 17-item Hamilton Depression Rating Scale (17-HDRS). The secondary endpoint included the scores from the Quick Inventory of Depressive Symptomatology (QIDS-SR), QOL-6, and safety. Adverse events (AEs) were monitored. The follow-ups were performed at the end of the 0th, 2nd, 4th, 6th, 8th, and 12th weeks of treatment.Results: Finally, 113 patients were included in the analyses: fluoxetine (n=37), fluoxetine+CBT (n=27), fluoxetine+bupropion (n=34), and fluoxetine+bupropion+brain stimulation (n=15). The 17-HDRS and QIDS-SR scores decreased in all four groups (all P< 0.05). There were no differences in the 17-HDRS scores among the four groups at the end of treatment (P=0.779), except for fluoxetine alone showing a better response regarding self-consciousness than fluoxetine+bupropion. The QOL-6 scores increased in all four groups. The occurrence of AEs among the four groups showed no significant difference (P=0.053).Conclusion: This preliminary trial suggests that all four interventions (fluoxetine, fluoxetine+CBT, fluoxetine+bupropion, and fluoxetine+bupropion+brain stimulation) achieved similar response and remission rates in patients with melancholic depression, but that fluoxetine had a better effect on self-consciousness than fluoxetine+bupropion. The safety profile was manageable.Keywords: major depressive disorder, melancholic depression, fluoxetine, bupropion, cognitive behavioral therapy, brain stimulation