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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

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

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

Xiaohua Liu,1,2,* Yun Wang,3,* Daihui Peng,3 Huifeng Zhang,3,* Yanqun Zheng,1 Yan Wu,3 Yun-Ai Su,4 Ming Liu,5 Xiancang Ma,6 Yi Li,7 Jianfei Shi,8 Xiaojing Cheng,9 Han Rong,10 Yiru Fang2,3,11 1Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Division of Mood 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 China*These authors contributed equally to this workCorrespondence: Yiru Fang; Daihui PengShanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 South Wan Ping Road, Shanghai 200030, People’s Republic of ChinaEmail yirufang@aliyun.com pdhsh@126.comBackground: Major depressive disorder (MDD) is a heterogeneous mental disease that encompasses different subtypes and specifiers. Clinically targeted treatments have not been identified yet, although standardized strategies are recommended by several clinical guidelines. The main aim of this study is to respectively identify the precise treatment for three different subtypes of MDD (ie, melancholic, atypical, and anxious).Methods: An 8-to-12-week, multicenter randomized controlled trial (RCT) with a parallel group design will be conducted to determine the most effective and appropriate treatment. A total of 750 adults diagnosed with MDD will be recruited, categorized into melancholic, atypical or anxious type based on the assessment of the Inventory of Depressive Symptomatology (IDS30) and the Hamilton Anxiety Scale (HAMA), and 1:1 randomly assigned to different intervention groups. Blood draw, EEG test, and MRI scan will be performed at baseline and endpoint. Clinical symptom and side-effects will be evaluated at critical decision points (CDP) including weeks two, four, six, eight, and 12 after treatment. The primary outcome is total score and reduction rate of the 17-Hamilton Depression Rating Scale (17-HDRS). The secondary outcomes include the scores of the Quick Inventory of Depressive Symptomatology-self-report (QIDS-SR), IDS30, HAMA and the Treatment Emergent Symptom Scale (TESS). All the data will be analyzed by SAS software.Discussion: The study commenced recruitment in August 2017 and is currently ongoing.Trial Registration: ClinicalTrials.gov Identifier: NCT03219008 (July 17, 2017).Keywords: major depressive disorder, MDD, subtype, antidepressant, physical therapy, computerized cognitive behavioral treatment, cCBT, randomized controlled trial, RCT

Weiping Xia,1,2 Rubai Zhou,1 Guoqing Zhao,1 Fan Wang,1 Ruizhi Mao,1 Daihui Peng,1 Tao Yang,1 Zuowei Wang,1,3 Jun Chen,1 Yiru Fang1,4,5 1Division of Mood Disorders, Shanghai Mental Health Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Medical Psychology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Mood Disorder Department, Hongkou District Mental Health Center of Shanghai, Shanghai, People’s Republic of China; 4State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, CAS, Shanghai, People’s Republic of China; 5Shanghai Key Laboratory of Psychotic Disorders, Shanghai, People’s Republic of China Background: Almost half of patients with major depressive disorder (MDD) also have clinically meaningful levels of anxiety. Anxious depression is a distinct clinical subtype of MDD, which has poor response to pharmacotherapy; however, the neural mechanisms behind are largely unknown. In the present study, we explored the white matter (WM) integrity traits of anxious depression in first-episode and medication-free (medication-naïve and medication washout) Chinese young adult patients by detecting differences in diffusion tensor imaging (DTI) with the tract-based spatial statistics (TBSS) method.Subjects and methods: DTI was obtained from 39 first-episode, medication-free anxious depressive patients, 45 nonanxious depressive patients, and 50 demographically similar healthy controls. All subjects underwent clinical assessments. TBSS was carried out to investigate the difference in WM integrity among three groups within DTI parameter maps. WM integrity was measured using fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity (RD). The correlations between WM integrity and clinical features were also computed.Results: When compared with nonanxious patients, lower FA values in anxious depressive patients were found in multiple regions of the brain, mainly involving left uncinate fasciculus (UF), superior longitudinal fasciculus (SLF), and forceps major and minor. Higher RD in forceps major and minor and SLF were also detected. The decreased FA values and increased RD values correlated with both anxiety level and depression level in the pooled depressive group.Conclusion: The anxious depressive patients had more abnormalities in WM integrity at the early phase than the nonanxious group. Alternations in WM integrity in fiber pathways, including SLF, UF, and forceps major and minor, may play a critical role in the neuropathology of anxious depression and might help to identify anxious MDD from nonanxious MDD. Further study with larger sample size, larger age range, and longitudinal design is needed to confer a robust inference to better understand the dynamic neurological change and neuropathology of WM integrity in anxious MDD. Keywords: diffusion tensor imaging, anxious depression, tract-based spatial statistics, micro-structure of whiter matter

Xiaohua Liu,1,* Tianhong Zhang,1,* Shen He,1 Bo Hong,1 Daihui Peng,1 Hui Su,1 Fei Li,1 Yingying Tang,1 Zhiguang Lin,2 Yiru Fang,1 Kaida Jiang11Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 2Biochemistry laboratory, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workBackground: Nerve growth factor (NGF) has received much attention for its role in mood disorders. The primary objective of the present study was to examine serum NGF levels in Chinese inpatients with depressive or manic episodes in the acute phase and to explore the changes in NGF levels after effective clinical treatments.Methods: One hundred and seven consecutive inpatients and outpatients with mood disorders (30with unipolar depression,23with bipolar depression, and54with bipolar mania), and50healthy controls were recruited. The serum NGF levels were detected by enzyme-linked immunosorbent assay.Results: Patients with bipolar mania presented higher serum NGF levels compared to those of healthy controls. After8weeks of medical treatment, there were significant improvements in symptoms in patients, but no significant changes in NGF levels.Conclusion: The present findings may help to strengthen and expand the understanding of the role of NGF in the acute stages of mood disorders.Keywords: neurotrophins, depression, mania, bipolar disorder, acute phase, clinical sample