Dihydroartemisinin Protects Mice from CUMS-induced Depression-like Behaviors by Regulating Gut Microbes.

Depression is one of the most common forms of psychopathology, which is associated with gut microbiota dysfunction. Dihydroartemisinin (DHA) has been shown to regulate gut microbiota and ameliorate neuropathies, but whether it can be used to treat depression remains unclear. Our study found that DHA treatment raised the preference for sugar water in chronic unpredictable mild stress (CUMS)-induced mice and reduced the immobility time in open field, forced swimming and tail suspension experiments, and promoted doublecortin expression. Additionally, DHA up-regulated the diversity and richness of intestinal microbiota in depression-like mice, and restored the abnormal abundance of microbiota induced by CUMS, such as Turicibacter, Lachnospiraceae, Erysipelotrichaceae, Erysipelatoclostridium, Eubacterium, Psychrobacter, Atopostipes, Ileibacterium, Coriobacteriacea, Alistipes, Roseburia, Rikenella, Eggerthellaceae, Ruminococcus, Tyzzerella, and Clostridia. Furthermore, KEGG pathway analysis revealed that gut microbiota involved in the process of depression may be related to glucose metabolism, energy absorption and transport, and AMPK signaling pathway. These results indicated that DHA may play a protective role in CUMS-induced depression by mediating gut-microbiome.

Inhibition of ferroptosis alleviates chronic unpredictable mild stress-induced depression in mice via tsRNA-3029b.

Depression is a common mental illness. Ferroptosis is a form of cell death that may be responsible for neurological disease, but the role of ferroptosis in depression remains unclear. tRNA-derived small RNA (tsRNA) is an emerging non-coding small RNA, making it an important medium for studying neurological diseases. Chronic unpredictable mild stress (CUMS) was used to construct the depression model in mice, which was treated with ferrostatin-1 (Fer-1). Classical behavioral test, immunofluorescence and small RNA sequencing were used to detect depression-like behaviors, neuronal proliferation and the expression profile of tsRNAs in mice, respectively. The primary neuronal cell damage model was constructed by corticosterone (CORT), and the function of key tsRNA was investigated by quantitative real-time PCR, western blot and CCK-8 assays. Here, Fer-1 reduced the depression-like behavior of CUMS-induced mice and promoted neuronal growth. In addition, CUMS caused the disorder of tsRNA expression profile in hippocampal tissues of mice, and Fer-1 alleviated the abnormal tsRNA expression, among which tsRNA-3029b was an effective target. In vitro experiments manifested that ROS accumulation and decreased expression of SLC7A11 and GPX4 were found in CORT-induced depression-like cell model, suggesting that ferroptosis was involved in neuronal injury. However, inhibition of tsRNA-3029b suppressed neuronal cell ferroptosis and facilitated neuronal regeneration. In conclusion, Fer-1 showed an antidepressant effect in CUMS-induced mice and alleviated the abnormal expression profile of tsRNA. tsRNA-3029b was a key target in depression, and silencing of tsRNA-3029b reduced the occurrence of ferroptosis and protected neurons from injury, which may provide novel target for the treatment of depression.

Infralow-frequency transcranial magnetic stimulation as a therapy for generalized anxiety disorder: A randomized clinical trial.

BACKGROUND: Generalized anxiety disorder (GAD) is a common chronic mental disorder, and it also can cause depressive symptoms and cognitive impairment. The primary aim of this study was to determine whether inflow-frequency transcranial magnetic stimulation (ILF-TMS) improves anxiety symptoms in patients with GAD. METHODS: Sixty-two patients with GAD were randomly divided into 2 groups. Thirty-one patients in the active ILF-TMS group and 31 patients in the sham ILF-TMS group. All participants were assessed at baseline, week 2, week 4 and week 12. The intention-to-treat methodology was used for the analysis. RESULTS: The response rate was higher in the active group than in the sham group, with a significant difference at week 12 (response rate: 80.6% vs. 54.8%, respectively; P = 0.03). Although the remission rate was higher in the active group at week 12, there was no statistically significant difference between the groups (remission rate: 71.0% vs. 48.4%; P > 0.05). No statistically significant differences on the Hamilton Depression Rating Scale, Clinical Global Impression scale, and neurocognitive test between groups were observed (overall P > 0.05). Adverse events that occurred in the active group were similar to those in the sham group, with no significant differences (P > 0.05). CONCLUSION: The response rate was higher in the active group at the end of the trial, which indicated that ILF-TMS may be an effective and safe adjunctive tool to improve anxiety symptoms in patients with GAD.

Survey of Insomnia and Related Social Psychological Factors Among Medical Staff Involved in the 2019 Novel Coronavirus Disease Outbreak.

OBJECTIVE: The outbreak of the 2019 novel coronavirus disease (COVID-19) not only caused particularly large public health problems, but also caused great psychological distress, especially for medical staff. We aimed to investigate the prevalence rate of insomnia and to confirm the related social psychological factors among medical staff in hospitals during the COVID-19 outbreak. METHOD: Medical staff members in China were recruited, including frontline medical workers. The questionnaire, administered through the WeChat program, obtained demographic data and asked self-design questions related to the COVID-19 outbreak, insomnia/depressive/anxiety symptoms, and stress-related symptoms. We used a logistic regression analysis to examine the associations between sociodemographic factors and insomnia symptoms. RESULT: There were a total of 1,563 participants in our study. Five-hundred-and-sixty-four (36.1%) participants had insomnia symptoms according to the Insomnia Severity Index (ISI) (total score ≥ 8). A multiple binary logistic regression model revealed that insomnia symptoms were associated with an education level of high school or below (OR = 2.69, p = 0.042, 95% CI = 1.0-7.0), being a doctor (OR = 0.44, p = 0.007, 95% CI = 0.2-0.8), currently working in an isolation unit (OR = 1.71, p = 0.038, 95% CI = 1.0-2.8), is worried about being infected (OR = 2.30, p < 0.001, 95% CI = 1.6-3.4), perceived lack of helpfulness in terms of psychological support from news or social media with regard to COVID-19 (OR = 2.10, p = 0.001, 95% CI = 1.3-3.3), and having very strong uncertainty regarding effective disease control (OR = 3.30, p = 0.013, 95% CI = 1.3-8.5). CONCLUSION: Our study found that more than one-third of the medical staff suffered insomnia symptoms during the COVID-19 outbreak. The related factors included education level, an isolation environment, psychological worries about the COVID-19 outbreak, and being a doctor. Interventions for insomnia among medical staff are needed considering the various sociopsychological factors at play in this situation.

Comparison of blood lipid profile/thyroid function markers between unipolar and bipolar depressed patients and in depressed patients with anhedonia or suicidal thoughts.

BACKGROUND: This study aimed to investigate the differences in the serum levels of glucose, lipid, and thyroid function markers between unipolar and bipolar depressed patients, as well as the effect of anhedonia and suicidal thoughts on the levels of these biochemical parameters. METHODS: A total of 287 unmedicated depressed patients from January 2016 to December 2017 were included in this study, including 92 bipolar depressions and 195 unipolar depressions. Anhedonia was determined using the item 32 of Symptom Checklist (SCL-90). Suicide ideation was assessed by item 15 of SCL-90. RESULTS: The bipolar group had significantly lower lipid levels (including triglycerides, cholesterol, low-density lipoprotein cholesterol [LDL], very low-density lipoprotein cholesterol [VLDL]) and insulin resistance index but higher levels of prolactin, low triiodothyronine (T3) and free T3 (FT3) as well as higher incidence of anhedonia as compared with the unipolar group. Depressed patients with anhedonia had significantly higher LDL level than those without anhedonia. Depressed patients with suicidal thoughts had cholesterol and high-density lipoprotein cholesterol (HDL) level. The above-mentioned differences were confirmed by logistic regression analysis. Receiver operating characteristic curve (ROC) analysis showed that the area under the ROC curve (AUC) ranged from 0.546 to 0.685. CONCLUSION: Triglycerides, cholesterol, LDL, VLDL T3, FT3 levels were significantly different between unipolar and bipolar depressed patients, which might have the potential to be the markers for differential diagnosis. Patients with anhedonia had lower LDL level, while patients with suicidal thoughts had higher levels of cholesterol and HDL as compared with the corresponding control groups.

Longitudinally Measured Changes in Somnolence Severity With a Visual Analog Scale in a Randomized Lithium Versus Quetiapine-IR Study in Bipolar Disorder.

OBJECTIVE: The aim of this study was to use a visual analog scale (VAS) longitudinally measuring somnolence severity in patients with bipolar disorder. METHODS: A data set of patients with bipolar spectrum disorders who were randomized to lithium or quetiapine-IR for 16 weeks was used. The somnolence severity was measured with a VAS from 0 to 100 (VAS based), and somnolence frequency was recorded according to incident report (incidence based) at each visit. The rates of VAS-based and incidence-based somnolence and changes in somnolence severity from baseline to the end of study were compared between the lithium and quetiapine groups. Longitudinal changes in somnolence severity were analyzed with linear regression analysis. RESULTS: Of 42 patients randomized, only 3 scored 0 on the VAS at baseline. The rates of incidence-based and VAS-based somnolence were similar in the lithium and quetiapine-IR groups. The VAS change scores from baseline to each visit varied in both groups with significant decreases at weeks 6 and 12 in the quetiapine-IR group only. The decrease at week 6 in the quetiapine-IR group was significantly different from that in the lithium group. Patterns of changes in somnolence severity were inconsistent in both groups. A significant interaction between time course and the decrease in VAS scores was observed in the quetiapine-IR group, but not in the lithium group. CONCLUSIONS: Baseline somnolence was highly prevalent in patients with bipolar disorder. The change in somnolence severity was different between lithium-treated and quetiapine-treated patients. Quantifying somnolence longitudinally is important in clinical trials and practice.

Correlation between depression/anxiety symptom severity and quality of life in patients with major depressive disorder or bipolar disorder.

OBJECTIVE: To study the correlation between depression/anxiety severity and the quality of life (QOL) in patients with major depressive disorder (MDD) or bipolar disorder (BP). METHODS: Two hundred forty-three outpatients diagnosed with MDD or BP were used to study the relationship between depression/anxiety severity and QOL. Depression and anxiety symptom-severity were measured with the QIDS-16-SR (the 16 Item Quick Inventory of Depressive Symptomatology - Self Report), and Zung-SAS (Zung Self-Rating Anxiety Scale). The QOL was measured with the Q-LES-Q short-form (the Quality of Life, Enjoyment and Satisfaction Questionnaire). Correlation was assessed with regression analysis. RESULTS: The percentage of maximum possible scores (MPS) of Q-LES-Q was 72.1%, 70.5%, and 67.6% for euthymic MDD, BPI, and BPII, respectively. Increases in QIDS-16-SR total scores significantly correlated to decreases in Q-LES-Q total scores, with an R2 = 0.61, R2 = 0.52, and R2 = 0.45 for MDD, BPI, and BPII, respectively. Increases in Zung-SAS scores also significantly correlated to decreases in Q-LES-Q total scores with an R2 = 0.20, R2 = 0.21, and R2 = 0.12 for MDD, BPI, and BPII. However, after controlling for depression severity, significant differences between Q-LES-Q and Zung-SAS scores disappeared in MDD and BP. After controlling for anxiety and other clinical variables, the negative correlation between QIDS-16-SR and Q-LES-Q scores remained significant in MDD and BP. CONCLUSIONS: In this outpatient sample, the MPS of Q-LES-Q in euthymic MDD and BP patients was at the lower end of non-psychiatric or medical community norm spectrum. Depression severity was the only independent variable negatively correlated to the QOL in both disorders.

[Depression and anxiety caused by pegylated interferon treatment in patients with chronic hepatitis B and the therapeutic effects of escitalopram and alprazolam].

OBJECTIVE: To evaluate the incidence of depression and anxiety caused by pegylated interferon α (PegIFN-α) treatment for chronic hepatitis B (CHB) and assess the efficacy of intervention with escitalopram and alprazolam. METHODS: A total of 165 CHB patients receiving PegIFN-α-based treatment for 12 weeks were assessed for moderate to severe depression and anxiety using Patient Health Questionnaire (PHQ-9) and 7-item Generalized Anxiety Disorder Scale (GAD-7)]. The patients identified to have moderate to severe depression and anxiety treated with escitalopram or alprazolam and the psychological condition of the patients was assessed at the 2nd, 4th and 8th weeks of the treatments. RESULTS: In the 165 patients receiving PegIFN-α treatment, 51 patients developed moderate to severe psychiatric symptoms, incuding 37 (22.4%) with depression, 31 (18.8%) with anxiety, and 17 (10.3%) with both. The symptoms of depression and anxiety was both significantly improved by intervention with escitalopram (P=0.000); alprazolam was effective for anxiety (P=0.001) but did not produce obvious effects on depression (P=0.904). Nevertheless, alprazolam had a much better therapeutic effect than escitalopram on anxiety in these patients (t=-3.198, P=0.010). CONCLUSION: Psychological symptoms are common in CHB patients receiving PegIFN-α treatment. The symptoms of depression and anxiety can be ameliorated by intervention with escitalopram and alprazolam, respectively.

Depression severity and quality of life of qualified and unqualified patients with a mood disorder for a research study targeting anhedonia in a clinical sample.

OBJECTIVE: To investigate the depression severity and quality of life of qualified and unqualified patients with a mood disorder for a research study based on anhedonia severity. METHODS: Diagnosis of major depressive disorder (MDD) or bipolar disorder (BPD) was ascertained with the MINI International Neuropsychiatric Interview. The severity of depression was measured with the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-16-SR), and Item 5, "feeling sad (sadness)," QIDS-16-SR Item 13, "change in general interest," was used to measure the severity of anhedonia. The quality of life was measured with the Quality of Life, Enjoyment and Satisfaction Questionnaire (Q-LES-Q). RESULTS: Of 96 patients with MDD and 147 with bipolar I or II disorder, the severity rating on sadness and anhedonia was similar. The severities of anhedonia and sadness were highly correlated with R2 of ≥0.91. Without considering depressive severity, 55% of patients would be eligible for a study if≥mild anhedonia was used as a severity criterion, but only 26% of patients eligible for a study if≥moderate anhedonia was used without considering substance use and medical comorbidities. If patients with ≥ moderate overall depressive symptoms were considered, 88.1% of patients would be eligible if≥mild anhedonia was required for a study, and 45.2% of patients would be eligible for a study if≥moderate anhedonia was required. For those who were unqualified for the study based on≥moderate anhedonia, about 1/3 had≥moderate overall depressive symptoms and less than 40% of maximum possible scores of Q-LES-Q. If only patients in remission based on overall depressive symptom severity were considered for a study of anhedonia, no patient would be eligible for the study. CONCLUSION: Depressive mood and anhedonia are highly correlated. Screening patients with a mood disorder and an overall moderate depressive severity is a cost-effective approach for a study targeting anhedonia, especially for a study requiring≥moderate severity of anhedonia. However, 1/3 of the unqualified patients will have≥moderate overall depressive symptoms and poor quality of life.

MeCP2 controls hippocampal brain-derived neurotrophic factor expression via homeostatic interactions with microRNA­132 in rats with depression.

Major depressive disorder (MDD) is a considerable public health concern, which affects patients worldwide. MDD is associated with psychosocial impairment, poor quality of life, and significant disability, morbidity and mortality. Stress is a major factor in depression, which impairs the structural and functional plasticity of the hippocampus. Previous studies have demonstrated that chronic unpredictable mild stress is able to downregulate the expression of brain­derived neurotrophic factor (BDNF) and methyl­CpG­binding protein 2 (MeCP2), and alter the expression levels of certain microRNAs (miR). The aim of the present study was to investigate the regulatory association between BDNF, MeCP2 and miR-132 in an animal model of chronic stress­induced depression. ELISA, western blot and qPCR were used to detect the expression levels of BDNF, MeCP2 and miR-132 in the peripheral blood samples of patients with MDD and in the hippocampi of depressed animals. In addition, a dual luciferase reporter gene system was used to determine whether miR-132 directly targets BDNF or MeCP2. The present study demonstrated that, as compared with normal subjects, miR­132 expression was increased in the peripheral blood samples of patients with MDD, whereas the expression of MeCP2 and BDNF was decreased; thus, the expression levels of MeCP2 and BDNF were negatively correlated with those of miR­132. In addition, in an animal model of chronic stress­induced depression, increased expression levels of miR­132, and decreased levels of MeCP2 and BDNF were detected in the hippocampi. Furthermore, knockdown of MeCP2 expression in primary hippocampal neurons increased the expression of miR­132 and decreased the expression levels of BDNF. The results of the present study demonstrated that miR­132 may directly target MeCP2, but not BDNF, and control its expression at the transcriptional and translational level. miR­132 was also shown to negatively regulate BDNF expression. The reduced expression levels of BDNF, as induced by MeCP2 knockdown, were enhanced by miR­132 mimics, and were rescued by miR­132 inhibitors. These results suggested that homeostatic interactions between MeCP2 and miR­132 may regulate hippocampal BDNF levels, which may have a role in the pathogenesis of MDD.

[Escitalopram for intervention of psychiatric adverse events during peginterferon-alfa-2a and ribavirin treatment for chronic hepatitis C].

OBJECTIVE: To evaluate the risk factors of psychiatric adverse events associated with PEG interferon and ribavirin treatment for chronic hepatitis C and assess the efficacy of escitalopram intervention for these adverse effects. METHODS: Fifty-nine patients with chronic hepatitis C undergoing interferon-based treatment for 12 weeks were assessed for major depression using DSM-IV and SCL-90, and the patients identified to have major depression received escitalopram treatment for intervention. SCL-90 was used to assess the psychological condition of the patients at the forth and eighth weeks of escitalopram treatment. RESULTS: A male gender, 1b genotype, and intravenous infection are all risk factors of major depression. The morbidity rate of interferon-based depression was 32.2% with rates of hostility, anxiety, depression and sensitivity of 19.7%, 9.2%, and 5.26%, respectively. The total score of SCL-90 and scores for hostility, anxiety, depression and sensitivity all significantly declined after escitalopram treatment in the 19 patients with major depression. CONCLUSIONS: Psychological symptoms are common in HCV patients receiving interferon treatment, for whom regular psychological assessment is essential especially for those patients with drug abuse. Prompt use of escitalopram is recommended for effective control of major depression or other psychological symptoms in these patients.