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Major depressive disorder is a burdensome condition with few treatment options, and traditional antidepressants are characterized by slow onset. Sub-anesthetic ketamine has rapid-onset effects for the treatment of major depressive disorder (MDD), the mechanisms of which remain elusive. In this study, we explored whether neuroplasticity, autophagy, and ferroptosis in the habenular nucleus are involved in the rapid antidepressant process of ketamine. The results showed that Chronic Restraint Stress (CRS) treated rats exhibited decreased neuroplasticity, inhibition of autophagy, and enhanced ferroptosis. Depression-like symptoms were significantly improved after ketamine treatment in CRS rats, with changes in physiological parameters. Ketamine-treated CRS rats showed a significant improvement in habenular nuclear neuroplasticity. Electron microscopy observed that ketamine triggered autophagy, with increased levels of autophagy-related proteins. Ferroptosis was inhibited by ketamine by electron microscopy, with increased FTH1 and GPX4 levels and decreased Tfr1 levels. In conclusion, our findings demonstrate that ketamine may exert rapid antidepressant effects by improving neuroplasticity, activating autophagy, and inhibiting ferroptosis in the nuclear complex.

Sub-anesthetic ketamine has rapid-onset effects for the treatment of major depressive disorder (MDD). However, the mechanism underlying ketamine's antidepressant properties remains unclear. Recent studies have reported an interrelationship between autophagy and the inflammasome, both of which are involved in the pathophysiology of MDD. In this study, we assess whether ketamine exerts its antidepressant effects via an association with the autophagy-NLRP3 inflammasome pathway.We established a depressive-like rat model by treating Wistar Kyoto rats with chronic restraint stress (CRS) for 28 days. Microglial cells from newborn Sprague-Dawley rats were used for in vitro experiments.We found sub-anesthetic ketamine treatment reversed depressive-like behavior in CRS rats. Ketamine triggered autophagy in the microglia of prefrontal cortex (PFC) and (hippocampus) HPC, with increased levels of LC3B, decreased levels of p62 protein, and elevated autophagosomes both in vivo and in vitro. Moreover, NLRP3 inflammasome activation was also inhibited by ketamine, with reduced expression of NLRP3-ASC-CASP1 assembly and decreased IL-1β levels in cerebrospinal fluid (CSF) as well as in the serum. Increased BDNF levels and synaptophysin levels were detected in the ketamine-treated group. The rapid anti-depressive effects, elevation of autophagy, reduction in NLRP3, and neuroplasticity-related factors induced by ketamine could be significantly blocked by the autophagy inhibitor Baf A1 (0.1 mg/kg).Our findings demonstrate that sub-anesthetic doses of ketamine exert their antidepressant-like effects by inhibiting inflammation and initiating neuroprotection via autophagy activation. These data might help expand future investigations on the antidepressant properties of ketamine.

Background: Polysomnography (PSG) is the gold standard for sleep monitoring and diagnosis, yet it is difficult to use in home environments. This study evaluated the performance of a wearable electroencephalographic(EEG) device, LANMAO Sleep Recorder in EEG recording and sleep staging algorithm by comparing with PSG. Method: Sleep of 7 Chinese adults were recorded concurrently with PSG and LANMAO devices. First, we validated the consistency of the raw signals with relative spectral power and Pearson correlation coefficient. Second, we evaluated the performance of the automated sleep staging algorithm integrated in the LANMAO device by comparing with the staging by experts. Results: The Pearson correlation coefficient between the relative spectral power of multiple frequency bands during the sleep stages ranged from 0.7613 to 0.8816, with the strongest correlation observed for delta waves (r=0.8816). The overall F1-Score of the automated sleep staging algorithm was 84.03%, with individual F1-Scores for each class as follows: Wake: 93.67%, REM: 87.23%, Light Sleep: 72.10%, and Deep Sleep: 82.82%. Conclusion: The results suggest that the EEG recorded by the LANMAO Sleep Recorder is precise and valid, and its automated sleep staging algorithm can accurately perform sleep staging with high accuracy. Therefore, in specific scenarios such as the home environment, LANMAO devices can work as a promising PSG alternative for sleep monitoring. Keywords: automatic sleep staging; PSG; forehead; EEG; wearable; machine learning

Backgroud: The problem of suicide has become increasingly common in individuals with major depressive disorder (MDD). Transcranial direct current stimulation (tDCS) is an effective treatment for MDD with2 milliamperes (mA) for at least thirty minutes per day for two weeks. This study aims to investigate the efficacy of daily duration-doubled tDCS as an adjunctive intervention for rapidly reducing suicidal ideation and improving depression in MDD patients. Methods and design: In this double-blind, randomized, sham-controlled study, 76 MDD patients with suicidal ideation are randomly assigned to either active (n=38) or sham (n=38) tDCS group. The anode and cathode are placed over the scalp areas corresponding to left and right dorsolateral prefrontal cortex (DLPFC), respectively, and each stimulation lasts for 60 minutes. The primary outcome is defined as change of Beck Scale for Suicide Ideation (BSI) after 10 sessions. The 17-item Hamilton Depression Rating Scale (HAMD-17), Wisconsin Card Sorting Test (WCST) and Stroop Color-Word Test (SCWT) are utilized to assess depressive symptoms, executive function. Blood biomarkers related to suicidal ideation are collected at baseline and after 10 sessions. Discussion: This study suggest the adjunctive duration-doubled tDCS might be a novel method to rapidly reduce suicidal ideation and improve depressive symptom. The variation of biomarkers could be potential predictive models of suicide risk. Trial registration: The trial protocol is registered with ClinicalTrials.gov under protocol registration number NCT05555927. Registered on September 25, 2022.

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. Sleep disturbances and benzodiazepine (BZD)/Z-drug use are common in patients with bipolar disorder (BD). Objective. To investigate the short- and long-term effects of BZD/Z-drug use during acute affective episode. Methods. Participants diagnosed with BD as well as sleep disturbance chose BZDs/Z-drugs or not at will. Manic and depressive symptoms were assessed by Mental Disorders Questionnaire (MDQ) and Quick Inventory of Depressive Symptoms (QIDS) as self-reporting surveys. The participants were assessed by trained evaluators at baseline and months 1, 3, 6, and 9. Results. 61 patients with BD combined sleep disturbances were studied. At baseline, patients who used BZDs/Z-drugs had more amount of mood stabilizers ( p = 0.038 ), other psychotropic medications ( p = 0.040 ), and more risk of suicide attempt ( p = 0.019 ). The BZD/Z-drug group had a significantly higher QIDS reductive ratio as compared with the no BZD/Z-drug group at month 1; no significant differences in the variability of MDQ, QIDS reductive ratio, or recurrence rate were found between these two groups at baseline, month 1, month 3, month 6, or month 9. Conclusions. During acute affective episode, patients with BD combined sleep disturbance who took BZDs/Z-drugs tended to use more amount of mood stabilizers. Polytherapy of BZDs/Z-drugs or other psychiatric drugs could increase suicide attempt during an acute affective episode. BZD/Z-drug use, however, had a significant effect on helping depressive symptoms alleviate during affective period.

Biological rhythm plays an important role in major depressive disorder (MDD). The efficacy of antidepressant in biological rhythm remains unclear. This study is designed to explore the efficiency of escitalopram and mirtazapine in improving circadian rhythm, diurnal mood variation(DMV) and daily activity in MDD patients.Four-hundred and fifty participants diagnosed with MDD were randomized to receive treatment with escitalopram (TWE), treatment with mirtazapine (TWM) or treatment as usual (TAU). Biological rhythm symptoms were assessed by relevant biological subscale in the Hamilton depression scale (HAMD) and the quick inventory of depressive symptomatology self-report (QIDS). The participants were assessed by trained evaluators at baseline and week 2, 4, 6 and 8.The differences of HAMD score among TWE(58%, 69%, 72%), TWM(56%, 64%, 76%) and TAU(49%, 57%, 68%) were significant(P0.05). But the differences were significant only in patients without DMV; (2) Sleep rhythm items (difficulty falling asleep and early-wake) were significantly improved in TWM (P0 .05) for both HAMD and QIDS. Decreased appetite and weight were significantly improved in TWM (P0 .05) for both scales. (3) For daily activity-related items, feeling slowed down and concentration were significantly improved in TWE. And the retardation was significantly improved in TWE and in TWM.Both escitalopram and mirtazapine have superior anti-depressive effect, especially for MDD patients without DMV. Escitalopram was significantly more effective in daily activity, feeling slowed down and concentration difficulty, while mirtazapine was significantly more effective in improving sleep, appetite and weight of MDD.

Background: Sleep disturbance and benzodiazepines (BZDs)/Z-drugs use are known to be common during affective episodes. Hence, we identified the probable outcomes of bipolar disorder that correlate with BZDs/Z-drugs use, aside from mood symptoms. We conducted an open-label, prospective study to describe the current use of BZDs and Z-drugs by patients with bipolar disorder during affective episodes. We evaluated the difference of characteristics between bipolar patients with sleep disturbance who chose BZDs/Z-drugs, and those who did not chose the drugs during and after affective disorder. The influences of BZDs/Z-drugs use on suicide attempt and psychotic symptoms during affective disorder were also investigated. Results: Seventy patients with current affective episodes were studied. Among them, 61 had sleep disturbances. The amount of mood stabilizers use in the BZDs/Z-drugs group was significantly greater than that in the no BZDs/Z-drugs group (p=0.038) during affective episodes. After affective episode, sleep disturbances, especially midnight wakes, became more improved in BZDs/Z-drugs group compared to the no BZDs/Z-drugs group. By contrast, attention and decisiveness became more improved in the no BZDs/Z-drugs group than in the BZDs/Z-drugs group. Furthermore, we observed that BZDs/Z-drugs had an OR of 4.338 (95% CI 1.068-17.623, p=0.040), and other psychiatric drugs had an OR of 1.835 (95% CI 1.105-3.047, p=0.019) in relation to suicide attempt. After nine months, we found that BZDs/Z-drugs use was of no significant effect to depressive or manic severity, or to recurrence rate.Conclusion: BZDs/Z-drugs use have no significant influence on variations in depressive or manic severity during the course of an affective episode. Nevertheless, BZDs/Z-drugs users took a greater amount of mood stabilizers than no BZDs/Z-drugs users. Finally, BZDs/Z-drugs or other psychiatric drugs polytherapy was regarded as a risk factor of suicide attempt during an affective episode.

Circular RNA from backspliced exons (or exonic circular RNA, circRNA) is a type of covalently closed non-colinear RNA that was recently rediscovered in eukaryotes. Although circRNAs are often expressed at low levels, emerging evidence indicates that many circRNAs are linked to physiological development and various diseases. Notably, circRNAs have been shown to serve as oncogenic stimuli or tumor suppressors in cancer. circRNAs may regulate gene expression through different mechanisms. In addition, circRNAs have been shown to be useful as biomarkers of diseases due to their stability, specific expression and relation to diseases both in cells and in extracellular fluid. This review summarizes current knowledge of human circRNAs and discusses the emerging role and clinical implication of these multifarious transcripts.

Background Measurement-based care (MBC) is a popular strategy of clinical management for patients with major depressive disorder (MDD). The consistency of self-report and clinical measurements is of importance, but whether individual symptom severity is in agreement for both self-report and clinician rating in MDD has not been comprehensively tested. This study aimed to test whether individual symptom severity of MDD was in agreement between self-report and clinician rating, and to explore factors affecting the agreement. Methods In the National Survey on Symptomatology of Depression (NSSD) of China, 3275 patients with a major depressive episode were evaluated by both self-report and a clinician-rated version of 62 questions. Results On average, 59% of all patients reached absolute agreement with their research clinicians. Among all questions, 73% returned with moderate positive strength of correlation, followed by 27% with low positive correlation. In 77% of the total questions, there was a tendency to rate higher in the self-report version compared with the clinician-rated version. After classifying the symptoms by six major domains, it was found that patients and clinicians showed more consistent answers in history and somatic questions (81% and 65% reached agreement), and that there were more differences in mood, energy, and anxiety questions (up to 56% in full agreement). “Outpatient”, “high financial status”, “poor working condition”, and “high education level” were found to be significant positive predictors for patients rating higher than clinicians or patients and clinicians reaching agreement as opposed to clinicians rating higher than patients. Limitations The cross-sectional nature of our study undermines the interpretation of the results across the MDD treatment course. Conclusions It is sufficient to use the self-report version of a questionnaire to screen, monitor, and detect remission for MDD symptoms. Complete assessment of depression severity should take both clinician-rated scales and self-reported measures into consideration. Factors other than source of admission, financial status, working condition, and education level should be further investigated for the discrepancy between self-report and clinician rating.

Circular RNAs (circRNAs) comprise a novel class of widespread non-coding RNAs that may regulate gene expression in eukaryotes. However, the characterization and function of circRNAs in human cancer remain elusive. Here we identified at least 5500 distinct circRNA candidates and a series of circRNAs that are differentially expressed in gastric cancer (GC) tissues compared with matched normal tissues. We further characterized one circRNA derived from the PVT1 gene and termed it as circPVT1. The expression of circPVT1 is often upregulated in GC tissues due to the amplification of its genomic locus. circPVT1 may promote cell proliferation by acting as a sponge for members of the miR-125 family. The level of circPVT1 was observed as an independent prognostic marker for overall survival and disease-free survival of patients with GC. Our findings suggest that circPVT1 is a novel proliferative factor and prognostic marker in GC.

Circular RNAs (circRNAs) represent a novel class of widespread non-coding RNAs in eukaryotes. They are unusually stable RNA molecules with cell type-specific expression patterns, and are predominantly present in the cytoplasm. We recently demonstrated the existence of abundant circRNAs in exosomes and suggest a potential application of exosomal circRNAs for cancer detection.