Refractory suicidal command hallucinations in major depressive episode with psychotic features constitute an acute clinical emergency, often unresponsive to multiple antipsychotics and electroconvulsive therapy (ECT), leaving clinicians with limited life-saving options. Stereotactic lesioning, as a last-resort intervention, may have some utility in such case; however, its long-term efficacy and the extent to which it depends on postoperative pharmacotherapy are not yet fully understood. A 20-year-old female with major depressive episode with psychotic features experienced 10–12 daily suicidal command hallucinations (with 4 suicide attempts within 1 week), refractory to 3 antipsychotics (Aripiprazole, Olanzapine, Risperidone) and 12 sessions of ECT (Montgomery-Asberg Depression Rating Scale [MADRS]: 30, Hoffman auditory hallucination score [Hoffman]: 25). Stereotactic bilateral lesioning of the anterior limb of the internal capsule and cingulate gyrus (SALIC-CG) resulted in a marked alleviation of symptoms within 1 week (MADRS: 7, Hoffman: 0). Notably, symptoms recurred 1 month postoperatively following antipsychotic discontinuation (MADRS: 22, Hoffman: 20) but resolved rapidly upon reintroducing Risperidone, with sustained remission at 6 months (MADRS: 6, Hoffman: 0) under continuous pharmacotherapy. This case offers preliminary evidence that stereotactic lesioning may act as a key intervention for alleviating symptoms in patients with psychotic major depressive episode—specifically those with intractable suicidal command hallucinations that do not respond to all conventional treatments. Critically, it underscores that postoperative long-term antipsychotic maintenance is not merely adjunctive but essential to preserve surgical benefits, establishing a “surgery + long-term pharmacotherapy” paradigm with direct implications for managing high-risk refractory cases. It is not a clinical trial, clinical trial number: not applicable.

BACKGROUND:Anhedonia is an important aspect of adolescent-onset major depressive disorder (MDD) and is associated with increased risk of suicidal behaviors and poor treatment outcomes. However, the neural circuitry underlying this deficit has not been well defined. This study aims to identify the relationships between anhedonia and changes in static and dynamic functional connectivity (FC) in adolescent-onset MDD patients compared with healthy control subjects (HCs) and adult-onset MDD patients. METHODS:A total of 157 participants completed the Snaith-Hamilton Pleasure Scale (SHAPS) to assess hedonic capacity. Resting-state functional imaging scans were analysed using graph theoretical analysis, network-based statistics (NBS) and sliding window correlation analysis to explore the potential patterns of neural network brain disruptions in adolescent-onset MDD. Pearson correlations and support vector machines regression (SVR) were used to explore correlations and predict network measures with SHAPS scores. RESULTS:Compared with those with adult-onset MDD, adolescent-onset MDD patients showed decreased FC in 7 nodes and 6 connections, with the right angular gyrus (AG), left AG and left paracentral lobule having the largest number of connected edges (P = 0.0396, NBS-corrected). Their average FC and SHAPS scores were positively correlated (r = 0.309, P = 0.035). Regarding dynamic FC, compared with HCs, adolescent-onset MDD patients showed a tendency towards a decreased frequency in moderate-intensity brain FC states (P = 0.014), which was significantly and positively correlated with SHAPS scores (r = 0.425, P = 0.003). SVR also revealed AG-centred FC and dynamic FC could predict SHAPS scores (MSE = 27.233, P = 0.001). CONCLUSIONS:These findings provide distinct evidence on the physiological mechanisms of adolescent-onset MDD and anhedonia.

BACKGROUND:Mental health problems are becoming increasingly common among college students, including depression, anxiety and sleep disturbances, which can affect their daily life and learning and even lead to suicide. The purpose of this study was to explore the gender differences in mental health symptoms among Chinese college students.METHODS:The study population included 29,099 college students. All participants were assessed with the Patient Health Questionnaire-9 (PHQ-9), the 7-item Generalized Anxiety Disorder Scale (GAD-7), the Insomnia Severity Index (ISI), and the Suicidal Behaviors Questionnaire-Revised (SBQ-R). We assessed and compared network and centrality in females and males separately, as well as students with suicidal ideation.RESULTS:Satisfaction with current sleep pattern (I4), worry about different things (A3) and irritable (A6) appeared to be the most central symptoms in the female network. In the male network, satisfaction with current sleep pattern (I4), tired or little energy (D4) and feeling down, hopeless (D2) were the most central symptoms. In both suicidal ideation networks, the top five central symptoms included four anxiety symptoms and one sleep symptom.LIMITATIONS:This study used cross-sectional data and could not examine the dynamic relationship between symptoms.CONCLUSION:There were gender differences in college students' mental health network. In addition to poor quality sleep, the central symptoms of the female network were anxiety symptoms, while those of the male were mainly depression symptoms. There were no gender difference in the suicidal ideation network and the central symptoms were anxiety symptoms and difficulty falling asleep.

BACKGROUND:Childhood traumas are well-established risk factors for major depressive disorder (MDD). However, the relationship between childhood traumas types and MDD symptoms is unclear. The present study tested the hypothesis that childhood traumas affect specific types of anhedonia in depression and the mediating role of dysfunctional attitude.METHODS:Within this cross-sectional study, 310 young adult patients with MDD completed the PHQ-9, CTQ-SF, DAS, and SHAPS. The statistical analyses used the Mann-Whitney U test, Spearman's rank correlation, and multiple regression analysis. Mediation analyses were tested by the structural equation model (SEM).RESULTS:Spearman's rank correlation analysis showed positive correlations between the SHAPS, CTQ-SF, and DAS total score (p < 0.05). The EA, EN, PN, and SHAPS scores were positively correlated (p < 0.05). Among the four factors of anhedonia, social interaction and interest/pastimes were positively correlated with EA, EN, and PN (p < 0.05), the sensory experience was positively correlated with EN (p < 0.01), and diet did not correlate with childhood traumas. Stepwise regression analysis showed that dysfunctional attitude and emotional neglect were the main influencing factors of sensory experience (p < 0.001) and social interaction (p < 0.001). Dysfunctional attitude and physical neglect were the main factors influencing interest/pastimes (p < 0.001). SEM analysis found that dysfunctional mediated between childhood traumas and anhedonia.CONCLUSIONS:The degree of anhedonia was related to dysfunctional attitudes and childhood traumas. The childhood emotional neglect experience was the most important and was related to sensory and social anhedonia. Dysfunctional attitudes played a mediating role between childhood neglect and anhedonia. Early psychotherapy targeting young adult MDD patients with childhood emotional neglect may help decrease symptoms of anhedonia.

The study was aimed to explore the brain imaging characteristics of major depressive disorder (MDD) patients with suicide ideation (SI) through resting-state functional magnetic resonance imaging (rs-fMRI) and to investigate the potential neurobiological role in the occurrence of SI. 50 MDD patients were selected as the experimental group and 50 healthy people as the control group. The brain images of the patients were obtained by MRI. Extraction of EEG biological features was from rs-fMRI images. Since MRI images were disturbed by noise, the initial clustering center of FCM was determined by particle swarm optimization algorithm so that the noise of the collected images was cleared by adaptive median filtering. Then, the image images were processed by the optimized model. The correlation between brain mALFF and clinical characteristics was analyzed. It was found that the segmentation model based on the FCM algorithm could effectively eliminate the noise points in the image; that the zALFF values of the right superior temporal gyrus (R-STG), left middle occipital gyrus (L-MOG), and left middle temporal gyrus (L-MTG) in the observation group were significantly higher than those in the control group (P < 0.05); and that the average zALFF values of left thalamus (L-THA) and left middle frontal gyrus (L-MFG) decreased. The mean zALFF values of L-MFG and L-SFG demonstrated good identification value for SI in MDD patients. In summary, MRI images based on FCM had a good convergence rate, and electrical biological characteristics of brain regions were abnormal in MDD patients with SI, which can be applied to the diagnosis and treatment of patients with depression in clinical practice.

The outbreak of coronavirus disease 2019 (COVID-19) has been a global emergency, affecting millions of individuals both physically and psychologically. The present research investigated the associations between social media exposure and depression during the COVID-19 outbreak by examining the mediating role of psychological distress and the moderating role of emotion regulation among members of the general public in China. Participants (N = 485) completed a set of questionnaires online, including demographic information, self-rated physical health, and social media exposure to topics related to COVID-19. The Impact of Event Scale-Revised (IES-R), the Beck Depression Inventory-II (BDI-II), and the Emotion Regulation Questionnaire (ERQ) were utilized to measure psychological distress about COVID-19, depression, and emotion regulation strategies, respectively. Results found that older age and greater levels of social media exposure were associated with more psychological distress about the virus (r = 0.14, p = 0.003; r = 0.22, p < 0.001). Results of the moderated mediation model suggest that psychological distress mediated the relationship between social media exposure and depression (β = 0.10; Boot 95% CI = 0.07, 0.15). Furthermore, expressive suppression moderated the relationship between psychological distress and depression (β = 0.10, p = 0.017). The findings are discussed in terms of the need for mental health assistance for individuals at high risk of depression, including the elderly and individuals who reported greater psychological distress and those who showed preference usage of suppression, during the COVID-19 crisis.

Background The global status of the COVID-19 pandemic is not optimistic. This is a particularly vulnerable time for patients with pre-existing headache disorders. The present study aimed to investigate the impact of the COVID-19 pandemic on headache patients in China. Methods A survey was conducted through an online survey platform on June 6, 2020. Demographic characteristics, the PHQ-9, the ISI, a COVID-19 questionnaire and a headache profile survey were included in the online questionnaire. Results Eventually, a total of 15,000 participants from China completed the online questionnaire. Among them, 2806 participants had pre-existing headache disorders. Our analysis showed reductions in the duration of headaches (3.414 ± 6.859 vs 4.033 ± 7.325 h, P <0.001), number of headache days per month (1.788 ± 2.989 vs 2.092 ± 3.694, P <0.001), and headache intensity (4.110 ± 1.609 vs 4.290 ± 1.680, P <0.001) during the COVID-19 pandemic. Smoking (OR = 1.397, 95% CI 1.090 to 1.790, P = 0.008) and getting support from family members during social isolation (OR = 1.656, 95% CI 1.075 to 2.550, P = 0.022) were independent factors affecting the reduction in the duration of headaches. Education level (OR = 1.478, 95% CI 1.103 to 1.980, P = 0.009) and having a relative or acquaintance who contracted COVID-19 (OR = 0.643, 95% CI 0.458 to 0.902, P = 0.011) were the independent factors affecting the reduction in headache severity. Living in the Wuhan area, having symptoms or a diagnosis of COVID-19 and having relatives or acquaintances who had contracted COVID-19 were associated with the worsening of headaches. Conclusions Participants experienced an overall trend towards the improvement of headaches during the COVID-19 pandemic. Family support might play an important role in the improvement of headaches.

The coronavirus disease 2019 (COVID-19) pandemic has imposed both physical and psychological burdens on healthcare workers (HCWs). What is more, few studies have focused on the gender differences in mental health problems (MHPs) among HCWs during such an outbreak. Thus, the current study investigated the prevalence and gender differences of various MHPs among HCWs in China during the COVID-19 outbreak. This nationwide survey was conducted online from January 29 to February 3, 2020. General information was collected by questions about socio-demographics, work-related factors, and living situations. Depressive, anxiety, stress, and insomnia symptoms were assessed by the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, the Impact of Event Scale-Revised, and the Insomnia Severity Index, respectively. Among the 2198 contacted HCWs, 1563 (71.1%) responded with valid data, of whom 1293 (82.7%) were females. The prevalences of depressive, anxiety, stress, and insomnia symptoms in participants were 50.7%, 44.7%, 52.5%, and 36.1%, respectively. Female HCWs had significantly higher scores in all four scales (p < 0.001) and higher prevalences in all MHPs involved (range, odds ratio [OR] 1.55?1.97). After adjusting for potential confounders, female HCWs still had higher risks for all MHPs involved than males (range, adjusted OR 1.36?1.96). HCWs present high prevalences of depressive, anxiety, stress, and insomnia symptoms during the COVID-19 outbreak. Furthermore, female HCWs are more vulnerable to all MHPs involved. These findings highlight the need for timely, special care and support for HCWs during the outbreak, especially for females.

INTRODUCTION:Recent theories in cognitive psychology suggest that working memory (WM) processing involves a set of specific functions, in particular the WM functions of maintenance and interference control. Previous findings on WM impairments in patients with major depressive disorder (MDD) had been inconsistent, partly because earlier studies did not take into account these two different functions of WM.METHOD:Forty-two participants with MDD and 39 controls completed the visuospatial change detection task. We estimated the WM function of maintenance, based on performance in trials using the targets only, and the WM function of interference control, based on performance in trials with distractor rectangles.RESULTS:Our results showed that participants with MDD had poorer WM function of maintenance and interference control than controls. However, the results of filtering efficiency did not show significant group difference, thus patients with MDD showed comparable impairments in WM function of maintanance as well as in WM function of interference control.CONCLUSION:Our findings suggested that patients with MDD appear to show generalised impairments on visuospatial WM function of maintenance and interference control. Future studies should use refined paradigms to assess the different functions of WM and their distinctive contributions to symptomatology of depression.

Objectives: The coronavirus disease 2019 (COVID-19) pandemic may have an impact on the psychological distress of organ transplant recipients. We aimed to assess the status of psychological distress and its association with quality of life (QoL) in organ transplant recipients during the COVID-19 pandemic. Materials and Methods: A cross-sectional survey was carried out with 305 organ transplant recipients during March 30 and April 2, 2020, in Wuhan. Psychological distress comprised depression, anxiety, insomnia, and post-traumatic stress disorder (PTSD), which were assessed using the Patient Health Questionnaire-9, the seven-item Generalized Anxiety Disorder questionnaire, the Insomnia Severity Index, and Impact of event scale-revised. QoL was assessed using the Chinese version of the short Form 36-item health survey. Results: The prevalence of depression, anxiety, insomnia, and PTSD in organ transplant recipients was 13.4, 6.9, 11.8, and 30.5%, respectively. Organ transplant recipients with depression had significantly lower scores in all eight dimensions of QoL compared with participants without depression (all p < 0.05). Lower scores on the QoL dimensions of role physical, bodily pain, general health, vitality, role emotional, and mental health were found in organ transplant recipients with anxiety, insomnia, or PTSD compared with their counterparts without the respective disorder (all p < 0.05). Limitation: The cross-sectional study design limited us to make causal conclusion and the influence of potential confounders cannot be ruled out. Conclusions: Psychological distress was prevalent in organ transplant recipients during the COVID-19 pandemic, and those with depression, anxiety, insomnia, and PTSD had poorer QoL. Therefore, timely psychological counseling, COVID-19 related health education, and essential community medical services should be provided to organ transplant recipients to relieve their psychological distress, and to improve their QoL.

Background: Patient self-reports and clinician ratings of depression severity can differ substantially. The aim of the current study was to explore factors associated with discrepancies between depressed patients' Patient Health Questionnaire (PHQ-9) self-reports and clinicians' Hamilton Rating Scale for Depression (HAMD-17) ratings. Methods: We first computed discrepancy scores defined as the standardized weighted HAMD-17 total score minus the standardized PHQ-9 total score. To assess correlates of inconsistent scores, results of patients with similar standardized scores were removed (i.e., within 1/2 standard deviation, n = 270). Positive values indicate underreporting (HAMD-17 > PHQ-9), i.e., the underreporting group (n = 200); and negative discrepancy scores indicate overreporting (PHQ-9 > HAMD-17), i.e., the overreporting group (n = 221). We examined the relationship of demographic, dysfunctional attitudes and personality variables to the discrepancies between self and observer rated depression. Results: There were significant differences in extraversion, psychoticism, neuroticism, dysfunctional attitudes and occupation between the underreporting group and the overreporting group (all p < .05). When controlling for potential confounding variables, being a working professional and having high neuroticism and dysfunctional attitudes were significantly associated with overestimating symptoms of depression (e.g., professional: OR, 2.89; 95% CI, 1.67-5.00; p < .001; high neuroticism: OR, 7.08; 95% CI, 1.47-34.08; p < .001;dysfunctional attitudes: OR, 1.01; 95% CI, 1.00-1.02; p =.030). People with average, or high extraversion tended to underestimate scores (average extraversion: OR, 0.59; 95% CI, 0.37-0.95; high extraversion: OR, 0.48; 95% CI, 0.24-0.98). Conclusions: This study is the first to use PHQ-9 and HAMD-17 to explore the discrepancies between self and observer rated depression. Discrepancies occurred between the PHQ-9 score and HAMD-17 score, which were related to neuroticism, extraversion, dysfunctional attitudes and being a working professional. Future research should clarify the relationship between these factors and therapeutic effects of treatments, including adverse outcomes.

BACKGROUND:Nonsuicidal self-injury (NSSI) is related to childhood abuse, family relationships, interpersonal relationships, personality, but the interaction between them is still unclear, and how they interact in major depressive disorder (MDD).METHODS:Collected data from 444 undergraduate degree students with MDD participated. Used the Eysenck Personality Questionnaire, Childhood Trauma Questionnaire, Interpersonal Relationship Comprehensive Diagnostic Scale, and Family Assessment Device to assess the patients' psychosocial factors. NSSI behavior was assessed through interviews. Use the Chi-square test, Wilcoxon rank-sum test, Kruskal-Wallis H-test, Distance Correlation, Structural Equation Mode for data analysis.RESULTS:Overall, 34.2% of patients with MDD had a history of NSSI. MDD patients with a history of NSSI had significant differences in psychoticism, neuroticism, emotional abuse, physical abuse, sexual abuse, emotional neglect, troubles in conversation, ability to make friends and family roles. Among these factors, psychoticism was most related to NSSI, and child abuse, interpersonal relationships and family roles played a variety of roles in mediating the relationship with NSSI.CONCLUSIONS:Psychosocial factors affect the occurrence of NSSI through chain intermediary effects.

Introduction The ability to suppress inappropriate prepotent response and to overcome the interference of irrelevant information are two important components of inhibitory control. Little is known, however, about the relevant contributions in these two components of inhibitory control to depression. The aim of the present study was to assess the prepotent response inhibition and interference control simultaneously in a group of patients diagnosed with major depression disorder (MDD). Methods A clinical group of patients with MDD (n = 41) and a control group of healthy volunteers (n = 39) were recruited and assessed using the stop-signal task and the Flanker task respectively. Results The results showed longer stop-signal reaction time in patients with MDD in the stop-signal task. Regarding the interference control function, the analysis showed the response accuracy under the incongruent condition was significantly lower in patients with MDD than healthy individuals. Conclusions In conclusion, patients with MDD showed impairments both in prepotent response inhibition and interference control. The present findings provide a better understanding of the mechanism of depression-related deficits in inhibition and have great implications for the development of cognitive training programmes to remediate cognitive dysfunction in depression.

Importance:Health care workers exposed to coronavirus disease 2019 (COVID-19) could be psychologically stressed. Objective:To assess the magnitude of mental health outcomes and associated factors among health care workers treating patients exposed to COVID-19 in China. Design, Settings, and Participants:This cross-sectional, survey-based, region-stratified study collected demographic data and mental health measurements from 1257 health care workers in 34 hospitals from January 29, 2020, to February 3, 2020, in China. Health care workers in hospitals equipped with fever clinics or wards for patients with COVID-19 were eligible. Main Outcomes and Measures:The degree of symptoms of depression, anxiety, insomnia, and distress was assessed by the Chinese versions of the 9-item Patient Health Questionnaire, the 7-item Generalized Anxiety Disorder scale, the 7-item Insomnia Severity Index, and the 22-item Impact of Event Scale-Revised, respectively. Multivariable logistic regression analysis was performed to identify factors associated with mental health outcomes. Results:A total of 1257 of 1830 contacted individuals completed the survey, with a participation rate of 68.7%. A total of 813 (64.7%) were aged 26 to 40 years, and 964 (76.7%) were women. Of all participants, 764 (60.8%) were nurses, and 493 (39.2%) were physicians; 760 (60.5%) worked in hospitals in Wuhan, and 522 (41.5%) were frontline health care workers. A considerable proportion of participants reported symptoms of depression (634 [50.4%]), anxiety (560 [44.6%]), insomnia (427 [34.0%]), and distress (899 [71.5%]). Nurses, women, frontline health care workers, and those working in Wuhan, China, reported more severe degrees of all measurements of mental health symptoms than other health care workers (eg, median [IQR] Patient Health Questionnaire scores among physicians vs nurses: 4.0 [1.0-7.0] vs 5.0 [2.0-8.0]; P = .007; median [interquartile range {IQR}] Generalized Anxiety Disorder scale scores among men vs women: 2.0 [0-6.0] vs 4.0 [1.0-7.0]; P < .001; median [IQR] Insomnia Severity Index scores among frontline vs second-line workers: 6.0 [2.0-11.0] vs 4.0 [1.0-8.0]; P < .001; median [IQR] Impact of Event Scale-Revised scores among those in Wuhan vs those in Hubei outside Wuhan and those outside Hubei: 21.0 [8.5-34.5] vs 18.0 [6.0-28.0] in Hubei outside Wuhan and 15.0 [4.0-26.0] outside Hubei; P < .001). Multivariable logistic regression analysis showed participants from outside Hubei province were associated with lower risk of experiencing symptoms of distress compared with those in Wuhan (odds ratio [OR], 0.62; 95% CI, 0.43-0.88; P = .008). Frontline health care workers engaged in direct diagnosis, treatment, and care of patients with COVID-19 were associated with a higher risk of symptoms of depression (OR, 1.52; 95% CI, 1.11-2.09; P = .01), anxiety (OR, 1.57; 95% CI, 1.22-2.02; P < .001), insomnia (OR, 2.97; 95% CI, 1.92-4.60; P < .001), and distress (OR, 1.60; 95% CI, 1.25-2.04; P < .001). Conclusions and Relevance:In this survey of heath care workers in hospitals equipped with fever clinics or wards for patients with COVID-19 in Wuhan and other regions in China, participants reported experiencing psychological burden, especially nurses, women, those in Wuhan, and frontline health care workers directly engaged in the diagnosis, treatment, and care for patients with COVID-19.

The severe 2019 outbreak of novel coronavirus disease (COVID-19), which was first reported in Wuhan, would be expected to impact the mental health of local medical and nursing staff and thus lead them to seek help. However, those outcomes have yet to be established using epidemiological data. To explore the mental health status of medical and nursing staff and the efficacy, or lack thereof, of critically connecting psychological needs to receiving psychological care, we conducted a quantitative study. This is the first paper on the mental health of medical and nursing staff in Wuhan. Notably, among 994 medical and nursing staff working in Wuhan, 36.9% had subthreshold mental health disturbances (mean PHQ-9: 2.4), 34.4% had mild disturbances (mean PHQ-9: 5.4), 22.4% had moderate disturbances (mean PHQ-9: 9.0), and 6.2% had severe disturbance (mean PHQ-9: 15.1) in the immediate wake of the viral epidemic. The noted burden fell particularly heavily on young women. Of all participants, 36.3% had accessed psychological materials (such as books on mental health), 50.4% had accessed psychological resources available through media (such as online push messages on mental health self-help coping methods), and 17.5% had participated in counseling or psychotherapy. Trends in levels of psychological distress and factors such as exposure to infected people and psychological assistance were identified. Although staff accessed limited mental healthcare services, distressed staff nonetheless saw these services as important resources to alleviate acute mental health disturbances and improve their physical health perceptions. These findings emphasize the importance of being prepared to support frontline workers through mental health interventions at times of widespread crisis.

To study the acute psychological effects of Coronavirus Disease 2019 (COVID-19) outbreak among healthcare workers (HCWs) in China, a cross-sectional survey was conducted among HCWs during the early period of COVID-19 outbreak. The acute psychological effects including symptoms of depression, anxiety, and post-traumatic stress disorder (PTSD) were assessed using the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder (GAD-7) questionnaire, and the Impact of Event Scale-Revised (IES-R). The prevalence of depression, anxiety, and PTSD was estimated at 15.0%, 27.1%, and 9.8%, respectively. Having an intermediate technical title, working at the frontline, receiving insufficient training for protection, and lacking confidence in protection measures were significantly associated with increased risk for depression and anxiety. Being a nurse, having an intermediate technical title, working at the frontline, and lacking confidence in protection measures were risk factors for PTSD. Meanwhile, not worrying about infection was a protective factor for developing depression, anxiety, and PTSD. Psychological interventions should be implemented among HCWs during the COVID-19 outbreak to reduce acute psychological effects and prevent long-term psychological comorbidities. Meanwhile, HCWs should be well trained and well protected before their frontline exposure.

Objective Accumulating evidences indicate that gastrin-releasing peptide receptor (GRPR) may contribute to the pathophysiology of depression. However, the mechanism of the involvement of GRPR in the progression of depression remains unclear. Here, we showed the extent to which stress and antidepressant treatment impact GRPR expression, and explored the interactions between 5-HT2a receptor (5-HT2aR) and GRPR at the cellular level. Methods The rat depression models were created with chronic unpredictable mild stress (CUMS). Then, these rats were treated with fluoxetine for 4 weeks after CUMS. We measured body weight and performed behavioral tests to determine the effects of stress and fluoxetine on depressive-like behaviors. Real-time PCR and western blotting were used to measure the mRNA and protein expression levels of GRPR in the hypothalamus. Then, Flag-tagged protein (pcmv-Flag-5HT2aR) and Myc-tagged protein (pcmv-Myc-GRPR) expression vectors were constructed, identified, and transfected into human embryo kidney 293 (HEK293) cells. The interaction between 5-HT2aR and GRPR was detected by coimmunoprecipitation and double-label immunofluorescence. Results The rats subjected to 4 weeks of CUMS showed depressive-like behaviors, including decreased body weight, sucrose preference, and distance traveled, rearing frequency and velocity in the open field test and increased immobility time in the forced swimming test. Fluoxetine treatment reversed CUMS-induced depressive-like behavior. The mRNA and protein expression of GRPR in the hypothalamus was significantly increased after 4 weeks CUMS exposure, and treatment with fluoxetine reversed these changes. Coimmunoprecipitation showed that 5-HT2aR and GRPR combine with each other in vitro. Immunofluorescence revealed that the 5-HT2aR and GRPR were colocalization in both the cell membrane and cytoplasm. Conclusion Our study enhances the understanding of the involvement of GRPR in depression. This study also provides in vitro experimental evidence of the interaction between 5-HT2aR and GRPR, which may play an important role in the pathogenesis of depression.

ObjectiveThe 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.MethodMedical 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.ResultThere 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).ConclusionOur 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.

Background: Acute lung injury (ALI) is a severe outcome of sepsis. Alveolar macrophages (AMs) play key roles in defense, resolution in ALI. The polarization of AMs is dependent on micro environmental stimuli and might influence the progression of ALI. Gainesville Tokushima scientists (GTS)-21, a selective a7 nicotinic acetylcholine receptor agonist of the cholinergic anti-inflammatory pathway (CAP), has recently been established to be promising in the treatment of ALI. However, the molecular mechanism underlying the GTS-21-mediated suppression of inflammatory responses has been explored only partially. In this study, we examined the relation between GTS-21 and AM polarization in ALI. Methods: The adoptive transfer of M1 (classically activated) and M2 (alternatively activated)-polarized AMswas performed to AM-depleted ALI mice, along with the administration of GTS-21 in a murine model of lipopolysaccharide (LPS)-induced ALI and in isolated AMs that had been stimulated by LPS in vitro. Results: The adoptive transfer of M1-polarized AMs aggravated the inflammatory response in the lung in contrast to the adoptive transfer of M2-polarized AMs. GTS-21 protected the lung from the effect of LPS, preventing injury and decreasing the number of AMs, AM-related pro-inflammatory cytokine levels, high mobility group box 1 expression levels in AMs. In addition, GTS-21 significantly diminished the number of M1-polarized AM and increased the number of M2-polarized AM, by flow cytometry, RT-PCR, enzyme-linked immunosorbent assay, and the Arg1 and iNOS activity assays. Conclusion: The GTS-21 substantially ameliorates LPS-induced ALI. This protection is predominantly associated with the inhibition of pulmonary AM M1 polarization and alteration in AM function.

The Th (T helper) 2 response is characteristic of allergic asthma, and Th17 cells are involved in more severe asthma. Recent studies demonstrated that HMGB1 (High mobility group box 1 protein) regulates airway inflammation and the Th2, Th17 inflammatory response in asthma. HMGB1 can interact with Toll-like receptors (TLR) 2 and 4, and the receptor for advanced glycation end products (RAGE), activating the NF-kappa B (nuclear factor kappa B) signaling pathway and inducing the release of downstream inflammatory mediators. Both Th cells and dendritic cells express TLR2, TLR4, and RAGE receptors. Therefore, we speculate that HMGB1 could regulate the differentiation of Th2, Th17 cells in asthma through direct and indirect mechanisms. An ovalbumin (OVA)-induced mouse asthmatic model was established. Anti-HMGB1 antibody or rHMGB1 was administered to OVA-sensitized mice 30 min prior to each challenge. For in vitro studies, magnetically separated CD4(+) naive T cells were stimulated with or without rHMGB1 and/or anti-HMGB1 antibody. BMDCs (bone marrow-derived dendritic cells)-stimulated with or without rHMGB1 and/or anti-HMGB1 antibody were cocultured with CD4(+) naive T cells. Our study showed that administration of rHMGB1 aggravated airway inflammation and mucus production, and induced Th2, Th17 polarization in asthmatic mice, and that anti-HMGB1 antibody weakened characteristic features of asthma and blocked the Th2, Th17 inflammatory responses. HMGB1 could directly act on naive T cells to induce differentiation of Th2, Th17 cells in vitro through activating the TLR2, TLR4, RAGE-NF-kappa B signal pathway in CD4(+) naive T cells. HMGB1 could also indirectly promote Th2, Th17 differentiation via activating the TLR2, TLR4, RAGE-NF-kappa B signal pathway in DCs to mediate their maturation and antigen-presenting ability in vitro.