Depressive State Research Articles

Seasonality in mood disorders: Probing association of accelerometer-derived physical activity with daylength and solar insolation

Mood disorders are the leading cause of disability worldwide. Up to 30 percent of individuals with major depressive disorder (MDD) and bipolar disorder (BD) display a seasonal pattern of onset, a phenomenon now recognized in the official diagnostic manuals (DSM-5 and ICD-11). Very little is known about the influence of day length (photoperiod) and sunlight intensity (solar insolation) on seasonal patterns in MDD and BD. Here we report a quantitative approach to examine the relationship between sunlight measures and objectively measured motor activity patterns to understand environmental factors driving seasonality in MDD and BD. Our generalized linear model (GLM) assessment of the Depresjon dataset, which includes short-term (up to two weeks) motor activity recordings of 23 unipolar and bipolar depressed patients and 32 healthy controls recruited to the study at the University of Bergen Norway (60.4° N latitude, 5.3° E longitude), revealed significant association of accelerometer-derived daytime physical activity with participant’s depressed state (p<0.001), photoperiod (p<0.001), and solar insolation (p<0.001). Our study presents a generalizable strategy to decipher the complex interplay between sunlight, physical activity, and depressed state using open-source digital tools. The ability to identify mood disturbances, particularly in seasonally susceptible individuals, using passive digital biomarker data offers great promise in informing next-generation predictive, personalized diagnostics in mental health.

Exploring the characteristics changes of cardiopulmonary exercise testing in patients with acute coronary syndrome after PCI before and during the COVID-19 pandemic

Objective: To investigate the changes in cardiopulmonary exercise testing (CPET) characteristics before and after the outbreak of COVID-19 in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI). Methods: This is a cross-sectional study that included ACS patients who underwent PCI at the General Hospital of the Northern Theater Command from July 2018 to February 2023. Based on the timeline of the COVID-19 pandemic, patients were divided into two groups: the pre-pandemic group and the during-pandemic group, with January 2020 as the dividing line. Clinical data were collected from both groups, and a comparative analysis was performed on their postoperative CPET outcomes, including peak oxygen uptake (peak VO2), peak metabolic equivalents (peak MET), and other indicators. Weber's classification was used to assess cardiac function. In addition, the 7-tiem generalized anxiety disorder scale (GAD-7) and the patient health questionnaire-9 (PHQ-9) were used to assess the patients' psychological anxiety and depression states, respectively. Multivariate logistic regression was used to analyze the influencing factors of CPET after PCI. Results: A total of 4 310 post-PCI ACS patients were included, with an average age of (58.7±9.1) years, and 3 464 (80.37%) were male. There were 1 698 patients in the pre-pandemic group and 2 612 patients in the during-pandemic group. The main indicator of the CPET, peak VO2 (15.04±3.93) ml·min-1·kg-1 in the during-pandemic group, was lower than that in the pre-pandemic group (15.52±3.68) ml·min-1·kg-1, and the difference was statistically significant (P<0.001). Multivariate logistic regression analysis showed that advanced age, female gender, high body mass index, elevated high-sensitivity C-reactive protein, reduced high-density lipoprotein cholesterol, smoking history, history of myocardial infarction, more severe ACS classification, and mild to moderate degree of depression were related to poor cardiopulmonary outcomes (P<0.05). Conclusion: The COVID-19 pandemic had a negative impact on the cardiopulmonary outcomes of ACS patients after PCI. Reduced physical activity, and increased psychological stress should be given consideration and attention regarding their impact on patients' cardiopulmonary function.

Characterizing the dynamics, reactivity and controllability of moods in depression with a Kalman filter.

Mood disorders involve a complex interplay between multifaceted internal emotional states, and complex external inputs. Dynamical systems theory suggests that this interplay between aspects of moods and environmental stimuli may hence determine key psychopathological features of mood disorders, including the stability of mood states, the response to external inputs, how controllable mood states are, and what interventions are most likely to be effective. However, a comprehensive computational approach to all these aspects has not yet been undertaken. Here, we argue that the combination of ecological momentary assessments (EMA) with a well-established dynamical systems framework-the humble Kalman filter-enables a comprehensive account of all these aspects. We first introduce the key features of the Kalman filter and optimal control theory and their relationship to aspects of psychopathology. We then examine the psychometric and inferential properties of combining EMA data with Kalman filtering across realistic scenarios. Finally, we apply the Kalman filter to a series of EMA datasets comprising over 700 participants with and without symptoms of depression. The results show a naive Kalman filter approach performs favourably compared to the standard vector autoregressive approach frequently employed, capturing key aspects of the data better. Furthermore, it suggests that the depressed state involves alterations to interactions between moods; alterations to how moods responds to external inputs; and as a result an alteration in how controllable mood states are. We replicate these findings qualitatively across datasets and explore an extension to optimal control theory to guide therapeutic interventions. Mood dynamics are richly and profoundly altered in depressed states. The humble Kalman filter is a well-established, rich framework to characterise mood dynamics. Its application to EMA data is valid; straightforward; and likely to result in substantial novel insights both into mechanisms and treatments.

Disrupted basolateral amygdala circuits supports negative valence bias in depressive states

Negative bias is an essential characteristic of depressive episodes leading patients to attribute more negative valence to environmental cues. This negative bias affects all levels of information processing including emotional response, attention and memory, leading to the development and maintenance of depressive symptoms. In this context, pleasant stimuli become less attractive and unpleasant ones more aversive, yet the related neural circuits underlying this bias remain largely unknown. By studying a mice model for depression chronically receiving corticosterone (CORT), we showed a negative bias in valence attribution to olfactory stimuli that responds to antidepressant drug. This result paralleled the alterations in odor value assignment we observed in bipolar depressed patients. Given the crucial role of amygdala in valence coding and its strong link with depression, we hypothesized that basolateral amygdala (BLA) circuits alterations might support negative shift associated with depressive states. Contrary to humans, where limits in spatial resolution of imaging tools impair easy amygdala segmentation, recently unravelled specific BLA circuits implicated in negative and positive valence attribution could be studied in mice. Combining CTB and rabies-based tracing with ex vivo measurements of neuronal activity, we demonstrated that negative valence bias is supported by disrupted activity of specific BLA circuits during depressive states. Chronic CORT administration induced decreased recruitment of BLA-to-NAc neurons preferentially involved in positive valence encoding, while increasing recruitment of BLA-to-CeA neurons preferentially involved in negative valence encoding. Importantly, this dysfunction was dampened by chemogenetic hyperactivation of BLA-to-NAc neurons. Moreover, altered BLA activity correlated with durable presynaptic connectivity changes coming from the paraventricular nucleus of the thalamus, recently demonstrated as orchestrating valence assignment in the amygdala. Together, our findings suggest that specific BLA circuits alterations might support negative bias in depressive states and provide new avenues for translational research to understand the mechanisms underlying depression and treatment efficacy.

Vinegar-processed Schisandra Chinensis enhanced therapeutic effects on colitis-induced depression through tryptophan metabolism

BackgroundUlcerative colitis (UC) is an inflammatory bowel disease characterized by its incurable nature and undefined etiology, which is often accompanied by a high prevalence of comorbid depression. The gut-brain axis has emerged as a promising treatment target in recent years. Purpose: This study aimed to investigate how vinegar-processed Schisandra Chinensis (VSC) enhances therapeutic effects on depressive behavior in chronic UC mice. Methods: A chronic UC model was induced in mice using dextran sulfate sodium. The therapeutic effects of both raw and vinegar-processed Schisandra Chinensis on UC and associated depressive symptoms were assessed. Colonic mucosal damage was evaluated using hematoxylin and eosin (H&E) and Alcian blue staining. The integrity of the blood-brain barrier (BBB) and synaptic structures was visualized via transmission electron microscopy (TEM). Enzyme-linked immunosorbent assay (ELISA) was employed to quantify inflammatory cytokine levels in the colon, serum, and brain, while western blotting was performed for protein expression analysis. Additionally, metagenomic analysis was conducted to investigate gut microbiota composition. Nissl staining and immunofluorescence were used to assess hippocampal neuronal damage, and behavioral assessments including the morris water maze, open field test, forced swimming test and tail suspension test, were implemented to evaluate depressive states. Serum metabolites were analyzed using UPLC-MS/MS. Results: Both raw and vinegar-processed Schisandra Chinensis significantly upregulated aryl hydrocarbon receptor (AhR), inhibited NF-κB p-p65 activation, and reduced levels of pro-inflammatory cytokine. These treatments also enhanced the expression of tight junction proteins, restored colonic mucosal and BBB integrity, alleviated damage to hippocampal neurons, and improved synaptic structure. Behavioral assessments indicated that VSC was particularly effective in ameliorating depressive-like behaviors in chronic UC mice. In the gut, both treatments reshaped the gut microbial composition, restoring the relative abundance of Duncaniella, Candidatus_Amulumruptor, Alistipes, Parabacteroides, Lachnospiraceae_bacterium, uncultured_Bacteroides_sp., Candidatus_Amulumruptor_caecigallinarius, with VSC showing more pronounced effects. Serum metabolomics revealed an increase in tryptophan levels and a decrease in kynurenine and xanthurenic acid levels with VSC, indicating that tryptophan metabolism shifted from the kynurenine pathway to the 5-HT or indole pathway. However, this phenomenon did not occur with Schisandra Chinensis (SC). Conclusion: This study demonstrated that the disruption of tryptophan metabolic balance served as a biological mechanism underlying the occurrence of depressive behaviors induced by UC. The application of SC following vinegar processing enhanced its regulatory effects on gut microbiota and tryptophan metabolism. This findings provided a new insight for the clinical management of gut-brain comorbidities.

Terbinafine Resistance in Trichophyton Strains Isolated from Humans and Animals: A Retrospective Cohort Study in Italy, 2016 to May 2024.

Background: In recent decades, globalization and international migration have increased the spread of infectious agents, including dermatophytes. Although considered minor infections, dermatophytoses are highly contagious, and they significantly reduce the quality of life, inducing itching, burning, sleep disturbances, and even depressive states. Moreover, the increasing resistance to antifungals threats the public health and burdens the costs for the healthcare system. Methods: DermaGenius® Resistance Multiplex real-time PCR assay allowed to analyze the terbinafine susceptibility/resistance of 172 Trichophyton strains, which were isolated from human and animal samples collected from 2016 to May 2024 and previously identified by Sanger sequencing. Results: All the 11 animal strains belonged to the T. interdigitale/T. mentagrophytes complex and tested terbinafine sensitive. Out of 161 human strains, 9 (5.6%) showed terbinafine resistance and 7 (4.3%) were identified as T. indotineae. Conclusions: This study provides preliminary data about behavior toward antifungals in animals and finalizes the scientific information currently available about human strains, highlighting the importance of the One Health concept. Moreover, it supports the relevant role of T. indotineae as an emerging dermatophyte with high proportion of terbinafine resistance.

Fibromyalgia in patients with non-psychotic mental disorders: Prevalence, associated factors and validation of a brief screening instrument.

Fibromyalgia (FM) is a chronic pain syndrome associated with significant distress and numerous unpleasant consequences. Mental health problems in people with FM have been reported in many studies. People with mental disorders are thought to be at higher risk of FM than the general population, but the prevalence has not been established. We aimed to investigate the prevalence of FM in a representative sample of inpatients with non-psychotic mental disorders. Additionally, we aimed to assess the psychometric properties of the Fibromyalgia Rapid Screening Tool (FiRST) in the Russian-speaking population of people with mental disorders. Consecutive inpatients admitted to the Moscow Research and Clinical Center for Neuropsychiatry for treatment of non-psychotic mental disorders were evaluated for FM by a neurologist and completed the FiRST, Beck Depression Inventory (BDI), and State and Trait Anxiety Inventory (STAI). Of the 1168 patients evaluated 9.0% met the diagnostic criteria for FM. FM was associated with being female, having a diagnosis of unipolar depression, and having higher total scores on the BDI and STAI. The psychometric properties of the FiRST were good (McDonald's omega 0.79, corrected item-total correlation greater than 0.45). An optimal cut-off point with the highest Yuden's index (J = 0.75) was >3 (AUC of 0.89). FM is a common comorbidity in people with non-psychotic mental disorders, associated with being female, having a diagnosis of unipolar depression, and having more severe anxiety and depression. The FiRST can be used for the FM screening with its cut-off >3 in people with non-psychotic mental disorders. It is the first study to determine the prevalence of FM in people with non-psychotic spectrum mental disorders. The study design included a consecutive sample in a real-life setting to avoid bias. In addition, we evaluated the psychometric properties of the FM screening instrument in a population of people with mental disorders and established the cut-off. The specificity of this subpopulation is explained by both the high prevalence of pain symptoms and the overlap of some psychiatric and FM symptoms.

Machine Learning Framework for Classifying and Predicting Depressive Behavior Based on PPG and ECG Feature Extraction

Depression is a significant risk factor for other serious health conditions, such as heart failure, dementia, and diabetes. In this study, a quantitative method was developed to detect depressive states in individuals using electrocardiogram (ECG) and photoplethysmogram (PPG) signals. Data were obtained from 59 people affiliated with the high-specialized medical center of Bajio T1, which consists of medical professionals, administrative personnel, and service workers. Data were analyzed using the Beck Depression Inventory (BDI-II) to discern potential false positives. The statistical analyses performed elucidated distinctive features with variable behavior in response to diverse physical stimuli, which were adeptly processed through a machine learning classification framework. The method achieved an accuracy rate of up to 92% in the identification of depressive states, substantiating the potential of biophysical data in increasing the diagnostic process of depression. The results suggest that this method is innovative and has significant potential. With additional refinements, this approach could be utilized as a screening tool in psychiatry, incorporated into everyday devices for preventive diagnostics, and potentially lead to alarm systems for individuals with suicidal thoughts.

The possibilities of improving the effectiveness of acne therapy

Acne is one of the most urgent problems of dermatology, since this dermatosis is widespread, often occurs during puberty, is accompanied by cosmetic defects, causes increased anxiety, dysmorphic phobia and depressive states. As a result, the quality of life and the possibility of social adaptation decrease in patients. Therefore, it is necessary to optimize the treatment of this disease with the inclusion of modern highly effective drugs. When prescribing treatment, it is necessary to take into account all links in the pathogenesis of acne, and also remember that inflammation plays an important role in the development of dermatosis (especially severe course). With mild acne, it is recommended to prescribe only external therapy, with medium – external therapy and, if necessary, systemic, with severe systemic therapy is used as the main one. The appointment of antibiotics for this dermatosis is dictated by the presence of bacterial flora. Clindamycin is one of the antibiotics that effectively reduce colonization of C. аcnes. To ensure the high efficiency and safety of topical therapy, as well as the prevention of the development of resistance of microorganisms, there is a need to use a combination of at least two drugs. Thus, the combination of clindamycin with benzoyl peroxide makes it possible to increase the effectiveness of therapy due to bactericidal, bacteriostatic, anti-inflammatory and keratolytic actions. The convenient mode of use and the rapid therapeutic effect make it possible to include this combination in the group of priority drugs for the treatment of acne. Comedonolytic, anti-inflammatory and bactericidal effects are also observed in azelaic acid, and therefore drugs containing this component show a high pathogenetic effect in acne.

Effects of positive psychology intervention based on the PERMA model on psychological status and quality of life in patients with Parkinson's disease

ObjectiveTo explore the effect of a positive psychology intervention based on the PERMA model on depressive mood and the quality of life of patients with Parkinson's disease (PD). MethodsA total of 60 patients with PD with depression hospitalised between February 2022 and February 2023 were selected using a convenience sampling method. They were divided into a study group (30 cases) and control group (30 cases) using the random number table method. The control group was given routine nursing, whereas the observation group was treated using the PERMA model of positive psychological intervention. The Unified Parkinson's Disease Rating Scale (UPDRS), Parkinson's Disease Quality-of-Life Questionnaire (PDQ-39), Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), Positive and Negative Affect Schedule (PANAS), and Connor–Davidson Resilience Scale (CD-RISC) scores were collected and compared before and after the intervention, and patient care satisfaction after the intervention was also recorded and compared. ResultsStatistically significant differences were identified in the UPDRS (t = 4.221, p < 0.001), PDQ-39 (t = 5.331, p < 0.001), HAMD (t = 4.298, p < 0.001), HAMA (t = 3.412, p < 0.001), CD-RISC (t = 3.426, p < 0.001), and PANAS (t = 3.432, t = 4.523, p < 0.001) scores. The UPDRS, PDQ-39, HAMD, HAMA, and negative emotion scores in the study group were lower than those in the control group, whereas the CD-RISC and positive emotion scores in the study group were higher than those in the control group. A significant difference in nursing satisfaction was also determined between the two groups (Z = −2.700, p = 0.012), and this result was higher in the study group (93.33 %) than in the control group (73.33 %). ConclusionA positive psychology intervention using the PERMA model can effectively counter the negative psychological states of depression, anxiety, and negative emotion in patients with PD, thereby significantly improving their quality of life, psychological resilience levels, and patient satisfaction.

The importance of monitoring neurological manifestations in rehabilitation after radical hysterectomy

Background. Hysterectomy is currently one of the most frequently performed surgical operations in obstetrics and gynecology, second only to cesarean section. However, such intervention is often associated with the risk of complications, including neurological ones. Neurological consequences, due to their characteristics, go beyond physical manifestations and exert psycho-emotional pressure on patients.Objective: to determine the need for monitoring neurological manifestations in women undergoing rehabilitation after hysterectomy.Material and methods. The search and selection of studies in Russian and English languages were conducted according to PRISMA recommendations in scientific databases and electronic libraries: PubMed/MEDLINE, ScienceDirect, Google Scholar, Microsoft Academic, DOAJ, eLibrary, CiberLeninka. In total, 2569 publications were revealed; after subsequent screening 57 articles were selected, which were devoted to the study of neurological adverse effects of hysterectomy and met all the screening criteria.Results. Among all the neurological complications mentioned, the most common is chronic postoperative pain. It is detected in 30% of cases. At the same time, in the vast majority of cases, such pains are rare and are tolerated as mild discomfort. However, there is no unambiguous understanding of the nature of this complication. There is a theory about the essential role of estrogen production and substance P ratio in pain manifestations. Thus, a decrease in estrogen production with unchanged synthesis of substance P significantly reduces the pain threshold in patients, which is the cause of the observed chronic pain. A certain contribution to the formation of this neurological complication is made by residual ovarian syndrome, which is associated with incomplete removal of the ovaries during ovariectomy, traumatic neuroma and mononervopathy. Damage to the nerves or their plexuses in the pelvic area can cause intestinal and urinary disorders, leading to a decrease in the quality of life of patients. Excessive anxiety and depression are additional risk factors for the development of chronic pain after hysterectomy, and the accompanying postoperative changes often have a physical manifestation, for example, in the form of insomnia, restless legs syndrome and sexual dysfunction.Conclusion. Hysterectomy is certainly an effective way to treat a number of gynecological diseases, but it often causes complications that require correction of the rehabilitation program. Neurological negative manifestations need special monitoring, since the depressive state of patients may lead to chronicity of pathological processes.

Neuromolecular and behavioral effects of cannabidiol on depressive-associated behaviors and neuropathic pain conditions in mice

Background and aimsNeuropathic pain (NP) has a high incidence in the general population, is closely related to anxiety disorders, and has a negative impact on the quality of life. Cannabidiol (CBD), as a natural product, has been extensively studied for its potential therapeutic effects on symptoms such as pain and depression (DP). However, the mechanism of CBD in improving NP with depression is not fully understood. MethodsFirst, we used bioinformatics tools to deeply mine the intersection genes associated with NP, DP, and CBD. Secondly, the core targets were screened by Protein-protein interaction network, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, molecular docking and molecular dynamics simulation. Next, the effects of CBD intervention on pain and depressive behaviors in the spinal nerve ligation (SNL) mouse model were evaluated using behavioral tests, and dose-response curves were plotted. After the optimal intervention dose was determined, the core targets were verified by Western blot (WB) and Quantitative Polymerase Chain Reaction (qPCR). Finally, we investigated the potential mechanism of CBD by Nissl staining, Immunofluorescence (IF) and Transmission Electron Microscopy (TEM). ResultsA total of five core genes of CBD most associated with NP and DP were screened by bioinformatics analysis, including PTGS2, GPR55, SOD1, CYP1A2 and NQO1. Behavioral test results showed that CBD by intraperitoneal administration 5 mg/kg can significantly improve the pain behavior and depressive state of SNL mice. WB, qPCR, IF, and TEM experiments further confirmed the regulatory effects of CBD on key molecules. ConclusionIn this study, we found five targets of CBD in the treatment of NP with DP. These findings provide further theoretical and experimental basis for CBD as a potential therapeutic agent.

Symptoms of depression, anxiety and stress in women with chronic pelvic pain attended at a private hospital in São Luís, Maranhão: a cross-sectional study

ABSTRACT The study aimed to evaluate the relation between depression, anxiety stress symptoms, duration and pain intensity in women with chronic pelvic pain (CPP). This study consisted of a sample of women diagnosed with CPP from April 2021 to August 2023, including women aged 18 years or older who agreed in writing to participate in the study with the Free Informed Consent Form, who could understand the study’s objectives and participate. Women between 31 and 37 years old, married or in a stable relationship, with a higher education degree predominated. Were observed outside the normal range scale 58.8 percent of depression, 66.7 percent of anxiety and 59.8 percent of stress. The level of alteration most often observed in patients was extremely severe in 24 percent of with depression and 33.3 percent of anxiety, and the level was mild in 19.6 percent of stress symptoms. No statistical association was found between duration of pain and emotional states of anxiety, depression or stress. Regarding pain intensity levels, there was no significant association with the presence or absence of symptoms of depression outside the normal range or its levels. It’s was significantly associated with the presence or absence of anxiety symptoms outside the normal range (p = .003) and with their levels (p = .005). Also significantly associated with the presence or absence of stress symptoms outside the normal range (p = .007), as was its levels (p = .023). The symptoms of depression, anxiety and stress occur frequently in women with CPP and that the intensity of pain experienced is significantly associated with the presence of stress and anxiety but not with depression.

Integration of basic and clinical researches to develop the biomarker of ‍depression

Because of absence of the objective biomarker for major depressive disorder (MDD) or depressive state, psychiatrists depend on subjective examinations in order to properly diagnose their patients. We recently identified the candidates of the objective biomarker of depressive state of late-onset MDD by profiling gene expressions in white blood cells of patients and model mice. We also investigated whether gene expression profiling of white blood cells was useful to elucidate the biological alterations in the brain. Furthermore, we newly developed transgenic mice which will be useful for elucidating the neurological mechanisms of emotional abnormalities in psychiatric disorder. In this review, I introduce our recent research to help for understanding of translational approaches to develop the biomarker of depression.

Depression Takes a Toll on Academic Performance: Evidence from Rural Students in China.

Depression is a growing public health concern around the world. For adolescents, depression not only impedes healthy development, but is negatively associated with academic performance. The purpose of this paper is to examine the prevalence of adolescent depressive symptoms in a sample of rural primary and junior high school students. Additionally, we examine various factors to identify subgroups within the sample that may be more vulnerable to depression. Finally, we explore the extent to which depression correlates with academic performance and conduct a series of heterogeneity analyses. We utilize cross-sectional data derived from 30 schools in underdeveloped regions of rural China encompassing primary and junior high school students (n = 1,609). We find a high prevalence of depression, with 23% and 9% of students experiencing general depression (depression score ≥ 14) and severe depression (depression score ≥ 21), respectively. Female gender, elevated stress and anxiety levels, boarding at school, exposure to bullying, and having depressed caregiver(s) are positively correlated with depressive symptoms, while high social support exhibits a negative association. Importantly, our analyses consistently show a significantly negative link between depression and academic performance, which is measured using standardized math tests. For instance, transitioning from a non-depressed state to a state of general depression (depression score ≥ 14) is linked to a decline of 0.348-0.406 standard deviations in math scores (p < 0.01). Heterogeneity analyses reveal that this adverse relationship is more pronounced for male students, boarding students, those with lower social support, individuals with more educated mothers, and those with lower family assets. Our findings underscore the high prevalence of depression in rural schools and the detrimental impact on academic performance. We advocate for the implementation of policies aimed at reducing student depression, particularly within vulnerable populations and subgroups.

Depression exacerbates myocardial ischemia-reperfusion injury in mice via CNR2 gene and MIF-AMPK signaling pathway

BackgroundMyocardial ischemia-reperfusion(I/R)injury constitute the fundamental pathophysiology of acute myocardial infarction (AMI). Ischemic heart releases macrophage migration inhibitory factor (MIF), which activates MIF- AMPK signaling pathway. Depression is a significant risk factor for AMI. In a state of depression, peripheral expression of cannabinoid receptor 2 (CNR2) genes was downregulated. AimsWe investigated the mechanism by which depression exacerbates myocardial I/R injury through the CNR2 and MIF-AMPK signaling pathways. MethodsWe established mouse models of depression and myocardial I/R. Left ventricular function was assessed using cardiac ultrasound and TTC staining. The protein levels of myocardial CNR2, MIF, AMPK, and ACC were determined by Western blot, while the expression level of CNR2 was measured using RT-qPCR. Additionally, MIF content in peripheral blood was quantified using ELISA. ResultsAfter I/R, the expression level of CNR2 was found to be lower in the depression group, leading to a deterioration in left heart function. Depressed mice exhibited lower secretion of MIF, accompanied by a decrease in the activation of the MIF-AMPK signaling pathway. However, injection of CNR2 agonist JWH133 prior to ischemia increased the activation of the MIF-AMPK signaling pathway, while CNR2 inhibitor AM630 decreased the activation. LimitationsFurther research is needed to investigate the specific neuroendocrine mechanism affecting myocardial CNR2 expression in depression. And these experimental conclusions require further verification at the cellular level. ConclusionsThe activation of CNR2 in myocardium following I/R is impeded by depression, thereby exacerbating myocardial I/R injury through attenuation of the MIF-AMPK signaling pathway activation.

What is this thing called misfit? A systematic review into how employee misfit has been defined and researched

AbstractSince 2015, there was a significant surge of interest in employee misfit. These studies demonstrate that although misfit is generally associated with negative outcomes such as organizational exit, social isolation, and depressive states, it can also be viewed more positively as an opportunity for job crafting, growth, and development. In these studies, misfit has been conceptualized, defined, and measured in a myriad of different ways making the interpretation of results problematic. This systematic review investigates how scholars have approached misfit with the goals of documenting and organizing the various ways it has been conceptualized and measured to highlight the main themes and forms of empirical misfit research. The systematic review surfaced 107 studies in 91 papers investigating workplace misfit within the domain of person-environment fit. Close analysis of the design and construction of these studies reveals that misfit has largely been conceptualized atomistically or as value incongruence and there is considerable variation in the way that researchers have defined the concept. It has mainly been measured using atomistic and molar measures rather than molecular ones, which are more suited to misfit investigation. The paper ends with a discussion of the elusiveness of misfit with an argument that it is an umbrella concept beyond definition. Instead, researchers take perspectives on the topic and six different perspectives of employee misfit are identified and defined. Avenues for future research are outlined for each perspective. There is also a discussion of the methodological challenges currently limiting misfit research.

LT-102, an AMPA receptor potentiator, alleviates depression-like behavior and synaptic plasticity impairments in prefrontal cortex induced by sleep deprivation

BackgroundSleep loss is closely related to the onset and development of depression, and the mechanisms involved may include impaired synaptic plasticity. Considering the important role of glutamate α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPARs) in synaptic plasticity as well as depression, we introduce LT-102, a novel AMPARs potentiator, to evaluate the potential of LT-102 in treating sleep deprivation-induced depression-like behaviors. MethodsWe conducted a comprehensive behavioral assessment to evaluate the effects of LT-102 on depression-like symptoms in male C57BL/6J mice. This assessment included the open field test to measure general locomotor activity and anxiety-like behavior, the forced swimming test and tail suspension test to assess despair behaviors indicative of depressive states, and the sucrose preference test to quantify anhedonia, a core symptom of depression. Furthermore, to explore the impact of LT-102 on synaptic plasticity, we utilized a combination of Western blot analysis to detect protein expression levels, Golgi-Cox staining to visualize neuronal morphology, and immunofluorescence to examine the localization of synaptic proteins. Additionally, we utilized primary cortical neurons to delineate the signaling pathway modulated by LT-102. ResultsTreatment with LT-102 significantly reduced depression-like behaviors associated with sleep deprivation. Quantitative Western blot (WB) analysis revealed a significant increase in GluA1 phosphorylation in the prefrontal cortex (PFC), triggering the Ca2+/calmodulin-dependent protein kinase II/cAMP response element-binding protein/brain-derived neurotrophic factor (CaMKII/CREB/BDNF) and forkhead box protein P2/postsynaptic density protein 95 (FoxP2/PSD95) signaling pathways. Immunofluorescence imaging confirmed that LT-102 treatment increased spine density and co-labeling of PSD95 and vesicular glutamate transporter 1 (VGLUT1) in the PFC, reversing the reductions typically observed following sleep deprivation. Golgi staining further validated these results, showing a substantial increase in neuronal dendritic spine density in sleep-deprived mice treated with LT-102. Mechanistically, application of LT-102 to primary cortical neurons, resulted in elevated levels of phosphorylated AKT (p-AKT) and phosphorylated glycogen synthase kinase-3 beta (p-GSK3β), key downstream molecules in the BDNF signaling pathway, which in turn upregulated FoxP2 and PSD95 expression. LimitationsIn our study, we chose to exclusively use male mice to eliminate potential influences of the estrous cycle on behavior and physiology. As there is no widely accepted positive drug control for sleep deprivation studies, we did not include one in our research. ConclusionOur results suggest that LT-102 is a promising therapeutic agent for counteracting depression-like behaviors and synaptic plasticity deficits induced by sleep deprivation, primarily through the activation of CaMKII/CREB/BDNF and AKT/GSK3β/FoxP2/PSD95 signaling pathways.

Sleep disturbance as a poor prognostic predictor in patients with advanced non-small-cell lung cancer treated with immune checkpoint inhibitors: A prospective study

BackgroundSleep disturbances are highly prevalent in oncology and often exacerbate symptoms, leading to reduced quality of life, which in turn may further affect the tolerability and efficacy of oncological treatments. Sleep disturbance and cancer have an intimate and complicated relationship, and may be a negative predictor of cancer treatment. The present study aimed to characterize the relationship between sleep disturbance and immune checkpoint inhibitor (ICI) therapy in patients with advanced non-small cell lung cancer (NSCLC). MethodsData from 171 patients with advanced NSCLC, who underwent ICI treatment between December 2020 and October 2022, were analysed in our prospective study. Sleep disturbances were evaluated according to the Pittsburgh Sleep Quality Index (PSQI), with a cut-off value of 5, to investigate the impact of sleep disturbance on the survival of patients with NSCLC and the efficacy of ICI treatment. ResultsThe median progression-free survival (PFS) was10.4 months (9 5% confidence interval [CI]:9.84–10.97). Univariate and multivariate analyses revealed that sleep disturbance and depressive symptom predicted worse prognosis with shortened PFS. Patients who experienced sleep disturbance exhibited a significant reduction in PFS (9.2 vs. 11.8 months; HR: 1.83 [9 5% CI 1.27–2.6 5]; p = 0.001), as did those with depressive states (HR 1.5 5 [9 5% CI 1.06–2.28]; p = 0.02 5). Additionally, patients with sleep disturbance and depressive symptoms exhibited significantly lower objective response rates and disease control rates. ConclusionSleep disturbance could be a factor for prognosis in patients with advanced NSCLC undergoing first- or second-line treatment with ICIs, including shorter PFS and reduced efficacy.

Stany depresyjne młodych matek a konceptualizacje macierzyństwa

The article analyses selected posts published by young mothers in two private Facebook groups entitled Noworodki, niemowlaki, dzieci – wymiana doświadczeń (Newborns, toddlers, children – sharing experiences) and Karmienie piersią i między karmieniami (Breastfeeding and between feedings). The issue influencing the analysis is conceptualisation which is one of the basic concepts in cognitive linguistics. The result of linguistic reflection is the observation of ways for conceptualising motherhood that are associated with psychophysical problems and depressive states of women in the perinatal period. Due to the thematic and temporal scope of the material, 45 entries published in 2022 and 2023 concerning the most difficult experiences were described. The collected examples were assigned to one of six distinguished conceptualisations, each related to the poor psychophysical condition of mothers.