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ETHNOPHARMACOLOGICAL RELEVANCE: Modified Danzhi Xiaoyao San (MDXS) is an effective clinical prescription for depression in China, which was deprived of Danzhi Xiaoyao San in the Ming Dynasty. MDSX has significant implications for the development of new antidepressants, but its pharmacological mechanism has been rarely studied. AIM OF THE STUDY: To reveal the active components and molecular mechanism of MDXS in treating depression through network pharmacology and experimental verification in vivo and in vitro. MATERIALS AND METHODS: UPLC-Q-TOF-MS/MS was used to identify the chemical components in the MDXS freeze-dried powder, drug-containing serum, and cerebrospinal fluid (CSF). Based on the analysis of prototype components in the CSF, the major constituents, potential therapeutic targets and possible pharmacological mechanisms of MDXS in treating depression were investigated using network pharmacological and molecular docking. Then corticosterone (CORT)-induced mice model of depression was established to investigate the antidepressant effects of MDXS. HT22 cells were cultured to verify the neuroprotective effects and core targets of the active components. RESULTS: There were 81 compounds in MDXS freeze-dried powder, 36 prototype components in serum, and 13 prototype components in CSF were identified, respectively. Network pharmacology analysis showed that these 13 prototype components in the CSF shared 190 common targets with depression, which were mainly enriched in MAPK and PI3K/AKT signaling pathways. PPI analysis suggested that AKT1 and MAPK1 (ERK1/2) were the core targets. Molecular docking revealed that azelaic acid (AA), senkyunolide A (SA), atractylenolide III (ATIII), and tokinolide B (TB) had the highest binding energy with AKT1 and MAPK1. Animal experiments verified that MDXS could reverse CORT-induced depression-like behaviors, improve synaptic plasticity, alleviate neuronal injury in hippocampal CA3 regions, and up-regulate the protein expression of p-ERK1/2 and p-AKT. In HT22 cells, azelaic acid, senkyunolide A, and atractylenolide III significantly protected the cell injury caused by CORT, and up-regulated the protein levels of p-ERK1/2 and p-AKT. CONCLUSIONS: These results suggested that MDXS may exert antidepressant effects partially through azelaic acid, senkyunolide A, and atractylenolide III targeting ERK1/2 and AKT.

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En este estudio transversal se investiga la asociación entre los principales síntomas del Trastorno bipolar (TB) y las dificultades asociadas a las estrategias de regulación emocional (ERE) adaptativas y desadaptativas. Además, este estudio examina los efectos mediadores de las ERE con el mindfulness rasgo y el TB. Método. Veinticuatro adultos con TB completaron la Escala de Conciencia de Atención Plena (MAAS), el Inventario de Depresión de Beck (BDI-II), la Escala de Autoevaluación de Manía de Altman (ARSM), el Inventario de Ansiedad Rasgo (STAI-R), y el Cuestionario de Regulación Emocional Cognitiva (CERQ). Resultados. El análisis de regresión múltiple mostró cómo la depresión se relacionaba significativa y positivamente con la autoculpabilización, mientras que la ansiedad rasgo estaba positivamente asociada con la autoculpabilización y el catastrofismo. En segundo lugar, el análisis de mediación mostró un efecto de mediación significativo para la autoculpabilidad en la relación entre mindfulness y depresión (a*b = -.15; ICB 95% [-.36, -.03]) y entre mindfulness y ansiedad rasgo (a*b = -.09; ICB 95% [-.27, -.01]). Conclusiones. Nuestros resultados informan del papel de la auto-culpabilidad y el catastrofismo en el TB y de cómo éstas podrían mediar significativamente entre el mindfulness rasgo y el TB. Estos resultados sugieren que una práctica de meditación enfocada en el catastrofismo y la autoculpabilidad puede ser especialmente útil para reducir los síntomas en los pacientes bipolares.(AU)

This cross-sectional study investigates the association between the main symptoms of Bipolar disorder (BD) and emotional regulation dif-ficulties in adaptive and maladaptive emotional regulation strategies (ERS). In addition, this study examines the possible mediating effects of ERS with dispositional mindfulnessand bipolar symptoms. Method.Twenty-four adults diagnosed with BD completed the Mindful Attention Awareness Scale (MAAS), the Beck Depression Inventory (BDI-II), the Altman Mania Self-Assessment Scale (ARSM), the Trait Anxiety Inventory (STAI-R), and the Cognitive Emotional Regulation Questionnaire (CERQ). Results. First, mul-tiple regression analysis showed how depression was significantly positively related to self-blame, whereas trait anxietywas positively associated with self-blame and catastrophizing. Second, the results of the mediation analy-sis have shown a significant mediation effect for the self-blamein the rela-tionship between mindfulnessand depression (a*b = -.15; BCI 95% [-.36, -.03]) and between mindfulnessand trait anxiety (a*b = -.09; BCI 95% [-.27, -.01]). Conclusions. Our results report the role of self-blame and catastrophiz-ing in BD and how these might significantly mediate between dispositional mindfulness and symptoms of depression and anxiety. These results suggest that a meditation practice focused on reducing catastrophizing and self-blame may be especially helpful for symptoms of depression and anxiety in bipolar patients.(AU)

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La comorbilidad es más la regla que la excepción en salud mental y, sobre todo, en el caso de la ansiedad y la depresión. Los modelos transdiagnósticos estudian los procesos subyacentes para mejorar el tratamiento y la comprensión de la salud mental. Objetivo: Esta revisión sistemática busca evidencias sobre los factores de riesgo transdiagnósticos para la ansiedad y la depresión en la población clínica diagnosticada de estas condiciones psicopatológicas, analizando los diferentes tipos o categorías de factores identificados. Método: Se registró una revisión sistemática en PROSPERO (número de registro CRD42022370327) y se diseñó de acuerdo con las guías PRISMA-P. La calidad del estudio fue evaluada por dos revisores independientes con conocimiento del campo para reducir el posible sesgo. Resultados: Cincuenta y tres artículos fueron examinados y las variables transdiagnósticas fueron agrupadas en tres categorías: psicológicas, biológicas y socioculturales. Conclusiones: La categoría más estudiada fue la de variables psicológicas, en especial los procesos cognitivos, afecto negativo y neuroticismo, intolerancia a la incertidumbre, sensibilidad a la ansiedad. Los factores biológicos y socioculturales requieren más estudio para sustentar su enfoque transdiagnóstico.(AU)

Comorbidity is more the rule than the exception in mental health, specifically in the case of anxiety and depression. Transdiagnostic models studied the underlying processes to improve mental health treat-ment and understating. Objective:This systematic review searchs for evi-dence on transdiagnostic risk factors for anxiety and depression in the clin-ical population diagnosed with these psychopathological conditions, by an-alysing the different types or categories of factors identified.Methods:A sys-tematic review was registered in PROSPERO (registration number CRD42022370327) and was designed according to PRISMA-P guidelines. Two independent reviewers with field knowledge assessed the study quality to reduce bias.Results: Fifty-three articles were examined, and the transdi-agnostic variables were grouped into three categories: psychological, bio-logical, and sociocultural.Conclusions:The most studied category was that of psychological variables, especially cognitive processes, negative affect, and neuroticism, intolerance of uncertainty, anxiety sensitivity. Biological and sociocultural factors require more study to support their transdiagnos-tic approach.(AU)

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El objetivo fue examinar, desde una aproximación multi-informante, las medidas del Síndrome de Desconexión Cognitiva (SDC) de padres/madres e hijos/as y su relación con síntomas internalizantes y externalizantes. 279 niños/as (9-13 años), y sus padres/madres completaron las evaluaciones sobre SDC, la inatención del trastorno por déficit de atención e hiperactividad (TDAH) y otras medidas internalizadas y externalizadas. Los ítems de las tres medidas de SDC convergieron razonablemente bien en el factor SDC. Se aportaron pruebas discriminantes de la validez de las relaciones entre las puntuaciones de las pruebas y las medidas de los tres constructos diferentes (SDC, soledad y preferencia por la soledad). La asociación más estrecha estuvo entre la evaluación parental de las medidas de SDC con ansiedad y depresión, y entre inatención con hiperactividad/impulsividad y trastorno negativista desafiante. Se observó capacidad predictiva de la medida de SDC sobre la soledad y preferencia por estar solo autoinformadas. Se encontró una posible asociación entre la medida del SDC evaluado por padres/madres y sexo y edad de los niños. En conclusión, los datos apoyan la inclusión de medidas autoinformadas en la evaluación del SDC. Las medidas del SDC en niños se vinculan con medidas internalizantes y, la inatención con las externalizantes.(AU)

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Evidence shows that the composition of the gut microbiota (GM) is associated with depression and anxiety disorders. However, the causal relationship between them remains controversial. To investigate the potential causal relationship between the GM and depression/anxiety disorders and to identify specific bacterial taxa, we conducted a 2-sample Mendelian randomization (MR) analysis on the gut microbiome implicated in depression and anxiety disorders. We incorporated summary data from genome-wide association studies (GWAS) of the microbiome derived from 7738 individuals in the Dutch Microbiome Project and 18,340 individuals in the MiBioGen consortium as our exposure variable. Concurrently, the GWAS of depression and anxiety disorders was employed as our outcome variable. The principal estimates were procured using the inverse-variance weighted test complemented by 4 robust methods: MR Egger, weighted median, simple mode, and weighted mode. In addition, we performed comprehensive sensitivity and directionality analyses. The results showed that 5 bacterial taxa were positively correlated with depression, 6 were negatively correlated; 5 were positively correlated with anxiety disorders, and 11 were negatively correlated. This study provides new insights into the connection between the GM and the pathogenesis of depression and anxiety disorders and offers new perspectives for the diagnosis and treatment of these disorders.

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AIMS: Suicide prevention strategies have shifted in many countries, from a national approach to one that is regionally tailored and responsive to local community needs. Previous Australian studies support this approach. However, most studies have focused on suicide deaths which may not fully capture a complete understanding of prevention needs, and few have focused on the priority population of youth. This was the first nationwide study to examine regional variability of self-harm prevalence and related factors in Australian young people. METHODS: A random sample of Australian adolescents (12-17-year-olds) were recruited as part of the Young Minds Matter (YMM) survey. Participants completed self-report questions on self-harm (i.e., non-suicidal self-harm and suicide attempts) in the previous 12 months. Using mixed effects regressions, an area-level model was built with YMM and Census data to produce out-of-sample small area predictions for self-harm prevalence. Spatial unit of analysis was Statistical Area Level 1 (average population 400 people), and all prevalence estimates were updated to 2019. RESULTS: Across Australia, there was large variability in youth self-harm prevalence estimates. Northern Territory, Western Australia, and South Australia had the highest estimated state prevalence. Psychological distress and depression were factors which best predicted self-harm at an individual level. At an area-level, the strongest predictor was a high percentage of single unemployed parents, while being in an area where ≥30% of parents were born overseas was associated with reduced odds of self-harm. CONCLUSIONS: This study identified characteristics of regions with lower and higher youth self-harm risk. These findings should assist governments and communities with developing and implementing regionally appropriate youth suicide prevention interventions and initiatives.

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BACKGROUND: Hemifacial spasm (HFS) is a debilitating disease characterized by involuntary tonic and clonic contractions of muscles innervated by the facial nerve. Botulinum toxin A (BTX-A) is the first-line option and the most effective medical treatment for HFS. The objective of this study was to evaluate the effect of BTX-A therapy on the physical and mental health of HFS patients. METHODS: Participants included 65 HFS patients and 65 matched healthy controls in the study. Cornell Medical Index (CMI) self-assessment questionnaire was used to detect the psychological health of all participants. Local injection of BTX-A was applied, and the Cohen hierarchical criteria were employed to stratify the degree of spasticity, further evaluating the efficacy of BTX-A before and two months after treatment in HFS patients. The HFS patients at two months post-treatment were re-evaluated by CMI self-assessment questionnaire, and the evaluated factors of these patients were compared with those of patients before treatment. RESULTS: The scores of somatization, depression, anxiety, inadaptation, sensitivity, anger, tension, M-R, and total scores in the HFS group were significantly higher than those in the control group (all P<0.05). Two months post-treatment, among 65 HFS patients who received with BTX-A treatment, 42 (64.6%) were completely relieved, 16 (24.6%) were significantly relieved, 7 (10.8%) were partially relieved, and 0 (0%) cases were invalid, and the total effective rate was 89.2%. Two months after BTX-A treatment, the scores of somatization, tension, anxiety, depression, sensitivity, M-R and total scores of patients with HFS were lower than those before treatment (all P<0.05). CONCLUSIONS: Patients with HFS are often accompanied by somatization, anger, inadaptation, sensitivity, anxiety, depression, and tension. BTX-A can not only alleviate the symptoms of HFS, but also improve the somatization, tension, anxiety, depression, and sensitivity.

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OBJECTIVES: This research simulates an adaptive version of the IDAS-II (IDAS-CAT). METHODS: 2021 participants from both community (n = 1692) and patients (n = 329) samples completed the IDAS-II. Item response theory metric properties of the IDAS-II full test and the 20-items of the general depression (GD) scale were obtained. The efficiency and accuracy of different computerized adaptive algorithms were simulated. Different subsamples completed additional external measures in order to gather evidence of validity of the scores estimated with the simulated adaptive algorithms selected. RESULTS: Both unidimensional computerized adaptive testing algorithm selected for the GD scale and the bifactor model chosen for the full test, allow 70% reduction in the length of administration, maintaining a measurement error below 0.30 on the general and 0.50 on the specific factors. Results show high correlations of the scores estimated with the adaptive algorithms and the estimates based on the full test, as well as correlations with external criteria almost equal to those generated with the full test. CONCLUSIONS: IDAS-CAT could be a reliable and fast tool for measuring internalizing spectrum.

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OBJECTIVE: To describe the profile of individuals with depression who received assistance at CAPS in Brazil between 2013 and 2019, focusing on their clinical and demographic characteristics, and to calculate the estimated coverage of CAPS across the national territory and its constituent federal units. METHODS: Descriptive, ecological, time-series study with secondary data from national databases, referring to care provided at CAPS in the country for adults aged 18 years or over-diagnosed with depression (F32-32.9 and F33-F33.9). The estimated coverage of CAPS was calculated for 2013 and 2019 using registered and active services. RESULTS: There was a 107% increase in the number of patients with depression receiving treatment at CAPS between 2013 and 2019. Women accounted for 77% of the patients, with the majority falling within the age range of 41 to 61years (49%). The predominant racial demographics were white (38%) and brown (34%). The diagnosis of depressive episodes was prevalent among 65% of the patients, and individual care was administrated to 75% of them. The presumed CAPS coverage was 71% in 2013 and increased to 87% in 2019 nationwide, although significant discrepancies were observed among different states. CONCLUSION: Progress was evident in the implementation of CAPS across Brazil during the period spanning 2013 to 2019. Nonetheless, disparities persist among the federative units, and there remains an underutilization of group and family care within CAPS services.

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Objectives: This study aimed to investigate the dynamic patterns of perception and expectations among COPD patients. Methods: Conducted at the Heart-Respiratory Rehabilitation Unit, IRCCS Fondazione Don Carlo Gnocchi, in Milan, Italy, the research involved 28 participants (16 males; mean age 72.8 ± 9.9) in face-to-face interviews. Utilizing a Grounded Theory approach, complemented by clinical data, recorded, and transcribed interviews underwent enhancement through the integration of two pictorial tools. Results: The central theme that emerged was a profound sense of responsibility toward their condition, perceived as a significant threat to life. Key symptoms, such as shortness of breath, coupled with negative expectations about their condition, contributed to depressive mood and avoidance behaviors. A notable proportion (N = 17; 60.71%) of participants struggled to envision a positive future, expressing a pervasive sense of hopelessness, which significantly influenced their health behaviors and adherence to medical recommendations. Conversely, individuals who felt supported and optimistic about treatment efficacy exhibited more positive expectations and adopted proactive coping strategies. Discussion: Recognizing the dynamic nature of patients' perceptions and negative illness expectations is essential to create personalized therapeutic interventions and meet the specific needs of COPD patients, ultimately improving the overall effectiveness of their care journey.

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BACKGROUND: While it is recognized that social support can alleviate mental health symptoms, this relationship is not well-understood among Chinese pregnant and parenting immigrants in the United States. This study aims to bridge this gap by exploring the relationships between different types of social support and women's anxiety and depression, and examining how these associations vary with pregnancy status. METHODS: Data were obtained from a cross-sectional survey conducted in Simplified Chinese or Mandarin between March-June 2021 among 526 women who were pregnant and/or parenting a child under five years. The Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, Depression, and Social Support scales were used to measure anxiety, depression, and social support levels. Descriptive statistics, t-tests, chi-square tests, and Pearson's correlations were employed for analysis. Hierarchical regression was conducted to investigate the main and interaction effects of social support types and pregnancy status on mental health outcomes. RESULTS: Compared to non-pregnant women, pregnant women reported higher mean scores for anxiety (non-pregnant: 55, pregnant: 59, p < 0.01) and depression (non-pregnant: 54, pregnant: 56, p = 0.02). Instrumental support displayed a significant main effect in relation to anxiety (ß=-0.13, p = 0.01) and depression (ß=-0.16, p < 0.01); emotional support exhibited a significant main effect solely on depression (ß=-0.13, p = 0.01). Notably, the interaction effects between pregnancy status and both instrumental (ß=-0.28, p = 0.01) and emotional support (ß=-0.42, p < 0.01) were significant for anxiety. In contrast, informational support did not exhibit a significant impact on either anxiety or depression. CONCLUSIONS: The findings indicate that tailoring support to the cultural context is crucial, especially for pregnant women in this Chinese immigrant community, with instrumental and emotional support being particularly beneficial in mitigating maternal anxiety.

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OBJECTIVE: To assess the effectiveness of Internet-based self-help interventions in treating depression in adolescents and young adults. METHODS: A systematic search was conducted across six databases, including PubMed, to identify randomized controlled trials (RCTs) that satisfied the specified inclusion and exclusion criteria. The intervention measure consisted of Internet-based self-help interventions. RESULTS: A total of 23 randomized controlled trials (RCTs) were included in this analysis. Meta-analysis indicated that Internet-based self-help therapies significantly reduced depression scores in adolescents and young adults. (OR = -0.68, 95%CI [-0.88, -0.47], P < 0.001). We examined the effects of patient recruitment from various regions, medication usage, therapist involvement, weekly intervention time, and intervention duration. Patients selected from school, primary healthcare centers, clinics and local communities had better results. Intervention lasting 30 to 60 min and 60 to180 minutes per week were effective in the short term. CONCLUSION: The internet-based self-help intervention can be effective in treating depression in adolescents and young adults. However, factors such as patient recruitment locations, medication usage, Therapists' involvement, weekly intervention time, and intervention duration interacted with the outcome. Subgroup analysis on potential adverse effects and gender was impossible due to insufficient data from the included studies.

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BACKGROUND: Effective medication adherence is vital for managing acute myocardial infarction (AMI) and enhancing patient well-being. This study aimed to evaluate medication adherence levels and associated factors among AMI patients using standardized assessment tools. METHODS: Employing a cross-sectional descriptive design, the study involved 210 patients diagnosed with acute myocardial infarction. Participants completed the General Medication Adherence Scale (GMAS), Hospital Anxiety and Depression Scale (HADS), and provided socio-demographic details. RESULTS: The study revealed partial adherence to medications among AMI patients, with mean scores of 24.89 (± 3.64) out of 33. Notably, good adherence was observed in non-adherence due to patient behavior (mean ± SD = 11.8 ± 2.3 out of 15) and additional disease burden (mean ± SD = 8.65 ± 2.21 out of 12), while partial adherence was noted in non-adherence due to financial constraints (mean ± SD = 4.44 ± 1.34 out of 6). Patients reported mild anxiety (mean ± SD = 8.38 ± 2.81) and no depressive symptoms (mean ± SD = 7.43 ± 2.42). Multiple linear regression analysis indicated that employed status, younger age, shorter duration of MI, lower anxiety, and depression levels were associated with higher medication adherence. However, factors such as monthly income, gender, educational level, and marital status did not predict medication adherence. CONCLUSION: The study highlights the significance of addressing anxiety and depression levels and considering socio-demographic factors when designing interventions to enhance medication adherence among AMI patients. Further research is needed to explore additional determinants of medication adherence and develop tailored interventions to improve patient outcomes post-AMI.

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BACKGROUND: Depression is often linked to inflammation in the brain. Researchers have been exploring ways to reduce this inflammation to improve depression symptoms. One potential target is a protein called RIPK1, which is known to contribute to brain inflammation. However, it's unclear how RIPK1 influences depression. Our study aims to determine whether RIPK1 inhibition could alleviate neuroinflammation-associated depression and elucidate its underlying mechanisms. METHODS: To investigate our research objectives, we established a neuroinflammation mouse model by administering LPS. Behavioral and biochemical assessments were conducted on these mice. The findings were subsequently validated through in vitro experiments. RESULTS: Using LPS-induced depression models, we investigated RIPK1's role, observing depressive-like behaviors accompanied by elevated cytokines, IBA-1, GFAP levels, and increased inflammatory signaling molecules and NO/H2O2. Remarkably, Necrostatin (Nec-1 S), a RIPK1 inhibitor, mitigated these changes. We further found altered expression and phosphorylation of eIF4E, PI3K/AKT/mTOR, and synaptic proteins in hippocampal tissues, BV2, and N2a cells post-LPS treatment, which Nec-1 S also ameliorated. Importantly, eIF4E inhibition reversed some of the beneficial effects of Nec-1 S, suggesting a complex interaction between RIPK1 and eIF4E in LPS-induced neuroinflammation. Moreover, citronellol, a RIPK1 agonist, significantly altered eIF4E phosphorylation, indicating RIPK1's potential upstream regulatory role in eIF4E and its contribution to neuroinflammation-associated depression. CONCLUSION: These findings propose RIPK1 as a pivotal mediator in regulating neuroinflammation and neural plasticity, highlighting its significance as a potential therapeutic target for depression.

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Depression is frequently reported in amyotrophic lateral sclerosis (ALS) due to the disastrous prognosis of progressive motor impairment, but the risk of depression in ALS is still unclear. Therefore, we investigated the risk of depression in ALS and analyzed the effect of ALS-related physical disability on the risk of developing depression using the Korean National Health Insurance Service (KNHIS) database. A total of 2241 ALS patients, as defined by the International Classification Diseases (ICD, G12.21) and Rare Intractable Disease codes (V123), and 1:10 sex- and age-matched controls were selected from the KNHIS. After applying exclusion criteria (non-participation in national health screening, history of depression, or having missing data), 595 ALS patients and 9896 non-ALS individuals were finally selected. Primary outcome is newly diagnosed depression during follow-up duration defined by ICD code (F32 or F33). A Cox regression model was used to examine the hazard ratios (HRs) after adjustment for potential confounders. During the follow-up period, 283 cases of depression in the ALS group and 1547 in the controls were recorded. The adjusted HR for depression in ALS was 9.1 (95% confidence interval [CI] 7.87-10.60). The risk of depression was slightly higher in the disabled ALS group (aHR 10.1, 95% CI 7.98-12.67) than in the non-disabled ALS group (aHR 8.78, 95% CI 7.42-10.39). The relative risk of depression was higher in younger patients than in older patients, and in obese patients than in non-obese patients. Our study showed that ALS patients have an increased risk of depression compared to non-ALS individuals.

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The coronavirus disease (COVID-19) pandemic and associated infection control measures have introduced significant uncertainty, and the unbearable nature of this uncertainty has heightened the risk of mental health issues among college students. This study aimed to assess the impact of unbearable uncertainty during the COVID-19 pandemic on college students' depression and investigate the mediating role of coping strategies between unbearable uncertainty and depression. A cross-sectional survey was conducted with 714 Chinese university students using the Intolerance of Uncertainty Scale (IUS-12), Brief Coping Style Questionnaire, and Beck Depression Inventory (BDI-II). SPSS PROCESS was used for the partial correlation analyses and structural equation modeling. (1) Negative coping strategies were significantly positively correlated with intolerable uncertainty and depressive symptoms, while positive coping strategies were negatively correlated with both intolerable uncertainty and depressive symptoms. Intolerable uncertainty was significantly and positively correlated with depressive symptoms. (2) Intolerance to uncertainty significantly predicted depressive symptoms. Both negative and positive coping strategies played parallel mediating roles in the relationship between unbearable uncertainty and depressive symptoms among college students. This study found that coping strategies played a mediating role in the relationship between unbearable uncertainty and depression during the pandemic in 2019. Future research and interventions should focus on enhancing tolerance of uncertainty and promoting positive coping strategies.

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Chronic diseases and pain exacerbate depressive symptom in Syria. Limited research on hospital-induced depressive symptom among Syrian patients with chronic diseases warrants further study. A cross-sectional study in four Damascus hospitals revealed high rates of pain and depressive symptom. This study aims to investigate the prevalence and severity of chronic pain and hospital-induced depressive symptom in Syrian patients, as well as the relationship between pain, depressive symptom, and medication behavior. This study analyzes the impact of pain, hospitalization, and medication on patients with chronic diseases. The four Damascus hospitals included 453 patients from various departments. Data were collected through structured interviews and internationally recognized scales such as the PSEQ, HADS, and MMAS. These findings offer insights into pain management and psychological well-being, with implications for patient care and support strategies. The study involved 453 patients with chronic diseases, with gender distribution showing 46.6% females and 53.4% males. The age range was from 7 to 87 years, with an average of 46.87 years. Chi-square tests revealed a significant connection between gender and HADS-A scores, where 48.3% of females had abnormalities (χ2 (1, N = 453) = 7.125, p = 0.028). Marital status was significantly associated with anxiety and depressive symptom levels, particularly among widowed and divorced patients. Employment status, education, and comorbidity were linked to abnormal HADS-A scores, while education level showed a positive correlation with HADS-D scores. ANOVA tests showed significant differences in MMAS scores across income groups (F (3, 449) = 3.167, p = 0.024), with a notable difference between low-income and lower-middle-income groups (mean difference = 0.389, p = 0.031. Chronic pain and HID are prevalent among Syrian patients with chronic diseases and influenced by socio-demographic factors. Personalized interventions are needed to address psychological symptoms and medication behavior.

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BACKGROUND: Depression is widely recognized as a common non-motor symptom of Parkinson's disease (PD). Across different studies, the reported prevalence of depression in PD varies widely, ranging from 2.7% to 90%, but it is unclear whether this association is due to genetic or acquired factors. Whether there is a causal relationship remains unknown. The aim of this study was to use a two-sample Mendelian randomization (MR) approach to investigate the causal effect of PD on depression. METHODS: Analyses were conducted separately for individuals of European and East Asian ancestry using publicly available summary data from genome-wide association studies. Depression was divided into two categories: ever depressed for a whole week and major depressive disorder (MDD). PD data were used as the exposure and were obtained from the International Parkinson's Disease Genomics Consortium and the BioBank Japan PheWeb, while depression data were used as the outcome and were obtained from the ntegrative Epidemiology Unit (IEU) Open GWAS Project(A public GWAS database） and the Psychiatric Genomics Consortium. The influence of PD on depression was assessed using inverse variance weighted (IVW), weighted median, MR-Egger, and weighted mode methods. Heterogeneity and pleiotropy were tested, and the results were validated using FinnGen GWAS data from version R9. RESULTS: In individuals of European ancestry, there was a causal relationship between PD and ever depressed for a whole week (IVW method, odds ratio [OR] = 0.990; 95% CI, 0.984-0.996; p = .002), but no causal relationship was observed between PD and MDD (IVW method, OR = 0.974; 95% CI, 0.942-1.009; p = .141). In individuals of East Asian ancestry, no causal relationship was observed between PD and ever depressed for a whole week (IVW method, OR = 1.001; 95% CI, 0.829-1.209; p = .990) and between PD and MDD (IVW method, OR = 1.017; 95% CI, 0.982-1.052; p = .342). The results of the three additional analysis methods were similar to those of the IVW method, and there was no heterogeneity according to Cochran's Q-test. There was no evidence of pleiotropy based on MR-Egger intercept test and MR-PRESSO. The FinnGen validation dataset supported these findings. The results are stable and reliable. CONCLUSION: The observed increase in depression among PD patients could potentially be attributed to modifiable acquired factors. Consequently, there is an urgent need to strengthen the management of PD patients in order to prevent the development of depression in the future.

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