Objective To explore the changes in serum lactate dehydrogenase （LDH）， monocyte chemoattractant protein-1 （MCP-1）， and transcription factor 4 （TCF4） levels in patients with cerebral small vessel disease complicated by depression and their clinical significance. Methods According to the inclusion and exclusion criteria， 90 patients admitted to the Kailuan General Hospital between January 2022 and August 2024 were selected as the study subjects， including 27 patients diagnosed with cerebral small vessel disease complicated by depression and 63 patients with cerebral small vessel disease uncomplicated by depression. An additional 45 healthy individuals with normal head MRI findings and no mental disorders during the same period at the hospital were selected as the control group. General information was collected from the three groups， including age， body mass index， systolic blood pressure， and diastolic blood pressure.The general information and the levels of serum LDH，MCP-1，and TCF4 in the three groups were compared. The correlations of serum LDH，MCP-1，and TCF4 levels with HAMD score in patients with cerebral small vessel disease and depression were analyzed. Logistic regression was applied to analyze possible factors leading to depression in patients with cerebral small vessel disease.The receiver operating characteristic curve was applied to analyze the efficacy of serum LDH， MCP-1， and TCF4 levels in diagnosing depression in patients with cerebral small vessel disease. Results The levels of serum LDH， MCP-1，and TCF4 were significantly higher in the cerebral small vessel disease complicated by depression group than in cerebral small vessel disease uncomplicated with depression group and the control group （P<0.05）， and these levels were significantly higher in the cerebral small vessel disease uncomplicated with depression group than in the control group （P<0.05）.The serum LDH，MCP-1 and TCF4 were positively correlated with HAMD score in patients with cerebral small vessel disease complicated with depression（r=0.606，0.798，0.672，all P<0.001）.Serum LDH， MCP-1， and TCF4 were influencing factors for depression in cerebral small vessel disease（P<0.05）.The area under the receiver operating characteristic curve of LDH， MCP-1，and TCF4 in combination in the diagnosis of depression in cerebral small vessel disease was 0.917， which was superior to serum LDH， MCP-1， and TCF4 alone （ZLDH-combination=2.457，P=0.014；ZMCP-1-combination=2.384， P=0.017； ZTCF4-combination=2.317， P=0.021）. Conclusion Serum LDH， MCP-1， and TCF4 levels increased in patients with cerebral small vessel disease complicated with depression. Their combination is valuable in the diagnosis of cerebral small vessel disease complicated with depression.
Depression

Objective To investigate the changing trend of sleep disturbance in patients with hepatolenticular degeneration and the bidirectional relationship between sleep disturbance and depression through a cross-lagged regression analysis. Methods A total of 80 patients who met the diagnostic criteria for WD from January to June 2024 were enrolled in this longitudinal study and were followed up for 3 months.Pittsburgh Sleep Quality Index （PSQI） was used to assess sleep quality， and Beck Depression Inventory （BDI） was used to assess the severity of depression， at the time of enrollment （T0）， at 1 month after enrollment （T1），and at 2 months after enrollment （T3）. An unconditional growth model was used to analyze the trajectory of sleep disturbance， and a cross-lagged regression model was used to investigate the temporal relationship between sleep disturbance and depression. Results From T0 to T2， there were significant increases in PSQI and BDI scores in all WD patients（P<0.05）. The variance of the intercept factor （the initial status of sleep disturbance） was estimated at 10.83（P<0.01），and the variance of the slope factor （the rate of change in sleep disturbance） was 1.20 （P<0.01），with a significant negative correlation between the intercept and the slope （r=-0.25，P<0.01）. The correlation analysis of PSQI and BDI scores across the three time points revealed a positive correlation between PSQI and BDI scores （r∈[0.19，0.96]，P<0.01）.The cross-lagged model analysis showed that sleep disturbance significantly predicted subsequent depression （P<0.01），with standardized regression coefficients （β） of 0.392 and 0.347， respectively； meanwhile， depression also significantly predicted subsequent sleep disturbance （P<0.01）， with β of 0.273 and 0.372， respectively. These findings suggested a bidirectional predictive relationship between sleep disturbance and depression in WD patients over time. Conclusion There is a bidirectional relationship between sleep disturbance and depression in patients with WD， and depression has a more pronounced influence on sleep disturbance. Therefore， clinical interventions should focus on both sleep and psychological state， and combined management should be performed to improve the effect of disease control.
Depression

Objective Observational studies have shown an association between Parkinson disease （PD） and mental illness， but further studies are needed to explore the causal relationship between them. This study aims to investigate such causal relationship using the method of two-sample Mendelian randomization （MR）. Methods Related data were extracted from GWAS， and summary statistics associated with PD， depression， sleep disorders， and anxiety phenotype-variants were obtained. Single nucleotide polymorphisms （SNPs） for PD were selected as instrumental variables， and MR-PRESSO was used to exclude outliers. Inverse variance weighting was used as the main method to assess causal effect estimates， and MR Egger， weighted median， simple mode， and weighted mode were used to verify the robustness of the findings. A sensitivity analysis was used to validate the reliability of the results， including the Cochran Q test， the MR-Egger intercept test， funnel plots， and the leave-one-out method. Results A total of 21 SNPs associated with PD were identified. The MR analysis showed that PD had a causal relationship with depression （OR=0.974，95%CI 0.934‒1.015， P=0.210）， sleep disorders （OR=1.056， 95%CI 0.970-1.149， P=0.211）， and anxiety （OR=0.998， 95%CI 0.996‒1.001， P=0.118）， with no statistical significance. Different MR analyses and sensitivity analyses showed that PD did not directly contribute to the development of mental illness. Conclusion There is no direct causal relationship between PD and depression/sleep disorders/anxiety. In clinical practice， healthcare professionals should pay attention to the mental health of patients with PD. Randomized controlled studies should be conducted in the future to further validate the results of this study.
Depression ; Anxiety

BACKGROUND AND OBJECTIVES

Climate anxiety is an emerging concept defined as increased anxiety about climate change and has been linked to negative mental health outcomes. As a relatively new concept, only a few have characterized it and its relationship with mental health, especially in the Global South populations. This study aimed to investigate the relationship between climate anxiety and depressive symptoms among undergraduate students from a college in a higher education institution in Manila, Philippines. Specifically, it aimed to (1) determine the proportion of undergraduate students who reported high levels of climate anxiety and depressive symptoms; and (2) determine the association between climate anxiety and depressive symptoms.

Using a cross-sectional design and a convenience sampling method, the investigators collected data through an online survey to assess levels of climate anxiety and depressive symptoms using the Climate Change Anxiety Scale (CCAS) and the Patient Health Questionnaire 9 (PHQ-9), respectively. Data was analyzed using multiple logistic regression.

Among the 148 respondents (N=325), 14.86% had high climate anxiety (i.e., CCAS score >= 3) and 62.84% had high depressive symptoms (i.e., PHQ-9 score >= 10). Regression analysis showed that the odds of those having high climate anxiety reporting high depressive symptoms are higher than those with low climate anxiety, though this is not significant (OR = 2.53, p=0.144).

The study verifies the existence of climate anxiety among undergraduate students and reflects an alarming mental health situation in the selected college. It is recommended that wide-scope investigations on the current state of climate anxiety and mental health among the youth be done to verify their impacts, along with inter-sectoral efforts such as increasing awareness through health education interventions to improve the youths’ mental health literacy and resilience to the effects of climate change, and promoting climate change-responsive mental health services to address these as pressing threats to youth health.

BACKGROUND AND OBJECTIVES

Ensuring the total well-being of healthcare workers (HCWs), including their mental health and psychological well-being, is an essential aspect in the delivery of patient care and the preservation of the health workforce. This study aimed to determine the level of mental well-being and emotional state of HCWs in terms of depression, anxiety, and stress using the DASS-21 scale in a tertiary government hospital during the COVID-19 pandemic in the Philippines and to identify the job-related factors that may be associated with these outcomes.

This is an analytical, cross-sectional study among HCWs involved in direct patient care in a tertiary government hospital in the Philippines during the COVID-19 pandemic. Data collection was conducted from February to March 2022 through an online self-administered questionnaire, which included the Demand-Control-Support Questionnaire (DCSQ), and the 21-item Depression Anxiety Stress Scale (DASS-21). This was sent to doctors, nurses, and allied medical workers actively working in the clinical areas. All responses were collected and analyzed.

Three hundred sixty-four healthcare workers were included in the study. Majority were single (62.62%), living with immediate family (50.82%), and working in a COVID-designated area (62.09%). High prevalence of depression (49.18%), anxiety (61.54%), and stress (30.22%) was found among the HCWs. Work in high infection/COVID-designated areas was significantly associated with anxiety and stress, and high-job demand was significantly associated with all three mental health states compared to low job-demand.

Focus should be placed on modifying the condition of high job demand among healthcare workers working in hospitals. This includes ensuring optimum staffing levels and patient to HCW ratio which avoids HCWs from being subjected to high workloads and time pressures that subsequently increase risk for stress, anxiety, and depression.

BACKGROUND

Anxiety and depression are prevalent during pregnancy. There is significant evidence that antenatal anxiety and depression are risk factors for adverse maternal and neonatal outcomes.

This study aims to determine the prevalence of anxiety and depression among pregnant women who undergo ultrasonographic detection of structural fetal anomalies in the Department of Maternal and Fetal Medicine of University of the Philippines–Philippine General Hospital, Manila, Philippines, for a 13-month period.

The study utilized a comparative cross-sectional study design comparing those who underwent congenital anomaly scan (CAS) with those who just underwent routine biometry. There were 177 research respondents for each group. The Filipino version of the Hospital Anxiety and Depression Scale (HADS-P) was used. The psychiatric interview was based on the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM V) particularly on the Major Depressive DIsorder and the Generalized Anxiety Disorder.

The results showed that the mean pre-diagnostics anxiety score of women who underwent CAS was significantly higher than the mean pre-diagnostics anxiety score of women who had biometry. The mean post-diagnostics depression score of women who underwent CAS was significantly higher than the mean post-diagnostics depression score of women who had biometry. However, all pregnant women had normal HADS-P score before and after CAS and biometry. Psychiatric evaluation showed that none was diagnosed to have generalized anxiety disorder or major depression in the conduct of the diagnostic tests.

This study indicates that generalized anxiety and depression among pregnant patients subjected to routine biometry and congenital scan were not problems in this tertiary hospital. Knowledge of CAS and awareness of risk factors for congenital anomalies are important for providing care and counseling pregnant women.

BACKGROUND: Over 65 million people have long COVID. Evidence for using Chinese herbal medicine (CHM) to treat long COVID is growing. A systematic review of evidence for guiding clinical decision is warranted. OBJECTIVE: To examine the effects and safety of CHM in alleviating the severity of dyspnea, fatigue, exercise intolerance, depression, anxiety and insomnia in long COVID adults based on registered randomized clinical trials (RCT). SEARCH STRATEGY: World Health Organization International Clinical Trials Registry Platform and Chinese Clinical Trial Registry were searched for registered trial protocols from database inception to February 10, 2023. English (PubMed, Embase, AMED and CINAHL) and Chinese databases (CNKI, Wanfang Data and CQVIP) were then searched to identify relevant publications from December 2019 through April 6, 2023. INCLUSION CRITERIA: Registered RCTs that compared the effects of Chinese herbal medicines or Chinese herbal formulas against a control treatment (i.e., the placebo or usual care) in adults with persistent symptoms of long COVID. The primary outcome of dyspnea, and secondary outcomes of fatigue, exercise intolerance, depression, anxiety and insomnia were measured using validated tools at the end of the treatment. DATA EXTRACTION AND ANALYSIS: Data were extracted, and eligible RCTs were evaluated using version 2 of the Cochrane risk-of-bias tool for randomized trials and Grading of Recommendations, Assessment, Development and Evaluations independently by two researchers. Effect sizes were estimated by random-effects modelling and mean difference (MD). Heterogeneity between trials was quantified by I². RESULTS: Among the 38 registered clinical trials we identified, seven RCTs (1,519 patients) were included in the systematic review. One RCT had a low overall risk of bias. Compared to the control, CHM reduces dyspnea on the Borg Dyspnea Scale score (MD = -0.2, 95% confidence interval [CI] = -0.65 to 0.25) with moderate certainty, and reduces fatigue on the Borg Scale (MD = -0.48, 95% CI = -0.74 to -0.22) with low certainty. CHM clinically reduces depression on Hamilton Depression Rating Scale score (MD = -6.00, 95% CI = -7.56 to -4.44) and anxiety on Hamilton Anxiety Rating Scale score (MD = -6.10, 95% CI = -7.67 to -4.53), and reduces insomnia on the Insomnia Severity Index (MD = -4.86, 95% CI = -12.50 to 2.79) with moderate certainty. Meta-analysis of two RCTs (517 patients) showed that CHM clinically improves exercise intolerance by increasing 6-minute walking distance (MD = -15.92, 95% CI = -10.20 to 42.05) with substantial heterogeneity (I² = 68%) and low certainty. CONCLUSION CHM is associated with a post-treatment clinical reduction in depression and anxiety in long COVID adults, compared to the control, but it does not have a strong treatment effect on dyspnea and insomnia. Effects of CHM on exercise intolerance and fatigue are uncertain, and the safety of using CHM remains questionable. Please cite this article as: Tsang MS, Zhou IW, Zhang AL, Xue CC. Chinese herbal medicine for dyspnea and persistent symptoms of long COVID: A systematic review and meta-analysis of randomized controlled trials. J Integr Med. 2025; 23(2): 126-137.
Humans ; Dyspnea/etiology* ; Drugs, Chinese Herbal/therapeutic use* ; Randomized Controlled Trials as Topic ; COVID-19/complications* ; Fatigue/drug therapy* ; SARS-CoV-2 ; Anxiety/drug therapy* ; Depression/drug therapy* ; Sleep Initiation and Maintenance Disorders/drug therapy* ; Betacoronavirus

OBJECTIVE: Comorbid pain and depression are common but remain difficult to treat. Electroacupuncture (EA) can effectively improve symptoms of depression and relieve pain, but its neural mechanism remains unclear. Therefore, we used resting-state functional magnetic resonance imaging (rs-fMRI) to detect cerebral changes after initiating a mouse pain model via constriction of the infraorbital nerve (CION) and then treating these animals with EA. METHODS: Forty male C57BL/6J mice were divided into 4 groups: control, CION model, EA, and sham acupuncture (without needle insertion). EA was performed on the acupoints Baihui (GV20) and Zusanli (ST36) for 20 min, once a day for 10 consecutive days. The mechanical withdrawal threshold was tested 3 days after the surgery and every 3 days after the intervention. The depressive behavior was evaluated with the tail suspension test, open-field test, elevated plus maze (EPM), sucrose preference test, and marble burying test. The rs-fMRI was used to detect the cerebral changes of the functional connectivity (FC) in the mice following EA treatment. RESULTS: Compared with the CION group, the mechanical withdrawal threshold increased in the EA group at the end of the intervention (P < 0.05); the immobility time in tail suspension test decreased (P < 0.05); and the times of the open arm entry and the open arm time in the EPM increased (both P < 0.001). There was no difference in the sucrose preference or marble burying tests (both P > 0.05). The fMRI results showed that EA treatment downregulated the amplitude of low-frequency fluctuations and regional homogeneity values, while these indicators were elevated in brain regions including the amygdala, hippocampus and cerebral cortex in the CION model for comorbid pain and depression. Selecting the amygdala as the seed region, we found that the FC was higher in the CION group than in the control group. Meanwhile, EA treatment was able to decrease the FC between the amygdala and other brain regions including the caudate putamen, thalamus, and parts of the cerebral cortex. CONCLUSION EA can downregulate the abnormal activation of neurons in the amygdala and improve its FC with other brain regions, thus exerting analgesic and antidepressant effects. Please cite this article as: Yin X, Zeng XL, Lin JJ, Xu WQ, Cui KY, Guo XT, Li W, Xu SF. Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression: a resting-state functional magnetic resonance imaging study. J Integr Med. 2025; 23(2): 159-168.
Animals ; Electroacupuncture ; Male ; Magnetic Resonance Imaging ; Depression/diagnostic imaging* ; Mice, Inbred C57BL ; Brain/diagnostic imaging* ; Disease Models, Animal ; Mice ; Pain/diagnostic imaging* ; Acupuncture Points

OBJECTIVE: This study investigated the antidepression mechanisms of Xiaoyaosan (XYS), a classic Chinese prescription, from the perspective of energy metabolism in the brain and intestinal tissues. METHODS: Chronic unpredictable mild stress model-a classic depression rat model-was established. Effects of XYS on behaviors and gastrointestinal motility of depressed rats were investigated. Effects of XYS on energetic charge (EC), adenosine triphosphate-related enzymes, and key enzymes of energy metabolism in both hippocampus and jejunum tissues of depressed rats were investigated using high-performance liquid chromatography, biochemical analysis, and real-time quantitative polymerase chain reaction, respectively. Spearman correlation analysis was conducted to construct a correlation network of "behavior-brain energy metabolism-intestinal energy metabolism" of depression. RESULTS: XYS significantly reduced the abnormal behaviors that observed in depressed rats and increased the EC and the activity of Na⁺-K⁺-adenosine triphosphatase (ATPase) and Ca²⁺-Mg²⁺-ATPase in hippocampus and jejunum tissues of depressed rats. XYS restored the key energetic pathways that had been interrupted by depression, including glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation. Furthermore, XYS exhibited antidepressive effects in terms of regulating energy metabolism in tissues of both brain and intestine. CONCLUSION XYS significantly corrected the disturbances in EC and energy metabolism-related enzymes of both brain and intestinal tissues, alleviating both core and concomitant symptoms of depression. The current findings underscore the role of energy metabolism in the antidepressive activity of XYS, providing a fresh perspective on depression, and novel research strategies for revealing the mechanism of actions of traditional Chinese medicines on multi-site and multi-symptom diseases. Please cite this article as: Xiao MT, Wang SY, Wu XL, Zhao ZY, Wang HM, Liu HM, Qin XM, Liu XJ. Antidepressant mechanism of Xiaoyaosan: A perspective from energy metabolism of the brain and intestine. J Integr Med. 2025; 23(6):706-720.
Animals ; Energy Metabolism/drug effects* ; Antidepressive Agents/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use* ; Brain/drug effects* ; Male ; Depression/metabolism* ; Rats ; Rats, Sprague-Dawley ; Intestines/drug effects* ; Hippocampus/drug effects*

Coronary artery disease (CAD), one of the most common cardiovascular diseases (CVD), poses a serious threat to physical and mental health, resulting in a severe disease burden. Psychocardiology medicine focuses on the vital role of psychological factors in the development, diagnosis, and treatment of CVD. The prevalence of depression and anxiety is high in patients with CAD. Furthermore, there is a vital interplay among depression, anxiety, mental stress-induced myocardial ischemia, cognitive impairment, and delirium. Both cognitive impairment and delirium adversely impact the prognosis of patients with CAD, warranting increasing attention and the development of interventions. To further direct the clinic diagnosis and treatment of cognitive impairment in patients with CAD complicated with depression and anxiety, and to thus improve the prognosis of such patients, the Psychocardiology Medicine Branch of Chinese Medical Association Beijing Branch, and Psychocardiology Education Professional Committee of China Medical Education Association, together with over 40 other organizations, including more than 50 experts from several related fields, have developed the association standards on guidelines for the cognitive clinical diagnosis and treatment of CAD complicated with depression and anxiety under the framework of the China standard association (No.T/CAS 812-2024).
Humans ; Depression/diagnosis* ; Coronary Artery Disease/psychology* ; Anxiety/diagnosis* ; Practice Guidelines as Topic