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

Objective To investigate the association between sleep behaviors （including bedtime， sleep quality， and nap duration） and academic performance among college students， as well as the regulatory effect of test anxiety and exercise habit on the association between sleep and academic performance. Methods A questionnaire survey was conducted to collect data. The grade of compulsory courses （with higher grades indicating better academic performance） was used as an ordinal dependent variable. All independent variables were coded by levels： for bedtime during exam and non-exam periods， higher levels indicated later bedtimes； for anxiety during the exam period， higher levels indicated more severe anxiety； for sleep quality during both exam and non-exam periods， higher levels indicated better sleep quality； for nap duration， higher levels indicated longer naps. Exercise habit was treated as a binary variable （yes/no）. Ordinal logistic regression （proportional odds model） was used for multivariable analysis， and OR and 95%CIwere calculated. In addition， sex-stratified models were established to investigate sex differences in the associations between these factors and academic performance. Results A total of 1 221 college students were included， among whom male students accounted for 33.7%. After controlling for confounding factors， bedtime during the exam period was significantly positively associated with the grade of compulsory courses， indicating that later bedtime was associated with a greater likelihood of achieving a higher grade （OR=1.32，95%CI 1.08‒1.62， P=0.007）. Sex was also an independent predictive factor， and the OR of achieving a higher grade in female students was 2.4 times that in male students （OR=2.41， 95%CI 1.90‒3.06， P<0.001）. Sleep quality during the exam period （OR=1.18，95%CI 0.99‒1.42， P=0.070） and exercise habit （OR=1.24， 95%CI 0.99‒1.55， P=0.064） showed marginally significant associations with grade. In contrast， bedtime during the non-exam period， nap duration， anxiety during the exam period， and self-rated sleep quality during the non-exam period showed no statistical significance （all P>0.05）. Sex-stratified analysis showed that among the male students， later bedtime during the exam period was associated with a greater likelihood of achieving a higher grade （OR=1.48， 95%CI 1.05‒2.09， P=0.025）， whereas higher anxiety during the exam period was associated with a lower likelihood （OR=0.79，95%CI 0.63‒0.98， P=0.032）； among the female students， better sleep quality during the exam period was associated with a greater likelihood of achieving a higher grade （OR=1.27， 95%CI 1.02‒1.57， P=0.033）， and bedtime during the exam period showed a positive association with academic performance， but without statistical significance （OR=1.25，95%CI 0.96‒1.62，P=0.091）. Conclusion The association between sleep behaviors and academic performance among college students varies with academic period and sex. Later bedtime during the exam period is associated with better academic performance， but this effect is observed only among male students. In addition， the academic performance of male students is negatively affected by test anxiety， whereas the academic performance of female students is positively associated with subjective sleep quality. Future interventions aimed at improving academic health should consider sex-specific strategies.
Anxiety ; Exercise

Objective To investigate the potential genetic mechanisms of insomnia and anxiety and the bidirectional causal relationship between them using Linkage Disequilibrium Score Regression （LDSC） and Mendelian Randomization （MR）. Methods Based on the data from genome-wide association studies， LDSC was used to analyze the genetic correlation of insomnia with anxiety and its subtypes. The inverse variance weighted （IVW） method was used as the main analytical method， supplemented by MR-Egger regression， weighted median， the simple model method， and weighted model. The Cochran’s Q test was used for heterogeneity testing， MR-Egger was used for pleiotropy testing， and the leave-one-out method was used for sensitivity analysis. Results The LDSC analysis revealed the genetic correlation of insomnia with anxiety and its subtypes. The results of IVW analysis showed that insomnia had a causal relationship with the increased risk of anxiety （OR=1.448，95%CI 1.025‒2.045，P=0.036，PFDR=0.178） and generalized anxiety disorder （OR=2.098，95% CI 1.105‒3.986， P=0.024， PFDR=0.314）. Conversely， the reverse MR analysis showed a causal relationship between generalized anxiety disorder and the increased risk of insomnia （OR=1.010， 95% CI 1.003‒1.017， P=0.008， PFDR=0.329）. No significant horizontal pleiotropy was detected for the instrumental variables （P>0.05）， and the sensitivity analysis showed that the results of MR analysis were stable. Conclusion Insomnia may be used as a risk factor for anxiety， and there is a genetic correlation between the two diseases.
Insomnia ; Anxiety

OBJECTIVES: To investigate the mechanisms of Modified Chaihu Guizhi Decoction (MCGD) for ameliorating anxiety- and depression-like behaviors in a mouse model of chronic unpredictable mild stress (CUMS). METHODS: The main chemical constituents of MCGD were identified through literature review, and network pharmacology analysis was performed to predict the potential pharmacological mechanisms of MCGD. For in vivo validation, male C57BL/6J mice were randomized into control group, CUMS model group, fluoxetine (FLX) treatment group, and low- and high-dose MCGD treatment groups (n=15), and in all but the control group, CUMS models were established by daily exposure to two randomized stressors for 28 consecutive days. Starting from 3 days prior to modeling, MCGD and fluoxetine treatments were administered daily via gavage and intraperitoneal injection, respectively. Depression- and anxiety-like behaviors of the mice were assessed using sucrose preference test, forced swim test, open field test and elevated plus maze test. The changes in mRNA expressions of the clock genes and inflammatory markers and expressions of the JAK2/STAT3 signaling proteins were detected using RT-qPCR and Western blotting, and immunofluorescence staining was used to detect microglia activation in the mice. RESULTS: The key active compounds in MCGD identified by network pharmacology analysis included quercetin, acacetin, formononetin, nobiletin, and baicalein. GO analysis identified 607 enriched pathways, and KEGG pathway enrichment revealed significant involvement of the JAK2/STAT3 and NF-κB signaling pathways. In the mouse models of CUMS, treatment with both fluoxetine and MCGD significantly alleviated anxiety- and depression-like behaviors. MCGD treatment significantly reduced Iba1 expression, improved the inflammatory markers, reversed the decrease in clock gene circadian rhythm amplitude, and obviously downregulated the expressions of JAK2, p-STAT3, p-NF-κB, IL-1β, and IL-6 proteins. CONCLUSIONS MCGD effectively alleviates anxiety- and depression-like behaviors in CUMS mice by modulating the inflammatory pathways and inhibiting the JAK2/STAT3 signaling pathway.
Animals ; Janus Kinase 2/metabolism* ; STAT3 Transcription Factor/metabolism* ; Signal Transduction/drug effects* ; Depression/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Male ; Mice, Inbred C57BL ; Anxiety/drug therapy* ; Stress, Psychological ; Disease Models, Animal

Anxiety disorder is a major symptom of autism spectrum disorder (ASD) with a comorbidity rate of ~40%. However, the neural mechanisms of the emergence of anxiety in ASD remain unclear. In our study, we found that hyperactivity of basolateral amygdala (BLA) pyramidal neurons (PNs) in Shank3 InsG3680 knock-in (InsG3680^+/+) mice is involved in the development of anxiety. Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs. Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680^+/+ mice. Further study found that the diminished control of the BLA by medial prefrontal cortex (mPFC) and optogenetic activation of the mPFC-BLA pathway also had a rescue effect, which increased the feedforward inhibition of the BLA. Taken together, our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680^+/+ mice.
Animals ; Prefrontal Cortex/metabolism* ; Basolateral Nuclear Complex/metabolism* ; Mice ; Anxiety/metabolism* ; Nerve Tissue Proteins/genetics* ; Male ; Gene Knock-In Techniques ; Pyramidal Cells/physiology* ; Mice, Transgenic ; Neural Pathways/physiopathology* ; Mice, Inbred C57BL ; Microfilament Proteins

The prelimbic cortex (PL) plays a critical role in processing both the sensory and affective components of pain. However, the underlying molecular mechanisms remain poorly understood. In this study, we observed a reduction in hyperpolarization-activated cation current (I_h) in layer V pyramidal neurons of the contralateral PL in a mouse model of spared nerve injury (SNI). The expression of hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) channels was also decreased in the contralateral PL. Conversely, microinjection of fisetin, a partial agonist of HCN2, produced both analgesic and anxiolytic effects. Additionally, we found that cyclin-dependent kinase 5 (CDK5) was activated in the contralateral PL, where it formed a complex with HCN2 and phosphorylated its C-terminus. Knockdown of CDK5 restored HCN2 expression and alleviated both pain hypersensitivity and anxiety-like behaviors. Collectively, these results indicate that CDK5-mediated dysfunction of HCN2 in the PL underlies nerve injury-induced mechanical hypersensitivity and anxiety.
Animals ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/metabolism* ; Hyperalgesia/metabolism* ; Cyclin-Dependent Kinase 5/metabolism* ; Neuralgia/metabolism* ; Male ; Anxiety/metabolism* ; Mice ; Potassium Channels/metabolism* ; Mice, Inbred C57BL ; Disease Models, Animal ; Pyramidal Cells/metabolism*

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: To elucidate the specific mechanisms by which electroacupuncture (EA) alleviates anxiety and fear behaviors associated with posttraumatic stress disorder (PTSD), focusing on the role of lipocalin-2 (Lcn2). METHODS: The PTSD mouse model was subjected to single prolonged stress and shock (SPS&S), and the animals received 15 min sessions of EA at Shenmen acupoint (HT7). Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear. Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex (PFC). Additionally, the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology. RESULTS: Mice subjected to SPS&S presented increased anxiety- and fear-like behaviors. Lcn2 expression in the PFC was significantly upregulated following SPS&S, leading to increased expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and suppression of PFC neuronal activity. However, EA at HT7 inhibited Lcn2 release, reducing neuroinflammation and hypoexcitability in the PFC. Lcn2 overexpression mitigated the effects of EA at HT7, resulting in anxiety- and fear-like behaviors. CONCLUSION EA at HT7 can ameliorate PTSD-associated anxiety and fear, and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC. Please cite this article as: Yang YD, Zhong W, Chen M, Tang QC, Li Y, Yao LL, et al. Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex. J Integr Med. 2025; 23(5):537-547.
Electroacupuncture ; Stress Disorders, Post-Traumatic/metabolism* ; Animals ; Lipocalin-2/metabolism* ; Prefrontal Cortex/physiopathology* ; Male ; Mice ; Neurons/physiology* ; Disease Models, Animal ; Fear ; Behavior, Animal ; Mice, Inbred C57BL ; Neuroinflammatory Diseases/metabolism* ; Anxiety/therapy* ; Acupuncture Points

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

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.