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

Chaihu and Longgu Muli Decoction has demonstrated significant efficacy in the treatment of tachyarrhythmia accompanied by anxiety and depression. However, there is a lack of standardized guidelines for its clinical application. In this study, the Chaihu and Longgu Muli Decoction was investigated through extensive research on ancient and modern literature, as well as a collection of clinical medical records. The basic information, medication details, and diagnostic information from medical records, personal experience literature, and clinical cases in the treatment of tachyarrhythmia accompanied by anxiety were extracted and analyzed to preliminarily identify the prescription characteristics and syndrome patterns. Subsequently, the Delphi method was employed to construct an item pool based on the data obtained in the first step. An expert questionnaire was prepared to collect scores and revision opinions from experts regarding these items. After statistical analysis and group discussions, a second round of questionnaires was formed by screening out certain items. This process was repeated until a final item set for the treatment of tachyarrhythmia accompanied by anxiety with Chaihu and Longgu Muli Decoction was determined. These findings provided guidance for clinical prescription practices. By extracting 71 syndromes and signs, as well as 33 tongue and pulse characteristics, the main syndrome features included palpitations, chest tightness, irritability, etc., which were basically consistent with the ancient syndromes. Through frequency analysis and group discussions, 71 items were screened out. After screening, modification, and primary and secondary division, 11 main diagnostic items and 10 secondary diagnostic items were determined. On this basis, the research team believes that Chaihu and Longgu Muli Decoction is mainly indicated for the following syndromes in the treatment of tachyarrhythmia accompanied by anxiety(palpitations, poor sleep, bitter taste, dry mouth, irritability/easily angered/anxiety/fearfulness/easily startled, red tongue with greasy yellow coating, rapid pulse, high work/life pressure, tachyarrhythmia on electrocardiogram/Holter monitor, and positive results on anxiety scale). Secondary syndromes include chest tightness, shortness of breath, feeling heavy and weak in the body, sweating, poor appetite, constipation, greasy white tongue coating, wiry pulse, slippery pulse, or knotted and intermittent pulse.
Drugs, Chinese Herbal/therapeutic use* ; Humans ; Delphi Technique ; Anxiety/complications* ; Tachycardia/psychology* ; Female ; Male ; Middle Aged ; Adult ; Aged

A single-center, randomized, double-blind, dose-controlled trial of modified Sini Powder in treating mild to moderate generalized anxiety disorder(GAD) in the patients with syndrome of liver depression transforming into fire was conducted at Xiyuan Hospital, China Academy of Chinese Medical Sciences. A total of 80 patients with mild to moderate GAD and the syndrome of liver depression transforming into fire were included. Patients were assigned by the central randomization system at a ratio of 3∶1 into an observation group(n=60, receiving a conventional-dose of granules of modified Sini Powder) and a control group(n=20, receiving low-dose granules with the active ingredients being 50% of that in observation group). Assessments were conducted before treatment(baseline), after 2 weeks of introduction, after 2/4/8 weeks of treatment, and after 4 weeks of follow-up. The results were summarized as follows. In terms of primary outcome indicators, the observation group(62.2%) showed higher total response rate than the control group(26.6%)(P<0.05), and greater Hamilton anxiety scale(HAMA) score reduction after 8 weeks of treatment(P<0.05). In terms of secondary outcome indicators, the HAMA score(somatic anxiety score), traditional Chinese medicine(TCM) syndrome scores, Pittsburgh sleep quality index(PSQI) scale, and clinical global impression(CGI) scale score in the observation group showed a significant compared to the control group at each visit points(P<0.05). Adverse events occurred in 10 cases, including 9(16.9%) cases in the observation group and 1(6.6%) case in the control group. No adverse reaction was observed. In conclusion, conventional-dose modified Sini Powder demonstrated superior efficacy and favorable safety for mild and moderate GAD in the patients with the syndrome of liver depression transforming into fire over low-dose treatment.
Humans ; Male ; Female ; Adult ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/administration & dosage* ; Anxiety Disorders/drug therapy* ; Treatment Outcome ; Young Adult ; Powders ; Aged ; Liver/drug effects* ; Generalized Anxiety Disorder

This study aims to investigate the mechanism through which Xiangshao Granules treat anxiety and depression using metabolomics and gut microbiota techniques, combined with animal experiments. Sixty female ICR mice were selected for the experiment and randomly divided into six groups: a control group, a model group, a low-dose Xiangshao Granules group, a medium-dose Xiangshao Granules group, a high-dose Xiangshao Granules group, and an estradiol(positive drug) group. Except for the control group, rats in other groups were induced for anxiety and depression model by ovariectomy(OVX) combined with chronic unpredictable mild stress(CUMS). After successful modeling, the mice received oral administration of Xiangshao Granules or estradiol for three weeks. Anxiety and depression behaviors in mice were evaluated using light-dark box tests, open field tests, and elevated plus-maze tests. The levels of substances closely related to anxiety and depression, such as serotonin(5-HT) and estrogen(E_2), were quantified in plasma and hippocampal tissue using enzyme-linked immunosorbent assay(ELISA). Metabolomics and 16S rDNA amplicon sequencing techniques were employed to analyze the regulatory effects of Xiangshao Granules on plasma metabolites and metabolic pathways in anxiety and depression mice, as well as their impact on the distribution of gut microbiota. Finally, the correlation between plasma metabolites and differential gut microbiota was constructed using the Spearman correlation coefficient method. Behavioral experimental results indicated that, compared to the control group, the model group exhibited significantly decreased dwell time in the light box, reduced total distance in the open field, and diminished dwell time in the open arm. In contrast, high dose of Xiangshao Granules were found to increase the dwell time in the light box and total distance in the open field. ELISA results indicated that the levels of 5-HT, gamma-aminobutyric acid(GABA), E_2 were significantly decreased, luteinizing hormone(LH), adrenocorticotropic hormone(ACTH), and corticosterone(CORT) were significantly elevated in the anxiety and depression mice, and treatment with middle, high dose of Xiangshao Granules reversed the levels of these substances. Additionally, in the anxiety and depression mouse model, the levels of follicle-stimulating hormone(FSH) were significantly increased, whereas middle, high dose of Xiangshao Granules decreased FSH levels. Metabolomics analysis revealed that Xiangshao Granules significantly changed the metabolic profile of the anxiety and depression mice, affecting central carbon metabolism, amino acid biosynthesis, and ABC transporter pathways. The results from 16S rDNA amplicon sequencing showed that Xiangshao Granules improved the relative abundance of genera such as Bacteroidia, Bacilli, Lactobacillales, and Lactobacillus. Spearman correlation analysis indicated a close association between specific differential gut microbiota and plasma differential metabolites. This study suggests that Xiangshao Granules significantly ameliorate anxiety and depression symptoms in mice by altering the levels of substances associated with these conditions, including 5-HT, GABA, E_2, LH, and ACTH. The metabolomics and gut microbiota data suggest that the therapeutic mechanism may be closely related to the regulation of amino acid biosynthesis, central carbon metabolism, and the alteration of key microbial community compositions.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Anxiety/microbiology* ; Depression/microbiology* ; Gastrointestinal Microbiome/drug effects* ; Mice ; Female ; Mice, Inbred ICR ; Metabolomics ; Serotonin/metabolism* ; Humans ; Disease Models, Animal ; Rats ; Behavior, Animal/drug effects*

BACKGROUND AND OBJECTIVE: Social anxiety arising from intensive social media usage (SMU) among adolescents and youth has gained extensive attention in recent years due to its negative influence on mental health and academic performance. In spite of that, there is a dearth regarding the etiology of SMU-related social anxiety. This study aims to further clarify the influence of introversion personality on SMU-related social anxiety and the mechanism underlying such an association and provide a new perspective for developing effective intervention strategies for the highly prevailing SMU-related anxiety among Chinese college students. METHODS: A cohort of 979 college students (266 males and 713 females) aged 20.90 ± 1.91 years was enrolled in this cross-sectional study. Four measures including the "extroversion" domain of Eysenck Personality Questionnaire Revised, Short Scale (EPQ-R-S E), Interaction Anxiousness Scale (IAS), Mobile Phone Addiction Index (MPAI), and Social Anxiety Scale for Social Media Users (SAS-SMU) were used to evaluate the influence of introversion personality on SMU-related social anxiety that was potentially mediated sequentially by interaction anxiousness and mobile phone addiction. Hayes PROCESS was used for correlation and mediation analysis. RESULTS: Interaction anxiousness (indirect effect = -1.331, 95% CI : -1.559 - -1.122) partially mediated the association between introversion personality and SMU-related social anxiety. Besides, a sequential mediation of interaction anxiousness and mobile phone addiction in the link between introversion personality and SMU-related social anxiety was revealed (indirect effect = -0.308, 95% CI : -0.404 - -0.220). No significant mediating effect was found with mobile phone addiction in the association between introversion personality and SMU-related social anxiety. CONCLUSION: Targeting interaction anxiousness and mobile phone addiction may represent an efficient strategy alleviating SMU-related social anxiety among Chinese college students with introversion personality.
Humans ; Male ; Female ; Social Media ; Students/psychology* ; Anxiety/psychology* ; Young Adult ; Cross-Sectional Studies ; Universities ; Behavior, Addictive/psychology* ; Cell Phone ; Adolescent ; Introversion, Psychological ; China ; Surveys and Questionnaires ; Internet Addiction Disorder/psychology*

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 AND OBJECTIVE

Filipino farmers face unique occupational challenges that increase the risk of mental health issues, particularly anxiety. This study aims to determine the different personal, environmental, socioeconomic, occupational, and psychosocial factors associated with anxiety symptoms among Filipino farmers in Central Luzon.

Chain referral sampling method was used to recruit participants for the study, who underwent screening based on the eligibility criteria. Eligible participants were then asked about anxiety symptoms using the Generalized Anxiety Disorder-7 (GAD-7), while the validated, researcher-constructed Data Collection Tool for Factors Associated with Anxiety Symptoms (DCFAAS) was used to determine the farmers’ exposure to a variety of factors. Microsoft Excel was utilized in computing for frequency and percent distribution of participants, in each factor. Binary logistic regression was used to compute crude and adjusted odds ratio of each factor thru IBM SPSS Statistics®.

Among the 113 eligible farmers enrolled in the study, only 19 (16.8%) experienced anxiety symptoms, with excessive worrying, which was seen among 45 participants (39.8%). The mental health of Filipino farmers was significantly affected by the presence of physical illness (OR = 10.70 [95% CI 1.367, 83.773]) and having relatives affecting work completion (OR = 6.45 [95% CI 1.346, 30.896]). 

Despite the low prevalence of anxiety symptoms in this study, the findings suggest government policies to improve mental health service access to farmers, to integrate psychosocial support into agricultural programs, and to address family-related work pressures. By addressing these factors, it can improve farmer productivity and promote overall well-being, putting emphasis on the mental health of the Filipino farmers.

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.