Effect of cranial electrotherapy stimulation as an add-on therapy on late-life generalized anxiety disorder: An open-label study.

INTRODUCTION: Cranial electrotherapy stimulation (CES) is beneficial in reducing anxiety in psychiatric patients. However, no studies have reported on elderly patients with generalized anxiety disorders (GAD). This study aimed to determine the efficacy and safety of a 6-week CES intervention for late-life GAD. MATERIALS AND METHODS: This single-arm pilot study assessed 6-week CES treatment (Alpha-Stim AID) for late-life GAD and 4-week follow-up post intervention. The Hamilton Rating Scale for Anxiety (HAMA) and Beck Anxiety Inventory (BAI) were used as baseline and outcome measures at weeks 4, 6, and 10, respectively. Treatment response was defined as 50 % or more reduction of the HAMA score and remission was defined as a of score ≤7 on the HAMA. Other measures included depression, sleep quality, and quality of life assessment. RESULTS: We included participants (n = 27) aged 68.0 ± 5.0 years, 81.5 % of whom were female. Fifteen (55.6 %), 18 (66.7 %), and 15 (55.6 %) patients were concurrently treated with antidepressants, BZDs, and antipsychotics, respectively. Intention-to-treat (ITT) analysis revealed a significant decrease in HAMA scores from baseline (20.96 ± 3.30) to week 6 (12.26 ± 7.09) and one-month (12.85 ± 7.08) follow-up at W10 (all p < 0.001). The response and remission rates were 33.3 %, 40.7 %, and 48.1 % and 25.9 %, 29.6 %, and 25.9 % at W4, W6, and W10, respectively. The CES improved depression and sleep conditions as measured by the Beck Depression Inventory-II and Pittsburgh Sleep Quality Index. CONCLUSION: CES clinically reduces symptoms of anxiety and depression and may improve sleep quality in late-life GAD. Future randomized controlled study is needed.

Acupuncture Treatment for Generalized Anxiety Disorder by Activating the Vagus Nerve and Improving Heart-Rate Variability and Heart-Rhythm Coherence, A Case-Series Study.

Objective: The goal of this case series was to observe the effectiveness of acupuncture for reducing sympathetic stress and anxiety-related symptoms in generalized anxiety disorder. The effect of acupuncture on the balance of the autonomic nervous system was also examined. Materials and Methods: This was a case-series study with 10 participants enrolled. Each participant received acupuncture treatment 2 times per week for 4 weeks. Participants were evaluated with the Generalized Anxiety Disorder-7 (GAD-7) scale and the Body Perception Questionnaire-Short Form (BPQ-SF) before and after the treatment program. Heart-rate variability heart-rhythm coherence (HRC) was also assessed during each acupuncture session. Results: Five participants completed the program. Both GAD-7 and BPQ mean scores showed significant reductions. The mean HRC high-coherence ratio also increased significantly after acupuncture treatment. No adverse effects occurred. Conclusions: Acupuncture may be an effective therapy for sympathetic stress and anxiety-related symptoms. The mechanism of action may be through activating the vagus nerve and improving the HRC high coherence ratio. It is feasible to conduct larger clinical trials with random controls, longer treatment durations, and long-term follow-ups to support the results of this study.

Acupuncture for generalized anxiety disorder: a study protocol for a randomized controlled trial

During the COVID-19 outbreak, there was a sharp increase in generalized anxiety disorder (GAD). Acupuncture therapy has the advantages of accurate clinical efficacy, safety and reliability, few adverse reactions, and no dependence, and is gradually becoming one of the emerging therapies for treating GAD. We present a study protocol for a randomized clinical trial with the aim of exploring the mechanism of brain plasticity in patients with GAD and evaluate the effectiveness and reliability of acupuncture treatment. Transcranial magnetic stimulation (TMS) will be used to assess cortical excitability in GAD patients and healthy people. Sixty-six GAD patients meeting the inclusion criteria will be randomly divided into two groups: TA group, (treatment with acupuncture and basic western medicine treatment) and SA group (sham acupuncture and basic western medicine treatment). Twenty healthy people will be recruited as the control group (HC). The parameters that will be evaluated are amplitude of motor evoked potentials (MEPs), cortical resting period (CSP), resting motor threshold (RMT), and Hamilton Anxiety Scale (HAMA) score. Secondary results will include blood analysis of γ-aminobutyric acid (GABA), glutamate (Glu), glutamine (Gln), serotonin (5-HT), and brain-derived nerve growth factor (BDNF). Outcomes will be assessed at baseline and after the intervention (week 8). This study protocol is the first clinical trial designed to detect differences in cerebral cortical excitability between healthy subjects and patients with GAD, and the comparison of clinical efficacy and reliability before and after acupuncture intervention is also one of the main contents of the protocol. We hope to find a suitable non-pharmacological alternative treatment for patients with GAD.

Self-guided imagery rescripting for worry images: A preliminary experimental investigation.

BACKGROUND: Mental images of feared events are overactive and intrusive in generalized anxiety disorder (GAD). Imagery rescripting involves integration of positive or neutral imagery and corrective information into images to facilitate emotional processing, reduce imagery intrusions, and re-structure underlying schema. Yet only one known study has applied the technique to treatment of worry. The present study aimed first to examine the relationship between trait worry and properties of future-oriented worry images, and second to examine the efficacy of a self-guided imagery rescripting intervention in improving individuals' response to their worries. METHODS: Participants recruited through Amazon Mechanical Turk (N = 365) identified their major worry and wrote the script of a worst-case scenario mental image. Participants were randomized to three conditions: re-writing the same worry image script (exposure), or writing scripts of either one or three positive alternative future-oriented images (rescripting conditions). RESULTS: In preliminary analyses, trait worry negatively predicted participants' ratings of worry images, including valence and ability to cope, and positively predicted distress, anticipated cost, and belief in their negative meaning. In experimental analyses, linear mixed-effects models revealed anxious response and cognitive appraisal of the threat were significantly lower among participants allocated to rescripting relative to exposure. There was no effect of rescripting type. CONCLUSIONS: This investigation demonstrated the impact of a future-oriented imagery rescripting task on anxiety and cognitive biases associated with real worries in an unselected sample. Results may contribute to the development of imagery rescripting interventions for GAD.

Knowledge and Behavior of Primary Care Physicians Regarding Utilization of Standardized Tools in Screening and Assessment of Anxiety, Depression, and Mood Disorders at a Large Integrated Health System.

INTRODUCTION: Standardized screening, objective evaluation, and management of behavioral health conditions are major challenges in primary care. The Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire (PHQ-9), and Mood Disorder Questionnaire (MDQ) provide standardized screening and symptom management tools for generalized anxiety disorder (GAD), major depressive disorder (MDD), and Mood Disorders (MD), respectively. This study explores family physicians' knowledge, attitudes, and practices regarding the utilization of GAD-7, PHQ-9, and MDQ in outpatient primary care offices. METHODS: The study method was a cross-sectional electronic and paper survey utilizing a self-administered questionnaire that assessed primary care physicians' demographics, knowledge, attitudes, and practices in rural and urban outpatient clinical settings regarding GAD-7, PHQ-9, and MDQ. Statistical software SAS 9.4 was used for descriptive and Chi-Square statistics. RESULTS: Out of 320 total participants,145 responded (45.3%). Responding family physicians demonstrated a high level of familiarity with the GAD-7 (97.9%), PHQ-9 (97.9%), and MDQ (81.3%) assessment tools. However, the reported utilization rates were relatively lower than knowledge, with 62.7%, 73.1%, and 31.9% extremely likely or likely to utilize the GAD-7, PHQ-9, and MDQ as screening and monitoring tools, respectively. Less than a quarter of the total respondents use the objective score for the future management of GAD, with significantly more residents utilizing the score for GAD-7 compared to attendings (P < .05). There was no statistical significance difference between residents and attendings for the objective evaluation of Major Depressive Disorder (P = .26) and Mood Disorders (P = .05). CONCLUSIONS: Despite being knowledgeable of the utility of GAD-7, PHQ-9, and MDQ, the primary care physicians in a large integrated health system in Central Pennsylvania and Northern Maryland report inconsistent utilization in their practice. Further studies are needed to determine the underlying factors contributing to the suboptimal usage of these screening tools and ways to increase it.

Which client with generalized anxiety disorder benefits from a mindfulness ecological momentary intervention versus a self-monitoring app? Developing a multivariable machine learning predictive model.

Precision medicine methods (machine learning; ML) can identify which clients with generalized anxiety disorder (GAD) benefit from mindfulness ecological momentary intervention (MEMI) vs. self-monitoring app (SM). We used randomized controlled trial data of MEMI vs. SM for GAD (N = 110) and tested three ML models to predict one-month follow-up reliable improvement in GAD severity, perseverative cognitions (PC), trait mindfulness (TM), and executive function (EF). Eleven baseline predictors were tested regarding differential reliable change from MEMI vs. SM (age, sex, race, EF errors, inhibitory dyscontrol, set-shifting deficits, verbal fluency, working memory, GAD severity, TM, PC). The final top five prescriptive predictor models of all outcomes performed well (AUC = .752 .886). The following variables predicted better outcome from MEMI vs. SM: Higher GAD severity predicted more GAD improvement but less EF improvement. Elevated PC, inhibitory dyscontrol, and verbal dysfluency predicted better improvement in most outcomes. Greater set-shifting and TM predicted stronger improvements in GAD symptoms and TM. Older age predicted more alleviation of GAD and PC symptoms. Women exhibited more enhancements in trait mindfulness and EF than men. White individuals benefitted more than non-White. PC, TM, EF, and sociodemographic data might help predictive models optimize intervention selection for GAD.

Effect of a Home-Based Simplified Tai Chi Exercise Program on Sleep Quality, Daytime Sleepiness, Quality of Life, and Psychological Well-Being in Egyptian Older Adults: A Quasi-Experimental Study.

Introduction: Sleep disturbances are common among older adults and can have detrimental effects on their overall well-being. Tai Chi exercise has shown promise in improving sleep quality, quality of life (QoL), and psychological well-being in various populations. Objective: To investigate the effect of a home-based simplified Tai Chi exercise program on sleep quality, daytime sleepiness, QoL, and psychological well-being in Egyptian older adults. Methods: A quasi-experimental design was employed, with 152 participants aged 60 years and above assigned to either an experimental group (n = 87) or a control group (n = 65). Thecontrol group received a health education program to improve their sleeping quality and life-style, while the experimental group received a similar health education program and Tai Chi exercise training program. The participants in the experimental group were instructed to perform 3 months Tai Chi exercise. Data on sleep quality, daytime sleepiness, QoL, generalized anxiety disorder (GAD), and depression symptoms were collected at baseline, and one month, and 3 months post-intervention using validated questionnaires. Repeated measures ANOVA was done to investigate the effectiveness of the intervention programsover 3 time periods. Results: The results showed significant improvements in sleep quality (p < .001), QoL (p < .005), GAD (p < .005), and depression symptoms (p < .005) post-interventions. Also, there were significant difference in the effectiveness of the intervention programs between both the experimental and control groups. The experimental group exhibited greater improvements compared to the control group. Conclusion: The findings support the beneficial effects of a home-based simplified Tai Chi exercise program on sleep quality, QoL, and psychological well-being in Egyptian older adults. These results have important implications for promoting healthy aging and improving overall well-being in this population. Further research is recommended to validate these findings and explore the underlying mechanisms of Tai Chi exercise on the outcomes of interest.

Chaihu Longgu Mulitang Relieves Generalized Anxiety Disorder in Rats via p38 MAPK/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo study whether Chaihu Longgu Mulitang can inhibit hypothalamic inflammation， mitigate anxiety-like behavior， and alleviate anxiety symptoms by regulating the p38 mitogen-activated protein kinase/nuclear factor-κB （p38 MAPK/NF-κB） signaling pathway in the rat model of generalized anxiety disorder （GAD）. MethodTwelve out of 74 Wistar rats were randomly selected as the blank group， and the remaining rats were subjected to chronic restraint stress for the modeling of GAD. The open field test （OFT） and elevated Porteus maze test （PMT） were conducted 14 days after modeling to detect the anxiety-like behaviors. Sixty successfully modeled rats were selected and randomized into model， low-， medium-， and high-dose （6， 12， and 24 g·kg-1， respectively） Chaihu Longgu Mulitang， and diazepam （1 mg·kg-1） groups （n=12） and administrated with corresponding drugs for 14 consecutive days. OFT and PMT were then carried out to examine the anxiety-like behaviors of the rats. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） in the hypothalamus and serum of rats were determined by the enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）was conducted to determine the mRNA levels of p38 MAPK， NF-κB p65， nuclear factor κB inhibitor α （IκBα）， and ionized calcium binding adaptor molecule 1 （Iba-1）. The protein levels of p38 MAPK， phosphorylated （p）-p38 MAPK， NF-κB p65， p-NF-κB p65， and IκBα in the hypothalamus of rats were determined by Western blot. The expression of Iba-1 in the hypothalamic microglia was detected by immunofluorescence assay. ResultCompared with the blank group， the model group had decreased body weight， scattered dark yellow fur， increased irritability， and preference to hibernation in the corner. In addition， the modeled rats showed increased edge movement distance and time in OFT （P<0.01） and decreased movement distance and time and the number of entries in the open arm in PMT （P<0.01）. The modeling increased the fluorescence intensity of Iba-1 in paraventricular nucleus of hypothalamus （P<0.01）， elevated the levels of IL-1β， IL-6， and TNF-α in the serum and hypothalamus （P<0.01）， up-regulated the protein and mRNA levels of p38 MAPK， NF-κB p65， p-p38 MAPK， p-NF-κB p65， and Iba-1 （P<0.05， P<0.01）， and down-regulated the protein and mRNA levels of IκBα （P<0.01） in the hypothalamus. Compared with the model group， medium- and high-dose Chaihu Longgu Mulitang and diazepam increased the body weight， improved the fur and behaviors， decreased the edge movement distance and time in OFT （P<0.05， P<0.01）， and increased the movement distance and time in the open arm in PMT （P<0.05， P<0.01）. Furthermore， they decreased the fluorescence intensity of Iba-1 in hypothalamic microglia （P<0.05， P<0.01）， lowered the levels of IL-1β， IL-6， and TNF-α in the serum and hypothalamic tissue （P<0.05， P<0.01）， down-regulated the mRNA and protein levels of p38 MAPK， NF-κB p65， p-p38 MAPK， p-NF-κB p65， and Iba-1 （P<0.05， P<0.01）， and up-regulated the mRNA and protein levels of IκBα （P<0.05， P<0.01） in the hypothalamus. ConclusionChaihu Longgu Mulitang can mitigate anxiety-like behaviors and relieve anxiety in GAD rats by inhibiting the p38 MAPK/NF-κB signaling pathway and reducing the activation of microglia and the levels of pro-inflammatory cytokines in the hypothalamus.

Efficacy of manual acupuncture vs. placebo acupuncture for generalized anxiety disorder (GAD) in perimenopausal women: a randomized, single-blinded controlled trial.

Background: Generalized anxiety disorder (GAD) is common among perimenopausal women. Acupuncture may be an effective treatment for GAD, but evidence is limited. The pathogenesis of GAD is not yet clear, but it is related to the hypothalamic-pituitary-adrenal axis and its excretion, cortisol (CORT), and the adrenocorticotropic hormone (ACTH). The objective of this study is to evaluate the efficacy of manual acupuncture (MA) vs. placebo acupuncture (PA) for perimenopausal women with GAD. Methods: This study is a single-center, randomized, single-blind clinical trial conducted in the First Affiliated Hospital of Guangzhou University of Chinese Medicine. A total of 112 eligible patients with GAD were randomly assigned (1:1) to receive MA (n = 56) or PA (n = 56) three times per week for 4 weeks. The primary outcome measure was the HAMA score. The secondary outcome measures were the GAD-7 and PSQI scores and the levels of CORT and ACTH. The evaluation will be executed at the baseline, 2 weeks, the end of the treatment, and a follow-up 3-month period. Results: Significant improvements in HAMA (p < 0.001, η2p = 0.465), GAD-7 (p < 0.001, η2p = 0.359) and ACTH (p = 0.050) values were found between T0 and T2 in the MA group compared to the PA group. No difference in PSQI (p = 0.613, η2p = 0.011) and CORT (p = 0.903) was found between T0 and T2 in the MA group compared to the PA group. Long-term improvements in HAMA (p < 0.001, p < 0.001) were found in the MA group and PA group. Conclusion: This study was the first completed study to evaluate the efficacy of acupuncture and placebo acupuncture for GAD in perimenopausal patients. Results suggested that placebo acupuncture has a therapeutic effect, however, acupuncture had a greater therapeutic effect than placebo acupuncture. This study supports the effectiveness of acupuncture and thereby contributes to extended treatment options for GAD.Clinical trial registration:http://www.chictr.org.cn, Chinese Clinical Trial Registry, ID: ChiCTR2100046604. Registered on 22 May 2021.

Cognitive control as a potential neural mechanism of protective role of spirituality in anxiety disorders among American Indian people: An ERP study.

Research suggests that traditional cultural factors are protective against mental health conditions in American Indian (AI) populations. This study aims to determine if cognitive control is a neurocognitive mechanism of the protective role of spirituality in AI people with generalized anxiety disorder (GAD). Participants self-identified as AI (n = 52) and included individuals with GAD (n = 16) and without GAD (n = 36). Electroencephalography was collected during a stop-signal task to probe cognitive control using the P3 event-related potential. Higher levels of spirituality attenuated the processing efficiency disruption among individuals with GAD as indicated by P3 amplitudes closer to that of individuals without GAD.

Effect of kava (Piper methysticum) on peripheral gene expression among individuals with generalized anxiety disorder: A post hoc analysis of a randomized controlled trial.

Kava is a South Pacific plant-based medicine with anxiolytic properties, but little is known about the impact kava has on gene expression or whether gene expression can serve as a marker of kava response. This study aimed to determine whether kava treatment alters the expression of genes with physiological relevance to anxiety pathophysiology and whether the baseline expression of these physiologically relevant genes modifies the efficacy of kava treatment. In this post hoc analysis, we examined the expression of 48 genes relevant to the pathophysiology of anxiety collected from a double-blind randomized controlled trial that assessed the efficacy of kava treatment in generalized anxiety disorder. Peripheral blood gene expression was measured in 71 (34 kava, 37 placebo) adults at baseline and in 40 (19 kava, 21 placebo) after 8 weeks of treatment by reverse transcription polymerase chain reaction (PCR). Results revealed that kava decreased the expression of a subunit of the GABAA -rho receptor gene (GABRR2) and catechol-O-methyltransferase (COMT), a gene related to catecholamine metabolism. Kava efficacy was not found to be modified by baseline (pretreatment) expression of relevant genes. Although these results did not withstand statistical correction for multiple comparisons and require external validation, they support the notion that kava's mechanism of action includes interaction with GABAergic and catecholaminergic systems.

Comparing Kundalini Yoga, cognitive behavioral therapy, and stress education for generalized anxiety disorder: Anxiety and depression symptom outcomes.

Increasingly, individuals with anxiety disorders are seeking mind-body interventions (e.g., yoga), but their effectiveness is unclear. This report summarizes seven additional, secondary outcomes measuring anxiety and depression symptoms from a study of 226 adults with generalized anxiety disorder who were randomized to 12-week Kundalini Yoga, Cognitive-Behavior Therapy (CBT) or stress education (control). At post-treatment, participants receiving CBT displayed significantly lower symptom severity, compared to those in the control group, on 6 of the 7 measures. Participants who received Yoga (vs. those in the control group) displayed lower symptom severity on 3 of the 7 measures. No significant differences were detected between participants receiving CBT vs those receiving Yoga. At the 6-month follow-up, participants from the CBT continued to display lower symptoms than the control group.

Pharmacotherapy for Depression and Anxiety in the Primary Care Setting.

The prevalence of mental health disorders is rising with the coronavirus of 2019 pandemic, and millions of Americans reside in areas with mental health professional shortages. Primary care providers have an opportunity to provide care for commonly occurring mental health disorders. Using a holistic conceptualization of recovery in mental illness, this report provides evidence-based guidance for initiation, titration, and discontinuation of pharmacotherapy for mild to moderate depression and anxiety in the primary care setting. The use of measurement-based care, selection of appropriate class and agent for individual candidates, and patient education are addressed. Best practices for troubleshooting, titration, and referral are discussed.

A randomized controlled trial of a 14-day mindfulness ecological momentary intervention (MEMI) for generalized anxiety disorder.

BACKGROUND: Little is known about whether brief mindfulness ecological momentary interventions (MEMIs) yield clinically beneficial effects. This gap exists despite the rapid growth of smartphone mindfulness applications. Specifically, no prior brief MEMI has targeted generalized anxiety disorder (GAD). Moreover, although theories propose that MEMIs can boost executive functioning (EF), they have largely gone untested. Thus, this randomized controlled trial (RCT) aimed to address these gaps by assessing the efficacy of a 14-day smartphone MEMI (versus self-monitoring placebo [SMP]). METHOD: Participants with GAD were randomly assigned to either condition (68 MEMI and 42 SMP). MEMI participants exercised multiple core mindfulness strategies and were instructed to practice mindfulness continually. Comparatively, SMP participants were prompted to practice self-monitoring and were not taught any mindfulness strategies. All prompts occurred five times a day for 14 consecutive days. Participants completed self-reports and neuropsychological assessments at baseline, posttreatment, and 1-month follow-up (1MFU). Piecewise hierarchical linear modeling analyses were conducted. RESULTS: MEMI (versus SMP) produced greater pre-1MFU reductions in GAD severity and perseverative cognitions (between-group d = 0.393-0.394) and stronger improvements in trait mindfulness and performance-based inhibition (d = 0.280-0.303). Further, MEMI (versus SMP) led to more considerable pre- to posttreatment reduction in state-level depression and anxiety and more mindfulness gains (d = 0.50-1.13). Overall, between-treatment effects were stronger at pre-1MFU than pre- to posttreatment for trait-level than state-level treatment outcome measures. CONCLUSIONS: Preliminary findings suggest that the beneficial effect of an unguided brief MEMI to target pathological worry, trait mindfulness, and EF is modest yet potentially meaningful. Other theoretical and clinical implications were discussed.

Mechanisms of improvement in generalized anxiety disorder: A mediation and moderated mediation analysis from a randomized controlled trial.

BACKGROUND: Generalized anxiety disorder (GAD) is associated with the lowest treatment response rate among all anxiety disorders. Understanding mechanisms of improvement may help to develop more effective and personalized treatments. AIM: The objective of the study was to investigate different improvement mechanisms in the treatment of individuals diagnosed with GAD. DESIGN: We reported data from a randomized controlled trial that evaluated three different GAD treatments (mindfulness-based intervention, BMT; fluoxetine, FLX; and an active comparison group, QoL) for 8 weeks. METHOD: Mediation analyses were performed evaluating the association between worry symptoms at baseline and anxiety scoring at the endpoint, considering self-compassion or mindfulness or its dimensions at mid-treatment as mediators for the whole sample (assessing GAD improvement mechanism) and the different interventions as moderators. RESULTS: Contrary to mindfulness state scoring (C = .06; 95% CI = -.05 to .20), self-compassion (C = .11; 95% CI = .01 to .28) and non-judgement of inner experience (C = .10; 95% CI = .004 to .21) mediated the association between worry symptoms at baseline and anxiety at the endpoint. When comparing BMT to FLX, the intervention modality did not moderate these associations. CONCLUSION: Self-compassion and non-judgement of inner experience seem to be essential targets in GAD treatment, contrary to the mindfulness state itself. Although no difference was found considering the intervention modality, future research may assess how to boost these dimensions in specific treatments for GAD.

Efficacy of B-vitamins and vitamin D therapy in improving depressive and anxiety disorders: a systematic review of randomized controlled trials.

OBJECTIVES: This systematic review aimed to evaluate the efficacy of B vitamins and vitamin D therapy in improving the standard treatment of depression and anxiety disorders. We also aimed to gather the evidence supporting the recommendations for supplementation in clinical practice. METHODS: Performed between March 2020 and September 2021, the main inclusion criteria were randomized controlled trials (RCTs), with patients ≥ 18 years old, both sexes, fulfilling target diagnoses of major depressive disorder (MDD), generalized anxiety disorder (GAD), or mild to severe depressive and anxiety symptoms. In addition, the RCTs were included if the scales to assess the severity of the symptoms were standardized rating scales in psychiatric. Trials that reported diagnoses of schizophrenia, perinatal depression, bipolar depression, sleep disorders, eating disorders, cancer, and multiple sclerosis in association with any of the mentioned diagnoses were excluded. RESULTS: We identified 20 RCTs that matched all eligibility criteria, totaling 2,256 subjects, diagnosed with MDD, GAD, and depressive or anxiety symptoms. Supplementation with folic acid or L-methylfolate, B1, B12 or methylcobalamin, and vitamin D (in different doses and study duration) significantly decreased depression score scales by increasing response to standard pharmacological treatment or as monotherapy, including partial or complete remission. As for anxiety symptoms, the availability of results is limited to adjuvant vitamin D therapy. DISCUSSION: B vitamins and vitamin D associated with other compounds also showed significant results, so the improvement in symptoms cannot be attributed strictly to those. Our results suggest that intervention with B vitamins and/or vitamin D may be an effective and well-tolerated adjuvant strategy for improving the symptoms of depression and anxiety, according to the patient's clinical status and nutritional biomarkers.

Validation and clinical application of the Metacognitions Questionnaire in a sample of Brazilian generalized anxiety disorder patients: the effects of different treatment interventions.

INTRODUCTION: Metacognitive beliefs about worry may trigger anxiety. However, the effect of generalized anxiety disorder (GAD) treatment on metacognition has not yet been investigated. OBJECTIVES: To validate the Metacognitions Questionnaire (MCQ-30) in a Brazilian GAD sample and verify whether different interventions reduce metacognitive beliefs. METHOD: We recruited 180 GAD individuals and randomized them to Body in Mind Training (BMT), Fluoxetine (FLX), or an active control group (Quality of Life [QoL]) for 8 weeks. The MCQ-30 was assessed for internal consistency, was evaluated with confirmatory and exploratory factor analyses, and was tested for convergent validity with the Penn State Worry Questionnaire (PSWQ). Generalized estimating equations (GEE) were employed to analyze differences after the interventions. RESULTS: The MCQ-30 demonstrated good internal consistency and acceptability; the original five-factor model was supported. There was a positive moderate correlation between MCQ-30 scores and worry. GEE showed a significant group x time interaction (p < 0.001). Both BMT (mean difference [MD] = -6.04, standard error [SE] = -2.39, p = 0.034) and FLX (MD = -5.78, SE = 1.91, p = 0.007) reduced MCQ-30 scores. FLX was superior to QoL, but not BMT, at weeks 5 and 8. There were no differences between BMT and QoL. CONCLUSION: The Brazilian-Portuguese version of MCQ-30 showed good psychometric properties. Furthermore, the positive effect of FLX and BMT on metacognition suggests it may represent a potential therapeutic target.

Research Progress of Chinese Medicine on Generalized Anxiety Disorder / 世界科学技术-中医药现代化

Generalized Anxiety Disorder(GAD)is a common mental illness with anxiety as its main clinical symptom.Its prevalence is increasing year by year,and it has the risk of chronic disability,which seriously affects human physical and mental health.This article mainly from the etiology and pathogenesis,syndrome differentiation and treatment method has combed the GAD′s research progress of traditional Chinese medicine(TCM),the results show that the occurrence of GAD may be a stimulus such as poor social life events,applies to susceptible individuals,heart and other internal viscera function disorder,further produce sputum,drinks,water,dampness,blood stasis,fire as the main etiology and pathogenesis,pathological factors.The syndrome differentiation types are mainly heart and kidney non-communication type,liver stagnation and fire type,phlegm and fire on the disturbance type,heart and spleen deficiency type,heart and gallbladder qi deficiency and Yin deficiency internal heat type.Treatment mainly include syndrome differentiation and treatment,acupuncture and massage,etc.,the clinical curative effect is distinct,and the forward curative effect is superior to western medicine treatment,but there is also a lack of objective and syndromes curative effect evaluation standard,lack of the mechanism and system of TCM in the treatment of GAD targets into issues of scientific research,in order to optimization and the pathogenesis of GAD for the future of the diagnosis and treatment to provide reference for further studies.

The intervention study of mindfulness-based cognitive therapy on mindful attention awareness, experiential avoidance and cognitive fusion in patients with generalized anxiety disorder / 中华行为医学与脑科学杂志

Objective:To investigate the effect of mindfulness-based cognitive therapy (MBCT) on mindfulness attention awareness, experiential avoidance, and cognitive fusion in individuals with general anxiety disorder(GAD).Methods:A total of 53 patients aged 18-60 years who met the GAD diagnostic criteria of DSM-5 were selected from the Seventh People's Hospital of Hangzhou from May 2021 to September 2022.After receiving routine treatment, patients were randomly assigned to two groups: MBCT group( n=26) for an 8-week mindfulness cognitive therapy and health education group( n=27) for an 8-week health education program. Participants were evaluated using the generalized anxiety disorder scale(GAD-7), acceptance and action questionnaire-2nd edition(AAQ-Ⅱ), cognitive fusion questionnaire(CFQ), and mindful attention awareness scale (MAAS) before and after the intervention.Data were analyzed using SPSS 26.0 software, with the chi-square test, independent sample t-test, and paired sample t-test. Results:(1)There was no significant difference in MAAS score between the two groups before the intervention (42.63±10.18, 47.67±9.52, t=-1.55, P=0.13). However, after the intervention, the MAAS score in MBCT group was significantly higher than that in the health education group(54.42±9.87, 47.83±7.59, t=-2.27, P=0.03). (2) No significant difference was observed in CFQ score between the two groups before the intervention (57.11±15.97, 53.50±12.01, t=-0.77, P=0.45). However, after the intervention, the CFQ score in the MBCT group was significantly lower than that in the health education group(38.32±10.31, 47.11±10.66, t=-2.51, P<0.01). (3) There was no significant difference in AAQ-Ⅱ scores between the two groups before the intervention(33.79±7.90, 30.00±7.23, t=1.52, P=0.14). After the intervention, the AAQ-Ⅱ score in the MBCT group was significantly lower than that in the health education group(21.89±8.69, 30.22±8.68, t=-3.51, P<0.01) . Conclusion:MBCT has a positive effect on enhancing mindfulness attention awareness, reducing cognitive fusion, and mitigating experiential avoidance in GAD patients.

Acupuncture point selection for prevention and treatment of generalized anxiety disorder from the perspective of Microbiota-Gut-Brain Axis / 国际中医中药杂志

Disorders of the gut flora (GF) affect the level of 5-hydroxytryptamine (5-HT) in the brain of patients with generalized anxiety disorder (GAD) and influence the development of the disease. Most of the acupuncture points selected for GAD are based on the principles of local acupuncture points and acupuncture points following the distant channels of the meridians, regarding Baihui (DU 20), Fengchi (GB 20), and Yintang (GV 29) as the main acupuncture points, and the acupuncture points selected for the regulation of GF are Zhongwan (CV 12), Tianshu (ST 25), and Guanyuan (RN 4) and Zusanli (ST 36). Recently, many studies have been conducted on the mechanism of action of acupuncture in the treatment of GAD from the perspective of GF, but few have investigated the theoretical of acupuncture points used to prevent and treat GAD. This paper discusses the theoretical basis of acupuncture to regulate the "microbiota-gut-brain axis" (MGBA) for the prevention and treatment of GAD, and proposes the method of "regulating the internal organs and calming the mind and relieving anxiety" through analyzing the researches on the regulation of GF and GAD.