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Introduction: Generalized anxiety disorder (GAD) has been associated with elevated levels of C-reactive protein (CRP) and proinflammatory cytokines. Despite robust evidence as an effective treatment for GAD, research on the effects of cognitive-behavioral therapies (CBT) in the inflammatory profile of patients with clinical anxiety has presented mixed results. Objective: The present study aimed to investigate the effect of an acceptance-based behavior therapy (ABBT) on inflammatory biomarkers and their association with anxiety levels in GAD patients in comparison to supportive therapy as an active control. Methods: Peripheral inflammatory biomarkers (CRP, IL-1ß, IL-4, IL-6, IL-10, TNF-α) were measured in 77 GAD patients who participated in a 14-week 10-session randomized clinical trial of group ABBT (experimental, n = 37) or supportive group therapy (ST: active control group, n = 40). Results: The concentrations of IL-1ß decreased in the control group and the concentrations of IL-6 increased in the experimental group from baseline to post-treatment, whereas no difference was identified in IL-4, IL-10, TNF, or CRP. Although anxiety and depression levels decreased in both treatment conditions, no correlation with inflammation markers was found for most clinical and biological variables. A negative correlation between changes in IL-6 and IL-10 and anxiety symptom score changes was identified. Conclusions: The present study results found that a short trial of acceptance-based behavior therapy did not change the proinflammatory profile which may be associated with GAD. Additional research is needed to evaluate the influence of other inflammation-related variables, longer periods of follow-up as well as the effect of supportive therapy on peripheral inflammatory biomarkers in GAD patients.

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Background and objectives A controversy regarding the duration of generalized anxiety disorders (GAD) and depressive symptoms during the COVID-19 pandemic arose, stating that these symptoms last a short time, perhaps a few months, or that they are more persistent over time. After more than three years of the pandemic, this is still a question that requires an answer. The main goal of this work was to record the levels of self-perceived GAD and depression in the Argentine population at several time points during the pandemic to characterize whether they were transient or persisted over the successive waves of contagion. Furthermore, we studied the association between anti-COVID-19 vaccination and the high frequency of physical activity with GAD and depression levels to evaluate a possible protective role of these factors on mental health. Methods We used a descriptive and correlational research design. We carried out a repeated cross-sectional study performing seven online surveys (collection period: four to 15 days) at different time points in October 2020, May, August, October, and December 2021, and February and April 2022. The participants (24,308) were recruited through Instagram campaigns performed by renowned local scientific communicators and responded to the survey through Google Forms (Google, Mountain View, CA). Generalized anxiety was assessed using the Generalized Anxiety Disorder-7 (GAD-7). Depression was assessed using the Patient Health Questionnaire (PHQ-9). The respondents reported their symptoms using a four-point Likert scale, which led us to calculate the scores and also the prevalence (% of the population with moderate to severe symptoms) for GAD and depression and the frequency they performed physical activity per week. Data were statistically analyzed using the unpaired Mann-Whitney U-test, chi-squared, Spearman correlation, or Tukey's post hoc test after two-way ANOVA. Results Our results show that the highest prevalence for GAD and depression correspond to those of the second wave of infections (May 2021: 57.3% and 54.19%, respectively) and that the lower levels were reported by the end of the third wave (April 2022: 43.21% and 43.65%, respectively). Such levels were even lower than those reported during the first wave at the beginning of our study (October 2020: 45.94% and 48.92%, respectively). In other words, even though the third wave tripled the number of people infected with respect to the second one, its effects on mental health were attenuated. The increment in the vaccine doses inoculated between the last two waves of contagion was associated with a decrease in the GAD score (mean ± SEM: 10.75 ± 0.06 vs. 8.88 ± 0.13) and the depressive symptoms (mean ± SEM: 10.76 ± 0.07 vs. 9.23 ± 0.14). Throughout the entire study period, the fraction of the population that practiced physical activity three or more times per week was self-perceived with lower levels of GAD and depression than those who exercised less frequently. Conclusions Of the three waves of contagion that the Argentine population suffered, the highest rates of GAD and depression were recorded in the second wave, and these symptoms decreased over the months, even during the third wave, which presented the highest number of infections. Our results also suggest that the progress of the vaccination campaign and the practice of physical exercises with high frequency could play a protective role in the mental health of the population during COVID-19.

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Despite being one of the main components of anxiety and playing a pivotal role in how an individual perceives and copes with anxiogenic situations or responds to a given treatment, trait anxiety is paradoxically omitted in most animal models of anxiety. This is problematic and particularly more concerning in models that are used to screen drugs and other treatments for specific anxiety disorders and to investigate their neurobiological mechanisms. Our group has been engaged in the search for specific anxiety-related traits in animal models of anxiety. We developed two new lines of rats with strong phenotypic divergence for high (Carioca High-conditioned Freezing [CHF]) and low (Carioca Low-conditioned Freezing [CLF]) trait anxiety as expressed in the contextual fear conditioning paradigm. Here, we summarize key behavioral, pharmacological, physiological, and neurobiological differences in one these lines, the CHF rat line, relative to randomized-cross controls and discuss how far they represent a valid and reliable animal model of generalized anxiety disorder and so high trait anxiety.

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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.

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OBJECTIVE: Explore the prevalence of generalized anxiety disorder (GAD) and associated factors in undergraduate dental students during the first wave of the COVID-19 pandemic in Brazil. MATERIALS AND METHODS: Cross-sectional study. A semi-structured questionnaire addressing the variables of interest was shared with dental students between July 8 and 27 2020. The outcome was determined using the seven-item generalized anxiety disorder (GAD-7) scale. A 'positive' diagnosis was defined as a total of ≥10 points on the scale. Statistical analysis involved descriptive, bivariate and multivariate analyses, with the significance level set at 5%. RESULTS: Among the 1050 students evaluated, 53.8% had a positive diagnosis for GAD. The multivariate analysis revealed that the prevalence of symptoms was higher among individuals who resided with more than three people, those enrolled at teaching institutions that suspended all clinical and laboratory activities, those who did not have an adequate home situation to maintain distance learning, those who had been diagnosed with COVID-19, those who felt anxious about having to see patients with a suspicion or diagnosis of COVID-19 and those who preferred to interrupt in-person academic activities until the population is vaccinated for the COVID-19 virus. CONCLUSION: The prevalence of GAD was high. Aspects related to the composition and organization of the home, the suspension of academic activities, a history of COVID-19 contamination, feelings of anxiety in providing dental care to patients with symptoms/suspected of COVID-19 infection and the preference to interrupt in-person academic activities until the population is vaccinated for COVID-19 were factors predisposing the students to anxiety during the first wave of the pandemic.

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Generalized anxiety disorder is a highly prevalent mental disorder. Previous data indicate that more than 18 million Brazilians suffer from this condition. Traditionally, generalized anxiety disorder has been considered a mild mental health disorder, despite its links to lower life expectancy, cardiovascular disease, and suicide. The aim of this article is to combine elements of systematic and critical reviews to produce a synthesis of the best evidence about generalized anxiety disorder treatment. Systematic reviews, meta-analyses, and randomized controlled trials were included. The descriptor used in the search was "generalized anxiety disorder," which resulted in 4,860 articles and seven other studies, of which 59 were selected. Antidepressants and benzodiazepines were indicated, as was pregabalin, and atypical antipsychotics, such as quetiapine, have been studied. Individual cognitive behavior therapy (third wave) has proven effective. There is extensive literature on many effective treatments for generalized anxiety disorder. The present review summarizes the therapeutic possibilities, emphasizing those available in Brazil. Further studies are needed to compare other available medications, assess psychotherapies and new treatments in greater depth, as well as to assess the ideal duration of therapy. Registration number: PROSPERO CRD42021288323.

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OBJECTIVE: To combine elements of a systematic review and critical review to produce best evidence synthesis for the treatament of GAD. METHOD: There was included systematic reviews, metanalysis, and randomized controlled trials. Descriptor used was "generalized anxiety disorder", resulting in 4860 articles and 7 other studies, of which 59 were selected. RESULTS: Antidepressants and benzodiazepines are indicated, as well as pregabalin. From, atypical antipsychotics quetiapine has been studied. Cognitive behavior therapy (third wave of behavioral and cognitive therapies) as well as individual CBT proven to be effective. CONCLUSION: There is extensive literature on many effective treatments for GAD. The present work summarizes the therapeutic possibilities, emphasizing those available in the Brazil. Further studies are still needed to compare other available medications, to assess psychotherapies in more depth, new treatments and specially to assess the ideal time for maintaining therapy.

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[This corrects the article DOI: 10.3389/fpsyg.2020.00356.].

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Social cognition impairments may be associated with poor functional outcomes, symptoms, and disability in social anxiety disorder (SAD) and generalized anxiety disorder (GAD). This meta-analysis aims to determine if emotion recognition and theory of mind (ToM) are impaired in SAD or GAD compared to healthy controls. A systematic review was conducted in electronic databases (PubMed, PsycNet, and Web of Science) to retrieve studies assessing emotion recognition and/or ToM in patients with SAD or GAD, compared to healthy controls, up to March 2022. Meta-analyses using random-effects models were conducted. We identified 21 eligible studies: 13 reported emotion recognition and 10 ToM outcomes, with 585 SAD patients, 178 GAD patients, and 753 controls. Compared to controls, patients with SAD exhibited impairments in emotion recognition (SMD = -0.32, CI = -0.47 - -0.16, z = -3.97, p < 0.0001) and ToM (SMD = -0.44, CI = -0.83 -0.04, z = -2.18, p < 0.01). Results for GAD were inconclusive due to the limited number of studies meeting the inclusion criteria (two for each domain). Relevant demographic and clinical variables (age, sex, education level, and anxiety scores) were not significantly correlated with emotion recognition or ToM impairments in SAD and GAD. Further studies employing ecological measures with larger and homogenous samples are needed to better delineate the factors influencing social cognition outcomes in both SAD and GAD.

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The impact of childhood experiences on the development of psychopathology is well established in the literature. Few studies, however, have assessed parental bonding during childhood as a predictor of response to anxiety disorders treatment. The aim of the study was to examine whether emotional memories of childhood parenting could predict short-term and long-term outcome in three different interventions for patients with generalized anxiety disorder (GAD): mindfulness-based intervention (Body in Mind Training [BMT]), fluoxetine (FLX), and an active control group (quality of life [QoL]). A total of 124 participants from a randomized controlled trial for GAD treatment were evaluated pre- and post-treatment and after 18 months. Patients were assessed for the severity of GAD symptoms (GAD-7, PSWQ, and DERS), early memories of warmth and safeness (EMWSS), and recall of perceived threat and subordination/submission in childhood (ELES). Negative childhood memories predicted a greater reduction in anxiety symptoms on BMT treatment compared to FLX and QoL, whereas positive childhood memories predicted more symptomatic improvement in the QoL group. Our findings suggest that individuals with GAD who have early memories of subordination and threat appear to benefit more from interventions that focus on developing emotion-regulation strategies and enhancing self-compassion, such as mindfulness-based interventions.

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