Background: Mental health burden has been massively reported during the COVID-19 pandemic period. Aiming to summarise these data, we present a meta-review of meta-analyses that evaluated the impact of COVID-19 pandemic on anxiety, depressive and stress symptoms, psychological distress, post-traumatic stress disorder/symptoms (PTSD), and sleep disturbance, reporting its prevalence on general public (GP) and health care workers (HCW).Methods: A search was performed in the PubMed, EMBASE, and the Web of Science. Sleep disturbances, psychological distress, stress, and burnout were grouped as “Psychophysiological stress,” and anxiety, depression, and PTSD were grouped as “Psychopathology.” A random-effects model, calculating the pooled prevalence together with 95% confidence interval was performed for each domain. Subgroup analyses were performed for each population type (GP and HCW) and for each mental health outcome. For anxiety and depression, subgroup analysis for population type was performed. Heterogeneity is reported as I2. Publication bias was assessed through visual inspection of the funnel plot, and further tested by Egger's test and trim and fill analyses.Results: A total of 18 meta-analyses were included. The prevalence of psychophysiological stress was 31.99% (CI: 26.88–37.58, I2 = 99.9%). HCW showed a higher prevalence (37.74%, CI: 33.26–42.45, I2 = 99.7%) than the GP (20.67%, 15.07–27.66, I2 = 99.9%). The overall prevalence of insomnia, psychological distress, and stress were, respectively, 32.34% (CI: 25.65–39.84), 28.25% (CI: 18.12–41.20), and 36% (CI: 29.31–43.54). Psychopathology was present at 26.45% (CI: 24.22–28.79, I2 = 99.9%) of the sample, with similar estimates for population (HCW 26.14%, CI: 23.37–29.12, I2 = 99.9%; GP: 26.99%, CI: 23.41–30.9, I2 = 99.9%). The prevalence of anxiety, depression, and PTSD was 27.77% (CI: 24.47–31.32), 26.93% (CI: 23.92–30.17), and 20% (CI: 15.54–24.37), respectively. Similar proportions between populations were found for anxiety (HCW = 27.5%, CI: 23.78–31.55; GP = 28.33%, CI: 22.1–35.5) and depression (HCW = 27.05%, CI: 23.14–31.36; GP = 26.7%, CI: 22.32–31.59). Asymmetry in the funnel plot was found, and a slight increase in the estimate of overall psychopathology (29.08%, CI: 26.42–31.89) was found after the trim and fill analysis.Conclusions: The prevalence of mental health problems ranged from 20 to 36%. HCW presented a higher prevalence of psychophysiological stress than the general population.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=252221, identifier: CRD42021252221.

Objective:The incidence rate of major depression in adolescents reaches approximately 14%. This disorder is usually recurrent, without remission of symptoms even after pharmacological treatment, and persists throughout adult life. Since the effects of antidepressants take approximately 2 weeks to begin, new pharmacological therapies are under continuous exploration. Recent evidence suggests that psychedelics could produce rapid antidepressant effects. In this study, we evaluated the potential antidepressant effects of ayahuasca in a juvenile non-human primate model of depression.Methods:While living with their families, juvenile marmosets (8 males; 7 females) were observed on alternate days for four weeks during a baseline phase. This was followed by 8 weeks of an induced depressive state protocol, the social isolated context (IC), in which the animals were monitored in the first and last weeks. Subsequently, five males and four females were randomly selected for treatment, first with a single administration of saline vehicle (1.67 mL/300 g of body weight, via gavage), followed by a single dose of ayahuasca (1.67 mL/300 g of body weight, via gavage). Both phases lasted 1 week and the animals were monitored daily. A third week of sampling was called the tardive-pharmacological effects phase. In all phases the marmosets were assessed for behavior, fecal cortisol levels, and body weight.Results:After IC, the animals presented typical hypocortisolemia, but cortisol recovered to baseline levels 24 h after an acute dose of ayahuasca; this recovery was not observed in vehicle-treated animals. Additionally, in males, ayahuasca, but not the vehicle, reduced scratching, a stereotypic behavior, and increased feeding. Ayahuasca treatment also improved body weight to baseline levels in both sexes. The ayahuasca-induced behavioral response had long-term effects (14 days). Thus, in this translational juvenile animal model of depression, ayahuasca presented beneficial effects.Conclusions:These results can contribute to the validation of ayahuasca as an antidepressant drug and encourage new studies on psychedelic drugs as a tool for treating mood disorders, including for adolescents with early-onset depression.

Background Psychological distress in University settings has grown and became a public health concern. In this context, contemplative practices such as mindfulness have been proposed as a strategy to help students on stress management. Methods Forty university students (20 female), aged between 18 to 30 years (mean = 24.15; SD = 3.56), with no previous experience with meditation or yoga were recruited at the Federal University of Rio Grande do Norte and randomized to a mindfulness training (MT) or active control (AC) groups. We analyzed measures of anxiety, affect, stress, as well as state and trait mindfulness in order to evaluate the effects of trait mindfulness and a brief mindfulness intervention in forty healthy young students. Participants were classified as Low (n = 27, females = 13) or High (n = 13, females = 7) Trait Mindfulness by k-means clustering and compared between them using Wilcoxon sum rank test. Furthermore, the sample was randomly allocated to an AC (n = 20, females = 10) or a MT (n = 20, females = 10) group, and mixed analysis of variance was performed to analyze the effect of interventions. The mechanisms and role of trait mindfulness in the intervention was assessed by a moderated mediation analysis. Results We found that High Trait individuals have lower anxiety trait, anxiety state and perceived stress levels. Only the MT group reduced their anxiety state and perceived stress after the intervention and increased their state mindfulness. Both groups reduced negative affect and cortisol, and no change was found in positive affect. Moderated mediation analysis showed that the training-induced change in state mindfulness mediated the increase in positive affect and the decrease in perceived stress and cortisol, regardless of trait mindfulness. For anxiety state the decrease only occurred in individuals with High Trait Mindfulness. Conclusions Together, these results suggest that higher trait mindfulness is associated with low levels of psychological distress and that a brief mindfulness-based intervention seems to be useful to reduce distress measures in university students. Trial registration ReBEC, U1111-1194-8661. Registered 28 March 2017—Retrospectively registered, http://www.ensaiosclinicos.gov.br/rg/RBR-7b8yh8

The comprehension of the pathophysiology of the major depressive disorder (MDD) is essential to the strengthening of precision psychiatry. In order to determine the relationship between the pathophysiology of the MDD and its clinical progression, analyzed by severity of the depressive symptoms and sleep quality, we conducted a study assessing different peripheral molecular biomarkers, including the levels of plasma C-reactive protein (CRP), serum mature brain-derived neurotrophic factor (mBDNF), serum cortisol (SC), and salivary cortisol awakening response (CAR), of patients with MDD (n = 58) and a control group of healthy volunteers (n = 62). Patients with the first episode of MDD (n = 30) had significantly higher levels of CAR and SC than controls (n = 32) and similar levels of mBDNF of controls. Patients with treatment-resistant depression (TRD, n = 28) presented significantly lower levels of SC and CAR, and higher levels of mBDNF and CRP than controls (n = 30). An increased severity of depressive symptoms and worse sleep quality were correlated with levels low of SC and CAR, and with high levels of mBDNF. These results point out a strong relationship between the stages clinical of MDD and changes in a range of relevant biological markers. This can assist in the development of precision psychiatry and future research on the biological tests for depression.

52The incidence of major depression in adolescents, aged between 15 to 18 years, reaches 53 approximately 14%. Usually, this disorder presents a recurrent way, without remission of

IntroductionThe understanding of biological responses to psychedelics with antidepressant potential is imperative. Here we report how a set of acute parameters, namely emotional (depressive symptoms), cognitive (psychedelic experience), and physiological (salivary cortisol), recorded during an ayahuasca dosing session, modulated serum brain-derived neurotrophic factor (BDNF), serum cortisol (SC), serum interleukin 6 (IL-6), plasma C-reactive protein (CRP), and salivary cortisol awakening response (CAR).MethodsResults were analyzed 2 days after the psychedelic intervention (ayahuasca) versus placebo in both patients with treatment-resistant depression and healthy volunteers. These measures were assessed as part of a randomized double-blinded, placebo-controlled trial (n = 72).ResultsResults revealed that larger reductions of depressive symptoms during the dosing session significantly moderated higher levels of SC in patients. Whereas lesser changes in salivary cortisol levels during the ayahuasca intervention were related to higher BDNF levels in patients with a larger clinical response in the reduction in depressive symptoms. No moderator was found for patient’s CAR, IL-6, and CRP responses to ayahuasca and for all biomarker responses to ayahuasca in healthy controls and in the placebo group.DiscussionIn summary, some specific emotional and physiological parameters during experimental ayahuasca session were revealed as critical moderators of the improvement of major depression biomarkers, mainly BDNF and SC two days after ayahuasca intake. These findings contribute to paving the way for future studies investigating the biological antidepressant response to psychedelic therapy.

Background Cognitive-Behavioral Therapy (CBT) has a signi cant adjunctive effect in the treatment of Major Depressive Disorder (MDD), however its uses as monotherapy is less explored, mainly the group-based approaches. Methods We assessed the responses of distinct psychophysiological domains after a intervention using groupbased CBT (gCBT, 16 weeks) in drug-free patients with mild-moderate MDD (n = 20; women = 11) and to compare with a healthy control group (n = 25, women = 13). Results Treatment resulted in 65% of response and 55% of remission rates. Reductions in depressive and anxiety symptoms and increase in self-esteem and sleep quality were observed as responses of gCBT. After treatment patients regulated their previous deregulated salivary cortisol awakening response (CAR) and sleep quality to healthy parameters. These improvements were correlated among themselves and dependent of remission condition. Remitted patients showed large progresses than non-remitted patients, who signi cantly changed only serum cortisol and self-perceived depressive symptoms. Further, better baseline sleep quality was predictor of remission. Conclusion These psychophysiological changes in response of gCBT support its use as tool with low cost and no side effects for treatment of mild-moderate major depression, as well as suggests a stronger exploration of these psychological domains in psychotherapies and stimulates furthers studies of neurobiology of MDD and alternatives treatments. Trial registration U1111-1215-4472. Registered 21 August 2018, http://www.ensaiosclinicos.gov.br/rg/RBR-3npbf8/ [38, 39]. However, studies that have measured the effects of CBT as a monotherapy on cortisol levels of MDD patients are few and inconsistent [40, 41]. Thus, this study investigated the responses of distinct psychophysiological domains, such as depression and anxiety symptoms, self-esteem, sleep quality and cortisol levels (salivary and serum), in MDD patients under group CBT monotherapy treatment. We expected to nd a reduction of depressive and anxious symptoms, associated with increases in self-esteem and in sleep quality, as well as an adjustment of cortisol levels, especially in remitted patients. Methods This open-label trial was conducted at the Federal University of Rio Grande do Norte (UFRN) between 2018-2019. It has been approved by the UFRN Human Ethics Committee (# 2628,202) and registered at http://clinicaltrials.gov (U1111-1215-4472). The procedures of this study comply with the ethical standards of the relevant national and institutional committees for human experimentation and with the Declaration of Helsinki of 1975, revised in 2008. All subjects provided written informed consent prior to participation and it was ensured freedom to withdraw from the study at any time and without any prejudice. All study's information has been kept con dential.

Observational studies of long-term users of ayahuasca, an Amazonian psychedelic brew, suggest an increase in resilience via improvements in emotion and cognition. Ayahuasca has also demonstrated clinical antidepressant effects in human and animal studies; however, its potential prophylactic action in depression has not been previously studied. Therefore, this experimental study sought to evaluate the potential prophylactic effects of repeated and long-term ayahuasca use, via the modulation of resilience, in a non-human primate animal model, Callithrix jacchus, subjected to a protocol for induction of depressive-like behavior. For the formation of the study groups, some juvenile marmosets were kept in their family groups (GF = 7), while for the two experimental groups, the animals were removed from the family and kept socially isolated. Then, part of the isolated animals made up the group in which ayahuasca was administered (AG, n = 6), while for others, no intervention was made (IG, n = 5). AG animals took ayahuasca (1.67 mL/300g body weight) at weeks 4 (before isolation), 8, and 12 (during isolation) of the study. More adaptive stress response was observed for the AG when compared to the IG. The AG showed higher cortisol reactivity and fecal cortisol levels than IG, while both measures were similar to FG. Moreover, AG animals showed no signs of anhedonia and no increase in chronic stress-related behaviors, which were expressed by the IG. Thus, ayahuasca seems to promote the expression of resilient responses, indicating a prophylactic action, buffering the emergence of depressive-like behaviors and cortisol alterations associated with major depression. These results are encouraging for further research on the prophylactic use of psychedelics to prevent psychopathologies associated with chronic stress.