Instituto Nacional de Ciência e Tecnologia Translacional em Medicina

OBJECTIVES: Ayahuasca (AYA), a natural psychedelic brew prepared from Amazonian plants and rich in dimethyltryptamine (DMT) and harmine, causes effects of subjective well-being and may therefore have antidepressant actions. This study sought to evaluate the effects of a single dose of AYA in six volunteers with a current depressive episode. METHODS: Open-label trial conducted in an inpatient psychiatric unit. RESULTS: Statistically significant reductions of up to 82% in depressive scores were observed between baseline and 1, 7, and 21 days after AYA administration, as measured on the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS). AYA administration resulted in nonsignificant changes in Young Mania Rating Scale (YMRS) scores and in the thinking disorder subscale of the BPRS, suggesting that AYA does not induce episodes of mania and/or hypomania in patients with mood disorders and that modifications in thought content, which could indicate psychedelic effects, are not essential for mood improvement. CONCLUSIONS: These results suggest that AYA has fast-acting anxiolytic and antidepressant effects in patients with a depressive disorder.

BACKGROUND: The growing concern about cannabis use, the most commonly used illicit drug worldwide, has led to a significant increase in the number of human studies using neuroimaging techniques to determine the effect of cannabis on brain structure and function. We conducted a systematic review to assess the evidence of the impact of chronic cannabis use on brain structure and function in adults and adolescents. METHODS: Papers published until August 2012 were included from EMBASE, Medline, PubMed and LILACS databases following a comprehensive search strategy and pre-determined set of criteria for article selection. Only neuroimaging studies involving chronic cannabis users with a matched control group were considered. RESULTS: One hundred and forty-two studies were identified, of which 43 met the established criteria. Eight studies were in adolescent population. Neuroimaging studies provide evidence of morphological brain alterations in both population groups, particularly in the medial temporal and frontal cortices, as well as the cerebellum. These effects may be related to the amount of cannabis exposure. Functional neuroimaging studies suggest different patterns of resting global and brain activity during the performance of several cognitive tasks both in adolescents and adults, which may indicate compensatory effects in response to chronic cannabis exposure. LIMITATIONS: However, the results pointed out methodological limitations of the work conducted to date and considerable heterogeneity in the findings. CONCLUSION: Chronic cannabis use may alter brain structure and function in adult and adolescent population. Further studies should consider the use of convergent methodology, prospective large samples involving adolescent to adulthood subjects, and data-sharing initiatives.

Loneliness and social isolation are associated with poor mental and physical health and may increase the likelihood of common mental disorders (depressive and anxiety disorders), substance use and cognitive decline (1, 2). At this moment, people around the globe have been urged to self-isolate and refrain from social interaction due to the COVID-19 pandemic. From public health and preventative care perspectives, there is a pressing need to provide individuals, communities and health agencies with information and interventions to maintain the healthiest possible lifestyle while in isolation. Healthy lifestyle (HL) behaviours have been consistently associated with reduced all-cause mortality, and increased lifespan and wellbeing (3). Unhealthy behaviours (poor-quality diet, lack of physical exercise, tobacco and alcohol use) are major contributors to the global burden of disease (4) and have also been associated with worse outcomes across psychiatric disorders (5). Moreover, it is increasingly acknowledged that unhealthy lifestyles may be a driving force in the epidemic of common mental disorders (6). Evidence suggests that the current pandemic-related, mandatory self-isolation may trigger depression and post-traumatic stress disorder (PTSD) (7) and that being a healthcare worker or having COVID-19 is risk factors for stress-related psychiatric disorders (8, 9). Given the lack of effective treatments for COVID-19, non-pharmacological interventions (NPIs) are mandatory to decrease disease transmission. NPIs include personal restrictions and physical-distancing policies, such as mass confinement and compulsory home isolation. NPIs may modify, for better or for worse, lifestyle behaviours. Increased adoption of unhealthy nutrition and sedentary behaviour, and decreased outdoor time and increased screen time are expected to occur. These behaviours may have unforeseen medium- and long-term consequences for mental and physical health (10). For instance, diminished physical activity resulting from home isolation may increase a wide range of negative cardio-metabolic and mental effects (11). Research has mostly focused on the psychological impact, rather than lifestyle issues under physical-distancing policies. Lifestyle behaviours including dietary changes, restricted physical activity and the effect of increased indoor and screen time remain an under-researched area (12). Of note, towards the end of the SARS epidemic, social support, mental health awareness and other lifestyles changes (exercise, more time for relaxation and restorative sleep) were all associated with decreased perceived stress and incidence of PTSD (13). The ongoing COVID-19 outbreak has led to an unprecedented public health crisis worldwide. From our perspective, several actions are required to minimize the transition to a social crisis with long-lasting consequences. It is time that such interventions start to include lifestyle guidelines with the aim to translate evidence into public health policies. This is crucial for the vulnerable groups, such as low-income families and children (14, 15), the elderly, socially isolated individuals and people with severe mental disorders (SMD). Regarding patients with SMD requiring admission, the field is recommending home hospitalizations to keep patients safe while avoiding formal hospital admissions (16). Regarding lifestyle guidelines, recent reviews have emphasized the role of maintaining a healthy nutritional status (17) and engaging in physical exercise at home (11) in the management of COVID-19 outbreak. Similar recommendations were made at the time of the influenza pandemic in 1918, when public health nurses adhered to precepts of good hygiene, nutrition, fresh air and rest (18). However, such lifestyle guidelines are not entirely evidence based. Indeed, they are basically the same guidance used during non-pandemic times. Observational data on how the general public and patients with psychiatric disorders actually deal with self-care, nutrition, physical activity or restorative sleep during confinement are lacking and represent a research gap. To address such gap, observational studies of lifestyle behaviours during the compulsory isolation are timely and clearly a necessary step for the design of rational and effective public policies. Such studies would provide the much-needed evidence to design interventions to prevent a new pandemic of psychiatric disorders and cardio-metabolic comorbidities as proposed by the COVID-19 Snapshot Monitoring (COSMO) initiative (19). Furthermore, data collection must be fast and provide useful and reliable information in real time to health authorities, media and citizens. Psychiatry and behavioural medicine may be particularly benefited from surveys and interventions carried out remotely to reach a large number of individuals in need. Large-scale surveys will require international networking to address changes in lifestyle behaviours and the expected consequences after the COVID-19 (9). We urge the field to embrace and extend eHealth and mobile health interventions, online monitoring surveys and big data technologies. Remote data collection using social networks, georeferencing and the available tools provided by data science is available, feasible and necessary in the context of this pandemic. Such tools provide the means of groups across the globe to connect and generate the real-time necessary data to inform policymakers. The authors received no financial support for the research, authorship and/or publication of this editorial. Dr. Balanzá-Martínez acknowledges the support from Instituto de Salud Carlos III (PI16/1770, PROBILIFE Study). Dr. De Boni acknowledges long-term funding from CNPq and FAPERJ. Dr. Balanzá-Martínez has been a consultant, advisor or Continuing Medical Education (CME) speaker over the last 3 years for the following companies: Angelini, Ferrer, Lundbeck, Nutrición Médica and Otsuka. The other authors declare no conflict of interest.

The microbiota-gut-brain axis is a bidirectional signaling mechanism between the gastrointestinal tract and the central nervous system. The complexity of the intestinal ecosystem is extraordinary; it comprises more than 100 trillion microbial cells that inhabit the small and large intestine, and this interaction between microbiota and intestinal epithelium can cause physiological changes in the brain and influence mood and behavior. Currently, there has been an emphasis on how such interactions affect mental health. Evidence indicates that intestinal microbiota are involved in neurological and psychiatric disorders. This review covers evidence for the influence of gut microbiota on the brain and behavior in Alzheimer disease, dementia, anxiety, autism spectrum disorder, bipolar disorder, major depressive disorder, Parkinson's disease, and schizophrenia. The primary focus is on the pathways involved in intestinal metabolites of microbial origin, including short-chain fatty acids, tryptophan metabolites, and bacterial components that can activate the host's immune system. We also list clinical evidence regarding prebiotics, probiotics, and fecal microbiota transplantation as adjuvant therapies for neuropsychiatric disorders.

Serotonergic psychedelics are emerging as potential antidepressant treatment tools, as suggested in a recent randomized controlled trial with ayahuasca for treatment-resistant depression. Preclinical and clinical studies have shown that serum brain-derived neurotrophic factor (BDNF) levels increase after treatment with serotoninergic antidepressants. However, the exact role of BDNF as a biomarker for diagnostic and treatment of major depression needs to be better explored. In this study, registered at http://clinicaltrials.gov (NCT02914769), we investigated serum BDNF levels in healthy controls (N= 45) and patients with treatment resistant depression (N = 28), before (baseline) and 48 hours after (D2) a single dose of ayahuasca or placebo. We found similar baseline levels of serum BDNF in both patients and healthy individuals. We detected lower levels of BDNF at baseline in a subgroup of subjects who also presented hipocortisolemia, with respect to individuals with eucortisolemia. Moreover, we found a baseline negative correlation between BDNF and serum cortisol in volunteers with eucortisolemia. After treatment (D2) we observed higher BDNF levels in both patients and controls that ingested ayahuasca (N= 35) when compared to placebo (N= 34). Moreover, in D2 just patients treated with ayahuasca (N= 14), and not with placebo (N= 14), presented a significant negative correlation between serum BDNF levels and depressive symptoms (MADRS scores). Few previous randomized controlled trials have evaluated serum BDNF levels in response to antidepressant treatments and their results are not conclusive. This is the first clinical trial to explore the modulation of BDNF in response to a psychedelic with antidepressant potential, and the results suggest a potential link between the observed antidepressant effects of ayahuasca and changes in serum BDNF, which contributes to the emerging view of using psychedelic substances in the treatment of resistant depression.

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 I 2 . 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, I 2 = 99.9%). HCW showed a higher prevalence (37.74%, CI: 33.26–42.45, I 2 = 99.7%) than the GP (20.67%, 15.07–27.66, I 2 = 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, I 2 = 99.9%) of the sample, with similar estimates for population (HCW 26.14%, CI: 23.37–29.12, I 2 = 99.9%; GP: 26.99%, CI: 23.41–30.9, I 2 = 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.

OBJECTIVES: To describe the cognitive and functional impairment in individuals with the first episode of major depressive disorder (MDD) as compared to controls and individuals with recurrent MDD. Also to describe the functional and cognitive trajectory after the first episode of MDD. METHODS: A total of 52 studies were included in our systematic review. 32 studies compared the cognitive performance between first episode of depression (FED) and controls, 11 studies compared the cognitive performance between recurrent depression (RD) and FED, 10 compared global functioning between RD and FED, four studies assessed cognition in FED over time, and two studies assessed global functioning in FED over time. RESULTS: The majority of studies (n = 22/32, 68.8%) found that FED subjects performed significantly worse than controls on cognitive tests, with processing speed (n = 12) and executive/working memory (n = 11) being the most commonly impaired domains. Seven out of 11 studies (63.6%) found that RD performed significantly worse than FED, with verbal learning and memory being the most commonly impaired domain (n = 4). Most studies (n = 7/10, 70%) did not find a significant difference in global functioning between RD and FED. In three of four longitudinal studies assessing cognition, subgroup analyses were used instead of directly assessing cognition in FED over time while the remaining study found significant cognitive declines over time in FED when compared to controls. The two longitudinal studies assessing functional trajectory found that functioning significantly improved over time, possibly due to the improvement of depressive symptoms. CONCLUSION: There is strong evidence that cognitive impairment is present during the first episode of depression, and individuals with multiple episodes display greater cognitive impairment than individuals with a single episode. Future studies aimed at identifying predictors of cognitive and functional impairment after the first episode of depression are needed to describe the functional and cognitive trajectory of individuals with the first episode of MDD over time.

Background: Ayahuasca is a traditional Amazon brew and its potential antidepressant properties have recently been explored in scientific settings. We conducted a double-blind placebo-controlled trial of ayahuasca with treatment-resistant depression patients ( n = 28) and healthy controls ( n = 45). Aims: We are evaluating the blood inflammatory biomarkers: C-reactive protein and interleukin 6, as a potential consequence of ayahuasca intake and their correlation with serum cortisol and brain-derived neurotrophic factor levels. Blood samples were collected at pre-treatment and 48 hours after substance ingestion to assess the concentration of inflammatory biomarkers, together with administration of the Montgomery-Åsberg Depression Rating Scale. Results: At pre-treatment, patients showed higher C-reactive protein levels than healthy controls and a significant negative correlation between C-reactive protein and serum cortisol levels was revealed ( rho = –0.40, n = 14). C-reactive protein in those patients was not correlated with Montgomery-Åsberg Depression Rating Scale scores. We observed a significant reduction of C-reactive protein levels across time in both patients and controls treated with ayahuasca, but not with placebo. Patients treated with ayahuasca showed a significant correlation ( rho = + 0.57) between larger reductions of C-reactive protein and lower depressive symptoms at 48 hours after substance ingestion (Montgomery-Åsberg Depression Rating Scale). No significant result with respect to interleukin 6 and brain-derived neurotrophic factor was found. Furthermore, these biomarkers did not predict the antidepressant response or remission rates observed. Conclusions: These findings enhance the understanding of the biological mechanisms behind the observed antidepressant effects of ayahuasca and encourage further clinical trials in adults with depression.

accumulation, Akt/mechanistic target of rapamycin signaling, levels of ionized calcium-binding adapter molecule 1 and glial fibrillary acidic protein, and behavioral deficits associated with cognitive decline. These results indicate that brain RAGE is an essential factor in the pathogenesis of neurological disorders following acute systemic inflammation.

To review and describe studies of the non-psychotomimetic constituent of Cannabis sativa, cannabidiol (CBD), as an anxiolytic drug and discuss its possible mechanisms of action. The articles selected for the review were identified through searches in English, Portuguese, and Spanish in the electronic databases ISI Web of Knowledge, SciELO, PubMed, and PsycINFO, combining the search terms “cannabidiol and anxiolytic”, “cannabidiol and anxiolyticlike”, and “cannabidiol and anxiety”. The reference lists of the publications included, review articles, and book chapters were handsearched for additional references. Experimental animal and human studies were included, with no time restraints. Studies using animal models of anxiety and involving healthy volunteers clearly suggest an anxiolytic-like effect of CBD. Moreover, CBD was shown to reduce anxiety in patients with social anxiety disorder. Future clinical trials involving patients with different anxiety disorders are warranted, especially of panic disorder, obsessive-compulsive disorder, social anxiety disorder, and post-traumatic stress disorders. The adequate therapeutic window of CBD and the precise mechanisms involved in its anxiolytic action remain to be determined. Revisar e descrever os estudos do constituinte não psicotomimético da Cannabis sativa, o canabidiol (CBD), como ansiolítico e discutir seus possíveis mecanismos de ação. Os artigos selecionados para a presente revisão foram identificados por meio de busca eletrônica em inglês, português e espanhol nos bancos de dados ISI Web of Knowledge, SciELO, PubMed e PsycINFO e combinando os termos “canabidiol e ansiolíticos”, “canabidiol e semelhante ao ansiolítico” e “canabidiol e ansiedade”. Foram também revisadas as listas de referências dos artigos incluídos, de revisões da literatura e de capítulos de livro. Incluímos trabalhos experimentais em humanos e em animais, sem limite de tempo. Estudos com modelos animais de ansiedade e envolvendo voluntários saudáveis sugerem claramente que o CBD possui efeitos ansiolíticos. Além disso, o CBD mostrou-se capaz de reduzir a ansiedade em pacientes com transtorno de ansiedade social. Futuros ensaios clínicos com pacientes portadores de diferentes transtornos de ansiedade, em especial pacientes com transtorno do pânico, obsessivo-compulsivo, ansiedade social e estresse pós-traumático, são oportunos. Além disso, ainda é necessário determinar a adequada faixa terapêutica do CBD e os exatos mecanismos envolvidos nessa ação ansiolítica.

A growing body of evidence has suggested that reactive oxygen species (ROS) may play an important role in the physiopathology of depression. Evidence has pointed to the β-carboline harmine as a potential therapeutic target for the treatment of depression. The present study we evaluated the effects of acute and chronic administration of harmine (5, 10 and 15 mg/kg) and imipramine (10, 20 and 30 mg/kg) or saline in lipid and protein oxidation levels and superoxide dismutase (SOD) and catalase (CAT) activities in rat prefrontal cortex and hippocampus. Acute and chronic treatments with imipramine and harmine reduced lipid and protein oxidation, compared to control group in prefrontal cortex and hippocampus. The SOD and CAT activities increased with acute and chronic treatments with imipramine and harmine, compared to control group in prefrontal cortex and hippocampus. In conclusion, our results indicate positive effects of imipramine antidepressant and β-carboline harmine of oxidative stress parameters, increasing SOD and CAT activities and decreasing lipid and protein oxidation.

Background: Growing evidence supports the existence of neurobiological trait abnormalities in individuals at genetic risk for bipolar disorder. The aim of this study was to examine potential differences in brain-derived neurotrophic factor, cytokines, oxidative stress, and telomere length markers between patients with bipolar disorder, their siblings, and healthy controls. Methods: Thirty-six patients with bipolar disorder type I, 39 siblings, and 44 healthy controls were assessed. Serum levels of brain-derived neurotrophic factor, interleukin-6, interleukin-10, tumor necrosis factor-α, C-C motif chemokine 11, C-C motif chemokine 24, and 3-nitrotyrosine were measured, as were the activities of glutathione peroxidase, glutathione reductase, and glutathione S-transferase. Telomere length (T/S ratio) was measured using quantitative polymerase chain reaction. Results: Telomere length was different between the 3 groups (P = .041) with both patients and siblings showing a shorter T/S ratio compared with healthy controls. Patients showed increased levels of interleukin-6 (P = .005) and interleukin-10 (P = .002) compared with controls as well as increased levels of interleukin-6 (p = 0.014) and CCL24 (P = .016) compared with their siblings. C-C motif chemokine 11 levels were increased in siblings compared with controls (P = .015), and a similar tendency was found in patients compared with controls (P = .045). Glutathione peroxidase activity was decreased in patients compared with controls (P = .006) and siblings (P = .025). No differences were found for the other markers. Conclusions: The present results suggest that unaffected siblings may present accelerated aging features. These neurobiological findings may be considered as endophenotypic traits. Further prospective studies are warranted.

To review and describe studies of the non-psychotomimetic constituent of Cannabis sativa, cannabidiol (CBD), as an anxiolytic drug and discuss its possible mechanisms of action. The articles selected for the review were identified through searches in English, Portuguese, and Spanish in the electronic databases ISI Web of Knowledge, SciELO, PubMed, and PsycINFO, combining the search terms “cannabidiol and anxiolytic”, “cannabidiol and anxiolyticlike”, and “cannabidiol and anxiety”. The reference lists of the publications included, review articles, and book chapters were handsearched for additional references. Experimental animal and human studies were included, with no time restraints. Studies using animal models of anxiety and involving healthy volunteers clearly suggest an anxiolytic-like effect of CBD. Moreover, CBD was shown to reduce anxiety in patients with social anxiety disorder. Future clinical trials involving patients with different anxiety disorders are warranted, especially of panic disorder, obsessive-compulsive disorder, social anxiety disorder, and post-traumatic stress disorders. The adequate therapeutic window of CBD and the precise mechanisms involved in its anxiolytic action remain to be determined. Revisar e descrever os estudos do constituinte não psicotomimético da Cannabis sativa, o canabidiol (CBD), como ansiolítico e discutir seus possíveis mecanismos de ação. Os artigos selecionados para a presente revisão foram identificados por meio de busca eletrônica em inglês, português e espanhol nos bancos de dados ISI Web of Knowledge, SciELO, PubMed e PsycINFO e combinando os termos “canabidiol e ansiolíticos”, “canabidiol e semelhante ao ansiolítico” e “canabidiol e ansiedade”. Foram também revisadas as listas de referências dos artigos incluídos, de revisões da literatura e de capítulos de livro. Incluímos trabalhos experimentais em humanos e em animais, sem limite de tempo. Estudos com modelos animais de ansiedade e envolvendo voluntários saudáveis sugerem claramente que o CBD possui efeitos ansiolíticos. Além disso, o CBD mostrou-se capaz de reduzir a ansiedade em pacientes com transtorno de ansiedade social. Futuros ensaios clínicos com pacientes portadores de diferentes transtornos de ansiedade, em especial pacientes com transtorno do pânico, obsessivo-compulsivo, ansiedade social e estresse pós-traumático, são oportunos. Além disso, ainda é necessário determinar a adequada faixa terapêutica do CBD e os exatos mecanismos envolvidos nessa ação ansiolítica.

Chronic exposure to paraquat (Pq), a toxic herbicide, can result in Parkinsonian symptoms. This study evaluated the effect of the systemic administration of Pq on locomotion, learning and memory, social interaction, tyrosine hydroxylase (TH) expression, dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels, and dopamine transporter (DAT) gene expression in zebrafish. Adult zebrafish received an i.p. injection of either 10 mg/kg (Pq10) or 20 mg/kg (Pq20) of Pq every 3 days for a total of six injections. Locomotion and distance traveled decreased at 24 h after each injection in both treatment doses. In addition, both Pq10- and Pq20-treated animals exhibited differential effects on the absolute turn angle. Nonmotor behaviors were also evaluated, and no changes were observed in anxiety-related behaviors or social interactions in Pq-treated zebrafish. However, Pq-treated animals demonstrated impaired acquisition and consolidation of spatial memory in the Y-maze task. Interestingly, dopamine levels increased while DOPAC levels decreased in the zebrafish brain after both treatments. However, DAT expression decreased in the Pq10-treated group, and there was no change in the Pq20-treated group. The amount of TH protein showed no significant difference in the treated group. Our study establishes a new model to study Parkinson-associated symptoms in zebrafish that have been chronically treated with Pq.

BACKGROUND: Essential workers have been shown to present a higher prevalence of positive screenings for anxiety and depression during the COVID-19 pandemic. Individuals from countries with socioeconomic inequalities may be at increased risk for mental health disorders. OBJECTIVE: We aimed to assess the prevalence and predictors of depression, anxiety, and their comorbidity among essential workers in Brazil and Spain during the COVID-19 pandemic. METHODS: A web survey was conducted between April and May 2020 in both countries. The main outcome was a positive screening for depression only, anxiety only, or both. Lifestyle was measured using a lifestyle multidimensional scale adapted for the COVID-19 pandemic (Short Multidimensional Inventory Lifestyle Evaluation-Confinement). A multinomial logistic regression model was performed to evaluate the factors associated with depression, anxiety, and the presence of both conditions. RESULTS: From the 22,786 individuals included in the web survey, 3745 self-reported to be essential workers. Overall, 8.3% (n=311), 11.6% (n=434), and 27.4% (n=1027) presented positive screenings for depression, anxiety, and both, respectively. After adjusting for confounding factors, the multinomial model showed that an unhealthy lifestyle increased the likelihood of depression (adjusted odds ratio [AOR] 4.00, 95% CI 2.72-5.87), anxiety (AOR 2.39, 95% CI 1.80-3.20), and both anxiety and depression (AOR 8.30, 95% CI 5.90-11.7). Living in Brazil was associated with increased odds of depression (AOR 2.89, 95% CI 2.07-4.06), anxiety (AOR 2.81, 95%CI 2.11-3.74), and both conditions (AOR 5.99, 95% CI 4.53-7.91). CONCLUSIONS: Interventions addressing lifestyle may be useful in dealing with symptoms of common mental disorders during the strain imposed among essential workers by the COVID-19 pandemic. Essential workers who live in middle-income countries with higher rates of inequality may face additional challenges. Ensuring equitable treatment and support may be an important challenge ahead, considering the possible syndemic effect of the social determinants of health.

INTRODUCTION: Mitochondrial dysfunction has been postulated to participate in the development of many neuropsychiatric disorders, but there is no consensus as to its role. The aim of this paper is to review recent studies and to outline the current understanding of the association between mitochondrial dysfunction and psychiatric disorders. METHODOLOGY: We reviewed articles that evaluated mitochondrial dysfunction and psychiatric disorders, with a particular focus on depression, bipolar disorder, anxiety disorders, obsessive-compulsive disorder, and autism spectrum disorder, and the association between mitochondrial dysfunction and development of these disorders. RESULTS: Evidence suggests that alterations in mitochondrial morphology, brain energy metabolism, and mitochondrial enzyme activity may be involved in the pathophysiology of different neuropsychiatric disorders, given their key role in energy metabolism in the cell. CONCLUSIONS: Understanding the interactions between mitochondrial dysfunction and development of psychiatric disorders may help establish more effective therapeutic strategies for these disorders and thus lead to better outcomes for affected subjects.

The increasing use of adult zebrafish in behavioral studies has created the need for new and improved protocols. Our investigation sought to evaluate the swimming behavior of zebrafish against a water current using the newly developed Spinning Task. Zebrafish were individually placed in a beaker containing a spinning magnetic stirrer and their latency to be swept into the whirlpool was recorded. We characterized that larger fish (>4 cm) and lower rpm decreased the swimming time in the Spinning Task. There was also a dose-related reduction in swimming after acute treatment with haloperidol, valproic acid, clonazepam, and ethanol, which alter coordination. Importantly, at doses that reduced swimming time in the Spinning Task, these drugs influenced absolute turn angle (ethanol increased and the other drugs decreased), but had no effect of distance travelled in a regular water tank. These results suggest that the Spinning Task is a useful protocol to add information to the assessment of zebrafish motor behavior.

The use of antipsychotic drugs represents an important approach for the treatment of schizophrenia. However, their efficacy is limited to certain symptoms of this disorder, and they induce serious side effects. As a result, there is a strong demand for the development of new drugs, which depends on reliable animal models for pharmacological characterization. The present review discusses the face, construct, and predictive validity of classical animal models for studying the efficacy and side effects of compounds for the treatment of schizophrenia. These models are based on the properties of antipsychotics to impair the conditioned avoidance response and reverse certain behavioral changes induced by psychotomimetic drugs, such as stereotypies, hyperlocomotion, and deficit in prepulse inhibition of the startle response. Other tests, which are not specific to schizophrenia, may predict drug effects on negative and cognitive symptoms, such as deficits in social interaction and memory impairment. Regarding motor side effects, the catalepsy test predicts the liability of a drug to induce Parkinson-like syndrome, whereas vacuous chewing movements predict the liability to induce dyskinesia after chronic treatment. Despite certain limitations, these models may contribute to the development of more safe and efficacious antipsychotic drugs.

Although different hypotheses have been formulated to explain schizophrenia pathogenesis, the links between them are weak. The observation that five psychotic patients on chronic warfarin therapy for deep-vein thrombosis showed long-term remission of psychotic symptoms made us suspect that abnormalities in the coagulation pathway, specifically low tissue plasminogen activator (tPA) activity, could be one of the missing links. Our hypothesis is supported by a high prevalence of conditions affecting tPA activity in drug-naive schizophrenia, such as antiphospholipid antibodies, elevated cytokine levels, hyperinsulinemia and hyperhomocysteinemia. We recently screened a group of schizophrenia patients and controls for conditions affecting tPA activity. Free-protein S deficiency was highly prevalent among patients, but not found in controls. Free-protein S and functional protein C are natural anticoagulants that form complexes that inhibit tPA inhibitors. All participants had normal protein C levels, suggesting that protein S could have a role in schizophrenia, independent of protein C. Chronic patients and those studied during acute episodes had between three and six conditions affecting tPA and/or protein S activity, while patients in remission had up to two, which led us to postulate that multiple conditions affecting tPA and/or protein S activity could contribute to the full expression of schizophrenia phenotype. This paper describes the physiological roles of tPA and protein S, reviewing how their activity influences pathogenesis and comorbidity of schizophrenia. Next, it analyzes how activity of tPA and protein S is influenced by biochemical abnormalities found in schizophrenia. Last, it suggests future directions for research, such as studies on animal models and on therapeutic approaches for schizophrenia aiming at increasing tPA and protein S activity.

OBJECTIVE: Depressive disorders, including major depression, are serious and disabling for affected patients. Although the neurobiological understanding of major depressive disorder focuses mainly on the monoamine hypothesis, the exact pathophysiology of depression is not fully understood. METHODS: Animals received daily intra-peritoneal injections of paroxetine (10 mg/kg), nortriptyline (15 mg/kg) or venlafaxine (10 mg/kg) in 1.0 ml/kg volume for 15 days. Twelve hours after the last injection, the rats were killed by decapitation, where the brain was removed and homogenised. The activities of mitochondrial respiratory chain complexes in different brain structures were measured. RESULTS: We first verified that chronic administration of paroxetine increased complex I activity in prefrontal cortex, hippocampus, striatum and cerebral cortex. In addition, complex II activity was increased by the same drug in hippocampus, striatum and cerebral cortex and complex IV activity in prefrontal cortex. Furthermore, chronic administration of nortriptyline increased complex II activity in hippocampus and striatum and complex IV activity in prefrontal cortex, striatum and cerebral cortex. Finally, chronic administration of venlafaxine increased complex II activity in hippocampus, striatum and cerebral cortex and complex IV activity in prefrontal cortex. CONCLUSION: On the basis of the present findings, it is tempting to speculate that an increase in brain energy metabolism by the antidepressant paroxetine, nortriptyline and venlafaxine could play a role in the mechanism of action of these drugs. These data corroborate with other studies suggesting that some antidepressants modulate brain energy metabolism.