Abstract Objectives Evidence suggests that ketamine’s influence on brain-derived neurotrophic factor (BDNF) might be involved in its mechanism of rapid antidepressant action. We aimed to evaluate the differential impact of ketamine and esketamine on serum BDNF levels and its association with response patterns in treatment-resistant depression (TRD). Methods Participants (n = 53) are from a randomized, double-blind clinical trial comparing the efficacy of single-dose ketamine (0.5mg/kg, n = 27) and esketamine (0.25mg/kg, n = 26) in TRD. Depression severity was assessed before and 24 hours, 72 hours, and 7 days after the intervention, using the Montgomery-Åsberg Depression Rating Scale (MADRS). Blood samples were collected before infusion, 24 hours, and 7 days afterwards. Results There were no significant changes in BDNF levels at post-infusion evaluation points, and no difference in BDNF levels comparing ketamine and esketamine. Both drugs exhibited similar therapeutic effect. There was no association between BDNF levels and response to treatment or severity of depressive symptoms. Conclusion There was no significant treatment impact on BDNF serum levels – neither with ketamine nor esketamine – despite therapeutic response. These results suggest that ketamine or esketamine intervention for TRD has no impact on BDNF levels measured at 24 hours and 7 days after the infusion. This clinical trial is registered on the Japan Primary Registries Network: UMIN000032355.

Objectives: Past suicide attempt (SA) is one of the most important risk factors for suicide death. An ideation-to-action framework posits that impulsivity, potentially traumatic events, and mental disorders also play a role in increasing suicide risk. This study aimed to assess the association between trait impulsivity, lifetime exposure to trauma, and post-traumatic stress disorder (PTSD) with SA in a sample of Brazilian college students. Methods: A total of 2,137 participants filled self-reported questionnaires consisting of a sociodemographic and clinical questionnaire, Trauma History Questionnaire, Post-Traumatic Stress Disorder Checklist – Civilian version, and Barratt Impulsiveness Scale. Results: Our findings suggest that trait impulsivity may be interpreted as exerting a distal effect on SA, even in the presence of other variables – such as trauma history, psychological neglect, and PTSD – which also increase the odds of SA. High and medium levels of impulsivity, history of trauma, and PTSD increased the likelihood of SA. Conclusions: Intervention strategies to prevent SA may target trait impulsivity and exposure to traumatic experiences.

Objectives: Previous studies have estimated the 30-day prevalence of alcohol use to be approximately 21% among youth in Brazil, despite the legal drinking age of 18 years. The present study aimed to determine the prevalence of underage drinking and its associated factors among adolescents in Brazil. Methods: The 3rd National Survey on Drug Use by the Brazilian Population (III Levantamento Nacional sobre o Uso de Drogas pela População Brasileira) is a nationwide, multi-stage, probability-sample household survey. Herein, youth between the ages of 12-17 years were included. Lifetime and 12-month alcohol use prevalence were estimated. Factors associated with 12-month alcohol use were evaluated through multivariate analysis considering survey weights and design. Results: Overall, 628 youth were interviewed. Estimated lifetime and 12-month alcohol use were 34.3% (standard error [SE] = 1.9) and 22.2% (SE = 1.7), respectively. Factors associated with 12-month drinking were: other/no religion vs. Christianity; living in rural vs. urban areas; self-reported diagnosis of depression vs. no self-reported depression; lifetime tobacco use vs. no history of tobacco use; and any illicit drug use vs. no history of illicit drug use. Conclusion: Considering that alcohol use is a major risk factor for early death among Brazilian youth, our findings highlight the importance of preventative measures to reduce underage drinking.

Objective: To identify suicide rates and how they relate to demographic factors (sex, race and ethnicity, age, location) among physicians compared to the general population when aggravated by the coronavirus disease 2019 (COVID-19) pandemic. Methods: We searched U.S. databases to report global suicide rates and proportionate mortality ratios (PMRs) among U.S. physicians (and non-physicians in health occupations) using National Occupational Mortality Surveillance (NOMS) data and using Wide-ranging Online Data for Epidemiologic Research (WONDER) in the general population. We also reviewed the effects of age, suicide methods and locations, COVID-19 considerations, and potential solutions to current challenges. Results: Between NOMS1 (1985-1998) and NOMS2 (1999-2013), the PMRs for suicide increased in White male physicians (1.77 to 2.03) and Black male physicians (2.50 to 4.24) but decreased in White female physicians (2.66 to 2.42). Conclusions: The interaction of non-modifiable risk factors, such as sex, race and ethnicity, age, education level/healthcare career, and location, require further investigation. Addressing systemic and organizational problems and personal resilience training are highly recommended, particularly during the additional strain from the COVID-19 pandemic.

Abstract Introduction Recent research has suggested an increase in the global prevalence of psychiatric symptoms during the COVID-19 pandemic. This study aimed to assess whether lifestyle behaviors can predict the presence of depression and anxiety in the Brazilian general population, using a model developed in Spain. Methods A web survey was conducted during April-May 2020, which included the Short Multidimensional Inventory Lifestyle Evaluation (SMILE) scale, assessing lifestyle behaviors during the COVID-19 pandemic. Depression and anxiety were examined using the PHQ-2 and the GAD-7, respectively. Elastic net, random forest, and gradient tree boosting were used to develop predictive models. Each technique used a subset of the Spanish sample to train the models, which were then tested internally (vs. the remainder of the Spanish sample) and externally (vs. the full Brazilian sample), evaluating their effectiveness. Results The study sample included 22,562 individuals (19,069 from Brazil, and 3,493 from Spain). The models developed performed similarly and were equally effective in predicting depression and anxiety in both tests, with internal test AUC-ROC values of 0.85 (depression) and 0.86 (anxiety), and external test AUC-ROC values of 0.85 (depression) and 0.84 (anxiety). Meaning of life was the strongest predictor of depression, while sleep quality was the strongest predictor of anxiety during the COVID-19 epidemic. Conclusions Specific lifestyle behaviors during the early COVID-19 epidemic successfully predicted the presence of depression and anxiety in a large Brazilian sample using machine learning models developed on a Spanish sample. Targeted interventions focused on promoting healthier lifestyles are encouraged.

Abstract Objective To conduct a systematic review to describe cognitive abilities in bipolar disorder (BD) in comparison to cognitive abilities in mild cognitive impairment (MCI) and dementia. Methods A literature search was performed with no year or language restrictions. The search yielded 1,461 articles, with 1,261 remaining after removal of duplicates, five of which were suitable for the systematic review: two for the comparison between BD and MCI and three comparing BD and dementia. Results Analyses from our systematic review showed that euthymic individuals with BD present impairments in cognitive domains such as attention and executive functioning, motor skills, conceptual thinking, and visuo-spatial abilities that are equally severe as or more severe than the impairments observed in individuals with MCI. In contrast, studies comparing BD and dementia indicated that Alzheimer’s disease (AD) dementia and behavioral variant frontotemporal dementia (bvFTD) both showed greater cognitive deficits than BD during euthymia, whereas BD during a mood episode demonstrated higher cognitive impairments than bvFTD. Conclusion Findings from our systematic review suggest that cognitive impairments in euthymic BD fall into a range between the impairments seen in MCI and those seen in dementia. More studies are needed to analyze these comparisons, while also focusing on comparing different clinical stages of BD with MCI and dementia to analyze the progression of the clinical course and cognitive dysfunction in BD.PROSPERO registration ID: CRD42020150412

Abstract Introduction Changes in brain-derived neurotrophic factor (BDNF) have been linked to the neuroadaptative consequences of chronic alcohol use and associated with disease severity and prognosis. Few studies have evaluated the influence of drug withdrawal and clinical and sociodemographic data on BDNF levels in severe alcohol users. Objectives Our goals were (1) to evaluate variation in BDNF levels during alcohol withdrawal and, (2) to assess the influence of putative confounding factors on BDNF levels. Methods Our sample consists of 62 men with alcohol use disorder undergoing a detoxification process. Serum BDNF levels were measured using a commercial sandwich-ELISA kit, at two points: before and after the detoxification period. Results We found an increase in BDNF levels during alcohol withdrawal (25.4±9.6 at admission vs. 29.8±10.2 ng/ml at discharge; p < 0.001), even after controlling for potential confounders (positive family history, number of days between blood sample collections, and age) (Generalized Estimating Equation: coefficient = -4.37, 95% confidence interval [95%CI] -6.3; -2.4; p < 0.001). Moreover, individuals who had first-degree relative with alcohol dependence had smaller increases in BDNF levels than individuals with no family history (14.8 [95%CI -5.3; 35.6] vs. 35.3 [95%CI 15.4; 74.8]; p = 0.005). Conclusions In summary, variation in BDNF levels seems to be influenced by withdrawal in severe alcohol users. A positive family history of alcohol dependence could also be a factor that influences variation in this biomarker.

Several stressors associated with the coronavirus disease 2019 (COVID-19) are expected to affect the mental health of global populations: the effects of physical distancing, quarantine, and social isolation; the emotional suffering of health and other frontline workers; neuropsychiatric sequelae in those affected by the virus; the impact to families of lives lost to the disease; differential effects for those with severe mental disorders; and the consequences of social and economic deterioration. In this context, we sought: to form a panel of Brazilian experts on child and adolescent health, neurodevelopment, health services, and adult and elderly mental health; and to compile evidence-based interventions to support suggested policy changes in Brazil to mitigate the expected increase in mental health disorders during the pandemic and its mental health consequences. The following actions are recommended: 1) invest in prevention programs for the safe return of students to schools; 2) adopt evidence-based psychosocial interventions to maintain an adequate environment for child and adolescent development; 3) target socially vulnerable populations and those experiencing discrimination; 4) train primary care teams to solve common mental health problems, provide needs-based assessments, and manage long-term, at-home care for older patients; 5) invest in technological advancements (e.g., telemedicine, e-Health, and web-based algorithms) to promote coordinated care; 6) increase access to and literacy in the use of computers and mobile phones, especially among older adults; 7) expand protocols for remote, brief psychotherapy interventions and psychoeducation to manage common mental health problems.

Abstract Introduction Neuroprogression has been proposed as the pathological rewiring of the brain that takes place in parallel with clinical and neurocognitive deterioration in the course of psychiatric disorders. This study aims to review the biological underpinnings and clinical outcomes related to neuroprogression in post-traumatic stress disorder (PTSD). Methods We performed a systematic review by searching PubMed, Embase, and Web of Science for articles published between January 1, 1960, and January 6, 2020. Inclusion criteria were met when articles assessed brain changes, neurocognition, functioning, inflammation, oxidative stress, and neurotrophins in patients with PTSD. Narrative review articles, case reports, and preclinical studies were excluded. Results A total of 965 abstracts were identified and 15 articles were included in our systematic review. It seems that for a subset of patients whose symptoms worsen or are maintained at a high intensity there is a progressive change in the frontal lobe, especially the prefrontal cortex, and worsening of both neurocognition (verbal memory and facial recognition) and functioning (physical, psychological, social and environmental). Conclusion Although current findings associate progressive reduction in frontal lobe size with neurocognitive impairment, further research is needed to characterize PTSD as a neuroprogressive disorder.