Angiotensin-converting enzymes as druggable features of psychiatric and neurodegenerative disorders.

The renin-angiotensin system (RAS) plays essential roles in maintaining peripheral cardiovascular homeostasis, with its potential roles in the brain only being recognized more recently. Angiotensin-I-converting enzyme (ACE) is the main component of the RAS, and it has been implicated in various disorders of the brain. ACE and other RAS components, including the related enzyme ACE2, angiotensin peptides and their respective receptors, can participate in the pathological state, as well as with potential to contribute to neuroprotection and/or to complement existing treatments for psychiatric illness. In this narrative review, we aimed to identify the main studies describing the functions of the RAS and ACEs in the brain and their association with brain disorders. These include neurodegenerative disorders such as Parkinson's and Alzheimer's diseases, psychiatric illnesses such as schizophrenia, bipolar disorder, and depression. We also discuss the possible association of a functional polymorphism of the ACE gene with these brain diseases and the relevance of the neuroprotective and anti-inflammatory properties of ACE inhibitors (ACEis) and angiotensin receptor blockers (ARBs). Based on this, we conclude that there is significant potential value to the inclusion of ACEis and/or ARBs as a novel integrated approach for the treatment of various disorders of the brain, and particularly for psychiatric illness.

The Interactions Between Vulnerabilities for HIV and Syphilis among Cisgender and Transgender People Who Use Drugs.

In Brazil, transgender people are most affected by HIV, and crack cocaine addiction may contribute to social vulnerability and exposure to sexual and violence-related risks. This cross-sectional study comprised 2393 individuals seeking addiction treatment, consisting of 43 trans women, 1995 cisgender men, and 355 cisgender women. Records of rapid test results for HIV and syphilis and screening responses of trans women were compared to both cisgender groups using a logistic regression model to identify associated risk factors. HIV prevalence was higher in the transgender group (39.5%) than in cis women and men (5.9% and 3.6%, respectively). Our study showed an eightfold higher chance of a positive HIV test among transgender individuals who used drugs (OR: 8.79, p < .01, 95% CI: 3.90-19.78) compared to cisgender people who used drugs. A lifetime history of syphilis infection was more common in transgender people (60.0%) and cis women (32.8%) than in cis men (9.5%). Active syphilis was also more common in the transgender population (OR: 5.46, p < .01, 95% CI: 2.63 11.32). In our sample, 44.2% of transgender individuals had a history of at least one suicide attempt in their lifetime. Our results showed that transgender women were at higher risk of crack cocaine use (OR: 5.51, p < .01, 95% CI: 2.16-14.06) than cisgender men and women. The study showed that trans women had a higher prevalence of syphilis and HIV, and a greater chance of being homeless. The synergy of these vulnerabilities may have led to our findings of high psychotic symptoms and a history of suicide attempts in transgender individuals.

Prescription psychostimulants for cocaine use disorder: A review from molecular basis to clinical approach.

Cocaine use is a public health concern in many countries worldwide, particularly in the Americas and Oceania. Overdose deaths involving stimulants, such as cocaine, have been increasing markedly in North America, especially with concurrent opioid involvement. To date, no pharmacological treatment is available to treat stimulant (including cocaine) use disorders. Prescription psychostimulants (PPs) could be useful to treat cocaine use disorder (CUD) as they share the pharmacological effects with cocaine, as evidenced by a recent meta-analysis that assessed 38 randomized clinical trials (RCTs). PPs were found to promote sustained abstinence and reduce drug use in patients with CUD. The aim of this paper is to provide a narrative review of the clinical pharmacology of PPs and comment on the current stage of evidence supporting PPs to treat CUD. We also propose a model of care that integrates PPs with evidence-based psychosocial interventions (such as cognitive-behavioural therapy [CBT] and contingency management [CM]), a harm reduction approach and case management with social support.

Recommendations for Reducing the Risk of Cannabis Use-Related Adverse Psychosis Outcomes: A Public Mental Health-Oriented Evidence Review.

Objective: Cannabis use is increasingly normalized; psychosis is a major adverse health outcome. We reviewed evidence on cannabis use-related risk factors for psychosis outcomes at different stages toward recommendations for risk reduction by individuals involved in cannabis use. Methods: We searched primary databases for pertinent literature/data 2016 onward, principally relying on reviews and high-quality studies which were narratively summarized and quality-graded; recommendations were developed by international expert consensus. Results: Genetic risks, and mental health/substance use problem histories elevate the risks for cannabis-related psychosis. Early age-of-use-onset, frequency-of-use, product composition (i.e., THC potency), use mode and other substance co-use all influence psychosis risks; the protective effects of CBD are uncertain. Continuous cannabis use may adversely affect psychosis-related treatment and medication effects. Risk factor combinations further amplify the odds of adverse psychosis outcomes. Conclusions: Reductions in the identified cannabis-related risks factors-short of abstinence-may decrease risks of related adverse psychosis outcomes, and thereby protect cannabis users' health.

Caregiver Social Capital and Supportive Relationships are Associated with Better Child Social-Emotional Development.

This study examined how different domains of social capital and of social support among caregivers are associated with social-emotional development in children ages 4-6 and how caregiver depressive symptoms modify these associations. Using a stratified random sample of preschools, data included a cross-sectional study of 1147 child-caregiver pairs (543 girls) in a low-income municipality in Brazil. Crude and adjusted linear regression models revealed that all domains of social support and two domains of social capital were associated with less social-emotional development delay in children. Given a significant proportion of children in low- and middle-income countries do not meet developmental milestones, strengthening caregiver social capital and support in these settings may have the potential to improve child social-emotional development.

Are Social Vulnerability and Family Social Support Associated with Children's Psychiatric Symptoms?

Social influence can shape early childhood at different levels. We explored the association between social vulnerability and lifetime caregiver alcohol use with children's psychiatric symptoms. Multivariable logistic regression assessed the association between child psychiatric symptoms and social vulnerability among 1275 preschool child-caregiver pairs with lifetime caregiver alcohol used as a control variable. Of the children, 15.78% (95% CI 15.17-16.42) had internalizing symptoms, 2.49% (95% CI 2.19-2.83) had externalizing symptoms, and 9.36% (95% CI 8.88-9.86) had internalizing/externalizing symptoms. High social vulnerability was positively correlated with internalizing (aRRR 1.54; 95% CI 1.41-1.68) and internalizing/externalizing symptoms (aRRR 1.77; 95% CI 1.58-2.00). Low family support was strongly associated with internalizing/externalizing symptoms (aRRR 2.60; 95% CI 2.20-3.10). Lifetime caregiver alcohol use was positively correlated with all three psychiatric symptoms (aRRR 1.33; 95% CI 1.18-1.51; aRRR 1.13; 95% CI 1.06-1.59; and aRRR 1.26; 95% CI 1.12-1.42). Their association with children's mental health outcomes calls for social policy changes at the macrosystem level.

Tobacco growing and tobacco use.

Tobacco use is associated with an annual global economic cost of two trillion dollars and mortality of half of its regular users. Tobacco leaf cultivation is the starting point of the tobacco cycle. Tobacco farming employs millions of small-scale tobacco farmers around the globe, most of whom are out growers who rely on the tobacco industry. This paper aims to map the regions of greatest tobacco production globally (i.e., the US, Brazil, China, Indonesia, India, and Zambia) and tobacco use rates in these locations. Smoking rates were higher in those areas, except for India, where important population subgroups reported an upward trend for tobacco smoking. In general, there was a relationship between tobacco farming and tobacco smoking. Tobacco farming may lead to a higher risk of tobacco use and lower adherence to tobacco control policies. Therefore, promoting viable alternative livelihoods for tobacco farmers must have dual benefits. Additionally, specific health prevention policies might be necessary for those populations reporting higher tobacco use and lower perception of tobacco-related health risks.

Cannabis and Inflammatory Mediators.

INTRODUCTION: Although the recreational cannabis use is expressive worldwide, the literature about medical potential of cannabis extracts, including its anti-inflammatory properties, remains inconclusive. METHODS: We screened all articles, published on the PubMed database, on inflammatory mediators and any information about cannabis use from 1980 to March 2019. RESULTS: Six studies were included, and the main findings were as follows: (i) among healthy volunteers and cannabis users, cannabinoids seemed to decrease the inflammatory response, thus decreasing the immune response, which led to a higher risk of infections; (ii) among patients with multiple sclerosis, cannabinoids seemed to have little impact on the inflammatory markers' levels. DISCUSSION: Although cannabis use can produce immune inflammatory suppression in healthy people, this effect is not robust enough to change inflammatory mediators' levels in situations of highly dysfunctional inflammatory activation. Nevertheless, the impact of cannabinoids in clinical outcomes of these conditions remains to be determined.

The association of psychiatric symptomatology with patterns of alcohol, tobacco, and marijuana use among Brazilian high school students.

BACKGROUND AND OBJECTIVES: Studies have highlighted psychosocial factors associated with drug use among adolescents. Association of specific psychiatric comorbidity with substance use has not been properly established in Brazil. This study aimed to investigate alcohol, tobacco, and marijuana use by 15-18-year-old high school Brazilian students and to estimate associations with psychiatric symptoms. METHODS: A cross-sectional survey of 4,034 students from 128 public and private schools in São Paulo State was carried out using a two-step probability sample. Data were collected through self-report standardized questionnaires including questions on substance use patterns and the Strengths and Difficulties Questionnaire (SDQ). Key outcome variables were past-month use and past-month frequent use of alcohol, tobacco and marijuana. Questionnaires with missing information were excluded, resulting in a final sample of 2,532 adolescents. Weighted data was analyzed through logistic regressions, adjusted by gender and by socio-economic status (SES). RESULTS: Regarding SDQ total score, 43.6% of students had no psychiatric symptoms, 7.9% had subclinical symptoms and 48.5% presented clinically significant symptoms. Respondents with a clinically significant SDQ score were more likely to be past month alcohol (aOR = 1.51; 95%CI 1.22-1.88), tobacco (aOR = 1.82; 95%CI 1.25-2.66), and marijuana (aOR = 1.79; 95%CI 1.21-2.64) users as compared to those with no symptomatology. DISCUSSION AND CONCLUSIONS: Psychopathological symptoms were associated with alcohol, tobacco and marijuana use by 15-18-year-old adolescents. These associations should also be considered when planning public policies of mental health promotion. SCIENTIFIC SIGNIFICANCE: This study discusses the importance of the association between psychopathological symptoms and substance use in a middle-income country, with high level of social inequalities, in a state representative sample. (Am J Addict 2016;25:416-425).

Stigmatization of psychiatrists and general practitioners: results of an international survey.

The stigma of mental illness affects psychiatry as a medical profession and psychiatrists. The present study aimed to compare the extent and correlation patterns of perceived stigma in psychiatrists and general practitioners. An international multicenter survey was conducted in psychiatrists and general practitioners from twelve countries. Responses were received from N = 1,893 psychiatrists and N = 1,238 general practitioners. Aspects of stigma assessed in the questionnaire included perceived stigma, self-stigma (stereotype agreement), attitudes toward the other profession, and experiences of discrimination. Psychiatrists reported significantly higher perceived stigma and discrimination experiences than general practitioners. Separate multiple regression analyses showed different predictor patterns of perceived stigma in the two groups. Hence, in the psychiatrists group, perceived stigma correlated best with discrimination experiences and self-stigma, while in the general practitioners group it correlated best with self-stigma. About 17% of the psychiatrists perceive stigma as a serious problem, with a higher rate in younger respondents. Against this background, psychiatry as a medical profession should set a high priority on improving the training of young graduates. Despite the number of existing antistigma interventions targeting mental health professionals and medical students, further measures to improve the image of psychiatry and psychiatrists are warranted, in particular improving the training of young graduates with respect to raising awareness of own stigmatizing attitudes and to develop a better profession-related self-assertiveness.

Biological markers in noninvasive brain stimulation trials in major depressive disorder: a systematic review.

OBJECTIVES: The therapeutic effects of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation in patients with major depression have shown promising results; however, there is a lack of mechanistic studies using biological markers (BMs) as an outcome. Therefore, our aim was to review noninvasive brain stimulation trials in depression using BMs. METHODS: The following databases were used for our systematic review: MEDLINE, Web of Science, Cochrane, and SCIELO. We examined articles published before November 2012 that used TMS and transcranial direct current stimulation as an intervention for depression and had BM as an outcome measure. The search was limited to human studies written in English. RESULTS: Of 1234 potential articles, 52 articles were included. Only studies using TMS were found. Biological markers included immune and endocrine serum markers, neuroimaging techniques, and electrophysiological outcomes. In 12 articles (21.4%), end point BM measurements were not significantly associated with clinical outcomes. All studies reached significant results in the main clinical rating scales. Biological marker outcomes were used as predictors of response, to understand mechanisms of TMS, and as a surrogate of safety. CONCLUSIONS: Functional magnetic resonance imaging, single-photon emission computed tomography, positron emission tomography, magnetic resonance spectroscopy, cortical excitability, and brain-derived neurotrophic factor consistently showed positive results. Brain-derived neurotrophic factor was the best predictor of patients' likeliness to respond. These initial results are promising; however, all studies investigating BMs are small, used heterogeneous samples, and did not take into account confounders such as age, sex, or family history. Based on our findings, we recommend further studies to validate BMs in noninvasive brain stimulation trials in MDD.

Z-Drug Use and Benzodiazepine Use and Misuse Among LGB Populations: The Role of Psychological Distress.

BACKGROUND: Z-drugs (hypnotics such as zolpidem, zopiclone, and zaleplon) and benzodiazepines (BZDs) are sedative medications with misuse liability. The goals of this study are to report the (1) prevalence of past-year any Z-drug use, any BZD use, and any BZD misuse by sexual identity category and psychological distress; (2) associations among these 3 categories between sexual identity and past-year psychological distress; (3) associations among these 3 categories with sexual identity by past-year psychological distress status. METHODS: Data were collected from the National Survey on Drug Use and Health (years 2015-2019 [n = 210,392]), a yearly representative national household survey of the American population. We report prevalences of any Z-drug use, any BZD use, and any BZD misuse by sexual identity and past-year psychological distress status. We ran logistic regressions with complex survey design with the 3 dichotomous variables described above as the dependent variables, stratified and not-stratified by psychological distress. RESULTS: Prevalence of any Z-drug an BZD use and any BZD misuse were higher among LGB (lesbian/gay/bisexual) populations, especially gay men and bisexual women. Psychological distress was positively associated with any Z-drug and BZD use and any BZD misuse. Women were at higher risk of Z-drug (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.18-1.37) and BZD use (OR, 1.64; 95% CI, 1.55-1.73), but lower risk of BZD misuse (OR, 0.82; 95% CI, 0.76-0.88). When stratifying by psychological distress, differences between LGB and heterosexuals were more pronounced among those without past-year psychological distress, especially gay men and bisexual women. CONCLUSIONS: The presence of psychological distress attenuates the disparities between LGB and heterosexual individuals in Z-drug use and BZD use and misuse.

The S20 Brazilian Mental Health Report for Building a Just World and a Sustainable Planet: Part I.

This is the first part of two documents prepared by experts for the Brazilian S20 mental health report. These reports outline strategies aimed at addressing the exacerbated mental health challenges arising from a post-pandemic world. Ongoing psychiatric epidemiology research has yielded evidence linking mental health with intricate social determinants, including gender, race/ethnicity, racism, socioeconomic status, social deprivation, and employment, among others. More recently, the focus has expanded to also encompass violence and social oppression. By prioritizing prevention and early intervention, harnessing technology, and fostering community support, we can mitigate the long-term impact of mental disorders emerging in life. Utilizing evidence-based practices and forging partnerships between the health and education sectors, S20 countries can promote health and safety of their student population, thereby paving the way for a more promising future for the next generations. The first document focuses on addressing the mental health concerns of vulnerable populations, catering to the needs of children, youth, and aging populations, assessing the current state of alcohol and drug addictions, scaling up psychosocial interventions in primary care, exploring the potential integration of health and educational systems, and emphasizing the imperative adoption of human rights in mental health policies.

Medical Trainees' Knowledge and Attitudes Towards Electronic Cigarettes and Hookah: A Multinational Survey Study.

BACKGROUND: The rising prevalence of electronic cigarette (e-cigarette) and hookah use among youth raises questions about medical trainees' views of these products. We aimed to investigate medical trainees' knowledge and attitudes toward e-cigarette and hookah use. METHODS: We used data from a large cross-sectional survey of medical trainees in Brazil, the United States, and India. We investigated demographic and mental health aspects, history of e-cigarettes and tobacco use, knowledge and attitudes toward e-cigarettes and hookah, and sources of information on e-cigarettes and hookah. Although all medical trainees were eligible for the original study, only senior students and physicians-in-training were included in the present analysis. RESULTS: Of 2,036 senior students and physicians-in-training, 27.4% believed e-cigarette use to be less harmful than tobacco smoking. As for hookah use, 14.9% believed it posed a lower risk than cigarettes. More than a third of trainees did not acknowledge the risks of passive e-cigarette use (42.9%) or hookah smoking (35.1%). Also, 32.4% endorsed e-cigarettes to quit smoking, whereas 22.5% felt ill equipped to discuss these tobacco products with patients. Fewer than half recalled attending lectures on these topics, and their most common sources of information were social media (54.5%), Google (40.8%), and friends and relatives (40.3%). CONCLUSIONS: Medical trainees often reported incorrect or biased perceptions of e-cigarettes and hookah, resorted to unreliable sources of information, and lacked the confidence to discuss the topic with patients. An expanded curriculum emphasis on e-cigarette and hookah use might be necessary because failing to address these educational gaps could risk years of efforts against smoking normalization.

Substance use among older adults: a review of the literature.

OBJECTIVES: To explore studies that have examined the effectiveness of possible interventions to reduce the substance use among older adults. METHODS: From the search, 295 abstracts were identified and 200 were excluded. Ninety-five remaining articles were reviewed, and 90 were excluded after full text review. Nine articles were included after reviewing bibliographic references on the topic. A total of 14 articles, which all met the inclusion criteria, were considered in the review. RESULTS: All 14 studies found that pharmacological and non-pharmacological interventions can reduce substance use (alcohol, cocaine, nicotine and benzodiazepines) among older adults (mean age 45 years or older). CONCLUSIONS: There are promising possibly pharmacological and non-pharmacological interventions that can be used to reduce substance use among older adults. In addition, other studies are needed to expand the therapeutic arsenal in this population.

Cannabinoids for Substance Use Disorder Treatment: What Does the Current Evidence Say?

Background: The prevalence of Substance Use Disorder (SUD) is increasing along with the need to develop approaches to reduce the harm associated with substance use, including investigating alternatives such as cannabinoids, which show promising results, although the current evidence is limited. This scoping review focuses on the limitations and potentials of cannabinoid-based treatments for SUDs. Methods: We examined between-subject randomized controlled trials (RCTs) investigating the use of CBD and THC as pharmacological treatment for SUDs in adults, with the procedures attending the expectations of the Preferred Reporting Items for Scoping reviews and Meta-Analyses (PRISMA) for Scoping Reviews guidelines and assessed risk of bias using the Cochrane Risk of Bias Assessment Tool 2. Results: Ten RCTs were included, with six demonstrating low risk of bias, and positive results were found for treating Cannabis Use Disorder, while contradictory results were found for Opioid Use Disorder, and inconclusive results for treating Cocaine Use Disorder. Conclusions: CBD and THC demonstrate potential for treating some SUDs, but evidence is limited. Robust RCTs with larger samples and longer follow-up periods are necessary to assess carefully developed outcomes for different SUD patients. New cannabinoid-based medications and scientific-based policies may advance SUD treatment. A comprehensive approach to treatment and careful methodological choices may benefit patients with SUD.