Use of psychotropic medications in São Paulo Metropolitan Area, Brazil: pattern of healthcare provision to general population.

PURPOSE: We estimate the proportion of psychotropic medication use (PMU) among adults in São Paulo Metropolitan Area, Brazil. We investigated whether socio-demographic factors, comorbidity, and disease severity influence PMU among individuals with psychiatric disorders. METHODS: Data are from the São Paulo Megacity Mental Health Survey, a cross-sectional, population-based study, the Brazilian branch of the World Mental Health Survey Initiative. Trained lay interviewers face-to-face assessed psychiatric disorders and PMU through the Composite International Diagnostic Interview. Respondents were asked about use of healthcare service and prescribed medications for mental disorders in the previous year. Information on PMU was collected for 2935 adult residents in the area and among those with disorders who received treatment. RESULTS: Around 6% of respondents reported PMU in the past year: hypnotics or sedatives were used by 3.7% and antidepressants by 3.5%. Among individuals with 12-month disorders, only 14% reported past year PMU. Gender, age, education, income, occupational status, comorbidity, and severity were significant predictors for PMU. Among those with 12-month DSM-IV disorders who obtained treatment in healthcare settings, almost 40% received medication only. Among those treated in specialty mental health service, around 23% received combination of medication and psychotherapy. CONCLUSION: Our study has pointed out that the recent trend of access to mental healthcare in Brazil depicts unmet needs, characterized by a low prevalence of PMU among individuals with psychiatric disorders. Policies that improve appropriate access to prescribed drugs for those most in need are urgent public health priority.

In vivo treatments with fulvestrant and anastrozole differentially affect gene expression in the rat efferent ductules.

Estrogen plays a key role in maintaining the morphology and function of the efferent ductules. We previously demonstrated that the antiestrogen fulvestrant markedly affected gene expression in the rat efferent ductules. The mechanism of fulvestrant action to modulate gene expression may involve not only the blockade of ESR1 and ESR2 estrogen receptors, but also the activation of ESR1 and ESR2 when the receptors are tethered to AP-1 or SP1 transcription factors, or the activation of the G protein-coupled estrogen receptor 1. We therefore compared the effects of two strategies to interfere with estrogen action in the rat efferent ductules: treatment with fulvestrant or with the aromatase inhibitor anastrozole. Whereas fulvestrant markedly increased Mmp7 and Spp1, and reduced Nptx1 mRNA levels, no changes were observed with anastrozole. Fulvestrant caused changes in epithelial morphology that were not seen with anastrozole. Fulvestrant shifted MMP7 immunolocalization in the epithelial cells from the supranuclear to the apical region; this effect was less pronounced with anastrozole. In vitro studies of (35)S-methionine incorporation showed that protein release was increased, whereas tissue protein content in the efferent ductules of fulvestrant-treated rats was decreased. Although fulvestrant markedly affected gene expression, no changes were observed on AP-1 and SP1 DNA-binding activity. The blockade of ESRs seems to be the major reason explaining the differences between both treatments. At least some of the effects of fulvestrant appear to result from compensatory mechanisms activated by the dramatic changes caused by ESR1 blockade.

Sociodemographic correlates of transitions from alcohol use to disorders and remission in the São Paulo megacity mental health survey, Brazil.

AIMS: To evaluate sociodemographic correlates associated with transitions from alcohol use to disorders and remission in a Brazilian population. METHODS: Data are from a probabilistic, multi-stage clustered sample of adult household residents in the São Paulo Metropolitan Area. Alcohol use, regular use (at least 12 drinks/year), DSM-IV abuse and dependence and remission from alcohol use disorders (AUDs) were assessed with the World Mental Health version of the Composite International Diagnostic Interview. Age of onset (AOO) distributions of the cumulative lifetime probability of each alcohol use stage were prepared with data obtained from 5037 subjects. Correlates of transitions were obtained from a subsample of 2942 respondents, whose time-dependent sociodemographic data were available. RESULTS: Lifetime prevalences were 85.8% for alcohol use, 56.2% for regular use, 10.6% for abuse and 3.6% for dependence; 73.4 and 58.8% of respondents with lifetime abuse and dependence, respectively, had remitted. The number of sociodemographic correlates decreased from alcohol use to disorders. All transitions across alcohol use stages up to abuse were consistently associated with male gender, younger cohorts and lower education. Importantly, low education was a correlate for developing AUD and not remitting from dependence. Early AOO of first alcohol use was associated with the transition of regular use to abuse. CONCLUSION: The present study demonstrates that specific correlates differently contribute throughout alcohol use trajectory in a Brazilian population. It also reinforces the need of preventive programs focused on early initiation of alcohol use and high-risk individuals, in order to minimize the progression to dependence and improve remission from AUD.

Alcohol use patterns and disorders among individuals with personality disorders in the Sao Paulo Metropolitan Area.

INTRODUCTION: Alcohol Use Disorders are frequently comorbid with personality disorders. However, the heterogeneity of the prevalence estimates is high, and most data come from high income countries. Our aim is to estimate the prevalence and association between alcohol use outcomes and the three DSM-5 clusters of personality disorders in a representative sample of the São Paulo Metropolitan Area. MATERIALS AND METHODS: A representative household sample of 2,942 adults was interviewed using the WHO Composite International Diagnostic Interview and the International Personality Disorder Examination Screening Questionnaire. Lifetime PD diagnoses were multiply imputed, and AUD diagnoses were obtained using DSM-5 criteria. We conducted cross-tabulations and logistic regression to estimate the associations between AUDs and PDs. RESULTS AND DISCUSSION: Our study did not find significant associations of PDs with heavy drinking patterns or mild AUD. Cluster B PD respondents tended to show the highest conditional prevalence estimates of most alcohol use patterns and AUD, including its severity subtypes. When alcohol outcomes were regressed on all PD Clusters simultaneously, with adjustment for sex and age, only cluster B was significantly associated with past-year alcohol use (OR 3.0), regular drinking (OR 3.2), and AUDs (OR 8.5), especially moderate and severe cases of alcohol use disorders (OR 9.7 and 16.6, respectively). These associations between Cluster B PDs and these alcohol outcomes were shown to be independent of other PD Clusters and individuals´ sex and age. CONCLUSION: The main finding of our study is that AUDs are highly comorbid with PDs. The presence of Cluster B PDs significantly increases the odds of alcohol consumption and disorders and of more severe forms of AUDs. Considering the local context of poor treatment provision, more specific prevention and intervention strategies should be directed to this population.

Experimentation with tobacco during adolescence as a factor influencing treatment of smoking in adulthood. A retrospective cohort.

BACKGROUND: There are still few studies on predictors of smoking cessation in Brazilian samples. Experimentation with tobacco during adolescence (ETA) may be one of the important predictors. OBJECTIVE: This study aimed, within the context of a treatment-seeking group of subjects, to test the hypothesis that ETA negatively affects the outcome of smoking cessation during adulthood. DESIGN AND SETTING: Retrospective (historic) cohort study conducted at a psychosocial care center in São Paulo, Brazil, between 2007 and 2010. METHODS: Data on sociodemographics, smoking and medical profiles were obtained through self-report questionnaires that were completed at the baseline and at any follow-up appointment. Logistic regression models were constructed to describe factors associated with the outcome of smoking cessation, measured according to the self-reported four-week success rate among 367 outpatient smokers. RESULTS: ETA was found to be associated with not quitting smoking through the treatment (odds ratio = 0.57; 95% confidence interval = 0.33-0.96; P < 0.05), even after adjustment for dependence level, sociodemographics, nicotine patch use and number of years of smoking. CONCLUSIONS: Early exposure to nicotine may lead to higher risk of continuing smoking after treatment, in adulthood.

Drinking patterns and alcohol use disorders in São Paulo, Brazil: the role of neighborhood social deprivation and socioeconomic status.

BACKGROUND: Research conducted in high-income countries has investigated influences of socioeconomic inequalities on drinking outcomes such as alcohol use disorders (AUD), however, associations between area-level neighborhood social deprivation (NSD) and individual socioeconomic status with these outcomes have not been explored in Brazil. Thus, we investigated the role of these factors on drink-related outcomes in a Brazilian population, attending to male-female variations. METHODS: A multi-stage area probability sample of adult household residents in the São Paulo Metropolitan Area was assessed using the WHO Composite International Diagnostic Interview (WMH-CIDI) (n = 5,037). Estimation focused on prevalence and correlates of past-year alcohol disturbances [heavy drinking of lower frequency (HDLF), heavy drinking of higher frequency (HDHF), abuse, dependence, and DMS-5 AUD] among regular users (RU); odds ratio (OR) were obtained. RESULTS: Higher NSD, measured as an area-level variable with individual level variables held constant, showed an excess odds for most alcohol disturbances analyzed. Prevalence estimates for HDLF and HDHF among RU were 9% and 20%, respectively, with excess odds in higher NSD areas; schooling (inverse association) and low income were associated with male HDLF. The only individual-level association with female HDLF involved employment status. Prevalence estimates for abuse, dependence, and DSM-5 AUD among RU were 8%, 4%, and 8%, respectively, with excess odds of: dependence in higher NSD areas for males; abuse and AUD for females. Among RU, AUD was associated with unemployment, and low education with dependence and AUD. CONCLUSIONS: Regular alcohol users with alcohol-related disturbances are more likely to be found where area-level neighborhood characteristics reflect social disadvantage. Although we cannot draw inferences about causal influence, the associations are strong enough to warrant future longitudinal alcohol studies to explore causal mechanisms related to the heterogeneous patterns of association and male-female variations observed herein. Hopefully, these findings may help guide future directions for public health.

Gender differences in drinking patterns and alcohol-related problems in a community sample in São Paulo, Brazil.

OBJECTIVE: To investigate drinking patterns and gender differences in alcohol-related problems in a Brazilian population, with an emphasis on the frequency of heavy drinking. METHODS: A cross-sectional study was conducted with a probability adult household sample (n = 1,464) in the city of São Paulo, Brazil. Alcohol intake and ICD-10 psychopathology diagnoses were assessed with the Composite International Diagnostic Interview 1.1. The analyses focused on the prevalence and determinants of 12-month non-heavy drinking, heavy episodic drinking (4-5 drinks per occasion), and heavy and frequent drinking (heavy drinking at least 3 times/week), as well as associated alcohol-related problems according to drinking patterns and gender. RESULTS: Nearly 22% (32.4% women, 8.7% men) of the subjects were lifetime abstainers, 60.3% were non-heavy drinkers, and 17.5% reported heavy drinking in a 12-month period (26.3% men, 10.9% women). Subjects with the highest frequency of heavy drinking reported the most problems. Among subjects who did not engage in heavy drinking, men reported more problems than did women. A gender convergence in the amount of problems was observed when considering heavy drinking patterns. Heavy and frequent drinkers were twice as likely as abstainers to present lifetime depressive disorders. Lifetime nicotine dependence was associated with all drinking patterns. Heavy and frequent drinking was not restricted to young ages. CONCLUSIONS: Heavy and frequent episodic drinking was strongly associated with problems in a community sample from the largest city in Latin America. Prevention policies should target this drinking pattern, independent of age or gender. These findings warrant continued research on risky drinking behavior, particularly among persistent heavy drinkers at the non-dependent level.

Mental disorders in megacities: findings from the São Paulo megacity mental health survey, Brazil.

BACKGROUND: World population growth is projected to be concentrated in megacities, with increases in social inequality and urbanization-associated stress. São Paulo Metropolitan Area (SPMA) provides a forewarning of the burden of mental disorders in urban settings in developing world. The aim of this study is to estimate prevalence, severity, and treatment of recently active DSM-IV mental disorders. We examined socio-demographic correlates, aspects of urban living such as internal migration, exposure to violence, and neighborhood-level social deprivation with 12-month mental disorders. METHODS AND RESULTS: A representative cross-sectional household sample of 5,037 adults was interviewed face-to-face using the WHO Composite International Diagnostic Interview (CIDI), to generate diagnoses of DSM-IV mental disorders within 12 months of interview, disorder severity, and treatment. Administrative data on neighborhood social deprivation were gathered. Multiple logistic regression was used to evaluate individual and contextual correlates of disorders, severity, and treatment. Around thirty percent of respondents reported a 12-month disorder, with an even distribution across severity levels. Anxiety disorders were the most common disorders (affecting 19.9%), followed by mood (11%), impulse-control (4.3%), and substance use (3.6%) disorders. Exposure to crime was associated with all four types of disorder. Migrants had low prevalence of all four types compared to stable residents. High urbanicity was associated with impulse-control disorders and high social deprivation with substance use disorders. Vulnerable subgroups were observed: women and migrant men living in most deprived areas. Only one-third of serious cases had received treatment in the previous year. DISCUSSION: Adults living in São Paulo megacity had prevalence of mental disorders at greater levels than similar surveys conducted in other areas of the world. Integration of mental health promotion and care into the rapidly expanding Brazilian primary health system should be strengthened. This strategy might become a model for poorly resourced and highly populated developing countries.

Estrogen receptors and function in the male reproductive system.

A substantial advance in our understanding on the estrogen signaling occurred in the last decade. Estrogens interact with two receptors, ESR1 and ESR2, also known as ERalpha and ERbeta, respectively. ESR1 and ESR2 belong to the nuclear receptor family of transcription factors. In addition to the well established transcriptional effects, estrogens can mediate rapid signaling, triggered within seconds or minutes. These rapid effects can be mediated by ESRs or the G protein-coupled estrogen receptor GPER, also known as GPR30. The effects of estrogen on cell proliferation, differentiation and apoptosis are often mediated by growth factors. The understanding of the cross-talk between androgen, estrogen and growth factors signaling pathways is therefore essential to understand the physiopathological mechanisms of estrogen action. In this review we focused on recent discoveries about the nature of the estrogen receptors, and on the signaling and function of estrogen in the male reproductive system.

Effects of the antiestrogen fulvestrant (ICI 182,780) on gene expression of the rat efferent ductules.

The efferent ductules express the highest amount of estrogen receptors ESR1 (ERalpha) and ESR2 (ERbeta) within the male reproductive tract. Treatment of rats with the antiestrogen fulvestrant (ICI 182,780) causes inhibition of fluid reabsorption in the efferent ductules, leading to seminiferous tubule atrophy and infertility. To provide a more comprehensive knowledge about the molecular targets for estrogen in the rat efferent ductules, we investigated the effects of ICI 182,780 treatment on gene expression using a microarray approach. Treatment with ICI 182,780 increased or reduced at least 2-fold the expression of 263 and 98 genes, respectively. Not surprisingly, several genes that encode ion channels and macromolecule transporters were affected. Interestingly, treatment with ICI 182,780 markedly altered the expression of genes related to extracellular matrix organization. Matrix metalloproteinase 7 (Mmp7), osteopontin (Spp1), and neuronal pentraxin 1 (Nptx1) were among the most altered genes in this category. Upregulation of Mmp7 and Spp1 and downregulation of Nptx1 were validated by Northern blot. Increase in Mmp7 expression was further confirmed by immunohistochemistry and probably accounted for the decrease in collagen content observed in the efferent ductules of ICI 182,780-treated animals. Downregulation of Nptx1 probably contributed to the extracellular matrix changes and decreased amyloid deposition in the efferent ductules of ICI 182,780-treated animals. Identification of new molecular targets for estrogen action may help elucidate the regulatory role of this hormone in the male reproductive tract.

Gender differences in drinking patterns and alcohol-related problems in a community sample in São Paulo, Brazil

OBJECTIVE: To investigate drinking patterns and gender differences in alcohol-related problems in a Brazilian population, with an emphasis on the frequency of heavy drinking. METHODS: A cross-sectional study was conducted with a probability adult household sample (n = 1,464) in the city of São Paulo, Brazil. Alcohol intake and ICD-10 psychopathology diagnoses were assessed with the Composite International Diagnostic Interview 1.1. The analyses focused on the prevalence and determinants of 12-month nonheavy drinking, heavy episodic drinking (4-5 drinks per occasion), and heavy and frequent drinking (heavy drinking at least 3 times/week), as well as associated alcohol-related problems according to drinking patterns and gender. RESULTS: Nearly 22% (32.4% women, 8.7% men) of the subjects were lifetime abstainers, 60.3% were non-heavy drinkers, and 17.5% reported heavy drinking in a 12-month period (26.3% men, 10.9% women). Subjects with the highest frequency of heavy drinking reported the most problems. Among subjects who did not engage in heavy drinking, men reported more problems than did women. A gender convergence in the amount of problems was observed when considering heavy drinking patterns. Heavy and frequent drinkers were twice as likely as abstainers to present lifetime depressive disorders. Lifetime nicotine dependence was associated with all drinking patterns. Heavy and frequent drinking was not restricted to young ages. CONCLUSIONS: Heavy and frequent episodic drinking was strongly associated with problems in a community sample from the largest city in Latin America. Prevention policies should target this drinking pattern, independent of age or gender. These findings warrant continued research on risky drinking behavior, particularly among persistent heavy drinkers at the non-dependent level.

Estrogen receptors and function in the male reproductive system: [review] / Receptores e função do estrógeno no sistema reprodutor masculino: [revisão]

A substantial advance in our understanding on the estrogen signaling occurred in the last decade. Estrogens interact with two receptors, ESR1 and ESR2, also known as ERα and ERβ, respectively. ESR1 and ESR2 belong to the nuclear receptor family of transcription factors. In addition to the well established transcriptional effects, estrogens can mediate rapid signaling, triggered within seconds or minutes. These rapid effects can be mediated by ESRs or the G protein-coupled estrogen receptor GPER, also known as GPR30. The effects of estrogen on cell proliferation, differentiation and apoptosis are often mediated by growth factors. The understanding of the cross-talk between androgen, estrogen and growth factors signaling pathways is therefore essential to understand the physiopathological mechanisms of estrogen action. In this review we focused on recent discoveries about the nature of the estrogen receptors, and on the signaling and function of estrogen in the male reproductive system.

Durante a última década, ocorreu um avanço substancial no conhecimento da sinalização do estrógeno. Estrógenos interagem com dois receptores, ESR1 e ESR2, também conhecidos como ERα e ERβ, respectivamente. ESR1 e ESR2 pertencem à família de receptores nucleares, que funcionam como fatores de transcrição. Além dos bem estabelecidos efeitos transcricionais, os estrógenos medeiam a sinalização rápida, desencadeada dentro de segundos ou minutos. Esses efeitos rápidos podem ser mediados por ESRs ou pelo receptor de estrógeno acoplado à proteína G, GPER, também conhecido como GPR30. Os efeitos de estrógenos sobre a proliferação celular, diferenciação e apoptose são, muitas vezes, mediados por fatores de crescimento. Portanto, a compreensão da interação entre as vias de sinalização de andrógeno, estrógeno e fatores de crescimento é essencial para entender os mecanismos fisiopatológicos envolvidos na ação estrogênica. Nesta revisão, foram abordadas descobertas recentes sobre a estrutura dos receptores, a sinalização e a função do estrógeno no sistema reprodutor masculino.