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SERPINA6 and SERPINA1 were recently identified as the main genes associated with plasma cortisol concentration in humans. Although dysregulation in the Hypothalamus-Pituitary-Adrenal (HPA) axis has been observed in Attention Deficit/Hyperactivity Disorder (ADHD), the molecular mechanisms underlying this relationship are still unclear. Evaluation of the SERPINA6/SERPINA1 gene cluster in ADHD may provide relevant information to uncover them. We tested the association between the SERPINA6/SERPINA1 locus, including 95 single nucleotide polymorphisms (SNPs), and ADHD, using data from a Brazilian clinical sample of 259 ADHD probands and their parents. The single SNP association was tested using binary logistic regression, and we performed Classification and Regression Tree (CART) analysis to evaluate genotype combinations' effects on ADHD susceptibility. We assessed SNPs' regulatory effects through the Genotype-Tissue Expression (GTEx) v8 tool, and performed a complementary look-up analysis in the largest ADHD GWAS to date. There was a suggestive association between ADHD and eight variants located in the SERPINA6 region and one in the intergenic region between SERPINA6 and SERPINA1 after correction for multiple tests (p 0.032). CART analysis showed that the combined effects of genotype GG in rs2144833 and CC in rs10129500 were associated with ADHD (OR = 1.78; CI95% = 1.24-2.55). The GTEx assigned the SNPs as eQTLs for genes in different tissues, including SERPINA6, and the look-up analysis revealed two SNPs associated with ADHD. These results suggest a shared genetic component between cortisol levels and ADHD. HPA dysregulation/altered stress response in ADHD might be mediated by upregulation of corticosteroid binding globulin (CBG, encoded by SERPINA6) expression.

Conduct problems are associated with an increased risk of a wide range of physical, mental, and social problems. However, there is still uncertainty about how early risk factors differentiate different developmental patterns of conduct problems and whether findings replicate across diverse social contexts. We aimed to identify developmental trajectories of conduct problems, and test early risk factors, in the 2004 Pelotas Birth Cohort in Brazil. Conduct problems were measured at ages 4, 6, 11, and 15 years from caregiver reports on the Child Behaviour Checklist (CBCL) and Strengths and Difficulties Questionnaire (SDQ). Conduct problem trajectories were estimated using group-based semi-parametric modeling (n = 3938). Multinomial logistic regression was used to examine associations between early risk factors and conduct problem trajectories. We identified four trajectories: three with elevated conduct problems, including early-onset persistent (n = 150; 3.8%), adolescence-onset (n = 286; 17.3%), and childhood-limited (n = 697; 17.7%), and one with low conduct problems (n = 2805; 71.2%). The three elevated conduct problem trajectories were associated with a wide range of sociodemographic risk factors, prenatal smoking, maternal mental health, harsh parenting, childhood trauma, and child neurodevelopmental risk factors. Early-onset persistent conduct problems were particularly associated with trauma, living without a father figure, and attention difficulties. The four trajectories of conduct problems from ages 4 to 15 years in this Brazilian cohort have similar longitudinal patterns to those identified in high-income countries. The results confirm previous longitudinal research and developmental taxonomic theories on the etiology of conduct problems in a Brazilian sample.

Obesity has been reported as an attention-deficit hyperactivity disorder (ADHD) comorbidity. So far, few studies have aimed to explore the potential causal relationship between ADHD and obesity, as well as used other measures of body composition like fat-free mass (FFM) and fat mass (FM) as measures of obesity. This study aimed to test the association between ADHD and body composition (body mass index [BMI] and others) and to evaluate the potential causal relationship with obesity.Data from the 1993 Pelotas (Brazil) birth cohort at age 11-, 15-, 18-, and 22-year follow-up was used. We performed a cross-lagged panel model (CLPM) analysis between ADHD symptoms and BMI to explore the causal relationship between both traits. Finally, we tested whether ADHD, inattention, and hyperactivity symptom scales were associated with BMI, FM, and FFM at 22 years.In the CLPM, higher ADHD scores at age 11 predicted higher BMI at age 15 (β = 0.055, 95% CI [0.037; 0.073]). ADHD symptoms at age 11 was also associated with a decrease in the FFM (β = -0.16, 95% CI [-0.28; -0.05]), and an increase in the BMI (β = 0.17, 95% CI [0.10; 0.23]) and FM (β = 0.17, 95% CI [0.06; 0.29]) at 22 years. At 22 years of age, ADHD was associated with FFM and FM. Moreover, an increase in BMI was observed with an increase in several symptoms of ADHD in general (β = 0.06, 95% CI [0.004; 0.12]), and hyperactivity symptoms (β = 0.15, 95% CI [0.05; 0.25]).ADHD at 11 years predicted a higher BMI at 15 years, and body fat composition in adulthood, suggesting higher scores on ADHD symptoms in early life may be a critical point for body composition in early adulthood. The hyperactivity symptoms may play an important role in the BMI increase.

Study ObjectivesTo evaluate the level of shared genetic components between attention-deficit/hyperactivity disorder (ADHD) and sleep phenotype, common pathways between them and a possible causal relationship between traits.MethodsWe used summary statistics of the largest genome-wide association studies available for ADHD and sleep-related phenotypes including insomnia, napping, daytime dozing, snoring, ease getting up, daytime sleepiness, sleep duration and chronotype. We estimated the genomic correlation between ADHD and sleep-related traits using cross-trait LD-score regression and investigated potential common mechanisms using gene-based cross-trait metanalyses and functional enrichment analyses. The causal effect between the sleep related traits and ADHD was estimated with two sample Mendelian randomization (TSMR), using the Inverse Variance Weighted method as the main estimator.ResultsPositive genomic correlation between insomnia, daytime napping, daytime dozing, snoring, daytime sleepiness, short and long sleep duration, and ADHD were observed. Insomnia, sleep duration, daytime sleepiness, and snoring shared genes with ADHD, which were involved in neurobiological functions and regulatory signaling pathways. The TSMR approach supported a causal effect of insomnia, daytime napping, and short sleep duration on ADHD, and of ADHD on long sleep duration and chronotype.ConclusionOur findings suggest that the comorbidity between sleep phenotypes and ADHD may be mediated by common genetic factors with an important role on neuronal signaling pathways. In addition, it may also exist a causal effect of sleep disturbances and short sleep duration on ADHD, reinforcing the role of these sleep phenotypes as predictors or early markers of ADHD.Statement of SignificanceOur findings suggest that the comorbidity between sleep phenotypes and ADHD may be linked to common genetic factors with an important role on neuronal signaling pathways. They also show that a causal effect of sleep disturbances and short sleep duration on ADHD may exist, reinforcing the role of these sleep phenotypes as ADHD early markers, being able to predict the disorder. This study adds important information about the relationship between sleep, circadian rhythm, and ADHD since it raises new questions about the complexity of the phenomenon involving them and may also provide new treatment insights in this research field.

We aimed to investigate the social inequalities in the fear of not having enough food for the household, a psychological domain of food insecurity, during the COVID-19 pandemic among mothers from the 2019 Rio Grande birth cohort. In 2019 we invited all mothers who gave birth to a singleton liveborn in the municipality of Rio Grande (southern Brazil) to respond to a standardized questionnaire. In 2020, we followed these mothers twice. In wave I we located 1,077 of all eligible mothers and 1,033 in wave II (follow-up rate of 52.1% and 50.4%). We estimated the absolute and relative inequalities of food insecurity according to the number of people living in the household, maternal education, family income, and income change during the pandemic using the slope index of inequalities (SII) and the concentration index (CIX), respectively. 1,021 mothers reported having food insecurity, and the prevalence was 42.8% and 44.7% for waves I and II, respectively. In wave I we observed inequities in the distribution of food insecurity, being higher among mothers living with ≥3 people (SII:-17.3; 95%CI[-29.6;-5.0]), with a lower education (SII:-36.7; 95%CI[-47.0;-26.4]), lower income (SII-48.9; 95%CI[-58.0;-39.7]), and with an income that decreased during the pandemic (SII:-47.1; 95%CI[-57.3;-36.9]). These inequities widened from wave I to wave II. This study describes the impact of the COVID-19 pandemic on maternal and family food insecurity and the increased social disparities during the pandemic, especially among the most vulnerable populations.

Attention-deficit/hyperactivity disorder (ADHD) persists in older age and is postulated as a risk factor for cognitive impairment and Alzheimer's Disease (AD). However, these findings rely primarily on electronic health records and can present biased estimates of disease prevalence. An obstacle to investigating age-related cognitive decline in ADHD is the absence of large-scale studies following patients with ADHD into older age. Alternatively, this study aimed to determine whether genetic liability for ADHD, as measured by a well-validated ADHD polygenic risk score (ADHD-PRS), is associated with cognitive decline and the development of AD pathophysiology in cognitively unimpaired (CU) older adults. We calculated a weighted ADHD-PRS in 212 CU individuals without a clinical diagnosis of ADHD (55-90 years). These individuals had baseline amyloid-β (Aβ) positron emission tomography, longitudinal cerebrospinal fluid (CSF) phosphorylated tau at threonine 181 (p-tau

Objective: To describe and compare measures of maternal depression, anxiety, and posttraumatic stress symptoms before and during the coronavirus disease 2019 (COVID-19) pandemic in a Brazilian birth cohort. Methods: All hospital births occurring in the municipality of Rio Grande (southern Brazil) during 2019 were identified. Mothers were invited to complete a standardized questionnaire on sociodemographic and health-related characteristics. Between May and July 2020, we tried to contact all cohort mothers of singletons, living in urban areas, to answer a standardized web-based questionnaire. They completed the Edinburgh Postnatal Depression Scale (EPDS) and Generalized Anxiety Disorder 7-item (GAD-7) in both follow-ups, and the Impact of Event Scale (IES) in the online follow-up. Results: We located 1,136 eligible mothers (n=2,051). Of those, 40.5% had moderate to severe stress due to the current pandemic, 29.3% had depression, and 25.9% had GAD. Mothers reporting loss of income during the pandemic (57.2%) had the highest proportions of mental health problems. Compared to baseline, the prevalence of depression increased 5.7 fold and that of anxiety increased 2.4-fold during the pandemic (both p < 0.001). Conclusion: We found a high prevalence of personal distress due to the ongoing COVID-19 pandemic, and a clear rise in both maternal depression and anxiety.

Objective:To investigate the relationship between ultra-processed food consumption and early childhood caries.Design:Cross-sectional analysis of baseline data from a cluster randomised controlled study. Outcomes included the prevalence of children with non-cavitated and cavitated caries. The main exposure was the total daily consumption of ultra-processed foods (up to three times and four times or more), assessed through a FFQ. Potential confounders were socio-demographic characteristics of the child and caregiver/family, child breast-feeding, oral hygiene and use of dental services. Poisson regression using robust variance adjustment was used to estimate prevalence ratios (PR) and their respective 95 % CI.Setting:Primary Healthcare Centers in an urban area of Pelotas, Southern Brazil.Participants:Children aged 0–3 years (n 309).Results:Consumption of ultra-processed foods four times or more a day was found in 67·6 % of children; 24·4 and 12·0 % presented non-cavitated and cavitated caries, respectively. After adjustment, children who consumed ultra-processed foods four times or more a day were more likely to present both non-cavitated caries (PR 2·25, 95 % CI 1·19, 4·27, P = 0·013) and cavitated caries (PR 3·48, 95 % CI 1·18, 10·30, P = 0·024) compared with those who have consumed them up to three times a day.Conclusions:Consumption of ultra-processed foods is associated with early childhood caries. Interventions aiming at reducing ultra-processed food consumption should be implemented to improve children’s oral health.

Objective:We aimed to assess the validity of maternal recall of exclusive breastfeeding (EBF) at 3 months obtained 12 months after childbirth.Design:A population-based birth cohort study. The gold standard is maternal report of EBF at the age of 3 months (yes or no) and age of introduction of other foods in the infant’s diet. EBF was considered when the mother reported that no liquid, semi-solid or solid food was introduced up to that moment. The variable to be validated was obtained at 12 months after childbirth when the mother was asked about the age of food introduction. The prevalence of EBF at 3 months, and sensitivity, specificity, positive (PPV) and negative predictive values (NPV), and accuracy of 12-month recall with 95 % CI were calculated.Setting:Pelotas, Brazil.Participants:3700 mothers of participants of the Pelotas 2004 Birth Cohort.Results:The prevalence of EBF at 3 months was 27·8 % (95 % CI 26·4, 29·3) and 49·0 % (95 % CI 47·4, 50·6) according to gold standard and maternal recall, respectively. The sensitivity of maternal recall at 12 months was 98·3 % (95 % CI 97·4, 99·0), specificity 70·0 % (95 % CI 68·2, 71·7), PPV 55·8 % (95 % CI 53·4, 58·1), NPV 99·1 % (95 % CI 98·6, 99·5) and accuracy 77·9 % (95 % CI 76·6, 79·2). When the analyses were stratified by maternal and infant characteristics, the sensitivity remained around 98 %, and the specificity ranged from 64·4 to 81·8 %.Conclusions:EBF recalled at the end of the first year of infant’s life is a valid measure to be used in epidemiological investigations.

Background Several studies have reported that there is an association between developmental and emotional/behavioural problems in children exposed to acetaminophen during foetal development. However, few studies have focused on development and behavioural outcomes in early life. Objectives To test the association between prenatal exposure to acetaminophen and low neurodevelopmental performance at 24 months and behavioural/emotional problems at 48 months of life. Methods We used data from the 2004 Pelotas Birth Cohort, a population-based longitudinal prospective study. Neurodevelopment was evaluated at 24 months using Battelle's Developmental Inventory (BDI) (n = 3737). We assessed global function as well as each domain (personal-social, adaptative, motor, cognitive, and communication). Behavioural/emotional problems were assessed at 48 months using the Child Behaviour Checklist (CBCL) (n = 3624). We used the CBCL total, externalising, and internalising symptomatology and individual subscales (withdrawn, somatic complaints, anxious/depressed, social problems, cognitive problems, attention problems, aggressive behaviour, and rule-breaking behaviour). Acetaminophen use during pregnancy was retrospectively assessed at the perinatal follow-up. Poisson regression and multiple linear regression analyses were used to test the association, adjusting for several family and maternal sociodemographic and health factors, medication use during pregnancy, and the sex of the child. Results Acetaminophen exposure during prenatal development was not associated with low neurodevelopmental performance at 24 months assessed using the BDI or to emotional and behavioural problems assessed at 48 months using the CBCL in the adjusted models. Conclusions We cannot confirm the existence of an association between acetaminophen used during pregnancy and low neurodevelopmental performance at 24 months and emotional/behavioural problems at 48 months of life based on the present results.

Background/Objectives Attention-deficit hyperactivity disorder (ADHD), one of the most common neurodevelopmental disorders in childhood and adolescence, is associated with obesity in observational studies. However, it is unclear whether ADHD contributes to, results from or is merely correlated with obesity. This study evaluates the presence and direction of a causal effect between ADHD and obesity. Subjects/Methods We performed a bidirectional two-sample Mendelian randomization using summary data from consortia of genome-wide association studies to investigate if ADHD (N = 55,374) has a causal effect on body mass index (BMI) in childhood (N = 35,668) and adulthood (N = 322,154–500,000), and vice-versa. The main analysis was performed using the inverse variance weighted (IVW) method. As sensitivity analyses, we used other Mendelian randomization methods that are more robust to horizontal pleiotropy (i.e., MR-Egger, weighted mode, and penalized weighted median estimators), as well as stratified the analysis by the putative mechanisms of genetic instruments (i.e., pathways involved or not in neurological processes). Results The IVW method indicated a positive causal effect of BMI on ADHD: β = 0.324 (95% CI 0.198 to 0.449, p

Participatory learning and action cycles with women’s groups have been recommended by the WHO to promote maternal and newborn health, but few studies have tested its feasibility and acceptability in mobile health (mHealth) interventions among mothers of toddlers. This was a mixed-method feasibility assessment of an 8-week WhatsApp-based maternal support group for mothers of toddlers (12–18 months of age) enrolled in a birth cohort study in Southern Brazil. Daily messages and weekly activities were sent by moderators to promote maternal–child outcomes: child nutrition, child sleep, nurturing care, and maternal psychosocial well-being (assessed pre- and post-intervention via self-reported questionnaire). The implementation and engagement of the mothers in the program were assessed by message extraction. Acceptability was evaluated through in-depth interviews (n = 5) and open-ended surveys (n = 10). 1481 messages were exchanged in 3 WhatsApp groups (n = 30 mothers). Mothers were most active on weekdays (68.6% of messages sent on Tuesdays and 72.6% on Thursdays), afternoons (2:00–4:00pm), and evenings (9:00–11:00 pm). Engagement was higher at weeks 1–4. Mothers enjoyed and considered topics relevant. Group interaction was perceived as low, which influenced their participation. The prevalence of depression symptoms decreased from pre- to post-intervention (9% to 5%; P = .04). A moderated mobile-based support group for mothers of toddlers was feasible. mHealth services to promote maternal support are a promising strategy to improve maternal–child outcomes, but engagement and use of the service remains a challenge. Program managers should work with community members to identify ways to support engagement and participation throughout the intervention.

Attention-deficit/hyperactivity disorder (ADHD) and anxiety disorders (AD) frequently co-occur, increasing morbidity and challenging treatment. Caffeine is a central nervous system stimulant and acts in the brain through adenosine receptors, influencing attention, alertness, and anxiety. In the present study, we performed a gene-set analysis to verify if genes related to caffeine response are associated with anxiety disorders in 240 children and 406 adults with ADHD. We demonstrated an association between the gene-set with AD in children (P = 0.0054) and with the number of anxiety disorders in adults (P = 0.0197). In order to test if this effect is a result of anxiety in general or is related to AD comorbid with ADHD, we evaluated the association between caffeine gene-set with AD in an adult control sample. The gene-set was neither associated with the AD presence (P = 0.3008) nor with the number of AD (P = 0.5594) in this control sample. We also test this gene set with ADHD (n = 55,374) and AD (n = 18,186) GWAS summary statistics, and we did not observe significant results with ADHD (P = 0.5587) or AD (P = 0.3930). These findings suggest the caffeine-related genes play a role in the etiology of an anxiety disorder phenotype present in children and adults with ADHD.

To investigate the relationship between ultra-processed food consumption and early childhood caries.Cross-sectional analysis of baseline data from a cluster randomised controlled study. Outcomes included the prevalence of children with non-cavitated and cavitated caries. The main exposure was the total daily consumption of ultra-processed foods (up to three times and four times or more), assessed through a FFQ. Potential confounders were socio-demographic characteristics of the child and caregiver/family, child breast-feeding, oral hygiene and use of dental services. Poisson regression using robust variance adjustment was used to estimate prevalence ratios (PR) and their respective 95 % CI.Primary Healthcare Centers in an urban area of Pelotas, Southern Brazil.Children aged 0-3 years (n 309).Consumption of ultra-processed foods four times or more a day was found in 67·6 % of children; 24·4 and 12·0 % presented non-cavitated and cavitated caries, respectively. After adjustment, children who consumed ultra-processed foods four times or more a day were more likely to present both non-cavitated caries (PR 2·25, 95 % CI 1·19, 4·27, P = 0·013) and cavitated caries (PR 3·48, 95 % CI 1·18, 10·30, P = 0·024) compared with those who have consumed them up to three times a day.Consumption of ultra-processed foods is associated with early childhood caries. Interventions aiming at reducing ultra-processed food consumption should be implemented to improve children's oral health.

MicroRNAs (miRNAs) play an important regulatory role in the expression of genes involved in brain functions during development. Genetic variants in miRNA genes may impact their regulatory function and lead to psychiatric disorders. To evaluate the role of genetic variants in genes of miRNAs differentially expressed during neurodevelopment on autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), schizophrenia (SCZ), and major depressive disorder (MDD).The miRNAs were identified in the literature. Summary statistics from the most recent genome-wide association studies to date were used to evaluate the association between the selected polymorphisms and each disorder in a look-up approach. In a global analysis, we compared the standardised risk effect of variants in neurodevelopment-related miRNAs with those in the remaining miRNAs from miRBase.The global analysis showed that variants in neurodevelopment-related miRNAs had higher risk effects compared to the other miRNAs for SCZ (Genetic variants in neurodevelopment-related miRNAs play an important role in the genetic susceptibility of psychiatric disorders, mainly SCZ and ADHD.

RESUMO: Objetivos: Descrever a ocorrência simultânea de fatores de risco para doenças crônicas não transmissíveis e os fatores associados à simultaneidade dessas prevalências em adultos residentes na zona rural de um município no sul do Brasil. Métodos: Trata-se de estudo transversal com 1.445 adultos da zona rural de Pelotas, RS. Foram considerados quatro fatores de risco: tabagismo, consumo de álcool, inatividade física e consumo inadequado de legumes/verduras. Para verificar a ocorrência simultânea, utilizou-se análise de clusters. A associação foi avaliada por regressão ordinal, obtendo-se estimativas em razões de odds. Resultados: Dos quatro fatores de risco avaliados, três foram mais prevalentes entre os homens, sendo apenas inatividade física maior entre as mulheres. Na análise de clusters, consumo de álcool + tabagismo + consumo inadequado de vegetais foi a única combinação que apresentou prevalência observada significativamente maior que a esperada (O/E = 2,67; IC95% 1,30; 5,48), sendo superior a encontrada em outro estudo no sul do país, dado que pode ser justificado pois tal estudo incluiu o consumo de frutas além de ter avaliado população urbana, enquanto para este estudo avaliou-se apenas a população rural. Após ajuste, os homens, indivíduos solteiros, de cor da pele preta, parda ou outra, com baixa escolaridade, pior condição socioeconômica, pior percepção de saúde e que não desenvolviam atividades rurais apresentaram maior odds ratio de acúmulo de fatores de risco. Conclusão: Os achados evidenciam a importância do desenvolvimento de ações prioritárias em relação à saúde da população rural com atenção específica aos subgrupos de maior risco identificados. ABSTRACT: Objectives: To describe the occurrence of simultaneous risk factors for chronic noncommunicable diseases, and factors associated with these prevalences in rural adults of a Southern Brazilian city. Methods: The design of this study was cross-sectional with a sample of 1,445 adults from the rural area of Pelotas, RS. Four risk factors were considered: smoking, alcohol consumption, physical inactivity and inadequate consumption of vegetables. To verify the simultaneous occurrence of the outcomes, a cluster analysis was used. The association was tested by ordinal regression resulting in odds ratios. Results: Among the four risk factors evaluated, three were the most prevalent among men, and only physical inactivity was greater among women. In the cluster analysis, only the combination of alcohol consumption + smoking + inadequate vegetable consumption presented an observed prevalence that was significantly higher than the expected (O/E = 2.67, 95%CI 1.30, 5.48), and higher than another study in the south of the country. This can be justified because that study included an evaluation of urban dwellers and the consumption of fruits. After adjustment, men, single individuals, non-white people, those with less schooling, those with a worse socioeconomic status, those who reported poor perception of health, and those who do not work in specifically rural activities had a greater probability of having the simultaneity of risk factors. Conclusion: The results show the importance of developing priority actions regarding the health of rural populations with special attention to the subgroups with an identified higher risk.

Objective: We aimed to investigate the mediating effect of violence by a family member or acquaintance on biological sex, depression and suicidal ideation. Methods: We used data from the 2013 Brazilian National Health Survey, a cross-sectional nationwide survey. Major depressive episode and suicidal ideation were evaluated with the Patient Health Questionnaire. Violence victimization and other sociodemographic variables were self-reported. We used logistic regression to estimate the OR, 95%CI and G-computation to calculate the natural direct and indirect effects. Results: A total of 60,202 individuals were evaluated. Women had higher prevalences of major depressive episode (OR = 2.36; 95%CI 2.03-2.74), suicidal ideation (OR = 2.02; 95%CI 1.73-2.36) and violence victimization (OR = 1.73; 95%CI 1.45-2.06). The mediation analysis showed that 10.6% of the association between sex and major depressive episode and 8.0% of the association between sex and suicidal ideation is explained by violence. Conclusions: Women in Brazil have an increased risk of major depressive episode and suicidal ideation, and this association is mediated, in part, by the fact that they suffer more violence from family members or acquaintances.

The gut microbiome is associated with psychiatric disorders; however, the molecular mechanisms mediating this association are poorly understood. The ability of host genetics to modulate the gut microbiome may be an important factor in understanding the association. In this study, we aimed to evaluate the role of genetic variants associated with the gut microbiome in the susceptibility of individuals to four psychiatric disorders: schizophrenia (SCZ), attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and major depressive disorder (MDD). A total of 201 host genetic markers associated with microbiome outcomes and reported in available genome-wide association studies (GWAS) were included in the analyses. We searched for these variants in the summary statistics of the largest GWAS on these disorders to date, which were published by the Psychiatric Genomic Consortium, and performed gene-based and gene set association analyses. Two variants were significantly associated with ASD (rs9401458 and rs9401452) and one with MDD (rs75036654). For the gene-based association analysis, eight genes were associated with SCZ (ASIC2, KCND3, ITSN1, SIPA1L3, RBMS3, BANK1, CSMD1, and LHFPL3), one with MDD (ACTL8), two with ADHD (C14orf39 and FBXL17), and one with ASD (PINX). The gene set comprising 83 genes was associated with SCZ (p = 0.047). These findings suggest that genes related to microbiome composition may affect the susceptibility of individuals to psychiatric disorders, mainly schizophrenia. Although less robust, the associations with ASD, ADHD, and MDD cannot be discarded.

To estimate the prevalence of pesticide exposure and associated factors among rural residents.A population-based, cross-sectional study conducted with 1,518 individuals in 2016. We randomly selected 24 census tracts from the eight rural districts of the city of Pelotas, RS. All individuals aged 18 years or older, living in the randomly selected households were eligible. A descriptive analysis was performed and the prevalence of contact with pesticides was presented. The association between outcome and independent variables was analyzed using Poisson regression according to the hierarchical model. The variables were all adjusted to the same level, including those at the previous level and those with p0.20 were kept in the model.The prevalence of contact with pesticides in the past year was 23.7% and among the participants, 5.9% reported having pesticide poisoning at some time in their lives. The probability of contact with pesticides in the past year was higher among men (PR=2,00; 95%CI 1.56 - 2.56), among those aged 40-49 years (PR = 2.00; 95%CI 1.12 - 1.80), among individuals with lower levels of education (PR = 2.06; 95%CI 1.39 - 3.10), in those who performed rural work (PR = 2.87; 95%CI 1.39 - 3.10) and in those who had lived in rural areas all their lives (PR = 1.28 95%CI 1.00 - 1.66).Approximately one in four adults in rural Pelotas had come into contact with pesticides in the year before the study. The findings show the existence of social inequalities related to exposure to pesticides and provide information for action aimed at reducing exposure and poisoning from these products.

To describe the occurrence of simultaneous risk factors for chronic noncommunicable diseases, and factors associated with these prevalences in rural adults of a Southern Brazilian city.The design of this study was cross-sectional with a sample of 1,445 adults from the rural area of Pelotas, RS. Four risk factors were considered: smoking, alcohol consumption, physical inactivity and inadequate consumption of vegetables. To verify the simultaneous occurrence of the outcomes, a cluster analysis was used. The association was tested by ordinal regression resulting in odds ratios.Among the four risk factors evaluated, three were the most prevalent among men, and only physical inactivity was greater among women. In the cluster analysis, only the combination of alcohol consumption + smoking + inadequate vegetable consumption presented an observed prevalence that was significantly higher than the expected (O/E = 2.67, 95%CI 1.30, 5.48), and higher than another study in the south of the country. This can be justified because that study included an evaluation of urban dwellers and the consumption of fruits. After adjustment, men, single individuals, non-white people, those with less schooling, those with a worse socioeconomic status, those who reported poor perception of health, and those who do not work in specifically rural activities had a greater probability of having the simultaneity of risk factors.The results show the importance of developing priority actions regarding the health of rural populations with special attention to the subgroups with an identified higher risk.

RESUMO: Objetivo: Investigar o papel da situação de domicílio na prevalência de obesidade geral e abdominal, usando dados da Pesquisa Nacional de Saúde de 2013. Metodologia: As prevalências de obesidade geral e abdominal, em zonas rural e urbana, foram descritas de acordo com o sexo e a macrorregião do país. A associação entre situação de domicílio e obesidade foi testada por regressão de Poisson bruta e ajustada com nível de significância de 5%. Resultados: Foram incluídos 59.226 indivíduos. Destes, 20,7% apresentaram obesidade geral e 38% obesidade abdominal (maiores em mulheres: 24,3 e 52%, respectivamente). Em zonas urbanas, as maiores prevalências de obesidade geral foram observadas na Região Sul (20,8 e 26,5% para homens e mulheres, respectivamente). Em zonas rurais, na Região Centro-Oeste (17,2%) em homens e na Região Sul (27,4%) em mulheres. Após ajuste por idade e cor da pele, em homens, viver em zonas rurais foi associado à menor prevalência de obesidade geral nas regiões Norte (razão de prevalência - RP = 0,60; intervalo de confiança de 95% - IC95% 0,40 - 0,89) e Nordeste (RP = 0,47; IC95% 0,38 - 0,59) e para a obesidade abdominal em todas as regiões. Para as mulheres, na Região Centro-Oeste, viver em zona rural foi associado a maiores prevalências de obesidade abdominal (RP = 1,11; IC95% 1,01 - 1,23). Conclusão: Os resultados evidenciam o papel da situação de domicílio entre os desfechos em nível nacional, com menores prevalências em homens residentes em zonas rurais, no entanto maiores prevalências foram encontradas entre as mulheres, principalmente para obesidade abdominal. ABSTRACT: Objective: To investigate the role of the domiciliary situation in the prevalence of general and abdominal obesity through the National Health Survey of 2013. Methodology: General obesity (body mass index ≥ 30 kg/m2) and abdominal obesity (waist circumference ≥ 102 cm in men and ≥ 88 cm in women) in rural and urban areas were described according to sex and macroregion. Crude and adjusted Poisson regression models were used to test the association between obesity and household situation, with the significance level of 5%. Results: The study included 59,226 individuals. Out of these, 20.7% presented general obesity and 38% abdominal obesity (higher in women: 24.3 and 52%, respectively). The highest prevalences of general obesity were observed in southern urban areas, for both sexes (20.8% in men and 26.5% in women). In rural areas, the highest prevalences were observed for the central-west region (17.2%) in men and in the south region (27.4%) in women. In males, after adjusting for demographic variables, living in rural areas was associated with lower prevalences of general obesity in the North (prevalence ratios - PR = 0.60; confidence interval of 95% - 95%CI 0.40 - 0.89) and Northeast (PR = 0.47, 95%CI 0,38 - 0.59), and for abdominal obesity in all regions. For women in the Midwest, the rural household situation was associated with lower prevalences of obesity. (PR = 1.11, 95%CI 1.01 - 1.23). Conclusions: The results evidenced the role of the domiciliary situation among outcomes at the national level, with lower prevalence of general and abdominal obesity in men living in rural areas. However, higher prevalences were found among women, especially for abdominal obesity.

Attention-deficit hyperactivity disorder (ADHD), one of the most common neurodevelopmental disorders in childhood and adolescence, is associated with obesity in observational studies. However, it is unclear whether ADHD contributes to, results from or is merely correlated with obesity. This study evaluates the presence and direction of a causal effect between ADHD and obesity.We performed a bidirectional two-sample Mendelian randomization using summary data from consortia of genome-wide association studies to investigate if ADHD (N = 55,374) has a causal effect on body mass index (BMI) in childhood (N = 35,668) and adulthood (N = 322,154-500,000), and vice-versa. The main analysis was performed using the inverse variance weighted (IVW) method. As sensitivity analyses, we used other Mendelian randomization methods that are more robust to horizontal pleiotropy (i.e., MR-Egger, weighted mode, and penalized weighted median estimators), as well as stratified the analysis by the putative mechanisms of genetic instruments (i.e., pathways involved or not in neurological processes).The IVW method indicated a positive causal effect of BMI on ADHD: β = 0.324 (95% CI 0.198 to 0.449, p 0.001; expressed as change in ln(odds ratio) of ADHD per each additional SD unit of BMI). IVW estimates were directionally consistent with other methods. On the other hand, we did not find consistent evidence for a causal effect of ADHD genetic liability on BMI.The results suggested that higher BMI increases the risk of developing ADHD, but not the other way around.

OBJECTIVE To evaluate the prevalence of general and abdominal obesity and the concomitant presence of both outcomes and their determinants among adults living in a rural area. METHODS This cross-sectional, population-based study was carried out in a medium-sized city in the southern region of Brazil. We evaluated three outcomes: general obesity (body mass index ≥ 30 kg/m 2 ), abdominal obesity (waist circumference ≥ 102 cm and ≥ 88 cm in men and women, respectively), and concomitant obesities, classified as: no risk, only one risk factor, and aggregate factors. We performed crude and adjusted Poisson regression analyses for each obesity outcome and multinomial logistic regression for metabolic risk. We considered demographic and socioeconomic characteristics as independent variables. RESULTS A total of 1,433 individuals were included in the study. Of them, 29.5% presented general obesity and 37.8% presented abdominal obesity. We observed the presence of a risk factor in 15.8% of the sample, while 25.8% presented aggregate factors. The risk of general and abdominal obesity and concomitant outcomes increased significantly with age in both sexes. Richer men were at increased risk for general obesity (PR = 1.7; 95%CI 1.0–2.9), abdominal obesity (PR = 1.8; 95%CI 1.1–2.9), and aggregate factors (OR = 1.9; 95%CI 1.4–5.8). An education level of twelve years or more was a protective factor for women in relation to abdominal obesity (PR = 0.4; 95%CI 0.2–0.8) and aggregate factors (OR = 0.2; 95%CI 0.05–0.7). Rural activity reduced the risk of general obesity (PR = 0.6; 95%CI 0.5–0.8) and aggregate factors (OR = 0.5; 95%CI 0.3–0.8) in women, and the risk of abdominal obesity (PR = 0.6; 95%CI 0.5–0.8) and presence of a risk factor (OR = 0.5; 95%CI 0.3–0.7) in men. Skin color and time lived in rural areas were not statistically associated with the outcomes studied. CONCLUSIONS We observed high prevalences of general and abdominal obesity in this population, which is consistent with the values found in urban populations. However, rural activities were a protective factor for obesity outcomes. RESUMO OBJETIVO Avaliar a prevalência de obesidade geral, abdominal e concomitância de ambos os desfechos e seus determinantes em adultos residentes na zona rural. MÉTODOS Este estudo transversal de base populacional foi conduzido em município de médio porte da região Sul do Brasil. Três desfechos foram avaliados: obesidade geral (índice de massa corporal ≥ 30 kg/m 2 ), abdominal (circunferência da cintura ≥ 102 cm e ≥ 88 cm em homens e mulheres, respectivamente) e concomitância de ambas, classificada em: sem risco; apenas um fator de risco; e fatores agregados. Foram realizadas análises brutas e ajustadas por regressão de Poisson para cada desfecho de obesidade e regressão logística multinomial para o risco metabólico. Características demográficas e socioeconômicas foram consideradas como variáveis independentes. RESULTADOS Foram incluídos no estudo 1.433 indivíduos. Desses, 29,5% apresentaram obesidade geral e 37,8%, abdominal. A presença de um fator de risco foi observada em 15,8% da amostra, enquanto 25,8% apresentaram fatores agregados. O risco de obesidade geral, abdominal e a concomitância dos desfechos aumentaram significativamente com a idade, em ambos os sexos. Homens mais ricos apresentaram risco aumentado para obesidade geral (RP = 1,7; IC95% 1,0–2,9), abdominal (RP = 1,8; IC95% 1,1–2,9) e fatores agregados (RO = 1,9; IC95% 1,4–5,8). Ter 12 anos ou mais de estudo se mostrou fator de proteção para mulheres em relação à obesidade abdominal (RP=0,4; IC95% 0,2–0,8) e fatores agregados (RO = 0,2; IC95% 0,05–0,7). Realizar atividade rural reduziu o risco de obesidade geral (RP = 0,6; IC95% 0,5–0,8) e fatores agregados (RO = 0,5; IC95% 0,3–0,8) em mulheres, e de obesidade abdominal (RP = 0,6; IC95% 0,5–0,8) e presença de um fator de risco (RO = 0,5; IC95% 0,3–0,7), em homens. Cor da pele e tempo de vida residido na zona rural não foram estatisticamente associados aos desfechos estudados. CONCLUSÕES Altas prevalências de obesidade geral e abdominal foram observadas nessa população, condizentes com os valores encontrados em populações urbanas. Entretanto, a realização de atividades rurais mostrou-se um fator de proteção para os desfechos de obesidade.

To investigate the role of the domiciliary situation in the prevalence of general and abdominal obesity through the National Health Survey of 2013.General obesity (body mass index ≥ 30 kg/m2) and abdominal obesity (waist circumference ≥ 102 cm in men and ≥ 88 cm in women) in rural and urban areas were described according to sex and macroregion. Crude and adjusted Poisson regression models were used to test the association between obesity and household situation, with the significance level of 5%.The study included 59,226 individuals. Out of these, 20.7% presented general obesity and 38% abdominal obesity (higher in women: 24.3 and 52%, respectively). The highest prevalences of general obesity were observed in southern urban areas, for both sexes (20.8% in men and 26.5% in women). In rural areas, the highest prevalences were observed for the central-west region (17.2%) in men and in the south region (27.4%) in women. In males, after adjusting for demographic variables, living in rural areas was associated with lower prevalences of general obesity in the North (prevalence ratios - PR = 0.60; confidence interval of 95% - 95%CI 0.40 - 0.89) and Northeast (PR = 0.47, 95%CI 0,38 - 0.59), and for abdominal obesity in all regions. For women in the Midwest, the rural household situation was associated with lower prevalences of obesity. (PR = 1.11, 95%CI 1.01 - 1.23).The results evidenced the role of the domiciliary situation among outcomes at the national level, with lower prevalence of general and abdominal obesity in men living in rural areas. However, higher prevalences were found among women, especially for abdominal obesity.Investigar o papel da situação de domicílio na prevalência de obesidade geral e abdominal, usando dados da Pesquisa Nacional de Saúde de 2013.As prevalências de obesidade geral e abdominal, em zonas rural e urbana, foram descritas de acordo com o sexo e a macrorregião do país. A associação entre situação de domicílio e obesidade foi testada por regressão de Poisson bruta e ajustada com nível de significância de 5%.Foram incluídos 59.226 indivíduos. Destes, 20,7% apresentaram obesidade geral e 38% obesidade abdominal (maiores em mulheres: 24,3 e 52%, respectivamente). Em zonas urbanas, as maiores prevalências de obesidade geral foram observadas na Região Sul (20,8 e 26,5% para homens e mulheres, respectivamente). Em zonas rurais, na Região Centro-Oeste (17,2%) em homens e na Região Sul (27,4%) em mulheres. Após ajuste por idade e cor da pele, em homens, viver em zonas rurais foi associado à menor prevalência de obesidade geral nas regiões Norte (razão de prevalência - RP = 0,60; intervalo de confiança de 95% - IC95% 0,40 - 0,89) e Nordeste (RP = 0,47; IC95% 0,38 - 0,59) e para a obesidade abdominal em todas as regiões. Para as mulheres, na Região Centro-Oeste, viver em zona rural foi associado a maiores prevalências de obesidade abdominal (RP = 1,11; IC95% 1,01 - 1,23).Os resultados evidenciam o papel da situação de domicílio entre os desfechos em nível nacional, com menores prevalências em homens residentes em zonas rurais, no entanto maiores prevalências foram encontradas entre as mulheres, principalmente para obesidade abdominal.

Table S1. Association analysis between covariates, exposure and relevant outcomes. (DOCX 22 kb)

Table S1. Association analysis between covariates, exposure and relevant outcomes. (DOCX 22 kb)