Maternal smoking during pregnancy and intelligence quotient of offspring aged 18 and 30 years: Evidence from two birth cohorts in southern Brazil.

Maternal smoking during pregnancy causes several harmful effects, including deficits in the intelligence quotient (IQ), a measure associated with academic achievements and higher socioeconomic position. We aimed to measure the association between maternal smoking during pregnancy and offspring's IQ in two birth cohorts from Pelotas, Brazil. Data from the 1982 and 1993 birth cohorts were analyzed. Smoking during pregnancy was ascertained at the perinatal follow-up, and IQ was measured at 30 years (1982) and 18 years (1993). Simple and multiple linear regressions were used for crude and adjusted analysis. Mediation analysis was performed using birth weight and breastfeeding as possible mediators. Data analysis was conducted in 2020. There were 3611 and 4050 participants from the 1982 and 1993 cohorts, respectively. After adjustment for potential confounders, the inverse association between smoking during pregnancy and children's IQ remained significant in both cohorts. Offspring of mothers who smoked during pregnancy had an average of 1.32 less IQ points (95%CI: -2.23, -0.242) in the 1982 cohort, and an average of 1.66 less IQ points (95%CI: -2.42, -0.90) in the 1993 cohort. Neither cohort showed association with paternal smoking (negative controls) after adjustment. Breastfeeding's mediated effects accounted for 26.2% and 23.9% of the association in the 1982 and 1993 cohorts, respectively, while birth weight's accounted for 6.8% and 30.1%, respectively; indirect effects were not significant. The inverse association between maternal smoking and IQ and the lack of association with paternal smoking reinforces our findings of a negative association between exposure and outcome.

Construction and validation of the Oxford Neurodevelopment Assessment (OX-NDA) in 1-year-old Brazilian children.

BACKGROUND: Over 250 million children under 5 years, globally, are at risk of developmental delay. Interventions during the first 2 years of life have enduring positive effects if children at risk are identified, using standardized assessments, within this window. However, identifying developmental delay during infancy is challenging and there are limited infant development assessments suitable for use in low- and middle-income (LMIC) settings. Here, we describe a new tool, the Oxford Neurodevelopment Assessment (OX-NDA), measuring cognition, language, motor, and behaviour, outcomes in 1-year-old children. We present the results of its evaluation against the Bayley Scales of Infant Development IIIrd edition (BSID-III) and its psychometric properties. METHODS: Sixteen international tools measuring infant development were analysed to inform the OX-NDA's construction. Its agreement with the BSID-III, for cognitive, motor and language domains, was evaluated using intra-class correlations (ICCs, for absolute agreement), Bland-Altman analyses (for bias and limits of agreement), and sensitivity and specificity analyses (for accuracy) in 104 Brazilian children, aged 12 months (SD 8.4 days), recruited from the 2015 Pelotas Birth Cohort Study. Behaviour was not evaluated, as the BSID-III's adaptive behaviour scale was not included in the cohort's protocol. Cohen's kappas and Cronbach's alphas were calculated to determine the OX-NDA's reliability and internal consistency respectively. RESULTS: Agreement was moderate for cognition and motor outcomes (ICCs 0.63 and 0.68, p < 0.001) and low for language outcomes (ICC 0.30, p < 0.04). Bland-Altman analysis showed little to no bias between measures across domains. The OX-NDA's sensitivity and specificity for predicting moderate-to-severe delay on the BSID-III was 76, 73 and 43% and 75, 80 and 33% for cognition, motor and language outcomes, respectively. Inter-rater (k = 0.80-0.96) and test-rest (k = 0.85-0.94) reliability was high for all domains. Administration time was < 20 minutes. CONCLUSION: The OX-NDA shows moderate agreement with the BSID-III for identifying infants at risk of cognitive and motor delay; agreement was low for language delay. It is a rapid, low-cost assessment constructed specifically for use in LMIC populations. Further work is needed to evaluate its use (i) across domains in populations beyond Brazil and (ii) to identify language delays in Brazilian children.

The neurodevelopmental nature of attention-deficit hyperactivity disorder in adults.

BACKGROUND: Population studies have suggested that most adults with attention-deficit hyperactivity disorder (ADHD) did not have the disorder in childhood, challenging the neurodevelopmental conceptualisation of ADHD. Arbitrary definitions of age at onset and lack of defined trajectories were accounted for the findings. AIMS: The objective of this study was to assess the proportion of individuals presenting with either a neurodevelopmental trajectory or late-onset disorder, and to assess risk factors associated with them. METHOD: Data of 4676 individuals from the 1993 Pelotas birth cohort at 11, 15, 18 and 22 years of age were used. Polythetic and latent class mixed model analyses were performed to define ADHD trajectories from childhood to adulthood, and characterise the neurodevelopmental or late-onset courses. Regression models were applied to assess factors associated with different trajectories. RESULTS: Classical polythetic analyses showed that 67% of those with ADHD at 22 years of age had a neurodevelopmental course of the disorder. Latent class mixed model analysis indicated that 78% of adults with ADHD had a trajectory of persistent symptoms, more common in males. The remaining adults with ADHD had an ascending symptom trajectory that occurred after puberty, with late-onset ADHD associated with female gender and higher IQ. CONCLUSIONS: Both polythetic and latent trajectories analyses provided empirical evidence supporting that the large majority of adults with ADHD had a neurodevelopmental disorder.

Low neurodevelopmental performance and behavioural/emotional problems at 24 and 48 months in Brazilian children exposed to acetaminophen during foetal development.

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.

Maternal depression is associated with injuries in children aged 2-4 years: the Pelotas 2004 Birth Cohort.

INTRODUCTION: Injuries during childhood, which mostly consist of falls, burns, drowning, poisonings and car crashes, are among the main causes of death among children and young adults in several countries. OBJECTIVES: To investigate the association between maternal depression and the incidence of injuries during childhood. METHODS: In 2004, children who were born in the municipality of Pelotas, Brazil, were enrolled in a population-based birth cohort, with evaluations at birth and at 3, 12, 24 and 48 months of age. Maternal depression during pregnancy was evaluated at the time of delivery. At 12 and 24 months post partum, the Edinburgh Postnatal Depression Scale (EPDS) was used. The injuries incidence rates at ages of 24-48 months and the crude and adjusted IRRs were calculated with 95% CI through Poisson's regression. RESULTS: A total of 3533 children were analysed. The incidence of injuries was higher among children whose mothers presented depressive symptoms during pregnancy and at 12 and 24 months compared with those whose mothers did not present any symptoms. In the adjusted analysis, the IRR among girls whose mothers presented depressive symptoms during pregnancy and EPDS ≥13 at 12 and 24 months was 1.31 (1.15-1.50); and, among boys, 1.18 (1.03-1.36). INTERPRETATION: Maternal depression is associated with higher incidence of injuries between 24 and 48 months of age, in both sexes.

Prevalence and risk factors of psychiatric disorders in early adolescence: 2004 Pelotas (Brazil) birth cohort.

PURPOSE: The present study aimed to evaluate the prevalence of psychiatric disorders in early adolescence, to examine the distribution of psychiatric disorders by maternal and child characteristics and to evaluate the occurrence of psychiatric comorbidities. METHODS: This was a prospective cohort study of all live births in the city of Pelotas, Brazil, in 2004 (n = 4231). A total of 3562 subjects were evaluated at 11 years of age. Psychiatric disorders were assessed using the Development and Well-Being Assessment. Crude and adjusted logistic regression was used to investigate risk factors for any psychiatric disorder. RESULTS: According to DSM-5 criteria, the overall prevalence of psychiatric disorders was 13.2% (n = 471), 15.6% among the boys and 10.7% among the girls. The most common disorders were anxiety disorders (4.3%), any attention deficit/hyperactivity disorder (4.0%) and any conduct/oppositional disorder (2.8%). Low maternal education, smoking during pregnancy, the presence of moods symptoms during pregnancy or maternal chronic and severe depressive symptoms in the first years of the adolescent´s life, male gender, 5-min Apgar score < 7 at birth and preterm birth were associated with higher odds of any psychiatric disorder at age 11. Psychiatric comorbidities were observed in 107 subjects (22.7%), of whom 73, 24, and 10 had two, three, and four psychiatric diagnoses, respectively. CONCLUSIONS: Our results underscore the importance of psychiatric disorders as a prevalent condition in early adolescence, which has a direct impact on the planning of public policies and specific mental health care services in this age group.

Social inequalities in mental disorders and substance misuse in young adults : A birth cohort study in Southern Brazil.

PURPOSE: To investigate the association between mental disorders and substance misuse at 30 years of age with gender, socioeconomic position at birth, and family income trajectories. METHODS: The 1982 Pelotas Birth Cohort was used; all 5914 children born alive at hospital were originally enrolled (99.2% of all city births). In 2012, 3701 subjects were located and interviewed (68% retention rate). Mental disorders and substance misuse were assessed, and their prevalence analysed according to gender, socioeconomic status at birth, and four different income trajectories: always poor, never poor, poor at birth/non-poor at age 30, and non-poor at birth/poor at age 30. RESULTS: While women presented higher prevalence of mental disorders, substance misuse was much more frequent among men. Individuals in the lowest income quintile at birth presented 2-5 times more mental disorders and substance misuse than those in the highest quintile. Young adults who were always poor or were not poor at birth but were poor at 30 years of age had a higher prevalence of mental disorders than the other groups. CONCLUSIONS: The high rates of mental disorders and lifetime suicide attempts in young adults, especially those who were always poor or became poor after childhood, suggest that recent socioeconomic-related stressful situations may have a higher impact on the current mental health than events earlier in life. However, we could not identify at what specific ages socioeconomic changes were more important.

Lifelong robbery victimisation and mental disorders at age 18 years: Brazilian population-based study.

PURPOSE: Urban violence is a major problem in Brazil and may contribute to mental disorders among victims. The aim of this study was to assess the association between robbery victimisation and mental health disorders in late adolescence. METHODS: At age 18 years, 4106 participants in the 1993 Pelotas Birth Cohort Study were assessed. A questionnaire about history of robbery victimisation was administered, the Self-Report Questionnaire was used to screen for common mental disorders, and the Mini International Neuropsychiatric Interview was used to assess major depressive disorder and generalised anxiety disorder. Cross-sectional prevalence ratios between lifetime robbery victimisation and mental disorders were estimated using Poisson regression with robust standard errors, adjusting for socioeconomic variables measured at birth and violence in the home and maltreatment measured at age 15. RESULTS: There was a dose-response relationship between frequency of lifetime robberies and risk of mental disorders. Adolescents who had been robbed three or more times had twice the risk (PR 2.04; 95% CI 1.64-2.56) for common mental disorders, over four times the risk for depression (PR 4.59; 95% CI 2.60-8.12), and twice the risk for anxiety (PR 1.93; 95% CI 1.06-3.50), compared with non-victims, adjusting for covariates. Experiencing frequent robberies had greater impact on common mental disorders than experiencing an armed robbery. Population attributable fractions with regard to robbery were 9% for common mental disorders, 13% for depression, and 8% for anxiety. CONCLUSIONS: Robberies are associated with common mental disorders in late adolescence, independently of violence between family members. Reducing urban violence could significantly help in preventing common mental illnesses.

Effect of childhood nutrition counselling on intelligence in adolescence: a 15-year follow-up of a cluster-randomised trial.

OBJECTIVE: The present study aimed to assess the effects of an early childhood nutrition counselling intervention on intelligence (as measured by the intelligence quotient (IQ)) at age 15-16 years. DESIGN: A single-blind, cluster-randomised trial. SETTING: In 1998, in Southern Brazil, mothers of children aged 18 months or younger were enrolled in a nutrition counselling intervention (n 424). Counselling included encouragement and promotion of exclusive breast-feeding until 6 months of age and continued breast-feeding supplemented by protein-, lipid- and carbohydrate-rich foods after age 6 months up to age 2 years. The control group received routine feeding advice. In 2013, the fourth round of follow-up of these individuals, at the age of 15-16 years, was undertaken. IQ was assessed using the short form of the Wechsler Adult Intelligence Scale (WAIS-III). Mental disorders (evaluated using the Development and Well-Being Assessment (DAWBA)) and self-reported school failure, smoking and alcohol use were also investigated. Adjusted analyses were conducted using a multilevel model in accordance with the sampling process. SUBJECTS: Adolescents, mean (sd) age of 15·4 (0·5) years (n 339). RESULTS: Mean (sd) total IQ score was lower in the intervention group than the control group (93·4 (11·4) and 95·8 (11·2), respectively) but the association did not persist after adjustment. The prevalence of any mental disorders was similar between intervention and control groups (23·1 and 23·5 %, respectively). There were no differences between groups regarding school failure, smoking and alcohol use. CONCLUSIONS: Nutrition counselling intervention in early childhood had no effect on intelligence measured during adolescence.

COMT and DAT1 genes are associated with hyperactivity and inattention traits in the 1993 Pelotas Birth Cohort: evidence of sex-specific combined effect.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) symptoms are dimensionally distributed in the population. This study aimed to assess the role of the catechol-O-methyltransferase (COMT) and of the dopamine transporter (DAT1) genes on ADHD symptoms in the general population. METHODS: We investigated 4101 individuals from the 1993 Pelotas Birth Cohort Study using the parent version of the Strengths and Difficulties Questionnaire (SDQ) at ages 11 and 15 years. The SDQ hyperactivity/inattention scores were the main outcomes. RESULTS: Linear regression analyses demonstrated that the increasing number of COMT158Val and DAT1 10R alleles significantly predicted increasing SDQ hyperactivity/inattention scores in boys at both 11 and 15 years of age (ß coefficient = 0.049, t = 2.189, p = 0.029, R2 = 0.012, and ß coefficient = 0.064, t = 2.832, p = 0.005, R2 = 0.008, respectively). The presence of both COMT158Val and DAT1 10R alleles was also associated with full categorical ADHD diagnosis at 18 years of age in boys (χ2 = 4.561, p = 0.033, odds ratio 2.473, 95% confidence interval 1.048-5.838) from this cohort. We did not observe these associations in girls. LIMITATIONS: Our analyses of SDQ hyperactivity/inattention scores were not corrected for SDQ scores of conduct problems because these variables were highly correlated. CONCLUSION: This study demonstrates a role for COMT and DAT1 genes on hyperactivity/inattention symptoms and provides further support for ADHD as the extreme of traits that vary in the population. It also confirms previous evidence for sexual dimorphism on COMT and DAT1 gene expression.

Infant sleep hygiene counseling (sleep trial): protocol of a randomized controlled trial.

BACKGROUND: Sleep problems in childhood have been found to be associated with memory and learning impairments, irritability, difficulties in mood modulation, attention and behavioral problems, hyperactivity and impulsivity. Short sleep duration has been found to be associated with overweight and obesity in childhood. This paper describes the protocol of a behavioral intervention planned to promote healthier sleep in infants. METHODS: The study is a 1:1 parallel group single-blinded randomized controlled trial enrolling a total of 552 infants at 3 months of age. The main eligibility criterion is maternal report of the infant's sleep lasting on average less than 15 h per 24 h (daytime and nighttime sleep). Following block randomization, trained fieldworkers conduct home visits of the intervention group mothers and provide standardized advice on general practices that promote infant's self-regulated sleep. A booklet with the intervention content to aid the mother in implementing the intervention was developed and is given to the mothers in the intervention arm. In the two days following the home visit the intervention mothers receive daily telephone calls for intervention reinforcement and at day 3 the fieldworkers conduct a reinforcement visit to support mothers' compliance with the intervention. The main outcome assessed is the between group difference in average nighttime self-regulated sleep duration (the maximum amount of time the child stays asleep or awake without awakening the parents), at ages 6, 12 and 24 months, evaluated by means of actigraphy, activity diary records and questionnaires. The secondary outcomes are conditional linear growth between age 3-12 and 12-24 months and neurocognitive development at ages 12 and 24 months. DISCUSSION: The negative impact of inadequate and insufficient sleep on children's physical and mental health are unquestionable, as well as its impact on cognitive function, academic performance and behavior, all of these being factors to which children in low- and middle-income countries are at higher risk. Behavioral interventions targeting mothers and young children that can be delivered inexpensively and not requiring specialized training can help prevent future issues by reducing the risk to which these children are exposed. TRIAL REGISTRATION: ClinicalTrial.gov NCT02788630 registered on 14 June 2016 (retrospectively registered).

Sex differences in the association between foetal growth and child attention at age four: specific vulnerability of girls.

BACKGROUND: Recent evidence suggests that impaired foetal growth may provide an early indication of increased risk of child attention problems. However, despite both foetal growth and child attention problems differing by sex, few studies have examined sex differences in this association. Furthermore, no studies have been conducted in low- and middle-income countries, where there are higher rates of perinatal problems. This study aimed to test for sex differences in the association between foetal growth indices and attention problems at age four, in a large, prospective birth cohort from a middle-income country. METHODS: A total of 3,749 neonates from the 2004 Pelotas birth cohort (Brazil) with foetal growth indices collected at birth [low birthweight (LBW), small-for-gestational age (SGA), head circumference (HC), head circumference-to-abdominal circumference ratio (HC/AC) and ponderal index (PI)], were assessed for attention problems using the Child Behaviour Checklist at age four. Ordinal logistic regression with successive adjustment for maternal, demographic, gestational, perinatal and child nutrition/mother-child morbidity, was conducted separately for girls and boys. RESULTS: In girls, attention difficulties were associated with being born SGA (OR = 1.40, CI = 1.08-1.82, p = .012), with a small HC (OR = 1.52, CI = 1.11-2.08, p = .009), or with a low PI (OR = 1.29, CI = 1.08-1.54, p = .005). There were no associations identified between attention difficulties and any foetal growth indices in boys. CONCLUSIONS: Our results show that girls with impaired foetal growth may be particularly at risk of attention difficulties in childhood. This is consistent with emerging research that female foetuses may be more vulnerable to certain suboptimal intrauterine environments, inducing epigenetic changes that lead to disturbed growth and long-term developmental impairment.

Perinatal and sociodemographic factors at birth predicting conduct problems and violence to age 18 years: comparison of Brazilian and British birth cohorts.

BACKGROUND: Many low- and middle-income countries have high levels of violence. Research in high-income countries shows that risk factors in the perinatal period are significant precursors of conduct problems which can develop into violence. It is not known whether the same early influences are important in lower income settings with higher rates of violence. This study compared perinatal and sociodemographic risk factors between Brazil and Britain, and their role in explaining higher rates of conduct problems and violence in Brazil. METHODS: Prospective population-based birth cohort studies were conducted in Pelotas, Brazil (N = 3,618) and Avon, Britain (N = 4,103). Eleven perinatal and sociodemographic risk factors were measured in questionnaires completed by mothers during the perinatal period. Conduct problems were measured in questionnaires completed by mothers at age 11, and violence in self-report questionnaires completed by adolescents at age 18. RESULTS: Conduct problems were predicted by similar risk factors in Brazil and Britain. Female violence was predicted by several of the same risk factors in both countries. However, male violence in Brazil was associated with only one risk factor, and several risk factor associations were weaker in Brazil than in Britain for both females and males. Almost 20% of the higher risk for conduct problems in Brazil compared to Britain was explained by differential exposure to risk factors. The percentage of the cross-national difference in violence explained by early risk factors was 15% for females and 8% for males. CONCLUSIONS: A nontrivial proportion of cross-national differences in antisocial behaviour are related to perinatal and sociodemographic conditions at the start of life. However, risk factor associations are weaker in Brazil than in Britain, and influences in other developmental periods are probably of particular importance for understanding male youth violence in Brazil.

Childhood behaviour problems predict crime and violence in late adolescence: Brazilian and British birth cohort studies.

PURPOSE: Most children live in low- and middle-income countries (LMICs), many of which have high levels of violence. Research in high-income countries (HICs) shows that childhood behaviour problems are important precursors of crime and violence. Evidence is lacking on whether this is also true in LMICs. This study examines prevalence rates and associations between conduct problems and hyperactivity and crime and violence in Brazil and Britain. METHODS: A comparison was made of birth cohorts in Brazil and Britain, including measures of behaviour problems based on parental report at age 11, and self-reports of crime at age 18 (N = 3,618 Brazil; N = 4,103 Britain). Confounders were measured in the perinatal period and at age 11 in questionnaires completed by the mother and, in Brazil, searches of police records regarding parental crime. RESULTS: Conduct problems, hyperactivity and violent crime were more prevalent in Brazil than in Britain, but nonviolent crime was more prevalent in Britain. Sex differences in prevalence rates were larger where behaviours were less common: larger for conduct problems, hyperactivity, and violent crime in Britain, and larger for nonviolent crime in Brazil. Conduct problems and hyperactivity predicted nonviolent and violent crime similarly in both countries; the effects were partly explained by perinatal health factors and childhood family environments. CONCLUSIONS: Conduct problems and hyperactivity are similar precursors of crime and violence across different social settings. Early crime and violence prevention programmes could target these behavioural difficulties and associated risks in LMICs as well as in HICs.

Cadherin-13 gene is associated with hyperactive/impulsive symptoms in attention/deficit hyperactivity disorder.

Several efforts have been made to find new genetic risk variants which explain the high heritability of ADHD. At the genome level, genes involved in neurodevelopmental pathways were pointed as candidates. CDH13 and CTNNA2 genes are within GWAS top hits in ADHD and there are emerging notions about their contribution to ADHD pathophysiology. The main goal of this study is to test the association between SNPs in CDH13 and CTNNA2 genes and ADHD across the life cycle in subjects with ADHD. This study included 1,136 unrelated ADHD cases and 946 individuals without ADHD. No significant association between CDH13 and CTNNA2 was observed between cases and controls across different samples (P ≥ 0.096 for all comparisons). No allele was significantly more transmitted than expected from parents to ADHD probands. The CDH13 rs11150556 CC genotype was associated with more hyperactive/impulsive symptoms in youths with ADHD (children/adolescents clinical sample: F = 7.666, P = 0.006, FDR P-value = 0.032; Pelotas Birth Cohort sample: F = 6.711, P = 0.011, FDR P-value = 0.032). Although there are many open questions regarding the role of neurodevelopmental genes in ADHD symptoms, the present study suggests that CDH13 is associated with hyperactive/impulsive symptoms in youths with ADHD.

Increase in child behavior problems among urban Brazilian 4-year olds: 1993 and 2004 Pelotas birth cohorts.

BACKGROUND: There are an increasing number of reports on time trends in child and adolescent psychological problems but none from low- and middle-income countries, and very few covering the preschool period. The aim was to investigate changes in preschool behavioral/emotional problems in two birth cohorts from a middle-income country born 11 years apart. METHODS: We analyzed data from the 1993 and 2004 Pelotas birth cohort studies from Brazil. A subsample of 4-year olds from the 1993 cohort (634) and all 4-year olds from the 2004 cohort (3750) were assessed for behavioral/emotional problems through maternal report using the Child Behavior Checklist (CBCL). Response rates in these two population-based cohorts were above 90%. RESULTS: We found a significant increase in CBCL total problems, internalizing and externalizing mean scores over the 11-year period. For 1993 and 2004 Pelotas cohorts, respectively, CBCL mean values (SE) total problems scores were 27.9 (0.8) and 34.7 (0.3); for internalizing scores, 5.7 (0.2) and 6.3 (0.1) and for externalizing scores, 12.4 (0.4) and 15.5 (0.1). After adjusting for confounding variables, the largest increase from 1993 to 2004 was identified in the aggressive behavior syndrome score (Cohen's d = .50), followed by the externalizing problem score (Cohen's d = .40) and CBCL total problem score (Cohen's d = .36), respectively. The rise in child psychological problems was more marked in children from families with fewer assets and with less educated mothers. CONCLUSIONS: Our findings provide evidence for a substantial increase in preschool behavioral problems among children in Brazil over an 11-year period.

Prevalence and comorbidity of psychiatric disorders among 6-year-old children: 2004 Pelotas Birth Cohort.

PURPOSE: Most studies published on the prevalence of psychiatric disorders in children were conducted in high-income countries despite the fact that nearly 90 % of the world's population aged under 18 live in low- and middle-income countries. The study aimed to assess the prevalence of psychiatric disorders among children of 6 years of age, to examine the distribution of psychiatric disorders by gender and socioeconomic status and to evaluate the occurrence of psychiatric comorbidities. METHODS: The 2004 Pelotas Birth Cohort originally comprised 4,231 live births from Pelotas, southern Brazil. A total of 3,585 (84.7 % of 4,231 births) children aged 6 years were assessed using the Development and Well-Being Assessment (DAWBA). RESULTS: Nearly 13 % of the children presented a psychiatric diagnosis according to DSM-IV, being more prevalent among males than females (14.7 and 11.7 %, respectively, p = 0.009). Anxiety disorders were the most prevalent of all disorders (8.8 %) and specific phobias (5.4 %) and separation anxiety disorder (3.2 %) were the most common subtypes. Attention deficit hyperactivity disorder (2.6 %), oppositional defiant disorder/conduct disorder (2.6 %), and depression (1.3 %) were also diagnosed. More than one psychiatric disorder was presented by 17 % of children. Socioeconomically disadvantaged children had a higher prevalence of psychiatric disorders. CONCLUSION: Our findings underline the early onset of psychiatric disorders among children and the frequent occurrence of psychiatric comorbidity. Early prevention is needed in the field of mental health in Brazil and should start during infancy.

Glutamatergic copy number variants and their role in attention-deficit/hyperactivity disorder.

Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder with a strong genetic component. The glutamate metabotropic receptor genes (GRMs) have been considered potential candidates for ADHD susceptibility. The aim of the present study was to investigate if copy number variants (CNVs) in GRM1, GRM5, and GRM8 genes are overrepresented in ADHD subjects. A total of 1038 individuals with ADHD and 1057 subjects without this disorder were investigated. No significant difference in the total number of CNVs was found comparing the entire ADHD sample and the population sample without ADHD (P = 0.326, OR = 1.112, 95% CI = 0.762-1.624). The presence of CNVs was associated with lower intelligence quotient (IQ) scores in ADHD samples (P = 0.026, OR = 1.824, 95% CI = 1.066-3.121) but not in the sample of individuals without ADHD. CNVs in GRM5 were associated with presence of anxiety disorders in ADHD cases (P = 0.002, OR = 3.915, 95% CI = 1.631-9.402), but not in individuals without ADHD. Taken together, our results suggest a role for glutamate in ADHD as CNVs in the glutamatergic genes investigated herein were associated with cognitive and clinical characteristics of ADHD individuals.

Gene-environment interaction in externalizing problems among adolescents: evidence from the Pelotas 1993 Birth Cohort Study.

BACKGROUND: The study of gene-environment interactions (G × E) is one of the most promising strategies to uncover the origins of mental disorders. Replication of initial findings, however, is essential because there is a strong possibility of publication bias in the literature. In addition, there is a scarcity of research on the topic originated from low- and middle-income countries (LMIC). The aim of this study was to replicate G × E hypotheses for externalizing problems among adolescents in a middle-income country. METHODS: As part of the Pelotas 1993 Birth Cohort Study, 5,249 children were enrolled at birth and followed up to the age of 15 years, with an 85.7% retention rate. We sought an interaction between the homozygosity of the 10-repeat allele at the dopamine transporter (DAT1) gene and prenatal maternal smoking in the development of hyperactivity problems during adolescence assessed by the Strengths and Difficulties Questionnaire. We also tested for an interaction between the uVNTR polymorphism at the monoamine oxidase A (MAOA) and the experience of childhood maltreatment in the occurrence of conduct problems among adolescent boys. RESULTS: Although there was a clear association between prenatal maternal smoking and hyperactivity scores in adolescence (p < 0.001), no main genetic or interaction effects for the DAT1 gene were detected. Similarly, childhood maltreatment showed to be associated with conduct problems among boys (p < 0.001), with no observable main genetic or interaction effects for the MAOA gene. CONCLUSIONS: In the largest mental health G × E study performed in a LMIC to date, we did not replicate previous positive findings from the literature. Despite the presence of main environmental effects, there was no evidence of effect modification by genotype status. Additional replication efforts to measure G × E are needed to better understand the origins of mental health and illness, especially in LMIC.

Epidemiology of childhood conduct problems in Brazil: systematic review and meta-analysis.

PURPOSE: This study aimed to review evidence on the prevalence of and risk factors for conduct problems in Brazil. METHODS: We searched electronic databases and contacted Brazilian researchers up to 05/2012. Studies were included in the review if they reported the prevalence of or risk factors for conduct problems, conduct disorder, or oppositional defiant disorder for 100 + Brazilian children aged ≤18 years, systematically sampled in schools or the community. Prevalence rates and sex differences were meta-analysed. Risk factor studies were reviewed one by one. RESULTS: The average prevalence of conduct problems in screening questionnaires was 20.8%, and the average prevalence of conduct disorder/oppositional defiant disorder was 4.1%. There was systematic variation in the results of screening studies according to methodology: recruitment location, informants, instruments, impairment criterion for case definition, and response rates. Risk factors previously identified in high-income countries were mainly replicated in Brazil, including comorbid mental health problems, educational failure, low religiosity, harsh physical punishment and abuse, parental mental health problems, single parent family, and low socioeconomic status. However, boys did not always have higher risk for conduct problems than girls. CONCLUSIONS: Studies using screening questionnaires suggest that Brazilian children have higher rates of conduct problems than children in other countries, but diagnostic studies do not show this difference. Risk factors in Brazil were similar to those in high-income countries, apart from child sex. Future research should investigate developmental patterns of antisocial behaviour, employ a variety of research designs to identify causal risk mechanisms, and examine a broader range of risk factors.