Publications by authors named "Luciana Tovo-Rodrigues"

58 Publications

Sleep-related traits and attention-deficit/hyperactivity disorder comorbidity: Shared genetic risk factors, molecular mechanisms, and causal effects.

World J Biol Psychiatry 2021 Apr 30:1-14. Epub 2021 Apr 30.

Post-Graduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.

Objectives: To evaluate the shared genetic components, common pathways and causal relationship between ADHD and sleep-related phenotypes.

Methods: We used the largest genome-wide association summary statistics available for attention-deficit/hyperactivity disorder (ADHD) and various sleep-related phenotypes (insomnia, napping, daytime dozing, snoring, ease getting up, daytime sleepiness, sleep duration and chronotype). We estimated the genomic correlation using cross-trait linkage disequilibrium score regression (LDSR) and investigated the potential common mechanisms using gene-based cross-trait metanalyses and functional enrichment analyses. The causal effect was estimated using two-sample Mendelian randomisation (TSMR), using the inverse variance weighted method as the main estimator.

Results: A positive genomic correlation between insomnia, daytime napping, daytime dozing, snoring, daytime sleepiness, short and long sleep duration, and ADHD was observed. Insomnia, daytime sleepiness, and snoring shared genes with ADHD, that are involved in neurobiological functions and regulatory signalling pathways. The TSMR supported a causal effect of insomnia, daytime napping, and short sleep duration on ADHD, and of ADHD on long sleep duration and chronotype.

Conclusion: Comorbidity between sleep phenotypes and ADHD may be mediated by common genetic factors that play an important role in neuronal signalling pathways. A causal effect of sleep disturbances and short sleep duration on ADHD reinforced their role as predictors of ADHD.
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http://dx.doi.org/10.1080/15622975.2021.1907719DOI Listing
April 2021

Genes and SNPs in the pathway of immune response and caries risk: a systematic review and meta-analysis.

Biofouling 2020 10 17;36(9):1100-1116. Epub 2020 Dec 17.

Department of Restorative Dentistry, Federal University of Pelotas, Pelotas, Brazil.

The aim of this systematic review and meta-analysis was to pool the data on Single Nucleotide Polymorphisms (SNPs) in immune response genes associated with dental caries. Nineteen studies were included in the review and 18 in the meta-analysis. Twenty-two SNPs were evaluated, which are linked to six different genes (, , , , and ). Most SNPs (81.8%) are related to the possible functional impact on protein coding. The gene was associated with caries experience in the analysis of the homozygote (OR = 2.12 CI95%[1.12-3.99]) and heterozygote (OR = 2.22 CI95%[1.44-3.44]) genotypes. The gene was associated according to an analysis of the heterozygous genotype (OR = 1.83 CI95%[1.08-3.09]). Thus, SNPs related to immune response genes are linked to the phenotype of caries experience. Although the meta-analysis showed that the genes and were associated with caries, these results should be interpreted with caution due to the quality of the evidence.
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http://dx.doi.org/10.1080/08927014.2020.1856821DOI Listing
October 2020

Second generation of the 1993 birth cohort, Pelotas (Brazil): Aims, design, preliminary results.

Health Sci Rep 2020 Dec 10;3(4):e199. Epub 2020 Nov 10.

Epidemiology Universidade Federal de Pelotas Pelotas Brazil.

Background And Aims: Longitudinal cohort studies examining different generations can explain how health problems can be transmitted through genetic and environmental mechanisms and their effects on the health of offspring. This study aimed to present the design and to describe the characteristics of the baseline sample of a second generation cohort.

Methods: The 93Cohort-II is a dynamic prospective cohort composed of a second generation from the original 1993 Pelotas Birth Cohort (offspring), whose parents had their last follow-up at 22 years old. Biological parents were asked to answer questions addressing the type of birth, general health status, family composition, dietary habits, breastfeeding habits, and child-caregiver(s), among others, and the children's anthropometric measurements were evaluated.

Results: Of 1650 children identified, 1212 were evaluated (response rate, 73.4%), and 21 died before the baseline assessment. The age of the offspring ranged from 0 to 10 years (mean [±SD], 2.9 ± 2.1 years); most children (65.6%) lived with both parents and were born to young mothers and poor families. One-third of the children were breastfed until 6 months of age, one-half were born by cesarean section, 63.9% had used medication in the previous 15 days, 26.4% experienced hospitalization at least once since birth, and 14% had no updated vaccination; asthma/bronchitis (20.4%) and bronchiolitis (13.4%) were the most frequently reported diseases. More than 60% consumed ultra-processed foods, and the prevalence of overweight among those <5 and ≥6 years of age was 10.2% and 18.9%, respectively. The mean total Child Behavior Checklist score was 44.1 ± 23.61 (≥16 months), and the mean intellectual quotient score in children ≥6 years of age was 97.9 ± 15.4.

Conclusion: Despite the difficulties in conducting intergenerational cohort studies, the results of the present investigation provide evidence supporting the feasibility of performing these types of studies in middle-income countries.
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http://dx.doi.org/10.1002/hsr2.199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654626PMC
December 2020

Host genetics influences the relationship between the gut microbiome and psychiatric disorders.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Mar 30;106:110153. Epub 2020 Oct 30.

Postgraduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Brazil. Electronic address:

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.
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http://dx.doi.org/10.1016/j.pnpbp.2020.110153DOI Listing
March 2021

Obesity and ADHD: Exploring the role of body composition, BMI polygenic risk score, and reward system genes.

J Psychiatr Res 2021 04 22;136:529-536. Epub 2020 Oct 22.

Postgraduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Brazil. Electronic address:

The association between obesity and attention-deficit hyperactivity disorder (ADHD) has been extensively reported in the literature. However, the potential mechanisms underlying this association are not completely understood. This study aimed to evaluate the association between body composition and ADHD and explore the possible genetic mechanisms involved. We used data from the 1982 Pelotas (Brazil) Birth Cohort at age 30-year follow-up (N = 3630). We first used logistic regression analysis to test whether body mass index (BMI), fat mass (FM), and fat-free mass (FFM) were associated with ADHD. We further tested the association between BMI polygenic risk score (BMI-PRS) and ADHD and the role of the genes upregulated in the reward system using a gene-set association approach. BMI (odds ratio [OR] = 1.05; 95% confidence interval [CI], 1.00-1.09; p = 0.038) and FM (OR = 1.04; 95% CI, 1.00-1.07; p = 0.043) were associated with ADHD. The BMI-PRS was associated with ADHD (using p-value threshold (P) = 0.4; OR = 1.65; 95% CI, 1.02-2.65) at a nominal level. In gene-set analysis, the reward system genes were associated with BMI in subjects with a high BMI-PRS score, considering P = 0.4 (p = 0.014). The results suggest that BMI genetic components, especially those genes related to the reward system, may be involved in this association.
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http://dx.doi.org/10.1016/j.jpsychires.2020.10.026DOI Listing
April 2021

Single nucleotide polymorphisms of taste genes and caries: a systematic review and meta-analysis.

Acta Odontol Scand 2021 Mar 25;79(2):147-155. Epub 2020 Oct 25.

Graduate Program in Dentistry, Federal University of Pelotas, Pelotas, Brazil.

Objective: The aim of the present study was to systematically review the literature investigating the single nucleotide polymorphisms (SNP) related to taste genes and their influence on caries.

Material And Methods: Search was performed in five databases to respond to the question: 'Are the polymorphisms of taste genes associated with dental caries?'. Studies in humans were included. Assessment of quality of studies, meta-analysis and sensitivity analysis were performed.

Results: Seven studies were included in the systematic review and two in meta-analysis. Most of studies (71.4%) presented cohort design with low-level of evidence. A total of 4,032 individuals were evaluated. Four different taste genes ( and ) and 12 SNPs were reported. Most SNPs of taste genes showed a protective effect of the minor allele against dental caries. Meta-analysis included the SNP rs713598 placed in the gene. The results suggest an effect of the heterozygote genotype (CG), which was associate with low caries experience (OR = 0.35 CI95% [0.17-0.75]). However, the genotype GG was not associated (OR = 0.17 CI95% [0.03-1.04]). Sensitivity analysis showed an important influence of one study in the results.

Conclusions: SNP of taste genes seems to be associated with caries experience. Causal inferences should be interpreted with caution and the results must be replicated in different populations.
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http://dx.doi.org/10.1080/00016357.2020.1832253DOI Listing
March 2021

Genetic variants in miRNAs differentially expressed during brain development and their relevance to psychiatric disorders susceptibility.

World J Biol Psychiatry 2020 Nov 10:1-12. Epub 2020 Nov 10.

Postgraduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Brazil.

Objectives: 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).

Methods: 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.

Results: The global analysis showed that variants in neurodevelopment-related miRNAs had higher risk effects compared to the other miRNAs for SCZ ( = 0.010) and ADHD ( = 0.001). , , and were significantly associated with SCZ, while 55.9% of the miRNAs were at least nominally associated with one or more psychiatric disorders ( < 0.05).

Conclusions: Genetic variants in neurodevelopment-related miRNAs play an important role in the genetic susceptibility of psychiatric disorders, mainly SCZ and ADHD.
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http://dx.doi.org/10.1080/15622975.2020.1834618DOI Listing
November 2020

Genes in the pathway of tooth mineral tissues and dental caries risk: a systematic review and meta-analysis.

Clin Oral Investig 2020 Nov 18;24(11):3723-3738. Epub 2020 Sep 18.

Federal University of Pelotas, 457, Gonçalves Chaves St. 5th floor, Pelotas, RS, 96015-560, Brazil.

Objectives: To perform a systematic review of the literature, investigating the influence of tooth mineral tissues genes on dental caries.

Materials And Methods: Five databases were searched. Only human studies with cross-sectional, longitudinal, and case-control design were included. Meta-analysis was performed for each polymorphism, providing allele and genotype estimates. A meta-analysis was performed, pooling several polymorphisms for each gene. A Funnel Plot and Egger's test were also performed.

Results: A total of 1124 records were found. Of these, 25 papers were included in the systematic review and 18 in the meta-analysis. Most of the studies (52%) were of medium quality. With regard to the allele analysis, the T allele of rs134136 (TFIP11) (OR 1.51; 95%CI 1.02-2.22) showed an association with high experience of caries and the summarization of polymorphisms investigated in the TFIP11 gene, after exclusion of SNP linkage disequilibrium, showed an association with caries experience (OR 1.64; 95%CI 1.08-2.50). An analysis of the homozygous genotype did not show any significant association. The pooled SNPs of AMBN showed associations with caries (OR 0.45; 95%CI 0.29-0.72). The pooled polymorphisms of AMELX were associated with caries experience (OR 1.78; 95%CI 1.23-2.56). In the analysis of the homozygous genotype, no SNP showed a significant association. Egger's test showed no significant publication bias for all models (p > 0.05).

Conclusion: The present findings showed that the genes TFIP11, AMBN, and AMELX play an important role in dental caries.

Clinical Relevance: Several single nucleotide polymorphisms related to the genes in the formation of tooth mineral are linked to the occurrence of dental caries, and these genes have proved to be important for an explanation of differences in the risk of dental caries.
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http://dx.doi.org/10.1007/s00784-019-03146-xDOI Listing
November 2020

Effects of parenting interventions on child and caregiver cortisol levels: systematic review and meta-analysis.

BMC Psychiatry 2020 07 15;20(1):370. Epub 2020 Jul 15.

Human Development and Violence Research Centre (DOVE), Federal University of Pelotas, Rua Marechal Deodoro 1160, Pelotas, RS, 96020-220, Brazil.

Background: Nurturing care, in which children are raised in engaging and safe environments, may reduce child stress and shape hypothalamic-pituitary-adrenal axis functioning. Hence, parent-training programs may impact child cortisol levels, as well as behavioral, social and health outcomes. We conducted a systematic review of the impact of parent-training interventions on children's and caregivers' cortisol levels, and meta-analyzed the results.

Methods: In January 2020, searches in PubMed, LILACS, ERIC, Web of Science, Scielo, Scopus, PsycNET and POPLINE databases were conducted, and two independent researchers screened the results for eligible studies - randomized trials that assessed the impact of parent-training interventions on child or caregiver cortisol levels. Random effects were used to pool the estimates, separately for children and caregivers, and for children's morning and evening cortisol levels, as well as change across the day.

Results: A total of 27 eligible studies were found. Data from 19 studies were extracted and included in the meta-analyses, with 18 estimates of child cortisol levels and 5 estimates for caregiver cortisol levels. The pooled effect size (standardized mean difference) for the effects of parent training programs on morning child cortisol was 0.01 (95%CI: - 0.14 to 0.16; I: 47.5%), and for caregivers it was 0.04 (95%CI: - 0.22 to 0.30; I: 0.0%). Similar null results were observed for child evening cortisol and for the slope between morning and evening child cortisol. No evidence of publication bias was found.

Conclusion: Existing evidence shows no effect of parent-training interventions on child or caregiver post-intervention cortisol. Researchers are encouraged to adopt standardized protocols to improve evaluation standards, to test for intervention effects on psychosocial outcomes that are theorized to mediate the effects on biomarkers, and to use additional biomarkers for chronic stress.
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http://dx.doi.org/10.1186/s12888-020-02777-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362449PMC
July 2020

Simultaneity of risk factors for chronic non-communicable diseases in a rural population of a Southern Brazilian city.

Rev Bras Epidemiol 2020 8;23:e200066. Epub 2020 Jul 8.

Programa de Pós-graduação em Epidemiologia, Universidade Federal de Pelotas, Pelotas, RS, Brazil.

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.
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http://dx.doi.org/10.1590/1980-549720200066DOI Listing
July 2020

Maternal perinatal depression and infant sleep problems at 1 year of age: Subjective and actigraphy data from a population-based birth cohort study.

J Sleep Res 2021 Apr 14;30(2):e13047. Epub 2020 Apr 14.

Division of Neurology, Pontifícia Universidade Católica do Rio Grande do Sul School of Medicine, Brain Institute (BRAIns), Porto Alegre, Brazil.

This study used data from 2,222 mothers and infants participating in a population-based birth cohort to verify whether maternal depression in the perinatal period was associated with poor infant sleep. Mothers who scored ≥13 points on the Edinburgh Postnatal Depression Scale at 16-24 weeks of gestation and/or 3 months after delivery were considered perinatally depressed. The main outcome variable was poor infant sleep at 12 months of age, defined as >3 night wakings, nocturnal wakefulness >1 hr or total sleep duration <9 hr. Infant sleep data were obtained with the Brief Infant Sleep Questionnaire (BISQ) and 24-hr actigraphy monitoring. Prevalence of perinatal depression in the sample was 22.3% (95% confidence interval [CI], 20.5-24.0). After Poisson regression, infants of depressed mothers showed an adjusted relative risk (RR) of 1.44 (95% CI, 1.00-2.08; p = .04) for >3 night wakings with questionnaire-derived data. When actigraphy data were analysed, no association was found between perinatal depression and poor infant sleep (adjusted RR, 1.20; 95% CI, 0.82-1.74; p = .35). In conclusion, although mothers in the depressed group were more likely to report more night wakings, objective data from actigraphy did not replicate this finding. Dysfunctional cognition, maternal behavioural factors and sleep impairment associated with perinatal depression may affect the mother's impression of her infant's sleep.
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http://dx.doi.org/10.1111/jsr.13047DOI Listing
April 2021

[Factors associated with sleep disorders in university students].

Cad Saude Publica 2020 23;36(3):e00074919. Epub 2020 Mar 23.

Universidade Federal de Pelotas, Pelotas, Brasil.

The objective was to investigate sleep disorders and associated sociodemographic and behavioral factors. A census of university students was carried out. Questions extracted from the Munich Chronotype Questionnaire investigated: insufficient sleep duration (< 6 hours/day for < 65 years and < 5 hours/day for other ages), long latency (> 30 minutes), low self-rated sleep quality, nocturnal awakenings (involuntary, in the middle of the night), and daytime sleepiness (difficulty concentrating). Independent variables included sociodemographic and behavioral characteristics. Adjusted analyses were performed with Poisson regression. Of the 1,865 students, 32% exhibited insufficient sleep on class days, 8.2% insufficient sleep on weekends, 18.6% long latency on class days, 17.2% long latency on weekends, 30% low self-rated sleep quality, 12.7% nocturnal awakenings, and 32.2% daytime sleepiness. Higher alcohol consumption was associated with insufficient sleep duration and long latency on class days, low quality sleep, awakenings, and daytime sleepiness. Smoking was associated with insufficient sleep duration on weekends, awakenings, and low-quality sleep. Black and brown skin color were associated with insufficient sleep duration on class days, low-quality sleep, and awakenings. Morning classes were associated with insufficient sleep and daytime sleepiness. Female gender was associated with low-quality sleep and awakenings. The most frequent sleep disorders were insufficient sleep on class days, low self-rated quality of sleep, and daytime sleepiness. Alcohol consumption and smoking and black and brown skin color were the principal factors associated with sleep disorders.
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http://dx.doi.org/10.1590/0102-311X00074919DOI Listing
August 2020

Health self-perception and morbidities, and their relation with rural work in southern Brazil.

Rural Remote Health 2020 03 24;20(1):5424. Epub 2020 Mar 24.

Post-graduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil

Introduction: Self-assessment of health status can be considered a good predictor of population morbidity and mortality. Sociodemographic, environmental and health conditions can influence health self-perception. However, in rural areas, the identification of morbidities that affect workers' health and their general health condition is unknown. This study aims to evaluate the relationship between health self-perception and the occurrence of morbidities according to type of work.

Methods: This was a cross-sectional, population-based study of a rural area of Brazil. Health self-perception outcomes were classified as good (very good or good) or not good (fair, poor or very poor). Rural work, classified as yes or no, was considered to be the exposure. Crude and adjusted Poisson regression analyses were performed, obtaining prevalence ratio (PR) estimates and the respective confidence intervals (95%CI). All analyses were stratified by sex and adjusted for confounding factors.

Results: The sample comprised 893 individuals. The not good health self-perception prevalence was 27.6%, with a significant difference between the sexes (24.2% of men v 32.5% of women, p=0.014). Although associated with rural work in the crude model, self-perception was not associated with type of work after adjustment (PR: 1.02, 95%CI: 0.83-1.27). The risk of developing obesity (PR: 0.65, 95%CI: 0.47-0.91) and cardiovascular diseases (PR: 0.32, 95%CI: 0.12-0.87) was lower in men who developed rural activities. Also, women who reported doing rural work presented a lower risk for respiratory diseases (PR: 0.47; 95%CI: 0.22-0.97).

Conclusion: The association between rural work and not good health self-perception, cardiovascular disease and obesity in women, and respiratory diseases in men seems to be highly dependent on sociodemographic context.
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http://dx.doi.org/10.22605/RRH5424DOI Listing
March 2020

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

Paediatr Perinat Epidemiol 2020 05 20;34(3):278-286. Epub 2020 Mar 20.

Departamento de Medicina Preventiva, Faculdade de Medicina FMUSP, Universidade de São Paulo, SP, Brazil.

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.
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http://dx.doi.org/10.1111/ppe.12649DOI Listing
May 2020

The role of CACNA1C gene and childhood trauma interaction on bipolar disorder.

Prog Neuropsychopharmacol Biol Psychiatry 2020 07 10;101:109915. Epub 2020 Mar 10.

Laboratory of Clinical Neuroscience, Post-graduation Program in Health and Behavior, Catholic University of Pelotas, Pelotas, Rio Grande do Sul, Brazil. Electronic address:

Studies on gene x environment interaction (GxE) have provided vital information for uncovering the origins of complex diseases. When considering the etiology of bipolar disorder (BD), the role of such interactions is unknown. Here, we tested whether trauma during childhood could modify the effect of two polymorphisms in the CACNA1C gene (rs1006737 and rs4765913) in terms of susceptibility to BD. The study enrolled 878 Caucasian young adults in a cross-sectional population-based survey. BD diagnosis was performed using a clinical interview MINI 5.0, and trauma was assessed with the childhood trauma questionnaire (CTQ). Binary logistic regression models were employed to test the main effects of polymorphisms, haplotypes, and GxE interactions using sex as a confounder. We did not observe an association between the polymorphisms and diagnosis of BD. However, we noted that childhood trauma modified the effect of the rs4765913 polymorphism (p = .018) and the AA haplotype (rs1006737 - rs4765913) (p = .018) on BD susceptibility. A allele carriers of the rs4765913 polymorphism or the AA haplotype exposed to childhood trauma are more likely to develop BD compared to the individuals without a genetic risk. Thus, this study showed that the risk of developing BD in individuals exposed to childhood trauma was influenced by the individual's genetic background, varying according to the CACNA1C genotypes.
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http://dx.doi.org/10.1016/j.pnpbp.2020.109915DOI Listing
July 2020

Validity of the Brief Infant Sleep Questionnaire (BISQ) in Brazilian children.

Sleep Med 2020 05 11;69:65-70. Epub 2020 Jan 11.

Post-graduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil; Post-graduate Program in Paediatrics and Child Health, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil.

Objective: To investigate the validity of the Brief Infant Sleep Questionnaire (BISQ), in assessing sleep quality in childhood.

Methods: This was a validation study with children from the Pelotas 2015 Birth Cohort. BISQ was applied to mothers when their children were 3, 6, 12, and 24 months of age. The poor sleep indicators analysed, as defined by BISQ, were >3 wakings per night, nocturnal wakefulness >1 h and total sleep duration <9/24 h, compared to number of wakings per night and nocturnal and total sleep duration defined by actigraphy taken as the gold standard. The Actiwatch wGT3X-BT device was used by the child consecutively during five days at three and six months and for three days at 12 and 24 months. At each age the prevalence, sensitivity, specificity, accuracy, and positive (PPV) and negative predictive values (NPV) of each sleep indicator was calculated.

Results: A total of 586 children were enrolled in the study. Nocturnal wakefulness >1 h was the most frequent indicator at all ages, with higher sensitivity (varying from 27.5% at six months to 54.8% at three) and lower specificity (53.4% at three months to 79.4% at six months), in comparison to the other sleep indicators. Specificity for >3 wakings and total sleep duration <9 h was greater than 85.0% at all the ages. Higher accuracies were observed for total sleep <9 h at 3 (85.6%), 6 (88.2%) and 12 months (73.6%) and for > 3 wakings at 24 months (84.5%). The sensitivity for the presence of at least one indicator decreased with age from 56.0% at three months to 35.8% at 24 months, whereas the specificity increased from 50.6% at three months to 63.8% at 24 months.

Conclusion: The high specificity of the BISQ sleep parameters supports the validity of parents' reports on sleep-related problems in childhood for use in epidemiological studies.
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http://dx.doi.org/10.1016/j.sleep.2019.12.018DOI Listing
May 2020

Associations of acetaminophen use during pregnancy and the first year of life with neurodevelopment in early childhood.

Paediatr Perinat Epidemiol 2020 05 22;34(3):267-277. Epub 2020 Jan 22.

Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.

Background: Over-the-counter analgesic use during pregnancy, particularly acetaminophen, may be associated with negative developmental outcomes in children.

Objective: Estimate associations of prenatal and early-life exposure to acetaminophen in early childhood with cognitive, motor, and language skills in two birth cohorts.

Methods: The American Project Viva cohort (1217 mother-child pairs enrolled 1999-2002) assessed cognition at approximately 3 years using the Peabody Picture Vocabulary Test and the Wide Range Achievement of Visual Motor Abilities (WRAVMA). The Brazilian 2015 Pelotas Birth Cohort (3818 mother-child pairs) assessed cognition at 2 years using the INTERGROWTH-21st Neurodevelopment Assessment. We used linear regression to estimate associations of acetaminophen use during pregnancy (Project Viva and Pelotas) and infancy (Project Viva) with children's cognitive scores adjusted for maternal age, pre-pregnancy body mass index, education, parity, race/ethnicity, smoking and alcohol use during pregnancy, depression during pregnancy, antibiotic and ibuprofen use during pregnancy, household income, and child's sex.

Results: In Project Viva, exposure to acetaminophen in both the 1st and 2nd trimester of pregnancy was associated with lower WRAVMA drawing scores (β -1.51, 95% CI -2.92, -0.10). However, in Pelotas, exposure to acetaminophen in both the 1st and 2nd trimester of pregnancy was not associated with INTER-NDA motor scores (β 0.02; 95% CI -0.05, 0.09) and was associated with higher INTER-NDA total scores (β 0.08, 95% CI 0.01, 0.16). Other comparisons did not show evidence for any associations.

Conclusions: Inconsistencies and lack of specificity of the findings did not clarify the research question considering that we still have a large variability and uncertainty to define the risk or safety in the use of acetaminophen related to cognition in early childhood. More studies using better exposure assessment and better confounding variables are needed to clarify these associations.
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http://dx.doi.org/10.1111/ppe.12632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192774PMC
May 2020

Is social jetlag similar to travel-induced jetlag? Results of a validation study.

Chronobiol Int 2020 04 20;37(4):542-551. Epub 2020 Jan 20.

Postgraduate Program in Epidemiology, Federal University of Pelotas-UFPEL, Pelotas, Rio Grande do Sul, Brazil.

Social jetlag (SJL) is defined as the misalignment between the biological clocks and the social clock imposed by work and social constraints. In order to accomplish the workdays duties, people tend to not respect the internally sleep-wake cycle during the week, often using alarm clock to wake-up, which would lead to a chronic form of travel-induced jetlag. This circadian misalignment has been found to be associated with increased health risk and health-impairing behaviors. In this cross-sectional study, we aimed to explore whether the SJL is a valid concept for the travel-induced jetlag symptoms, as well as what is the cutoff point with best parameters for defining the presence of SJL, in a sample of undergraduate students of a university in Southern Brazil. We assessed SJL by the Munich ChronoType Questionnaire (MCTQ) and defined the concept as the difference between the midsleep point on free days and the midsleep point on classes days. The gold standard was defined as having at least one travel-induced jetlag symptom (fatigue, sleepiness or difficulty concentrating). Relative SJL, sensitivity and specificity were calculated for different cutoff points, plotted on ROC curves. A total of 452 students with complete sleep information were included in the analysis. The relative SJL mean was 2 h 23 min (SD = 1 h 24 min; range -3 h to 7 h 58 min) and 63.7% of the students had ≥2 h of relative SJL. All the tested cutoff points of the instrument had low sensitivity and specificity values, covering a small area under the ROC curve (0.487). The best parameters were for the cutoff point ≥2 h, with 63.4% sensitivity and 35.9% specificity. SJL did not revealed to be a valid concept for the studied sample comparing it to travel-induced jetlag symptomatology. One possible explanation for the lack of validity of our results regards the fact that SJL may not have the same apparent wide-term effects as the travel-induced jetlag. Then, the symptoms of SJL do not well represent the symptoms of travel-induced jetlag.
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http://dx.doi.org/10.1080/07420528.2020.1712413DOI Listing
April 2020

Effect of Parental Counseling on Infants' Healthy Sleep Habits in Brazil: A Randomized Clinical Trial.

JAMA Netw Open 2019 12 2;2(12):e1918062. Epub 2019 Dec 2.

Department of Paediatrics, The Hospital for Sick Children, Research Institute, University of Toronto, Toronto, Ontario, Canada.

Importance: Poor sleep during early childhood is associated with adverse outcomes, including obesity, cognitive impairment, and mental and behavioral disorders.

Objective: To assess the efficacy of an educational intervention in the promotion of nighttime sleep duration.

Design, Setting, And Participants: This single-blind, intent-to-treat randomized clinical trial included participants in Pelotas, Brazil, aged 3 months who were followed up until age 24 months. Eligibility criteria included healthy infants aged approximately 3 months who slept less than 15 hours per 24 hours. Infants were randomized to the intervention group or control group.

Interventions: Information on sleep characteristics, improvements in the environment, establishment of a nighttime sleep routine, and waiting before attending nocturnal awakenings was delivered to mothers in the intervention group by trained home-visitors at baseline. The intervention group received a telephone call on the first and second day after the intervention and a home visit on the third day after the intervention. The intervention's content was reinforced at health care visits for ages 6 months and 12 months. Mothers allocated to the control group were counseled on the benefits of breastfeeding for the mother's and child's health and given written material with content on breastfeeding.

Main Outcomes And Measures: Nighttime sleep duration was measured by interview and actigraphy at baseline and ages 6, 12, and 24 months and diaries at baseline and age 6 months. At ages 3 and 6 months, nighttime sleep self-regulation was calculated by subtracting nighttime sleep duration recorded by actigraphy from nighttime sleep duration recorded in the diaries and at ages 12 and 24 months by subtracting nighttime sleep duration recorded by actigraphy from nighttime sleep duration obtained by interview.

Results: Among 1812 mother-infant dyads invited to participate, 798 met the inclusion criteria and 586 agreed to participate. The intervention group included 298 infants (154 [52.9%] boys), and the control group included 288 infants (164 [58.2%] boys). At age 6 months, mean (SD) nighttime sleep duration recorded in diaries was 9.80 (1.85) hours in the intervention group and 9.49 (2.07) hours in the control group, a difference of 19 minutes longer for the intervention group. At age 12 months, mean (SD) nighttime sleep duration based on the Brief Infant Sleep Questionnaire was 8.43 (1.35) hours in the intervention group and 8.52 (1.35) hours in the control group, a difference of 5 minutes shorter for the intervention group. At age 24 months, compared with information from the interview, actigraphy records showed that children in the intervention group stayed awake at night without signalizing for a mean (SD) of 0.52 (2.52) hours, whereas children in the control group stayed awake at night without signalizing for a mean (SD) of 0.23 (2.43) hours. There were no statistically significant difference between groups in any of the sleep parameters investigated.

Conclusions And Relevance: This randomized clinical trial found that the educational intervention did not achieve longer nighttime sleep duration among infants in the intervention group.

Trial Registration: ClinicalTrials.gov identifier: NCT02788630.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.18062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6991232PMC
December 2019

The Role of Sleep Duration and Sleep Problems During Childhood in the Development of ADHD in Adolescence: Findings From a Population-Based Birth Cohort.

J Atten Disord 2020 02 16;24(4):590-600. Epub 2019 Oct 16.

Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Rio Grande do Sul, Brazil.

We aimed to investigate the association between sleep in early life and ADHD in adolescence. As a secondary analysis, we tested whether the associations may be specific to ADHD. Data from 3,467 participants of the 2004 Pelotas Birth Cohort were used. Information on their sleep duration and problems was collected at 12, 24, and 48 months of age. ADHD diagnosis and hyperactivity/inattention problems were assessed with the Development and Well-Being Assessment (DAWBA) and the Strengths and Difficulties Questionnaire (SDQ) among participants at 11 years of age. Difficulty going to sleep at 24 months, nightmares at 24 months and at 48 months, and restless sleep at 48 months were consistently associated with ADHD as well as with other mental disorders. The results suggest that sleep disturbances may be more important ADHD predictors than sleep duration or sleep duration trajectories. However, it may also be considered early markers of other mental disorders.
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http://dx.doi.org/10.1177/1087054719879500DOI Listing
February 2020

Repeated high blood pressure at 6 and 11 years at the Pelotas 2004 birth cohort study.

BMC Public Health 2019 Sep 12;19(1):1260. Epub 2019 Sep 12.

Postgraduate Program in Epidemiology, Federal University of Pelotas (UFPel), Cep: 96020-220 - Caixa Postal 464, Rua Marechal Deodoro, 1160 - 3° Piso. Bairro Centro, Pelotas, Rio Grande do Sul, Brazil.

Background: We evaluated the prevalence and the factors associated with repeated high systolic (SBP) and diastolic blood pressure (DBP) at 6- and 11-year follow-ups of children from the Pelotas (Brazil) 2004 Birth Cohort.

Methods: All live births to mothers living in the urban area of Pelotas were enrolled in the cohort. Blood pressure (BP) values were transformed into Z-scores by sex, age, and height. High SBP and DBP were defined as repeated systolic and diastolic BP Z-scores on the ≥95th percentile at the two follow-ups. Prevalence (95% confidence interval) of repeated high SBP, DBP, and both (SDBP) were calculated. Associations with maternal and child characteristics were explored in crude and adjusted logistic regression analyses.

Results: A total of 3182 cohort participants were analyzed. Prevalence of repeated high SBP, DBP and SDBP was 1.7% (1.2-2.1%), 2.3% (1.8-2.9%) and 1.2% (0.9-1.6%), respectively. Repeated high SBP was associated with males, gestational diabetes mellitus (2.92; 1.13-7.58) and obesity at 11 years (2.44; 1.29-4.59); while repeated high DBP was associated with females, family history of hypertension from both sides (3.95; 1.59-9.85) and gestational age < 34 weeks (4.08; 1.52-10.96). Repeated high SDBP was not associated with any of the characteristics investigated.

Conclusion: Prevalence of repeated high SBP, DBP, and SDBP were within the expected distribution at the population level. Nonetheless, gestational diabetes mellitus, obesity, family history of hypertension, and prematurity increased the risk of repeated high blood pressure measured at two occasions 5 years apart.
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http://dx.doi.org/10.1186/s12889-019-7544-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739988PMC
September 2019

Prevalence of obesity in rural and urban areas in Brazil: National Health Survey, 2013.

Rev Bras Epidemiol 2019 Aug 22;22:e190049. Epub 2019 Aug 22.

Programa de Pós-graduação em Epidemiologia, Faculdade de Medicina, Universidade Federal de Pelotas - Pelotas (RS), Brasil.

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.
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http://dx.doi.org/10.1590/1980-549720190049DOI Listing
August 2019

The Role of in Shared Susceptibility of Psychiatric Disorders during Childhood: A Population-Based Birth Cohort Study.

Genes (Basel) 2019 08 20;10(8). Epub 2019 Aug 20.

Departamento de Medicina Preventiva, Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 01246-903, Brasil.

Background: It has been suggested that microRNAs (miRNAs; short non-protein-coding RNA molecules that mediate post-transcriptional regulation), including mir-9 and mir-34 families, are important for brain development. Current data suggest that mir-9 and mir-34 may have shared effects across psychiatric disorders. This study aims to explore the role of genetic polymorphisms in the (rs4916723) and (rs4938723) genes on the susceptibility of psychiatric disorders in children from the 2004 Pelotas Birth Cohort.

Methods: Psychiatric disorders were assessed in 3585 individuals using Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), criteria through the application of standard semi-structured interviews (using the Development and Well-Being Assessment, DAWBA) at the six-years-of-age follow-up. The outcome was defined as the presence of any mental disorder. We also considered two broad groups of internalizing and externalizing disorders to further investigate the role of these variants in mental health.

Results: We observed an association between rs4916723 () and the presence of any psychiatric disorder (odds ratios (OR) = 0.820; 95% CI = 0.7130-0.944; = 0.006) and a suggestive effect on internalizing disorders (OR = 0.830; 95% CI = 0.698-0.987; = 0.035). rs4938723 () was not associated with any evaluated outcome.

Conclusion: The study suggests that may have an important role on a broad susceptibility for psychiatric disorders and may be important mainly for internalization problems.
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http://dx.doi.org/10.3390/genes10080626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723948PMC
August 2019

Association of modifiable risk factors and IL-6, CRP, and adiponectin: Findings from the 1993 Birth Cohort, Southern Brazil.

PLoS One 2019 9;14(5):e0216202. Epub 2019 May 9.

Federal University of Pelotas-Postgraduate Program in Epidemiology, Pelotas, Brazil.

Background: The literature on the relationship between lifestyle behaviors and inflammatory markers is scarce.

Methods: A birth cohort was followed since birth up to 22 years in Southern Brazil. Interleukin-6 (IL-6), C-reactive protein (CRP) and adiponectin were measured in nonfasting blood samples drawn at 18 and 22 years of age. Exposures including smoking, alcohol intake, physical inactivity and obesity, were collected at 15, 18 and 22 years. Cross sectional analyses were based on the number of follow-up visits with these exposures and the association with IL-6, CRP and adiponectin at 22 years old. We also carried out a longitudinal Generalized Least Squares (GLS) random-effects analysis with outcomes at 18 and at 22 years old. All analyses were adjusted for several covariates.

Results: The sample comprised 3,479 cohort members at 22 years. The presence of obesity at ≥ 2 follow-ups showed the highest mean values (SE) for IL-6 [2.45 (1.05)] and CRP [3.74 (1.11)] and the lowest mean value for adiponectin [8.60 (0.37)] (adjusted analyses, females) compared with other exposures; the highest mean of IL-6 [1.65 (1.05)] and CRP [1.78 (1.11)] and the lowest mean of adiponectin [9.98 (0.38)] were for the number of follow-ups with ≥2 exposures compared to those with no exposures at any follow-up (adjusted analyses, females). The longitudinal analysis showed an increase in obesity associated with IL-6 and CRP in both sexes and an inverse association with adiponectin in females; smoking (in males) was associated with IL-6 and CRP, harmful alcohol intake was associated with CRP in males, and increased in physical activity was inversely associated with CRP in men.

Conclusion: We concluded that obesity is the main exposure positively associated with IL-6 and CRP and inversely associated with adiponectin (mainly in females). Smoking is also associated with these markers in the longitudinal analysis (in males).
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0216202PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6508856PMC
January 2020

The effects of two early parenting interventions on child aggression and risk for violence in Brazil (The PIÁ Trial): protocol for a randomised controlled trial.

Trials 2019 May 2;20(1):253. Epub 2019 May 2.

University of Reading, Reading, UK.

Background: Children in many low- and middle-income countries (LMICs) are at high risk for exposure to violence and later violent behaviour. The World Health Organization has declared an urgent need for the evaluation and implementation of low-cost parenting interventions in LMICs to prevent violence. Two areas of significant early risk are harsh parenting and poor child cognitive and socio-emotional development. Parenting interventions suitable for LMIC contexts have been developed targeting these risk factors and have been shown to have promising effects. However, their impact on child aggression, a key precursor of violence, has yet to be determined. The Pelotas Trial of Parenting Interventions for Aggression (PIÁ) has been designed to address this issue.

Methods: We are conducting a randomised controlled trial to evaluate two early parenting interventions for mothers of children aged between 30 and 42 months in a Brazilian city. The first of these, dialogic book-sharing (DBS), aims to promote child cognitive and socio-emotional development; and the second, the ACT Raising Safe Kids Program (ACT), is designed to reduce harsh parenting. These interventions are being compared with a control group receiving neither intervention. Three hundred and sixty-nine families in a birth cohort are being randomly allocated to one of the three groups (DBS, ACT, Control). Facilitators deliver the interventions to groups of five to 10 mothers at weekly sessions for 8 weeks in DBS and 9 weeks in ACT. Independent assessments of parenting and child development are being made before the interventions, shortly afterwards, and at follow-up 6 months later. The primary outcome is child aggression, and the two main secondary outcomes are: (1) child cognitive and socio-emotional development and (2) harsh parenting. Longer-term outcomes will be investigated as the birth cohort is followed into late childhood, adolescence, and adulthood.

Discussion: The Pelotas Trial of Parenting Interventions for Aggression (PIÁ) aims to evaluate the impact of two early parenting interventions on child aggression and several other key risk factors for the development of violence, including aspects of parenting and child cognition and socio-emotional functioning. The study is being carried out in a LMIC context where violence constitutes a major social and health burden. Since the two interventions are brief and, with modest levels of training, readily deliverable in LMIC settings, a demonstration that they benefit parenting and reduce risk factors for violence would be of major significance.

Trial Registration: Brazilian Ministry of Health Register of Clinical Trials, ID: RBR-2kwfsk . Registered on 6 June 2018.
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http://dx.doi.org/10.1186/s13063-019-3356-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6498476PMC
May 2019

Assessing causality in the association between attention-deficit/hyperactivity disorder and obesity: a Mendelian randomization study.

Int J Obes (Lond) 2019 12 18;43(12):2500-2508. Epub 2019 Apr 18.

Postgraduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Brazil.

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 < 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.

Conclusions: The results suggested that higher BMI increases the risk of developing ADHD, but not the other way around.
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http://dx.doi.org/10.1038/s41366-019-0346-8DOI Listing
December 2019

Synergistic effects between ADORA2A and DRD2 genes on anxiety disorders in children with ADHD.

Prog Neuropsychopharmacol Biol Psychiatry 2019 07 1;93:214-220. Epub 2019 Apr 1.

Post-Graduate Program in Biosciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil. Electronic address:

The prevalence of anxiety disorders in patients with Attention Deficit/Hyperactivity Disorder (ADHD) is around 15-40%, three times higher than in the general population. The dopaminergic system, classically associated with ADHD, interacts directly with the adenosinergic system through adenosine A receptors (A) and dopamine D receptors (D) forming A-D heterodimers. Both dopaminergic and adenosinergic systems are implicated in anxiety disorders. Therefore, the aims of this study were: a) to investigate the main effects of ADORA2A and DRD2 gene variants on anxiety disorders in an ADHD sample of children and adolescents; b) to test potential synergism between ADORA2A and DRD2 genes on the same outcome; c) to explore ADORA2A variants functionality using an in silico approach. The sample consists of 478 children and adolescents with ADHD and their parents, totalizing 1.239 individuals. An association between the ADORA2A rs2298383 TT genotype with the presence of anxiety disorders (P = .004) and an interaction between ADORA2A-DRD2 risk haplotypes with the same outcome (P = .005) was detected. The in silico analyses showed that rs2298383 has the highest score for regulatory function among all variants in the ADORA2A gene described up to date. Altogether, the present findings suggested that the ADORA2A gene and the interaction of ADORA2A and DRD2 genes may play a role in anxiety disorders in children and adolescents with ADHD.
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http://dx.doi.org/10.1016/j.pnpbp.2019.03.021DOI Listing
July 2019

Breastfeeding exclusivity and duration: trends and inequalities in four population-based birth cohorts in Pelotas, Brazil, 1982-2015.

Int J Epidemiol 2019 Apr;48(Suppl 1):i72-i79

Post Graduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.

Background: Brazil has made substantial improvements in the duration of breastfeeding. We use data from four population-based cohorts to examine how trends and inequalities in breastfeeding indicators changed over time in a Brazilian city.

Methods: Data from four birth cohorts, each including all births in a calendar year (1982, 1993, 2004 and 2015) in the city of Pelotas were used. Information on breastfeeding was collected when children were aged between 3 and 20 months. The prevalences of continued breastfeeding at 1 year of age and of exclusive breastfeeding at 3 months were calculated according to family income, maternal skin colour and sex.

Results: Prevalence of breastfeeding at 12 months increased from 16% to 41% in the 33-year period. The prevalence of exclusive breastfeeding at 3 months increased from 7% in 1993 to 45% in 2015. Increases in exclusive breastfeeding at 3 months were seen in all socioeconomic groups, but the 2015 rates remain highest (57.2%) among the women in the richest quintile, and lowest among those in the poorest quintile (34.6%). Black mothers were more likely to breastfeed at 12 months than Whites in the four cohorts. In the earlier cohorts, breastfeeding at 12 months was more common among the poor, but by 2015 these differences had disappeared.

Conclusions: There were important positive changes in breastfeeding practices during this period, but less than half of the children in 2015 were receiving the full benefits of breast milk. Improved breastfeeding practices are being adopted by high-income women to a greater extent than by poor women.
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http://dx.doi.org/10.1093/ije/dyy159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422059PMC
April 2019

Trends and inequalities in maternal and child health in a Brazilian city: methodology and sociodemographic description of four population-based birth cohort studies, 1982-2015.

Int J Epidemiol 2019 Apr;48(Suppl 1):i4-i15

Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.

Background: Few low-middle-income countries have data from comparable birth cohort studies spanning over time. We report on the methods used by the Pelotas cohorts (1982, 1993, 2004 and 2015) and describe time trends in sociodemographic characteristics of the participant families.

Methods: During the four study years, all maternity hospitals in the city were visited daily, and all urban women giving birth were enrolled. Data on socioeconomic and demographic characteristics were collected using standardized questionnaires, including data on maternal and paternal skin colour, age and schooling, maternal marital status, family income and household characteristics. The analyses included comparisons of time trends and of socioeconomic and ethnic group inequalities.

Results: Despite a near 50% increase in the city's population between 1982 and 2015, the total number of births declined from 6011 to 4387. The proportion of mothers aged ≥35 years increased from 9.9% to 14.8%, and average maternal schooling from 6.5 [standard deviation (SD) 4.2] to 10.1 (SD 4.0) years. Treated water was available in 95.3% of households in 1982 and 99.3% in 2015. Three-quarters of the families had a refrigerator in 1982, compared with 98.3% in 2015. Absolute income-related inequalities in maternal schooling, household crowding, household appliances and access to treated water were markedly reduced between 1982 and 2015. Maternal skin colour was associated with inequalities in age at childbearing and schooling, as well as with household characteristics.

Conclusions: During the 33-year period, there were positive changes in social and environmental determinants of health, including income, education, fertility and characteristics of the home environment. Socioeconomic inequality was also reduced.
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http://dx.doi.org/10.1093/ije/dyy170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422064PMC
April 2019

Polymorphisms in Attention-Deficit/Hyperactivity Disorder (ADHD): Further Evidence Linking Sleep and Circadian Disturbances and ADHD.

Genes (Basel) 2019 01 28;10(2). Epub 2019 Jan 28.

Federal University of Pelotas, Post-Graduate Program in Epidemiology, Pelotas 96020-220, Brazil.

Circadian and sleep disorders, short sleep duration, and evening chronotype are often present in attention-deficit/hyperactivity disorder (ADHD). , considered the master gene in the circadian rhythm, has been explored by few studies. Understanding the relationship between ADHD and may provide additional information to understand the correlation between ADHD and sleep problems. In this study, we aimed to explore the association between ADHD and , using several genetic markers to comprehensively cover the gene extension. A total of 259 ADHD children and their parents from a Brazilian clinical sample were genotyped for eight single nucleotide polymorphisms (SNPs) in the locus. We tested the individual markers and the haplotype effects using binary logistic regression. Binary logistic and linear regressions considering ADHD symptoms among ADHD cases were conducted as secondary analysis. As main result, the analysis showed a risk effect of the G-A-T-G-G-C-G-A (rs534654, rs1801260, rs6855837, rs34897046, rs11931061, rs3817444, rs4864548, rs726967) haplotype on ADHD. A suggestive association between ADHD and rs534654 was observed. The results suggest that the genetic susceptibility to circadian rhythm attributed to the gene may play an important role on ADHD.
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http://dx.doi.org/10.3390/genes10020088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410065PMC
January 2019