Insomnia Polygenic Component on Attention Deficit-Hyperactivity Disorder: Exploring this Association Using Genomic Data from Brazilian Families.

Introduction Insomnia is highly prevalent among individuals with Attention-Deficit/Hyperactivity Disorder (ADHD). However, the biological mechanisms shared between both conditions is still elusive. We aimed to investigate whether insomnia's genomic component is able to predict ADHD in childhood and adolescence. Methods A Brazilian sample of 259 ADHD probands and their biological parents were included in the study. Their genomic DNA genotypes were used to construct the polygenic risk score for insomnia (Insomnia PRS), using the largest GWAS summary statistics as a discovery sample. The association was tested using logistic regression, under a case-pseudocontrol design. Results Insomnia PRS was nominally associated with ADHD (OR = 1.228, p = 0.022), showing that the alleles that increase the risk for insomnia also increase the risk for ADHD. Discussion Our results suggest that genetic factors associated with insomnia may play a role in the ADHD genetic etiology, with both phenotypes likely to have a shared genetic mechanism.

IFITM3 rs12252 polymorphism association with COVID-19 severity and mortality in a Brazilian sample: an update and a meta-analysis.

This study investigated the association between the IFITM3 rs12252 polymorphism and the severity and mortality of COVID-19 in hospitalized Brazilian patients. A total of 102 COVID-19 patients were included, and the outcomes of interest were defined as death and the need for mechanical ventilation. Genotypes were assessed using Taqman probes. No significant associations were found between the rs12252 polymorphism and COVID-19 outcomes in the original sample, both for death and the need for mechanical ventilation. A meta-analysis, incorporating previous studies that used death as a severity indicator, revealed no association in the allelic and C-recessive models. However, due to the rarity of the T allele and its absence in the sample, further replication studies in larger and more diverse populations are needed to clarify the role of rs12252 in COVID-19 prognosis.

Gene - maltreatment interplay in adult ADHD symptoms: main role of a gene-environment correlation effect in a Brazilian population longitudinal study.

Childhood maltreatment correlates with attention-deficit/hyperactivity disorder (ADHD) in previous research. The interaction between ADHD genetic predisposition and maltreatment's impact on ADHD symptom risk remains unclear. We aimed to elucidate this relationship by examining the interplay between a polygenic score for ADHD (ADHD-PGS) and childhood maltreatment in predicting ADHD symptoms during young adulthood. Using data from the 2004 Pelotas (Brazil) birth cohort comprising 4231 participants, we analyzed gene-environment interaction (GxE) and correlation (rGE). We further explored rGE mechanisms through mediation models. ADHD symptoms were assessed at age 18 via self-report (Adult Self Report Scale - ASRS) and mother-reports (Strength and Difficulties Questionnaire - SDQ). The ADHD-PGS was derived from published ADHD GWAS meta-analysis. Physical and psychological child maltreatment was gauged using the Parent-Child Conflict Tactics Scale (CTSPC) at ages 6 and 11, with a mean score utilized as a variable. The ADHD-PGS exhibited associations with ADHD symptoms on both ASRS (ß = 0.53; 95% CI: 0.03; 1.03, p = 0.036), and SDQ (ß = 0.20; 95% CI: 0.08; 0.32, p = 0.001) scales. The total mean maltreatment score was associated with ADHD symptoms using both scales [(ßASRS = 0.51; 95% CI: 0.26;0.77) and (ßSDQ = 0.24; 95% CI: 0.18;0.29)]. The ADHD-PGS was associated with total mean maltreatment scores (ß = 0.09; 95% CI: 0.01; 0.17; p = 0.030). Approximately 47% of the total effect of ADHD-PGS on maltreatment was mediated by ADHD symptoms at age 6. No evidence supported gene-environment interaction in predicting ADHD symptoms. Our findings underscore the significant roles of genetics and childhood maltreatment as predictors for ADHD symptoms in adulthood, while also indicating a potential evocative mechanism through gene-environment correlation.

Association between breast feeding and food consumption according to the degree of processing in Brazil: a cohort study.

BACKGROUND: The benefits of breast feeding may be associated with better formation of eating habits beyond childhood. This study was designed to verify the association between breast feeding and food consumption according to the degree of processing in four Brazilian birth cohorts. METHODS: The duration of exclusive, predominant and total breast feeding was evaluated. The analysis of the energy contribution of fresh or minimally processed foods (FMPF) and ultra-processed foods (UPF) in the diet was evaluated during childhood (13-36 months), adolescence (11-18 years) and adulthood (22, 23 and 30 years). RESULTS: Those who were predominantly breastfed for less than 4 months had a higher UPF consumption (ß 3.14, 95% CI 0.82 to 5.47) and a lower FMPF consumption (ß -3.47, 95% CI -5.91 to -1.02) at age 22 years in the 1993 cohort. Exclusive breast feeding (EBF) for less than 6 months was associated with increased UPF consumption (ß 1.75, 95% CI 0.25 to 3.24) and reduced FMPF consumption (ß -1.49, 95% CI -2.93 to -0.04) at age 11 years in the 2004 cohort. In this same cohort, total breast feeding for less than 12 months was associated with increased UPF consumption (ß 1.12, 95% CI 0.24 to 2.19) and decreased FMPF consumption (ß -1.13, 95% CI -2 .07 to -0.19). Children who did not receive EBF for 6 months showed an increase in the energy contribution of UPF (ß 2.36, 95% CI 0.53 to 4.18) and a decrease in FMPF (ß -2.33, 95% CI -4 .19 to -0.48) in the diet at 13-36 months in the 2010 cohort. In this cohort, children who were breastfed for less than 12 months in total had higher UPF consumption (ß 2.16, 95% CI 0.81 to 3.51) and lower FMPF consumption (ß -1.79, 95% CI -3.09 to -0.48). CONCLUSION: Exposure to breast feeding is associated with lower UPF consumption and higher FMPF consumption in childhood, adolescence and adulthood.

Adolescent Mental Health Before and During COVID-19: Longitudinal Evidence From the 2004 Pelotas Birth Cohort in Brazil.

PURPOSE: There is great interest in examining the consequences of the COVID-19 pandemic on adolescent mental health, but most studies were conducted in high-income countries. The identification of overall effects and protective factors is essential to understand the determinants of mental wellbeing in contexts of stress. We aimed to study changes in adolescent mental health during the pandemic and the risk and protective factors associated with these changes in a Brazilian birth cohort. METHODS: One thousand nine hundred forty nine adolescents from the 2004 Pelotas Birth Cohort were assessed prepandemic (T1, November 2019 to March 2020, mean age 15.69 years) and mid-pandemic (T2, August to December 2021, mean age 17.41 years). Mental health was assessed using the Strengths and Difficulties Questionnaire. Prepandemic and pandemic-related predictors were examined as predictors of change in multivariate latent change scores models. RESULTS: There was a mean increase in adolescent total mental health difficulties (M = 1.071, p < .001), hyperactivity/inattention (M = 0.208, p < .001), emotion symptoms (M = 0.409, p < .001), and peer problems (M = 0.434, p < .001) during the pandemic. This increase was associated with several negative family context variables, including harsh parenting and maternal depressive symptoms at T2. Higher emotion regulation levels protected against increases in adolescent mental health difficulties related to the COVID-19 pandemic. DISCUSSION: Family-context variables emerged as important risk factors for the deterioration of adolescent mental health during the COVID-19 pandemic. Interventions promoting emotion regulation strategies are a promising approach to protecting adolescent wellbeing in periods of stress.

Changes in splenic tissue and immune response profile of Schistosoma mansoni infected mice submitted to chronic ethanol intake.

In Schistosoma mansoni infection, the spleen is one of the organs affected, causing its enlargement (splenomegaly). Intake of ethanol through alcoholic beverages can cause spleen atrophy and interfere with immune activity. To gain knowledge of this association on the spleen and on the immune response profile, male mice were used as an experimental model. These animals were divided into four groups: C. control; EC. uninfected/ethanol gavage; I. infected; and IE. infected/ethanol gavage. Groups I and IE were infected with about 100 cercariae (BH strain) of S. mansoni and in the fifth week of infection, gavage 200 µL/day/animal of 18 % ethanol was started for 28 consecutive days. At the end of the gavage (9th week of infection) all animals were euthanized. The spleen was removed and longitudinally divided in two parts. After histological processing, the sections were stained with H&E and Gomori's Reticulin for histopathological and stereological analyses, white pulp morphometry and quantification of megakaryocytes. The other fragment was macerated (in laminar flow) and the cell suspension, after adjusting the concentration (2 × 106), was plated to obtain cytokines produced by spleen cells that were measured by flow cytometry (Citometric Bead Array). Histopathological and quantitative analyzes in the spleen of the IE group showed an increase in the number of trabeculae and megakaryocytes, a decrease in reticular fibers, as well as important organizational changes in the white pulp and red pulp. Due to the decrease in the levels of cytokines measured and the result of the calculation of the ratio between the IFN-y and IL-10 cytokines (p = 0.0079) of the infected groups, we suggest that ethanol decreased the inflammatory and anti-inflammatory response generated by the infection (group IE, the production of cytokines was significantly decreased (p < 0.01). These changes demonstrate that ethanol ingestion interferes with some parameters of experimental S. mansoni infection, such as changes in splenic tissue and in the pattern of cytokine production.

Bilateral Peters' anomaly, aniridia and Wilms tumour (WAGR syndrome) in monozygotic twins.

AIM: This study reports the bilateral association of Peters' anomaly and congenital aniridia in monozygotic twins subsequently diagnosed with Wilms tumour (WAGR syndrome). METHODS: Two monozygotic female twins were referred at age 2 months with bilateral corneal opacity. A diagnosis of Peters' anomaly associated to aniridia was made in both eyes of both twins. Physical examination and ultrasonography were carried out at 12 months of age to explore the possibility of WAGR-related anomalies, specifically Wilms tumour. DNA were isolated and subjected to whole exome sequencing. RESULTS: Peters' anomaly associated to aniridia in both eyes as well as bilateral Wilms tumour in both children were diagnosed. Exome analyses showed a large heterozygous deletion encompassing 6 648 473 bp in chromosome 11p13, using Integrative Genomics Viewer and AnnotSV software. CONCLUSION: WAGR syndrome is a rare contiguous gene deletion syndrome with a greater risk of developing Wilms tumour associated with Peters' anomaly and congenital aniridia. However, co-occurrence of both anomalies was rarely reported in twins, and never in both eyes of monozygotic twins. Here, we report the bilateral association of Peters' anomaly and congenital aniridia in monozygotic twins with WAGR syndrome.

Is rest-activity rhythm prospectively associated with all-cause mortality in older people regardless of sleep and physical activity level? The 'Como Vai?' Cohort study.

OBJECTIVE: This study aims to test the association of rest-activity rhythm (intradaily variability and interdaily stability) with all-cause mortality in an older adult cohort in Brazil. It also assesses whether the amount of time spent at each intensity level (i.e., physical activity and nocturnal sleep) interferes with this association. METHODS: This cohort study started in 2014 with older adults (≥60 years). We investigated deaths from all causes that occurred until April 2017. Rest-activity rhythm variables were obtained using accelerometry at baseline. Intradaily variability indicates higher rhythm fragmentation, while interdaily stability indicates higher rhythm stability. Cox proportional-hazard models were used to test the associations controlling for confounders. RESULTS: Among the 1451 older adults interviewed in 2014, 965 presented valid accelerometry data. During the follow-up period, 80 individuals died. After adjusting the analysis for sociodemographic, smoking, morbidity score, and number of medicines, an increase of one standard deviation in interdaily stability decreased 26% the risk of death. The adjustment for total sleep time and inactivity did not change this association. On the other hand, the association was no longer significant after adjusting for overall physical activity and moderate to vigorous physical activity. CONCLUSION: Rest-activity rhythm pattern was not associated with mortality when physical activity was considered, possibly because this pattern could be driven by regular exercise. Promoting physical activity remains a relevant strategy to improve population health.

Are nocturnal awakenings at age 1 predictive of sleep duration and efficiency at age 6: Results from two birth cohorts.

Objective: To investigate the association of nighttime awakenings at 12 months with the duration and efficiency of nighttime sleep at 6 years of age. Methods: Data from two population-based prospective studies (The Pelotas 2004 and The Pelotas 2015 Birth Cohorts) were used. Information on nighttime awakenings was provided by mothers during the 12-month follow-up interview. Infants who awakened >3 times after sleep onset at 12 months were considered frequent wakeners. Sleep duration and sleep efficiency were obtained by actigraphy at the 6-year follow-up. Children wore the device at the wrist of the non-dominant arm continuously for 3-7 days, including at least one weekend day. Unadjusted and adjusted beta coefficients were obtained by linear regression for each cohort separately. Results: 2500 children from the 2004 and 2793 from the 2015 cohort had full information on nighttime awakenings at 12 months and actigraphy at 6 years and were analyzed. Prevalence of frequent wakeners was 6.3 % and 5.9 % in the 2004 and 2015 cohort, respectively. Mean bedtime and wake-up time at 6 years were, respectively, 23:23 and 08:41 h in the 2004 cohort, and 00:10 and 09:00 h int the 2015 cohort. Nighttime sleep lasted on average 7.54 and 7.24 h respectively in the 2004 and the 2015 cohort, and the sleep efficiency was 81.1 and 82.5 % respectively. In adjusted analyses, no associations were found between awakening at 12 months and sleep duration or sleep efficiency at 6 years of age. Conclusion: In both cohorts sleep duration and efficiency were below the recommendation for school-age children (respectively 9-11 h and 85 %). There was no relationship between the number of nighttime awakenings at 12 months and sleep duration or efficiency at 6 years.

Variation in ultra-processed food consumption from 6 to 15 years, body weight and body composition at 15 years of age at The Pelotas 2004 Birth Cohort.

BACKGROUND: The association of ultra-processed food (UPF) consumption with obesity and adipose tissue in children/adolescents remains poorly understood. OBJECTIVE: To assess the association of UPF consumption with excessive weight (EW-defined as BMI-for-age ≥+1 z-score) and body composition at 15 years. METHODS: In a birth cohort, daily UPF consumption was estimated by Food Frequency Questionnaires at 6 and 15 years. Those in the higher tercile of UPF consumption at both follow-ups were the 'always-high consumers'. Air-displacement plethysmography provided fat mass (FM-kg), fat-free mass (FFM-kg), %FM, %FFM, FM index (FMI-kg/m2 ) and FFM index (FFMI-kg/m2 ). Logistic regression and linear regression were used to estimate, respectively, odds ratios and beta coefficients. RESULTS: Amongst 1584 participants, almost one in every seven were always-high consumers. In crude analyses, there was no association between variation in UPF consumption and EW, and body fat parameters were lower in the always-high consumer group than amongst the always-low consumers, in both sexes. With adjustment for confounders, the odds ratio for EW was higher in the always-high consumer than amongst the always-low consumer group, and the direction of the associations with FM parameters was reversed: males from the always-high consumer group presented almost twice as high FM (10.5 vs. 18.6 kg; p < 0.001) and twice as high FMI (3.4 vs. 6.3 kg/m2 ; p < 0.001) than the always-low consumer group, and females from the always-high consumer group presented on average 32% more FM and FMI than the always-low consumer group. CONCLUSIONS: In crude and adjusted analyses there was a strong association between high UPF consumption from childhood to adolescence, EW and higher body fat parameters at 15 years, but its deleterious association with body adiposity was only uncovered after adjusting for confounders.

Accelerometer-based sleep metrics and gut microbiota during adolescence: Association findings from a Brazilian population-based birth cohort.

BACKGROUND: Sleep and gut microbiota are emerging putative risk factors for several physical, mental, and cognitive conditions. Sleep deprivation has been shown to be linked with unhealthy microbiome environments in animal studies. However, in humans, the results are mixed. Epidemiological studies evaluating the effect of accelerometer-based sleep measures on gut microbiome are scarce. This study aims to explore the relationship between sleep duration and efficiency with the gut microbiota in adolescence. METHODS: A subsample of 352 participants from the 2004 Pelotas (Brazil) Birth Cohort Study with sleep and fecal microbiota data available were included in the study. Sleep duration and sleep efficiency were obtained from actigraphy information at 11 years old whereas microbiota information from fecal samples was collected at 12 years. The fecal microbiota was analyzed via Illumina MiSeq (16S rRNA V3-V4 region) and the UNOISE pipeline. Alpha was assessed in QIIME2. Association measures for sleep variables and microbial α-diversity, and bacterial relative abundance were assessed through generalized models (linear and logistic regression), adjusting for maternal and child variables confounders. RESULTS: Adjusted models showed that sleep duration was positively associated with Simpson index of α-diversity (ß = 0.003; CI95 %: 0.00004; 0.01). Both sleep duration (OR = 0.43; CI95 % 0.25; 0.74) and efficiency (OR = 0.55; CI95 % 0.38; 0.78) were associated with lower Bacteroidetes abundance. CONCLUSION: Our results suggest that sleep duration and efficiency are linked to gut microbiota diversity and composition even with 1-2 years gap from exposure to outcome. The findings support the role of sleep in the gut-brain axis as well as provide insights on how to improve microbiota health.

Evaluation of genomic factors and early childhood stimulation on intelligence in children from a Brazilian birth cohort: The primary role of independent factors.

BACKGROUND: Childhood cognitive abilities are a predictor of health outcomes and adult income potential. Identifying factors associated with childhood intelligence and their interactions is essential in behavioral research. We assessed the impact of genetic variants and early child stimulation (ECS) on child intelligence and examined their possible interaction as potential modifiers of IQ in a population-based longitudinal study. METHODS: Participants of the 2004 Pelotas Birth Cohort study (N = 4231) underwent intelligent quotient (IQ) by WISC-III assessment at 6 years of age. At 24 and 48-months, mothers answered five ECS marker questions, whose sum was used to create a score. The polygenic score for intelligence (IQ-PGS) was constructed from the GWAS-weighted estimate of cognition. Association was assessed using multiple linear regression models adjusted for maternal, family, and child confounding variables. To explore the possible influence of skin color and ethnoracial classification, the regression models were stratified according to the skin color variable, as a sensitivity analysis. RESULTS: In the adjusted analysis, IQ-PGS (ß = 0.79, 95% confidence interval [95% CI] 0.26;1.31) as well as ECS (ß = 2.34; 95% CI: 1.76;2.92) were associated with IQ in this sample. The association between IQ-PGS and IQ was significant only in the white Brazilian group in the sensitivity analysis. However, there was no interaction between IQ-PGS and ECS on IQ (p(IQ-PGS x ECS) = 0.46). CONCLUSIONS: ECS did not modify the impact of genetic potential on intellectual development during childhood, suggesting that genetic factors and ECS exert independent effects on the IQ levels of children.

Trajectory of maternal depression and parasomnias.

Maternal depressive symptoms are associated with poorer sleep quality in their children. Although parasomnias can occur at any age, this group of sleep disorders is more common in children. The aim of this study was to assess whether maternal depression trajectories predict parasomnias at the age of 11 years. Data were from a Birth Cohort of 4231 individuals followed in the city of Pelotas, Brazil. Maternal depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale (EPDS) at 12, 24, and 48 months, and 6 and 11 years postpartum. Maternal depression trajectories were calculated using a group-based modelling approach. Information on any parasomnias (confused arousals, sleepwalking, night terrors, and nightmares) was provided by the mother. Five trajectories of maternal depressive symptoms were identified: chronic-low (34.9%), chronic-moderate (41.4%), increasing (10.3%), decreasing (8.9%), and chronic-high (4.4%). The prevalence of any parasomnia at the age of 11 years was 16.8% (95% confidence interval [CI] 15.6%-18.1%). Confusional arousal was the most prevalent type of parasomnia (14.5%) and varied from 8.7% to 14.7%, 22.9%, 20.3%, and 27.5% among children of mothers at chronic-low, moderate-low, increasing, decreasing, and chronic-high trajectories, respectively (p < 0.001). Compared to children from mothers in the chronic-low trajectory, the adjusted prevalence ratio for any parasomnia was 1.58 (95% CI 1.29-1.94), 2.34 (95% CI 1.83-2.98), 2.15 (95% CI 1.65-2.81), and 3.07 (95% CI 2.31-4.07) among those from mothers in the moderate-low, increasing, decreasing, and chronic-high trajectory groups, respectively (p < 0.001). In conclusion, parasomnias were more prevalent among children of mothers with chronic symptoms of depression.

Early risk factors for conduct problem trajectories from childhood to adolescence: the 2004 Pelotas (BRAZIL) Birth Cohort.

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

Risk factors for executive function impairment in adolescence: an analysis of data from the 2004 Pelotas Birth Cohort study

Objective: To investigate risk factors associated with impaired attention-related executive functions (EFs) at age 11 and working memory at age 15. Methods: Data from participants of the population-based 2004 Pelotas Birth Cohort at ages 11 (n=3,582) and 15 (n=1,950) were analyzed. The study measured attentional control, cognitive flexibility, and selective attention using the Test of Everyday Attention for Children (TEA-Ch). Spatial working memory was assessed by the Cambridge Neuropsychological Test Automated Battery (CANTAB). Logistic regression was employed to explore the relationship between perinatal and childhood exposures and EF impairment. Results: Low maternal education had a significant negative impact on EFs. At age 11, it was associated with decreased attentional control (OR = 3.04; 95%CI 2.09-4.43), and at age 15, it was linked to impaired spatial working memory (OR = 2.21; 95%CI 1.58-3.09). Additional risk factors included low household income, black or brown maternal skin color, high parity, prematurity, low birth weight, and multiple siblings. Breastfeeding, regardless of duration, was found to be a protective factor against impaired cognitive flexibility (OR = 0.38; 95%CI 0.22-0.65). Conclusion: This study underscores the lasting impact of perinatal exposures on EF development. Policies that mitigate the negative effects of risk factors and promote EF development, especially among vulnerable populations, are needed.

Risk factors for executive function impairment in adolescence: an analysis of data from the 2004 Pelotas Birth Cohort study.

OBJECTIVE: To investigate risk factors associated with impaired attention-related executive functions (EFs) at age 11 and working memory at age 15. METHODS: Data from participants of the population-based 2004 Pelotas Birth Cohort at ages 11 (n=3,582) and 15 (n=1,950) were analyzed. The study measured attentional control, cognitive flexibility, and selective attention using the Test of Everyday Attention for Children (TEA-Ch). Spatial working memory was assessed by the Cambridge Neuropsychological Test Automated Battery (CANTAB). Logistic regression was employed to explore the relationship between perinatal and childhood exposures and EF impairment. RESULTS: Low maternal education had a significant negative impact on EFs. At age 11, it was associated with decreased attentional control (OR = 3.04; 95%CI 2.09-4.43), and at age 15, it was linked to impaired spatial working memory (OR = 2.21; 95%CI 1.58-3.09). Additional risk factors included low household income, black or brown maternal skin color, high parity, prematurity, low birth weight, and multiple siblings. Breastfeeding, regardless of duration, was found to be a protective factor against impaired cognitive flexibility (OR = 0.38; 95%CI 0.22-0.65). CONCLUSION: This study underscores the lasting impact of perinatal exposures on EF development. Policies that mitigate the negative effects of risk factors and promote EF development, especially among vulnerable populations, are needed.