Cord serum cytokines at birth and children's trajectories of mood dysregulation symptoms from 3 to 8 years: The EDEN birth cohort.

There is growing evidence that in utero imbalance immune activity plays a role in the development of neurodevelopmental and psychiatric disorders in children. Mood dysregulation (MD) is a debilitating transnosographic syndrome whose underlying pathophysiological mechanisms could be revealed by studying its biomarkers using the Research Domain Criteria (RDoC) model. Our aim was to study the association between the network of cord serum cytokines, and mood dysregulation trajectories in offsprings between 3 and 8 years of age. We used the data of a study nested in the French birth cohort EDEN that took place from 2003 to 2014 and followed mother-child dyads from the second trimester of pregnancy until the children were 8 years of age. The 2002 mother-child dyads were recruited from the general population through their pregnancy follow-up in two French university hospitals. 871 of them were included in the nested cohort and cord serum cytokine levels were measured at birth. Children's mood dysregulation symptoms were assessed with the Strengths and Difficulties Questionnaire Dysregulation Profile at the ages 3, 5 and 8 years in order to model their mood dysregulation trajectories. Out of the 871 participating dyads, 53% of the children were male. 2.1% of the children presented a high mood dysregulation trajectory whereas the others were considered as physiological variations. We found a significant negative association between TNF-α cord serum levels and a high mood dysregulation trajectory when considering confounding factors such as maternal depression during pregnancy (adjusted Odds Ratio (aOR) = 0.35, 95% Confidence Interval (CI) [0.18-0.67]). Immune imbalance at birth could play a role in the onset of mood dysregulation symptoms. Our findings throw new light on putative immune mechanisms implicated in the development of mood dysregulation and should lead to future animal and epidemiological studies.

Does early child negative emotionality moderate the association between maternal stimulation and academic readiness and achievement?

We investigated whether child temperament (negative emotionality, 5 months) moderated the association between maternal stimulation (5 months-2½ years) and academic readiness and achievement (vocabulary, mathematics, and reading). We applied structural equation modeling to the data from the Quebec Longitudinal Study of Child Development (N = 1121-1448; mostly Whites; 47% girls). Compared to children with low negative emotionality, those with high negative emotionality had higher levels of academic readiness (6 years) and mathematics achievement (7 years) when exposed to high levels of maternal stimulation (ß = 3.17, p < .01 and ß = 2.91, p < .01, respectively). The results support the differential susceptibility model whereby highly emotionally negative children were more susceptible to the influences of low and high levels of maternal stimulation in academic readiness and mathematics achievement's developments.

Prospective associations between ADHD symptoms and physical conditions from early childhood to adolescence: a population-based longitudinal study.

BACKGROUND: The co-occurrence between attention-deficit hyperactivity disorder (ADHD) and physical conditions is frequent but often goes unrecognised. Most available evidence on the links between ADHD and physical conditions relies on cross-sectional studies. Understanding temporal sequences of associations is key to inform appropriate treatment and preventive strategies. We aimed to assess possible longitudinal associations between ADHD symptoms and a broad range of physical conditions, adjusting for several confounding factors. METHODS: Participants came from the population-based Quebec Longitudinal Study of Child Development. Participants were selected from the Quebec Birth Registry, recruited between October, 1997, and July, 1998, from the province of Quebec, Canada, and followed up in early childhood (n=2120; age 5 months-5 years), middle childhood (n=1750; age 6-12 years), and adolescence (n=1573; age 13-17 years). Main outcome measures included ADHD symptom severity and physical conditions, which were reported by the person most knowledgeable of the child in early childhood, by teachers in middle childhood, and self-reported in adolescence. Multivariable regression analyses were conducted to study the prospective associations between ADHD symptoms and later physical conditions, and physical conditions and later ADHD symptoms, adjusting for multiple confounders. FINDINGS: We found several prospective associations between ADHD symptoms and physical conditions including asthma, high BMI (≥1 SD above the mean), epilepsy, dental caries, acute infections, injuries, and sleep problems. After adjusting for key confounding factors, several associations remained: ADHD symptoms in early childhood were associated with later high BMI during middle childhood (odds ratio [OR] 1·19 [95% CI 1·05-1·35]) and adolescence (OR 1·14 [1·01-1·29]), and with unintentional injuries during adolescence (OR 1·10 [1·01-1·21]). ADHD symptoms in middle childhood were significantly associated with later dental caries during adolescence (OR 1·10 [1·01-1·20]). Unintentional injuries in early childhood were associated with later ADHD symptoms in middle childhood (standardised mean difference [SMD] 0·15 [0·05-0·24]) and adolescence (SMD 0·13 [0·04-0·23]), and restless legs syndrome symptoms in middle childhood were associated with later ADHD symptoms in adolescence (SMD 0·15 [0·05-0·25]). INTERPRETATION: Our results point to the need to carefully monitor children with ADHD in early or middle childhood for several physical conditions, and to monitor children with particular physical conditions for ADHD symptoms. Our study also calls for policies to promote more integrated health-care systems for children with complex mental and physical needs, bridging the current gap between mental and physical health-care services. FUNDING: Québec Government's Ministry of Health, Ministry of Education, and Ministry of Family Affairs; The Lucie and André Chagnon Foundation; the Robert-Sauvé Research Institute of Health and Safety at Work; the Québec Statistics Institute; the Fonds de Recherche du Québec-Santé; the Fonds de Recherche du Québec-Societé et Culture; Canada's Social Science and Humanities Research Council; the Canadian Institutes of Health Research, the Sainte-Justine Research Center; and the French National Research Agency. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Medical conditions and Attention-Deficit/Hyperactivity Disorder symptoms from early childhood to adolescence.

The comorbidity between physical and mental health conditions is challenging and frequently goes unrecognized in practice. Associations between Attention-Deficit/Hyperactivity Disorder (ADHD) and physical conditions have been reported in youth. However, prior research failed to: (1) address the patterns of associations in early childhood, middle childhood, and adolescence within the same population sample; (2) consider a large set of physical disorders at the same time; (3) take confounders into account. Our goal was to assess the associations between ADHD symptoms and a broad set of physical conditions across developmental periods. This birth cohort study (n = 2057) is the first to explore the associations between ADHD and a wide range of medical conditions by encompassing the whole early development from 5 months to 17 years in the same sample and relying on innovative network analyses. We found significant associations between ADHD symptoms and several physical conditions, some of which were observed in early childhood, middle childhood, and adolescence (e.g., asthma, sleep problems) or were confounded by socioeconomic status or psychiatric comorbidities (e.g., body mass index, dental caries). The study calls for an effective integrated care model encompassing mental and general healthcare across the developmental period.

Pacific and English Language Fluency and Mental Disorder Symptom Indications Among Pacific Mothers in New Zealand: Findings From the Pacific Islands Families Study.

Within New Zealand (NZ), Pacific people experience higher prevalence of mental disorder than non-Pacific people. Bilinguals are believed to have psychological advantages over monolinguals, although the empirical evidence base is equivocal. A prospective cohort of Pacific mothers was studied at 6 weeks (n = 1272), 1-year (n = 1135), and 2-year (n = 1059) postpartum. At 6 weeks, 343 (27.0%) mothers were fluent in both Pacific and English languages, 519 (40.8%) only fluent in Pacific language(s), and 410 (32.2%) only fluent in English. Over assessment waves, 16.0%, 12.5%, and 8.7% of mothers had mental disorder symptom indications. In adjusted generalized estimating equation analysis, mothers speaking English only had odds of mental disorder symptom indication of 2.24 as compared to bilingual mothers, while those who spoke Pacific language(s) only had odds of 1.52. Supporting Pacific and English languages within NZ may confer mental health benefits to new Pacific mothers and potentially others.

Developmental profiles of childhood attention-deficit/hyperactivity disorder and irritability: association with adolescent mental health, functional impairment, and suicidal outcomes.

BACKGROUND: Irritability is frequently comorbid with ADHD. Although irritability alone has been linked to deleterious mental health and adaptive issues, the joint developmental course of ADHD and irritability symptoms during childhood as well as its association with later mental health and suicidal outcomes is not fully understood. We aimed to describe the developmental trajectories of childhood ADHD and irritability symptoms and to quantify their association with adolescent mental health and suicidal outcomes. METHODS: The Quebec Longitudinal Study of Child Development (QLSCD) included 1407 participants from the general population followed up from age 5 months to 17 years. We used a multitrajectory approach to identify developmental trajectories of childhood (6-12 years) ADHD and irritability symptoms. Outcome measures were adolescent (13-17 years) mental health (psychiatric symptoms/functional impairment) and suicidal outcomes. RESULTS: We identified distinct developmental profiles: combined absent or very low ADHD and absent or very low irritability (940 [66.8%]; reference group), moderately high irritability and low ADHD (158 [11.2%]), moderately high ADHD and low irritability (198 [14.1%]), and combined high ADHD and high irritability (111 [7.9%]). Multivariate modeling showed that, compared to children in the reference group, those in the combined high ADHD and high irritability profile showed higher levels of ADHD continuity (d ranges = 0.40-0.50), externalizing (d ranges = 0.25-0.59), internalizing (d ranges = 0.20-0.29), and functional impairments (d ranges = 0.17-0.48) and suicidal behaviors (odds ratio (OR) = 2.12, confidence interval (CI) = 1.47-3.06) in adolescence. CONCLUSIONS: The presence of persistently high levels of irritability along with ADHD symptoms during childhood significantly predicts adolescent ADHD continuity, externalizing, internalizing, and suicidal outcomes. Systematic consideration of irritability when assessing and treating ADHD may improve long-term mental health outcomes.

Prenatal Diet and Children's Trajectories of Anxiety and Depression Symptoms from 3 to 8 Years: The EDEN Mother-Child Cohort.

BACKGROUND: Maternal diet quality during pregnancy has been linked to offspring's physical and mental health outcomes across the lifespan. However, few studies have examined its association with subsequent offspring's anxiety and depression issues. OBJECTIVES: The objective of the study was to examine the relationship between maternal prenatal dietary patterns and offspring's anxiety and depression symptoms from 3 to 8 years. METHODS: We used data from 1242 children enrolled in the French EDEN (Etude des déterminants pré- et postnatals précoces du développement et de la santé de l'enfant) birth cohort. Maternal third trimester dietary patterns-namely, "Healthy" (i.e., high intake in fruit, vegetables, fish, and whole-grain cereals) and "Western" (i.e., high intake in processed and snacking foods) patterns-were evaluated using a validated qualitative FFQ. Children's anxiety and depression symptoms (i.e., fears, worries, misery, nervousness, and somatic symptoms) were assessed by mothers using the Strengths and Difficulties Questionnaire at ages 3, 5, and 8 years, from which trajectories were derived using group-based trajectory modeling. We used logistic regressions to analyze the associations between maternal dietary patterns and children's anxiety and depression symptom trajectories. RESULTS: We identified 2 trajectories of anxiety and depression symptoms from 3 to 8 years of age: low to moderate (n = 1058; reference group) and moderately high (n = 184). Maternal low adherence to the Healthy dietary pattern in the third trimester was significantly associated with moderately high children's anxiety and depression symptom trajectories from 3 to 8 years (OR, 1.87; 95% CI, 1.40-2.51), in crude and adjusted analyses. The maternal Western dietary pattern was not significantly associated with anxiety and depression symptom trajectories. CONCLUSIONS: High maternal prenatal adherence to a Healthy dietary pattern was negatively related to anxiety and depression symptoms in children. As maternal diet is a key lifestyle factor, further research should investigate its association with subsequent offspring anxiety and depression symptoms in aiming to later inform prevention strategies focusing on pregnancy.

Cord Serum Cytokines at Birth and Children's Anxiety-Depression Trajectories From 3 to 8 Years: The EDEN Mother-Child Cohort.

BACKGROUND: Recent research suggests that immune dysregulation in pregnancy could be a risk factor for anxiety and depression symptoms in offspring. Whereas animal studies have demonstrated the importance of the link between perinatal cytokines and abnormal behaviors in offspring, human epidemiological studies in this area remain limited. The objectives of the study were to describe the network of cord serum cytokines at birth and test whether they are associated with subsequent anxiety and depression symptom trajectories in offspring. METHODS: We used data and biological samples from 871 mother-child pairs followed up from pregnancy to 8 years of age and participating in the French mother-child cohort EDEN (a study on the pre- and early postnatal determinants of child health and development). Cord serum cytokines were measured at birth. Children's symptoms of anxiety and depression were assessed with the emotional difficulties subscore of the Strength and Difficulties Questionnaire at ages 3, 5, and 8 years, from which trajectories of anxiety-depression symptoms were derived. RESULTS: Results showed a significant association between cord serum interleukin-7 at birth and the trajectories of children's anxiety-depression symptoms between ages 3 to 8 years (adjusted odds ratio, 0.73; 95% confidence interval, 0.57-0.93). The associations considered relevant confounders, including prenatal maternal depressive symptoms. CONCLUSIONS: Early immune changes may contribute to subsequent anxiety and depression symptoms in childhood. Beyond the understanding of mechanisms underlying the occurrence of emotional difficulties in children, our findings open avenues for future research in human and animals.