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Twin studies suggest that expressive vocabulary at ~24 months is modestly heritable. However, the genes influencing this early linguistic phenotype are unknown. Here we conduct a genome-wide screen and follow-up study of expressive vocabulary in toddlers of European descent from up to four studies of the EArly Genetics and Lifecourse Epidemiology consortium, analysing an early (15-18 months, 'one-word stage', N(Total) = 8,889) and a later (24-30 months, 'two-word stage', N(Total)=10,819) phase of language acquisition. For the early phase, one single-nucleotide polymorphism (rs7642482) at 3p12.3 near ROBO2, encoding a conserved axon-binding receptor, reaches the genome-wide significance level (P=1.3 × 10(-8)) in the combined sample. This association links language-related common genetic variation in the general population to a potential autism susceptibility locus and a linkage region for dyslexia, speech-sound disorder and reading. The contribution of common genetic influences is, although modest, supported by genome-wide complex trait analysis (meta-GCTA h(2)(15-18-months) = 0.13, meta-GCTA h(2)(24-30-months) = 0.14) and in concordance with additional twin analysis (5,733 pairs of European descent, h(2)(24-months) = 0.20).

Background: Little is known about the genetic determinants of sensitive parenting. Two earlier studies examined the effect of the serotonin transporter polymorphism (5-HTTLPR) on sensitive parenting, but reported opposite results. In a large cohort we further examined whether 5-HTTLPR is a predictor of observed maternal sensitivity and whether observed child social fearfulness moderates the effect of 5-HTTLPR on maternal sensitivity., Methods: The population-based cohort consisted of 767 mother-child dyads. Maternal sensitivity was repeatedly observed at the child's age of 14 months, 36 months and 48 months. Sensitivity was coded using the Ainsworth's rating scales for sensitivity and cooperation and the revised Erickson rating scales for Supportive presence and Intrusiveness. Child social fearfulness was observed using the Stranger Approach episode of the Laboratory Temperament Assessment Battery at 36 months., Results: Repeated measurement analyses showed a consistent main effect of maternal 5-HTTLPR on sensitivity; mothers carrying the S-allele were more sensitive toward their children (p = .005). This effect was not explained by the child's 5-HTTLPR genotype. We found no evidence that child social fearfulness moderated the effect of 5-HTTLPR on sensitivity., Conclusions: This study suggests that variations in maternal 5-HTTLPR genotype appear to be involved in the etiology of parenting behavior. The observed effects of this genetic variation are consistent with the notion that parenting may have a genetic component, but large studies are needed to find the specific small molecular effects., (© 2014 The Authors. Journal of Child Psychology and Psychiatry. © 2014 Association for Child and Adolescent Mental Health.)

Intelligence in childhood, as measured by psychometric cognitive tests, is a strong predictor of many important life outcomes, including educational attainment, income, health and lifespan. Results from twin, family and adoption studies are consistent with general intelligence being highly heritable and genetically stable throughout the life course. No robustly associated genetic loci or variants for childhood intelligence have been reported. Here, we report the first genome-wide association study (GWAS) on childhood intelligence (age range 6-18 years) from 17,989 individuals in six discovery and three replication samples. Although no individual single-nucleotide polymorphisms (SNPs) were detected with genome-wide significance, we show that the aggregate effects of common SNPs explain 22-46% of phenotypic variation in childhood intelligence in the three largest cohorts (P=3.9 × 10(-15), 0.014 and 0.028). FNBP1L, previously reported to be the most significantly associated gene for adult intelligence, was also significantly associated with childhood intelligence (P=0.003). Polygenic prediction analyses resulted in a significant correlation between predictor and outcome in all replication cohorts. The proportion of childhood intelligence explained by the predictor reached 1.2% (P=6 × 10(-5)), 3.5% (P=10(-3)) and 0.5% (P=6 × 10(-5)) in three independent validation cohorts. Given the sample sizes, these genetic prediction results are consistent with expectations if the genetic architecture of childhood intelligence is like that of body mass index or height. Our study provides molecular support for the heritability and polygenic nature of childhood intelligence. Larger sample sizes will be required to detect individual variants with genome-wide significance.

Background: It is unclear how the course of maternal depressive symptoms affects child development. We modelled trajectories of maternal depressive symptoms from mid-pregnancy to 3 years after childbirth to better determine their associations with child problem behaviour., Method: Mother-child dyads (n = 4167) participated in a population-based prospective cohort in The Netherlands. Depressive symptoms were assessed with the Brief Symptom Inventory during pregnancy and at 2, 6 and 36 months postnatally. When children were 3 years old, problem behaviour was assessed with the Child Behaviour Checklist completed by each parent. A group-based modelling technique was used to model trajectories of maternal depressive symptoms and to examine their association with child problem behaviour. The added value of trajectory modelling was determined with successive linear regressions., Results: We identified four trajectories of maternal depressive symptoms; 'no' (34%), 'low' (54%), 'moderate' (11%) and 'high' (1.5%). Child problem behaviour varied as a function of maternal trajectory membership. Whether rated by mother or father, children of mothers assigned to higher trajectories had significantly more problem behaviours than children of mothers assigned to lower trajectories. The model including trajectories had additive predictive value over a model relying only on a summed repeated measure of severity and a predefined chronicity variable., Conclusions: Depending on their course, maternal depressive symptoms have different effects on child problem behaviour. More information is gained by studying trajectories of symptoms, than only predefined measures of severity and chronicity. Moreover, trajectories can help identifying clinically depressed mothers who are possible candidates for early interventions.

Prenatal maternal psychopathology affects child development, but some children seem more vulnerable than others. Genetic variance in hypothalamic-pituitary-adrenal axis genes may influence the effect of prenatal maternal psychological symptoms on child emotional and behavioral problems. This hypothesis was tested in the Generation R Study, a population-based cohort from fetal life onward. In total, 1727 children of Northern European descent and their mothers participated in this study and were genotyped for variants in the glucocorticoid receptor (GR) gene (rs6189/rs6190, rs10052957, rs41423247, rs6195, and rs6198) and the FK506-binding protein 5 (FKBP5) gene (rs1360780). Prenatal maternal psychological symptoms were assessed at 20 weeks pregnancy and child behavior was assessed by both parents at 3 years. In a subsample of 331 children, data about cortisol reactivity were available. Based on power calculations, only those genetic variants with sufficient minor allele frequencies (rs41423247, rs10052957, and rs1360780) were included in the interaction analyses. We found that variation in GR at rs41423247 moderates the effect of prenatal maternal psychological symptoms on child emotional and behavioral problems (beta 0.41, SE 0.16, p=0.009). This prenatal interaction effect was independent of mother's genotype and maternal postnatal psychopathology, and not found for prenatal psychological symptoms of the father. Moreover, the interaction between rs41423247 and prenatal psychological symptoms was also associated with decreased child cortisol reactivity (beta -2.30, p-value 0.05). These findings emphasize the potential effect of prenatal gene-environment interaction, and give insight in possible mechanisms accounting for children's individual vulnerability to develop emotional and behavioral problems.

Serotonin is involved in the development of neural circuits modulating emotional behavior. The short allele (s) of a polymorphism (5-HTTLPR) of the serotonin transporter gene is a risk factor for psychopathology in the presence of environmental stressors. Maternal smoking is associated with growth restriction of the human fetal brain and adverse effects of nicotine on the developing serotonin system have been documented. We hypothesized that maternal smoking interacts with both child and mother 5-HTTLPR genotype as a risk factor for later child emotional problems. In a sample of n = 1,529 mother-child dyads, smoking habits were assessed by questionnaires during pregnancy. Child emotional problems were measured by the Child Behavior Checklist at the child's age of 3 years. Maternal smoking during pregnancy significantly increased the risk for emotional problems in children carrying the s-allele; β = 0.24, P = 0.03 (mother-report), and β = 0.46, P = 0.001 (father-report). In children heterozygous at 5-HTTLPR and exposed to maternal prenatal smoking (n = 79) risk of emotional problems increased with each additional s-allele the mother carried. The associations between 5-HTTLPR and child emotional problems were not moderated by paternal prenatal smoking. These findings imply that the vulnerability for emotional problems in s-allele carriers may already originate in fetal life., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: Family history is a major risk factor for child problem behaviour, yet few studies have examined the association between grandparental psychiatric disorder and child problem behaviour. Results are inconsistent as to whether the effect of grandparental depression on child problem behaviour is independent of parental psychopathology., Methods: Mothers and their children participated in an ethnically Dutch subcohort of a population-based prospective cohort in the Netherlands. N = 816 (66%) mothers and n = 691 fathers participated in the prenatal interviews. N = 687 (84%) mothers and children and n = 565 (82%) fathers participated three years postpartum. (Grand)parental psychopathology was assessed during pregnancy of the mothers with the Family Informant Schedule and Criteria (FISC), the Composite International Diagnostic Interview (CIDI) and the Brief Symptom Inventory (BSI). Child behaviour was assessed with the Child Behavior Checklist (CBCL) by mother and father when the child was three years old., Results: Grandparental anxiety disorder predicted maternal reports of children's internalizing problems (OR = 1.98, 95% C.I. (1.20, 3.28), p-value<0.01) and externalizing problems (OR = 1.73, 95% C.I. (1.04, 2.87), p-value = 0.03), independent of parental psychopathology. Results were similar for grandparental depression; internalizing OR = 1.75, 95% C.I (1.11, 2.75), p-value = 0.02 and externalizing OR = 1.67, 95% C.I. (1.05, 2.64) p-value = 0.03. However, grandparental psychopathology was not associated with children's problem behaviour as reported by the father., Limitations: Information on grandparental lifetime psychiatric disorder was assessed through a parental interview which may have led to an underestimation of the prevalence rates., Conclusions: These results confirm the importance of a family history including not only the parental but also the grandparental generations., (Copyright © 2010 Elsevier B.V. All rights reserved.)