Adult Outcomes of Childhood Dysregulation: A 14-year Follow-up Study

Objective: Using a general population sample, the adult outcomes of children who presented with severe problems with self-regulation defined as being concurrently rated highly on attention problems, aggressive behavior, and anxious-depression on the Child Behavior Checklist Dysregulation Profile (CBCL-DP) were examined. Method: Two thousand seventy-six children from 13 birth cohorts 4 to 16 years of age were drawn from Dutch birth registries in 1983. CBCLs were completed by parents at baseline when children from the different cohorts were 4 to 16 years of age and sampled every 2 years for the next 14 years. At year 14 the CBCL and DSM interview data were collected. Logistic regression was used to compare and contrast outcomes for children with and without dysregulation, as measured by the latent-class defined CBCL-DP. Sex and age were covaried and concurrent DSM diagnoses were included in regression models. Results: Presence of childhood CBCL-DP at wave 1 was associated with increased rates of adult anxiety disorders, mood disorders, disruptive behavior disorders, and drug abuse 14 years later. After controlling for co-occurring disorders in adulthood, associations with anxiety and disruptive behavior disorders with the CBCL-DP remained, whereas the others were not significant. Conclusions: A child reported to be in the CBCL-DP class is at increased risk for problems with regulating affect, behavior, and cognition in adulthood. J. Am. Acad. Child Adolesc. Psychiatry, 2010;49(11)1105-1116

Classes of oppositional-defiant behavior: concurrent and predictive validity

Background: Oppositional defiant disorder (ODD) has components of both irritability and defiance. It remains unclear whether children with variation in these domains have different adult outcomes. This study examined the concurrent and predictive validity of classes of oppositional defiant behavior. Methods: Latent class analysis was performed on the oppositional defiant problems scale of the Child Behavior Checklist in two samples, one in the US (the Achenbach Normative Sample, N = 2029) and one in the Netherlands (the Zuid-Holland Study, N = 2076). A third sample of American children (The Vermont Family Study, N = 399) was examined to determine concurrent validity with DSM diagnoses. Predictive validity over 14 years was assessed using the Zuid-Holland Study. Results: Four classes of oppositional defiant problems were consistent in the two latent class analyses: No Symptoms, All Symptoms, Irritable, and Defiant. Individuals in the No Symptoms Class were rarely diagnosed concurrently with ODD or any future disorder. Individuals in the All Symptoms Class had an increased frequency of concurrent childhood diagnosis of ODD and of violence in adulthood. Subjects in the Irritable Class had low concurrent diagnosis of ODD, but increased odds of adult mood disorders. Individuals in the Defiant Class had low concurrent diagnosis of ODD, but had increased odds of violence as adults. Conclusions: Only children in the All Symptoms class were likely to have a concurrent diagnosis of ODD. Although not diagnosed with ODD, children in the Irritable Class were more likely to have adult mood disorders and children in the Defiant Class were more likely to engage in violent behavior

Adverse Life Events and Allele-Specific Methylation of the Serotonin Transporter Gene (SLC6A4) in Adolescents: The TRAILS Study

Objectives Adverse life events increase vulnerability to affective disorders later in life, possibly mediated by methylation of the serotonin transporter gene (SLC6A4). We investigated the relationship of SLC6A4 methylation with various types of adversity (perinatal adversity, traumatic youth experiences and stressful life events [SLEs]), as well as with the timing of SLEs (during childhood [0-11 years] or during adolescence [12-15 years]). In addition, we investigated whether different serotonin-transporter-linked polymorphic region genotypes were equally sensitive to SLE-related methylation. Methods In a population sample of 939 adolescents (mean age = 16.2 years), we assessed SLC6A4 methylation, SLC6A4 functionality (serotonin-transporter-linked polymorphic region long and short alleles, and rs25531), and adverse life events. Results Only a higher number of SLEs was positively associated with higher SLC6A4 methylation (B = 0.11, p = .011). Adolescent SLEs were associated with higher SLC6A4 methylation (B = 0.13, p = .004) independently of childhood SLEs (B = 0.02, p = .57). L-allele homozygotes showed a greater impact of SLEs on methylation (B = 0.37, p < .001) than did s-allele carriers (B = 0.04, p = .66), resulting in higher levels of SLC6A4 methylation for l-allele homozygotes among those experiencing high levels of SLEs. Conclusions Our findings demonstrate a higher level of SLC6A4 methylation after SLEs in adolescents, with a more pronounced association for SLEs during adolescence than during childhood. Considering the allele-specific sensitivity of SLC6A4 methylation to SLEs, this study may help clarify the role of SLC6A4 in the development of affective disorders

Glucocorticoid receptor gene (NR3C1) methylation following stressful events between birth and adolescence. The TRAILS study

Stress early in life is a known risk factor for the development of affective disorders later in life. Epigenetic mechanisms, such as DNA methylation, may have an important role in mediating that risk. Recent epigenetic research reported on the long-term relationship between traumatic stress in childhood and DNA methylation in adulthood. In this study, we examined the impact of various types of stress (perinatal stress, stressful life events (SLEs) and traumatic youth experiences) on methylation of the glucocorticoid receptor gene (NR3C1) in the blood of a population sample of 468 adolescents (50.4% female, mean age 16.1 years). Second, we determined whether stress at different ages was associated with higher NR3C1 methylation. NR3C1 methylation rates were higher after exposure to SLEs and after exposure to traumatic youth experiences. NR3C1 methylation in adolescence was not higher after exposure to perinatal stress. Experience of SLEs in adolescence was associated with a higher NR3C1 methylation, independently of childhood SLEs. We demonstrate that not only traumatic youth experiences but also (more common) SLEs are associated with higher NR3C1 methylation. In addition, our findings underline the relevance of adolescent stress for epigenetic changes in the NR3C1 gene

Blunted HPA axis response to stress is related to a persistent Dysregulation Profile in youth

The Child Behavior Checklist Dysregulation Profile (DP) in youth has been shown to be a predictor of psychopathology later in life. We examined the activity of the hypothalamic pituitary adrenal (HPA) axis in youth with remitted, new, persistent, and no DP. Data from 489 youth (47% boys) participating in a Dutch longitudinal general population study were included (Wave 1 mean age = 11.5, Wave 2 = 14.2). Wave 2 diurnal cortisol patterns and levels in response to a laboratory stress paradigm were compared in youth with DP at Wave 1 only, Wave 2 only, both Waves, and neither Wave. Youth with the DP at Wave 2 only or at both time points showed blunted cortisol responses to stress relative to the other two groups. There were no group or sex differences in diurnal cortisol activity. More research is needed to determine how the association between DP symptoms and HPA axis functioning changes over time. (C) 2013 Elsevier B.V. All rights reserved

Recognition of scared faces and the serotonin transporter gene in young children: the Generation R Study

Background: Previous research highlights the significance of a functional polymorphism located in the promoter region (5-HTTLPR) of the serotonin transporter gene in emotional behaviour. This study examined the effect of the 5-HTTLPR polymorphism on emotion processing in a large number of healthy preschoolers. Methods: The 5-HTTLPR genotype was classified in 605 children as homozygous for the short allele (SS), homozygous for the long allele (LL), or heterozygous (LS). Emotion-processing was assessed using age-appropriate computer tasks where children matched happy, sad, angry, and fearful facial expressions preceded by a shape-matching task to assess basic matching ability. Results: We found that young children could differentiate between emotion categories (F = 12.1, p .05). Conclusions: Results indicate that 5-HTTLPR allele status selectively impacts the processing of fearful but not other facial expressions. This pattern is already apparent in very young typically developing children. Results may signal an early vulnerability for affective problems before disorders emerge