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Introduction: In previous longitudinal studies in the US, lower socioeconomic status (SES) was associated with more emotional and behavioral problems. It remains unclear whether these findings can be generalized outside the US, as different countries vary in their health care systems and prevention of psychopathology in youth. Therefore, we studied the same associations in a comparable sample in The Netherlands and directly tested for differences between the US and The Netherlands.Methods: The US (N=833) and Dutch (N=708) population samples were followed-up for 9 years. Age at baseline ranged from 8 to 16 years. Parents filled out behavior checklists.Results: Analyses revealed very few differences between the two countries. In both countries, SES predicted syndrome scores and cumulative prevalence rates for internalizing and externalizing problems (withdrawn and aggressive behavior) and for thought and attention Problems. The SES gradient in syndrome scores was stable over time. Only for withdrawn behavior, the gradient was larger in young adulthood.Conclusion: Although the health care systems differ between the US and The Netherlands, the socioeconomic disparities in emotional and behavioral problems were similar. [ABSTRACT FROM AUTHOR]

Anxiety disorders (ADs), namely generalized AD, panic disorder and phobias, are common, etiologically complex conditions with a partially genetic basis. Despite differing on diagnostic definitions based on clinical presentation, ADs likely represent various expressions of an underlying common diathesis of abnormal regulation of basic threat-response systems. We conducted genome-wide association analyses in nine samples of European ancestry from seven large, independent studies. To identify genetic variants contributing to genetic susceptibility shared across interview-generated DSM-based ADs, we applied two phenotypic approaches: (1) comparisons between categorical AD cases and supernormal controls, and (2) quantitative phenotypic factor scores (FS) derived from a multivariate analysis combining information across the clinical phenotypes. We used logistic and linear regression, respectively, to analyze the association between these phenotypes and genome-wide single nucleotide polymorphisms. Meta-analysis for each phenotype combined results across the nine samples for over 18 000 unrelated individuals. Each meta-analysis identified a different genome-wide significant region, with the following markers showing the strongest association: for case-control contrasts, rs1709393 located in an uncharacterized non-coding RNA locus on chromosomal band 3q12.3 (P=1.65 × 10(-8)); for FS, rs1067327 within CAMKMT encoding the calmodulin-lysine N-methyltransferase on chromosomal band 2p21 (P=2.86 × 10(-9)). Independent replication and further exploration of these findings are needed to more fully understand the role of these variants in risk and expression of ADs., Competing Interests: The authors declare no conflicts of interest.

Background: Hypothalamic-pituitary-adrenal axis functioning, with cortisol as its major output hormone, has been presumed to play a key role in the development of psychopathology. Predicting affective disorders from diurnal cortisol levels has been inconclusive, whereas the predictive value of stress-induced cortisol concentrations has not been studied before. The aim of this study was to predict mental disorders over a 3-year follow-up from awakening and stress-induced cortisol concentrations., Method: Data were used from 561 TRAILS (TRacking Adolescents' Individual Lives Survey) participants, a prospective cohort study of Dutch adolescents. Saliva samples were collected at awakening and half an hour later and during a social stress test at age 16. Mental disorders were assessed 3 years later with the Composite International Diagnostic Interview (CIDI)., Results: A lower cortisol awakening response (CAR) marginally significantly predicted new disorders [odds ratio (OR) 0.77, p = 0.06]. A flat recovery slope predicted disorders with a first onset after the experimental session (OR 1.27, p = 0.04). Recovery revealed smaller, non-significant ORs when predicting new onset affective or anxiety disorders, major depressive disorder, or dependence disorders in three separate models, corrected for all other new onsets., Conclusions: Our results suggest that delayed recovery and possibly reduced CAR are indicators of a more general risk status and may be part of a common pathway to psychopathology. Delayed recovery suggests that individuals at risk for mental disorders perceived the social stress test as less controllable and less predictable.

Early life adversity and psychopathology are thought to be linked through HPA-axis deregulation. Changes in methylation levels of stress reactivity genes such as the glucocorticoid receptor gene (NR3C1) can be induced by adversity. Higher NR3C1 methylation levels have been associated with a reduced NR3C1 expression, possibly leading to impaired negative feedback regulation of the HPA-axis. In this study we tested whether methylation levels of NR3C1 were associated with HPA-axis regulation, operationalized as cortisol responses. In 361 adolescents (mean age 16.1, SD=0.6), salivary cortisol samples were collected before, during, and after a social stress task, from which response measures (cortisol activation and recovery) were calculated. Higher NR3C1 methylation levels were associated with a flattened cortisol recovery slope, indicating a delayed recovery time. Cortisol response activation was not associated with NR3C1 methylation. These results suggest that methylation of NR3C1 may impair negative feedback of the HPA-axis in adolescents., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Individuals with autistic traits are considered to be prone to develop psychosexual problems due to their limited social skills and insight. This study investigated the longitudinal relation between autistic traits in childhood (T1; age 10-12 years) and parent-reported psychosexual problems in early adolescence (T2; age 12-15 years). In a general population cohort study (n = 1873; the Tracking Adolescents' Individual Lives Survey (TRAILS)), autistic traits and psychosexual problems were determined. Logistic regression analyses were used to investigate whether childhood autistic traits, in individuals displaying no psychosexual problems in childhood, predicted the presence of psychosexual problems in adolescence, while controlling for pubertal development and conduct problems. Higher levels of autistic traits at T1 significantly predicted mild psychosexual problems at T2, above and beyond pubertal development and conduct problems. Particularly two dimensions of autistic traits at T1 were significant predictors; i.e. 'reduced contact/social interest' and 'not optimally tuned to the social situation'. Children with autistic traits - especially those with limited social interest and social regulation problems - showed to have a higher risk to develop psychosexual problems, albeit mild, in early adolescence as reported by parents. Although we showed that autistic traits predict psychosexual problems, it is only one of multiple predictors., (© The Author(s) 2014.)

Background: The relationship between early adverse life events and later internalizing problems could be mediated by DNA methylation. Adversity has been associated with higher methylation levels in the glucocorticoid receptor gene (NR3C1) and the serotonin transporter gene (SLC6A4) in adolescents. We investigated cross-sectional and prospective associations of NR3C1 and SLC6A4 methylation with adolescents׳ clinical diagnoses of internalizing disorders and internalizing symptom scores., Methods: In a population sample (mean age=16.2) we measured DNA methylation in three regions of NR3C1 (NR3C1_1, N=454; NR3C1_2, N=904; NR3C1_3, N=412) and one region of SLC6A4 (N=939) at baseline. Internalizing problems were operationalized as clinical DSM-IV diagnoses, assessed at 3 year follow-up with a diagnostic interview, and internalizing symptom scores, assessed with Self-Report questionnaires at baseline and follow-up., Results: Only NR3C1_1 methylation was positively associated with risk of lifetime internalizing disorders, and with symptom scores at follow-up. However, after accounting for baseline symptom scores there was only a tendency for association with internalizing symptom scores at follow-up. There was no association between SLC6A4 methylation and risk of lifetime internalizing disorders. SLC6A4 methylation and internalizing symptom scores showed a tendency for association, also after accounting for baseline symptom scores., Limitations: There was no repeated measure of DNA methylation to study causality between methylation and internalizing problems. Gene expression data were not available., Conclusions: Although the role of gene methylation in the development of internalizing problems remains unclear, our findings suggest that gene methylation, particularly of NR3C1, may be involved in the development of internalizing problems in adolescence., (Copyright © 2015 Elsevier B.V. All rights reserved.)

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.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Background: Some adolescents function poorly in apparently benign environments, while others thrive despite hassles and difficulties. The aim of this study was to examine if adolescents with specialized skills in the recognition of either positive or negative emotions have a context-dependent risk of developing an anxiety or depressive disorder during adolescence, depending on exposure to positive or harsh parenting., Methods: Data came from a large prospective Dutch population study (N = 1539). At age 11, perceived parental rejection and emotional warmth were measured by questionnaire, and emotion recognition skills by means of a reaction-time task. Lifetime diagnoses of anxiety and depressive disorders were assessed at about age 19, using a standardized diagnostic interview., Results: Adolescents who were specialized in the recognition of positive emotions had a relatively high probability to develop an anxiety disorder when exposed to parental rejection (Bspecialization*rejection = 0.23, P < 0.01) and a relatively low probability in response to parental emotional warmth (Bspecialization*warmth = -0.24, P = 0.01), while the opposite pattern was found for specialists in negative emotions. The effect of parental emotional warmth on depression onset was likewise modified by emotion recognition specialization (B = -0.13, P = 0.03), but the effect of parental rejection was not (B = 0.02, P = 0.72). In general, the relative advantage of specialists in negative emotions was restricted to fairly uncommon negative conditions., Conclusions: Our results suggest that there is no unequivocal relation between parenting behaviors and the probability to develop an anxiety or depressive disorder in adolescence, and that emotion recognition specialization may be a promising way to distinguish between various types of context-dependent reaction patterns.

Substance use often starts in adolescence and poses a major problem for society and individual health. The dopamine system plays a role in substance use, and catechol-O-methyltransferase (COMT) is an important enzyme that degrades dopamine. The Val(108/158) Met polymorphism modulates COMT activity and thus dopamine levels, and has been linked to substance use. COMT gene methylation, on the other hand, may affect expression and thus indirectly COMT activity. We investigated whether methylation of the COMT gene was associated with adolescents' substance use. Furthermore, we explored whether the COMT Val(108/158) Met polymorphism interacts with COMT gene methylation in association with substance use. In 463 adolescents (mean age=16, 50.8% girls), substance use (cigarette smoking, alcohol and cannabis use) was assessed with self-report questionnaires. From blood samples, COMT Val(108/158) Met genotype and methylation rates of membrane bound (MB) and soluble (S) COMT promoters were assessed. MB-COMT promoter methylation was associated with non-daily smoking [odds ratio (OR)=1.82, P=0.03], but not with daily smoking (OR=1.20, P=0.34), MB-COMT promoter methylation was not associated with alcohol use. Adolescents with the Met/Met genotype and high rates of MB-COMT promoter methylation were less likely to be high-frequent cannabis users than adolescents with the Val/Val or Val/Met genotype. S-COMT promoter methylation was not associated with substance use. These results indicate that there is an association between substance use and COMT gene methylation. Although this association is complex, combining genetic and epigenetic variation of the COMT gene may be helpful in further elucidating the influence of the dopamine system on substance use in adolescence., (© 2014 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.)

Background: Empirical research on mental health care use and its determinants in young school-aged children is still scarce. In this study, we investigated the role of ethnicity, socioeconomic position (SEP) and perceived severity by both parents and teachers on mental health care use in 5- to 8-year old children with emotional and/or behavioural problems., Methods: Data from 1,269 children with a high score([P90) on the Strengths and Difficulties Questionnaire (SDQ) in the school year 2008–2009 were linked to psychiatric case register data over the years 2010–2011. Cox proportional hazards models were used to predict mental health care use from ethnicity, SEP and perceived severity of the child's problems., Results: During the follow-up period, 117 children with high SDQ scores (9.2 %) had used mental health care for the first time. Ethnic minority children were less likely to receive care than Dutch children (HR Moroccan/Turkish:0.26; 95 % CI 0.13-0.54, HR other ethnicity: 0.26; 95 %CI 0.12-0.58). No socioeconomic differences were found.After correction for previous care use, ethnicity and parental perceived severity, impact score as reported by teachers was significantly associated with mental healthcare use (HR 1.58; 95 % CI 1.01–2.46)., Conclusions: Ethnicity is an important predictor of mental health care use in young children. Already in the youngest school-aged children, ethnic differences in the use of mental health care are present.A distinct predictor of care use in this age group is severity of emotional and behavioural problems as perceived by teachers. Therefore, teachers may be especially helpful in the process of identifying young children who need specialist mental health care.

An underrepresentation of ethnic minority children in mental health care settings is consistently reported. Parents of ethnic minority children are, however, less likely to perceive problem behaviour in their children. Our hypothesis was that, as a result of ethnic differences in problem perception, referral to care by a child health professional (CHP) would be lower for 5- to 6-year-old (high-risk) children from ethnic minority backgrounds than for their peers from the ethnic majority (Dutch origin). For 10,951 children in grade two of elementary school, parents and/or teachers completed the Strengths and Difficulties Questionnaire (SDQ) as well as questions on problem perception (PP) and perceived need for professional care (PN). Referral information was obtained from the Electronic Child Records (ECR) for 1,034 of these children. These children had a high (>90th percentile) SDQ score, and were not receiving mental health care. CHP's referred 144 children (14 %) during the routine health assessments. A lower problem perception was reported by parents of ethnic minority children (40-72 %) than by parents of the ethnic majority group (80 %; p < 0.001), but there were no ethnic differences in referral (OR range 0.9-1.9-p > 0.05). No ethnic differences were found for parental PN, nor for teacher's PP or PN. Despite a lower problem perception in ethnic minority parents when compared to ethnic majority parents, no ethnic differences were found in referral of children with problem behaviour in a preventive health care setting.

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.

Background: The Strengths and Difficulties Questionnaire (SDQ) is a valuable screening tool for identifying psychosocial problems. Its performance in a multi-ethnic society, common to many paediatric health care workers, has not been investigated. Because it is important that screening instruments are valid and reliable for all ethnic groups within one society, we examined differences in the SDQ's psychometric properties in a multi-ethnic society., Methods: The SDQ parent (n = 8114) and teacher form (n = 9355) were completed as part of a preventive health check for children aged 5-6 years of Dutch and non-Dutch ethnic backgrounds. The Child Behaviour Checklist (CBCL)/Teacher Report Form (TRF) was administered to a subsample., Results: Factor analysis of the parent-rated SDQ showed different rating patterns for two of the five subscales for non-Dutch children as compared with Dutch children. Cronbach's alpha for the total difficulties score varied by ethnic group (0.73-0.78 parent-rated SDQ, 0.80-0.83 teacher-rated SDQ), and coefficients were generally smaller for non-Dutch than for Dutch children (P < 0.05). Alpha coefficients for subscales varied between 0.31-0.85 for ethnic groups. Inter-rater correlations between parents and teachers for the total difficulties score varied between 0.20-0.41 between ethnic groups and were larger for Dutch than for non-Dutch children (P < 0.05). Concurrent validity was acceptable for most scales and most ethnic groups., Conclusion: The total difficulties score of the parent- and teacher-rated SDQ is valid and reliable for different ethnic groups within Dutch society. However, there are differences in reliability and validity of the subscales, which makes interpretation of the subscales difficult for certain ethnic groups.

Elevated levels of corticotropin (ACTH)-reactive immunoglobulins (ACTH IgG) were found in males with conduct disorder, suggesting their involvement in the biology of antisocial behavior. We first aimed to confirm these findings in a large general population sample of adolescents. Secondly, we studied the association between ACTH IgG levels and hypothalamic-pituitary-adrenal (HPA) axis response to stress. Free and total ACTH IgG levels were measured in sera of 1230 adolescents (15-18 years). HPA axis activity was determined by measuring salivary cortisol before, during, and after a social stress test. Antisocial behavior was assessed using the Antisocial Behavior Questionnaire. ACTH peptide and IgG affinity kinetics for ACTH were assayed in a subsample of 90 adolescents selected for high or low ACTH IgG levels. In boys, higher total ACTH IgG levels were associated with higher antisocial behavior scores (β=1.05, p=0.04), especially at high levels of free ACTH IgG. In girls, antisocial behavior was associated with low free ACTH IgG levels (β=-0.20, p=0.04). Stress-induced cortisol release was associated with free ACTH IgG in boys (βareaunderthecurve=-0.67, p<0.01), and with total ACTH IgG in girls (βrecovery=0.84, p=0.05). The affinity kinetics assay showed that ACTH IgG association rates were lower in both boys and girls with high ACTH IgG levels. These data show that ACTH IgG levels are related to antisocial behavior and HPA axis response to stress in adolescents. The mechanisms behind these associations, including different ACTH binding properties of IgG in subjects with antisocial behavior, deserve further attention., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

We assessed if the Revised Child Anxiety and Depression Scale (RCADS) measures anxiety symptoms similarly across age groups within adolescence. This is crucial for valid comparison of anxiety levels between different age groups. Anxiety symptoms were assessed biennially in a representative population sample (n = 2226) at three time points (age range 10-17 years) using the RCADS anxiety subscales (generalized anxiety disorder [GAD], obsessive-compulsive disorder [OCD], panic disorder [PD], separation anxiety [SA], social phobia [SP]). We examined longitudinal measurement invariance of the RCADS, using longitudinal confirmatory factor analysis, by examining the factor structure (configural invariance), factor loadings (metric invariance) and thresholds (strong invariance). We found that all anxiety subtypes were configural invariant. Metric invariance held for items on the GAD, OCD, PD and SA subscales; yet, for the SP subscale three items showed modest longitudinal variation at age 10-12. Model fit decreased modestly when enforcing additional constraints across time; however, model fit for these models was still adequate to excellent. We conclude that the RCADS measures anxiety symptoms similarly across time in a general population sample of adolescents; hence, measured changes in anxiety symptoms very likely reflect true changes in anxiety levels. We consider the instrument suitable to assess anxiety levels across adolescence., (Copyright © 2013 John Wiley & Sons, Ltd.)

Objective: To identify developmental trajectories of anxiety symptoms for adolescent girls and boys. Trajectories were compared with regard to early-adolescent risk factors and psychiatric outcomes during adolescence and in young adulthood., Method: A community sample of 2,230 adolescents was assessed three times across a six-year interval (10-17 years). Symptom scores of anxiety were analyzed with growth mixture models, stratified by gender., Results: Three gender-specific anxiety trajectories were identified for both girls (93.3% low, 4.1% mid-adolescence limited, 2.6% mid-adolescence increasing) and boys (84.4% low, 9.5% mid-adolescence limited, 6.1% early-adolescence decreasing). Child, family and peer factors at baseline predicted group membership of the mid-adolescence limited anxiety trajectory and the early-adolescence decreasing anxiety trajectory in boys. Parental emotional problems predicted the early-adolescence anxiety increase trajectory in girls. Prevalence of anxiety disorders and depression during adolescence and in early adulthood was higher in both the mid-adolescence limited and the mid-adolescence anxiety increase trajectory., Conclusions: The longitudinal course of anxiety symptoms during adolescence was characterized by three distinct gender-specific developmental trajectories. The most at-risk trajectory in girls was the mid-adolescence anxiety increase trajectory, and in boys the mid-adolescence limited trajectory. None of the environmental (i.e., child, family and peer) factors distinguished the at-risk trajectories from the other trajectories.

Objective: The aim of this study is to evaluate a method, "Counseling in Dialogue" (CD), developed to increase the quality of counseling in youth mental health. Decisional conflict was used as indicator of the quality of counseling and shared decision-making., Methods: 94 children aged 2-12 years were randomized into a CD group and a care as usual (CU) group. In a before-and-after design decisional conflict was measured using the decisional conflict scale (DCS) for parents (N=133) and the Provider Decision Process Assessment Instrument for therapists (PDPAI, N=20). 81 children had follow-up data., Results: Compared with parents of the CU group, parents of the CD group reported significantly less decisional conflict after counseling (difference mothers: -0.38 (95%CI -0.56; -0.19), p<.001; fathers: -0.22 (95%CI -0.44; -0.01), p=.045). 98% of the mothers and 96% of the fathers in the CD group accepted the recommended treatment, compared to 71% (fathers) and 77% (mothers) in the CU group, p<0.05. Decisional conflict of the therapists was low in both groups after counseling (difference: -0.03 (95%CI -0.19; 0.14), p=.741)., Conclusion: The counseling procedure significantly lowered decisional conflict of the parents and promoted the acceptance of the recommended treatment., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background:  Problem perception and perceived need for professional care are important determinants that can contribute to ethnic differences in the use of mental health care. Therefore, we studied ethnic differences in problem perception and perceived need for professional care in the parents and teachers of 5- to 6-year-old children from the general population who were selected for having emotional and behavioural problems., Methods: A cross-sectional study with data of 10,951 children from grade two of the elementary schools in the Rotterdam-Rijnmond area, The Netherlands. Parents and teachers completed the strengths and difficulties questionnaire (SDQ) as well as questions on problem perception and perceived need for care. The SDQ was used to identify children with emotional and behavioural problems. We included Dutch, Surinamese, Antillean, Moroccan and Turkish children in our sample with high (>P90) SDQ scores (N = 1,215), who were not currently receiving professional care for their problems., Results: Amongst children with high SDQ scores, problem perception was lower in non-Dutch parents than in Dutch parents (49% vs. 81%, p < 0.01). These lower rates of problem perception could not be explained by differences in socioeconomic position or severity of the problems. No ethnic differences were found in parental perceived need and in problem perception and perceived need reported by teachers. Higher levels of problem perception and perceived need were reported by teachers than by parents in all ethnic groups (PP: 87% vs. 63% and PN: 48% vs. 23%)., Conclusions: Child health professionals should be aware of ethnic variations in problem perception as low problem perception in parents of non-Dutch children may lead to miscommunication and unmet need for professional care for the child., (© 2012 The Authors. Journal of Child Psychology and Psychiatry © 2012 Association for Child and Adolescent Mental Health.)

Childhood characteristics are associated with life-course-persistent antisocial behavior in epidemiological studies in general population samples. The present study examines this association in an inpatient sample. The purpose is to identify easily measurable childhood characteristics that may guide choice of treatment for adolescent psychiatric inpatients with severe disruptive behavior. Patients (N = 203) were divided into two groups with either early-onset (EO) or adolescent-onset (AO) disruptive behavior, based on ages at which professional care was used for disruptive behavior, referral to special education, and criminal offences. Both groups differed on several childhood characteristics. No gender differences in these characteristics were found. Logistic regression analysis indicated that individuals with grade retention in primary school, childhood impulsive behavior, and a history of physical abuse, had the highest probability of being member of the EO group. These characteristics are reasonably easy to identify, likely apply to other clinical samples as well, and may help clinicians to target their treatment.

Background: The Dutch TRAILS-study focuses on development from early adolescence into adulthood. An important aspect of this development is the development of anxiety. Hitherto little has been known about typical development of symptoms of anxiety during adolescence., Aim: To describe both the normative development of anxiety during adolescence, and the risk indicators for high levels of anxiety in adolescents., Method: Studies were embedded in trails, a large cohort study that followed children from the age of 10 to adulthood., Results: Our results showed that, on average, levels of anxiety decrease in early adolescence and subsequently increase in middle or late adolescence, depending on the subtype of anxiety involved. Child-, parent- and peer-factors at age 10-12 years were related to higher subsequent anxiety levels. Some factors, such as the style of upbringing, were related to higher anxiety levels solely in early adolescence, whereas other factors such as being bullied by peers were related to continuing higher anxiety levels throughout adolescence, irrespective of later victimisation., Conclusion: Our study should, we hope, lead to a better understanding of the normative development of anxiety in the general adolescent population.

Background: Panic attacks are a source of individual suffering and are an independent risk factor for later psychopathology. However, much less is known about risk factors for the development of panic attacks, particularly during adolescence when the incidence of panic attacks increases dramatically. We examined whether internalizing and externalizing problems in childhood predict the onset of panic attacks in adolescence., Method: This study is part of the TRacking Adolescents' Individual Lives Survey (TRAILS), a Dutch longitudinal population cohort study (N = 1,584). Internalizing and Externalizing Problems were collected using the Youth Self-Report (YSR) and the parent-report Child Behavior Checklist (CBCL) at baseline (age 10-12). At age 18-20, DSM-IV defined panic attacks since baseline were assessed with the Composite International Diagnostic Interview (CIDI). We investigated whether early adolescent Internalizing and Externalizing Problems predicted panic attacks between ages 10-20 years, using survival analysis in univariate and multivariate models., Results: There were N = 314 (19.8%) cases who experienced at least one DSM-IV defined panic attack during adolescence and N = 18 (1.2%) who developed panic disorder during adolescence. In univariate analyses, CBCL Total Problems, Internalizing Problems and three of the eight syndrome scales predicted panic attack onset, while on the YSR all broad-band problem scales and each narrow-band syndrome scale predicted panic attack onset. In multivariate analyses, CBCL Social Problems (HR 1.19, p<.05), and YSR Thought Problems (HR 1.15, p<.05) and Social Problems (HR 1.26, p<.01) predicted panic attack onset., Conclusion: Risk indicators of panic attack include the wide range of internalizing and externalizing problems. Yet, when adjusted for co-occurring problem behaviors, Social Problems were the most consistent risk factor for panic attack onsets in adolescence.

Objectives: A commonly encountered situation for evaluating clinicians is a history of significant problems in one setting with little or no difficulties in another. This study aims to describe this phenomenon and to examine its relations with other child and family characteristics., Method: A total of 1,730 children (mean age 11.05 years) was studied from the first wave of the Tracking Adolescents' Individual Lives Survey (TRAILS), a large population-based study of Dutch youth. Parent and teacher ratings of aggression, rule breaking, inattention, and hyperactivity were obtained. Children were assigned to groups according to the presence of clinically relevant problems at home only, at school only, or in both settings. The rate of setting specific problems was calculated and comparisons between groups were made., Results: Setting specific, especially home-specific, problems were quite common. Among children whom parents rated as having at least borderline-clinical problems, teachers reported clear or very clear behaviors at school at the following rates: aggression (22%), rule breaking (12.5%), inattention (55%), and hyperactivity/impulsivity (33%). Compared with the school-specific group, the home-specific group contained a significantly higher percentage of girls with regard to inattention or hyperactivity and a significantly lower percentage of girls with regards to rule breaking. Logistic regression analyses revealed that home- versus school-specific problems were related to sex, child effortful control, and parental stress., Conclusion: Externalizing problems are frequently encountered only in one setting between home and school and are related to sex, child effortful control, and parental stress.

The first aim of this study was to identify developmental trajectories of Attention Problems in twins followed from age 6 to 12 years. Second, we investigated whether singletons follow similar trajectories. Maternal longitudinal ratings on the Attention Problems (AP) subscale of the Child Behavior Checklist were obtained for a sample of 12,486 twins from the Netherlands Twin Register and for a general population sample of 1,346 singletons. Trajectories were analyzed by growth mixture modeling in twins, and compared with singletons. Teacher ratings on the AP subscale of the Teachers' Report Form were available for 7,179 twins and 1,211 singletons, and were used for cross-sectional mean comparisons at each age. All analyses were conducted for boys and girls separately. We identified three linear trajectories in both boys and girls, i.e., stable low (62-71%), low-increasing (15-18%), and high-decreasing (14-21%). Singletons followed three identical trajectories, with similar class proportions. Teacher ratings yielded no differences in mean levels of Attention Problems between twins and singletons. The development of Attention Problems from age 6 to 12 years can be characterized by stable low, low-increasing, and high-decreasing developmental trajectories. Twins and singletons are comparable with respect to the development of Attention Problems in childhood.

Background: The aim was to identify risk indicators from preadolescence (age period 10-12) that significantly predict unfavorable deviations from normal anxiety development throughout adolescence (age period 10-17 years)., Methods: Anxiety symptoms were assessed in a community sample of 2,220 boys and girls at three time-points across a 5-year interval. Risk indicators were measured at baseline and include indicators from the child, family, and peer domain. Associations with anxiety were measured with multilevel growth curve analyses., Results: A stable difference in anxiety over adolescence was found between high and low levels of a range of child factors (frustration, effortful control), family factors (emotional warmth received from parents, lifetime parental internalizing problems), and peer factor (victims of bullying) (P <.001). In contrast, the difference in anxiety between high and low levels of factors, such as self-competence, unfavorable parenting styles, and bully victims, decreased over adolescence (P <.001). For other family factors, associations were weaker (.05

In many societies the prevalence of behavioural problems in school-aged children varies by national origin. We examined the association between national origin and behavioural problems in 1½-year-old children. Data on maternal national origin and the Child Behavior Checklist for toddlers (n = 4943) from a population-based cohort in the Netherlands were used. Children from various non-Dutch backgrounds all had a significantly higher mean behavioural problem score. After adjustment for family risk factors, like family income and maternal psychopathology, the differences attenuated, but remained statistically significant. Non-Dutch mothers with immigration risk factors, such as older age at immigration or no good Dutch language skills, reported significantly more behavioural problems in their offspring. In conclusion, the present study indicated more behavioural problems in immigrant toddlers from various backgrounds. Researchers and policymakers aiming to tackle disparities in behavioural problems should take into account that risks associated with national origin are intertwined with unfavourable family and immigration characteristics.

For prevention of anxiety in children and adolescents, it is important to know whether family stress is a predictor of anxiety. We studied this in 1,875 adolescents from the Tracking Adolescents' Individual Lives Survey (TRAILS) who were followed up for 2 years, from age 10-12 to 12-14 years. Adolescents reported anxiety and depression symptoms at both assessments, and parents reported family stress (family dysfunction and parenting stress) at the first assessment. Family dysfunction was not associated with future anxiety, whereas high parenting stress was. Furthermore, family dysfunction was more strongly associated with anxiety than with depression, whereas parenting stress was more strongly associated with depression. Level of parental psychopathology explained part of the association of family stress with anxiety. The associations were modest and the understanding of the origins of adolescents' anxiety will require identifying other factors than family stress that account for more of the variance.

Background: It is well known that functional somatic symptoms (FSS) are associated with anxiety and depression. However, evidence is lacking about how they are related to FSS. The aim of this study was to clarify these relationships and examine whether anxiety and depression are distinctly related to FSS. We hypothesized that anxiety contributes to the development of FSS and that depression is a consequence of FSS., Methods: FSS, anxiety, and depression were measured in adolescents (N = 2230, 51% women) by subscales of the Youth Self-Report during three assessment waves (adolescents successively aged: 10-12, 12-14, and 14-17) and by corresponding subscales of the Child Behavior Checklist. Using structural equation models, we combined trait and state models of FSS with those of anxiety and depression, respectively. We identified which relationships (contemporaneous and two-year lagged) significantly connected the states of FSS with the states of anxiety and depression., Results: Trait variables were all highly interrelated (r = .54-.63). Contrary to our hypothesis, both state anxiety (beta = .35) and state depression (beta = .45) had a strong contemporaneous effect on state FSS. In turn, state FSS had a weak two-year lagged effect on state anxiety (beta = .11) and an even weaker effect on state depression (beta = .06)., Conclusions: While the effect of anxiety and depression on FSS is strong and immediate, FSS exert a weaker and delayed influence on anxiety and depression. Further research should be done to detect the exact ways in which anxiety and depression lead to FSS, and FSS lead to anxiety and depression.

Research on twin-singleton differences in externalizing and internalizing problems in childhood is largely cross-sectional and yields contrasting results. The goal of this study was to compare developmental trajectories of externalizing and internalizing problems in 6- to 12-year-old twins and singletons. Child Behavior Checklist (CBCL) maternal reports of externalizing and internalizing problems were obtained for a sample of 9651 twins from the Netherlands Twin Register and for a representative general population sample of 1351 singletons. Latent growth modeling was applied to estimate growth curves for twins and singletons. Twin-singleton differences in the intercepts and slopes of the growth curves were examined. The developmental trajectories of externalizing problems showed a linear decrease over time, and were not significantly different for twins and singletons. Internalizing problems seem to develop similarly for twins and singletons up to age 9. After this age twins' internalizing symptoms start to decrease in comparison to those of singletons, resulting in less internalizing problems than singletons by the age of 12 years. Our findings confirm the generalizability of twin studies to singleton populations with regard to externalizing problems in middle and late childhood. The generalizability of studies on internalizing problems in early adolescence in twin samples should be addressed with care. Twinship may be a protective factor in the development of internalizing problems during early adolescence.

Background: Little is known about the development of anxiety symptoms from late childhood to late adolescence. The present study determined developmental trajectories of symptoms of separation anxiety disorder (SAD), social phobia (SoPh), generalized anxiety disorder (GAD), panic disorder (PD), and obsessive-compulsive disorder (OCD) in a large prospective community cohort., Methods: Anxiety symptoms were assessed in a community sample of 2220 boys and girls at three time-points across a 5-year interval. The Revised Child Anxiety and Depression Scale (RCADS) was used to assess anxiety symptoms, and multilevel growth-curve analyses were performed., Results: All subtypes of anxiety first showed a decrease in symptoms (beta for age ranged from -.05 to -.13, p < .0001), followed by a leveling off of the decrease, and a subsequent slight increase in symptoms (beta for age-squared ranged from .006 to .01, p < .0001) from middle adolescence (GAD, SoPh, SAD) or late adolescence (PD and OCD) onwards. This increase in anxiety symptoms could not be explained by a co-occurring increase in depression symptoms. Girls had more anxiety symptoms than boys, and this difference remained stable during adolescence (p < .0001). Gender differences were strongly attenuated by adjustment for symptoms of depression., Conclusions: The current study shows that, in the general population, anxiety symptoms first decrease during early adolescence, and subsequently increase from middle to late adolescence. These findings extend our knowledge on the developmental course of anxiety symptoms during adolescence. This is the first study to separate the development of anxiety symptoms from that of symptoms of depression.

The recommended dietary allowance (RDA) differs between men and women for some vitamins, but not for folate. The RDA for folate is derived mainly from metabolic studies in women. We assessed if men differ from women in their response of erythrocyte folate to folic acid supplementation. We used data from 2 randomized placebo-controlled trials with folic acid: a 3-y trial in which subjects ingested 800 mug/d of folic acid (294 men and 112 women) and a 12-wk trial in which 187 men and 129 women ingested 0, 50, 100, 200, 400, 600, or 800 microg/d of folic acid in a parallel design (n = 38-42 per treatment group). In the 3-y trial, the erythrocyte folate concentration increased 10% (143 nmol/L, [95%CI 46, 241]) less in men than in women. In the 12-wk trial, regression analysis showed that the response of erythrocyte folate upon folic acid intake for men was 47 nmol/L lower than for women (P for beta(gender) = 0.022); for an intake of 800 microg/d folic acid, this resulted in a 5% lower response in men than in women. Differences in lean body size explained 56% of the difference in response of erythrocyte folate between men and women in the 3-y trial and 70% in the 12-wk trial. Men need more folic acid than women to achieve the same erythrocyte folate concentration, mainly because men have a larger lean body mass. This could be an indication that the RDA for folate should be higher for men than for women, or that the RDA should be expressed per kilogram of lean body mass.

Unlabelled: STUDY BACKGROUND AND AIMS: Ethnic disparities in mental health in adolescence may play a role in the development of ethnic disparities in educational attainment. The aim of this study was to assess the contribution of ethnic disparities in mental health problems in adolescence to ethnic disparities in educational attainment in adulthood., Methods: We followed two community samples of respectively 486 Dutch native and 168 Turkish migrant adolescents (11-15 years old) into adulthood (21-25 years old). Mental health was measured in adolescence, and educational attainment was assessed in adulthood. The contribution of mental health disparities to educational disparities was estimated by the degree of attenuation of the odds ratio (OR) for low education after adjustment for mental health problems., Results: Adult Turkish men more often had attained lower education than Dutch men (OR 1.81 (1.01-3.25)). Additional adjustment for mental health problems during adolescence did not change the OR. In Turkish women, however, the OR was 1.94 (1.04-3.62), and adjustment for mental health problems lowered it by 96% to 1.04 (0.51-2.14). The contribution was mostly due to ethnic disparities in internalizing problems., Conclusion: In women, but not in men, ethnic disparities in mental health, especially internalizing problems, were a strong predictor for the development of ethnic disparities in educational attainment. Prevention or treatment of internalizing problems among Turkish girls will probably contribute to the prevention of educational disparities.

Background: Little is known about changes in ethnic disparities in mental health during the development of adolescents into young adults. The aim of this study was to study the development of disparities in internalizing and externalizing problems between Dutch natives and Turkish migrant children from adolescence into adulthood., Methods: Turkish migrants (n = 217) and Dutch natives (n = 723) completed two comparable questionnaires about internalizing and externalizing problems: the Youth Self-Report at age 11-18 and the (Young) Adult Self-Report ten years later, at age 21-28. We used mixed linear regression models to model development of mental health problems and to test changes in disparities in mental health between Turkish migrants and Dutch natives., Results: Both in adolescence and in adulthood migrants reported more internalizing and externalizing problems than natives, most pronounced for internalizing problems. Disparities decreased from adolescence into adulthood for both internalizing problems (-52%, p < .0001) and externalizing problems (-67%, p = .01), independently of gender, age, country of birth of Turkish adolescents, and parental socio-economic position. The favorable changes in the disparities over time were due to more favorable development among Turkish migrants than among natives., Conclusions: In this prospective study, ethnic disparities in internalizing and externalizing problems decreased as adolescents entered adulthood. Different explanations are discussed.

Background: It is important for prevention of social class disparities to know how ethnic disparities in social class arise among migrant children. We contribute to this understanding by examining the role of problem behaviour in adolescence., Methods: Prospective observational study with 753 Dutch native and 217 Turkish migrant adolescents (11-18 year) followed for 10 years. Internalising and externalising problems were assessed in adolescence and employment status and occupational level were assessed in adulthood. The difference in odds ratios (OR) before and after adjustment for internalising and externalising problems was an indication of the predictive value of disparities in internalising and externalising problems for the development of social class disparities., Results: A total of 135 (62%) of the Turkish and 602 (80%) of the Dutch adults were employed. Internalising and externalising problems were not associated with employment status. Of the employed, 65 (48%) Turkish and 179 (30%) Dutch adults worked in low-level occupations (p < 0.0001). Internalising and externalising problems were associated with both ethnicity and occupation. The OR for low-level occupation for Turkish adults was 1.78 (1.19-2.65), indicating ethnic disparities. Adjustment for internalising problems lowered the OR with 36% to 1.50 (0.97-2.31), and adjustment for externalising problems lowered it with 8% to 1.72 (1.15-2.57). Findings were similar for men and women and did not vary by age., Conclusions: Ethnic disparities in occupational level in adulthood could partly be attributed to disparities in mental health between Turkish migrants and Dutch natives in adolescence. Prevention of ethnic disparities in mental health at young age may therefore also contribute to the prevention of occupational differences in adulthood.

Background: As little is known about the determinants of smoking in large ethnic minorities in the Netherlands and other Western European countries, we studied the determinants of smoking young adult offspring of Turkish migrants to the Netherlands., Methods: Cross-sectional survey of 439 Turkish adults (18-28 y) in 2003. Smokers were compared with never smokers for five groups of determinants: demographic and socioeconomic factors, behavioral and emotional problems, psychosocial factors, and cultural factors. Associations were measured by prevalence rate ratios., Results: Prevalences for men were 51% for daily smoking, 12% for former smoking, and 38% for never smoking. For women they were 44%, 11%, and 47%, respectively. Without adjustment for other determinants, higher prevalence was associated with: emotional problems, boredom, life events, and being male; and, specifically among women, with low self-esteem and having children. The strongest determinants of daily smoking In multivariate models were alcohol use and demographic and socio-economic factors. Of the cultural factors only strong Muslim identification was associated with lower smoking prevalence., Conclusion: The high prevalence of smoking warrants action. Many of the well-known determinants of smoking in Western countries were also important among young adults from ethnic minorities. Women with children and people of a low educational level deserve special attention.

Objective: To compare the prevalence of internalising and externalising behaviour of Dutch and Turkish migrant young adults in the Netherlands. We will also assess associations with socio-economic position., Method: Dutch natives (1,236) and Turkish migrants (438), age 18-28, completed the Young Adult Self-Report. Scores above the 90th percentile of the distribution of the Dutch sample were defined as deviant., Results: Turkish migrants more often reported deviant scores than natives for internalising problems, especially for the Anxious/Depressed syndrome. For externalising problems, Turkish migrants less often had deviant scores for Intrusive Behaviour, whereas Turkish women more often had deviant scores for Aggressive and Delinquent Behaviour. Similar results were found for comparison between mean scores. After adjustment for socio-economic position, the disparities in men remained, whereas disparities in women largely disappeared., Conclusion: Compared with Dutch young adults, Turkish migrant young adults reported more problems. Ethnic disparities were strongly associated with socio-economic disparities among women, but not among men.

Study Objectives: To assess the direct and indirect contributions of material, behavioural, and psychosocial factors to the explanation of educational inequalities in mortality simultaneously., Design: Prospective observational study (1991-1998)., Setting: General population from south east Netherlands., Participants: 3979 men and women aged 15-74 years without severe chronic disease at baseline (1991)., Main Results: Material factors (type of health insurance, financial problems, and housing tenure), psychosocial factors (life events and external locus of control), and behavioural factors (smoking habits and physical activity) together reduced the relative risk of mortality of the lowest educated group from 2.57 (95%CI 1.43 to 4.64) to 1.01 (95%CI 0.50 to 2.03). Of these three groups of factors, material factors contributed most to the educational inequalities. Part of the contribution of material factors was via psychosocial factors and part via behavioural factors. Psychosocial factors contributed to educational inequalities, partly via behavioural factors. Behavioural and psychosocial factors contributed only marginally to the explanation independent of material factors., Conclusion: Educational inequalities in mortality were explained by material, psychosocial, and behavioural factors. Material factors contributed most to the explanation, partly via psychosocial and behavioural factors. Improving the material situation of lower educated people may substantially reduce educational inequalities in mortality, partly via the psychosocial and behavioural consequences of improved material circumstances.

Background: To investigate whether the cooccurrence of two lifestyle risk factors (smoking, excessive alcohol consumption, physical inactivity in leisure time) has an additional contribution to the explanation of education inequalities in mortality, over and above the contribution of single risk factors., Methods: Prospective cohort study, 1991-1998, in the South East of the Netherlands. Participants were 16,980 men and women aged 15-74 years at baseline., Results: Education differences in the cooccurrence of risk factors were of a similar magnitude as education inequalities seen for single risk factors. A significant (P = 0.04) interaction effect on mortality was found between smoking and physical inactivity. Adjustment for both smoking and inactivity reduced the mortality hazard ratio of the lowest level of education by 30% (from 1.66 to 1.46). Further adjustment for the interaction between the two risk factors did not change the hazard ratio significantly., Conclusion: The cooccurrence of lifestyle risk factors did not provide any additional contribution to the explanation of education inequalities in mortality, over and above that of single risk factors. However, because risk factors tend to cooccur and have a higher prevalence among lower-educated people, it is still useful to focus interventions on more than one risk factor.

Background: Elevated homocysteine concentrations, a likely risk factor for cardiovascular disease, can be lowered effectively with folic acid. The minimum dose of folic acid required for maximal reduction of homocysteine concentrations is not yet known reliably., Objective: We aimed to determine the lowest folic acid dose that decreases plasma homocysteine concentrations adequately in healthy older adults., Design: A dose-response trial with a randomized, double-blind, parallel-group, placebo-controlled design was carried out among 316 Dutch men and women aged 50-75 y. Subjects received daily for 12 wk either a placebo or 1 of the 6 following folic acid doses: 50, 100, 200, 400, 600, or 800 micro g. The relative changes in plasma homocysteine concentration in response to increasing doses of folic acid were used to calculate the dose-response curve. An adequate dose of folic acid was defined as the dose that induced >or= 90% of the maximal reduction in homocysteine concentration., Results: The relative decrease in plasma homocysteine concentration was associated exponentially with increasing doses of folic acid. From the dose-response curve, the adequate daily dose of folic acid was estimated to be 392 micro g, which decreased plasma homocysteine concentrations 22%., Conclusion: In older adults, daily supplementation with folic acid effectively lowers plasma homocysteine concentrations, and a daily dose of approximately 400 micro g is the minimum dose required for adequate homocysteine reduction.

Hormone replacement therapy (HRT) may reduce atherosclerosis among postmenopausal women, partly by reducing vascular endothelium damage. We have tested this hypothesis by evaluating the association of HRT with firstly, carotid intima media thickness (IMT) and plaques, and secondly, with endothelial cell damage, indicated by soluble thrombomodulin (sTM). Then, we tested the association between the two markers of atherosclerosis and the levels of sTM. Among 747 postmenopausal women included into the EVA study, we compared 154 HRT users (including 80% transdermal treatment) with 593 never users. Carotid IMT and plaques were measured with B-mode ultrasonography and sTM with ELISA. At least one plaque was detected among 13.6% of HRT users and 27.3% of never users. After adjustment for confounding factors, the odds ratio for the presence of plaque was 0.45 (95% confidence interval, 0.25-0.78, P=0.005) in HRT users in comparison with nonusers. HRT users had a slightly lower crude mean IMT than nonusers, but the difference was not significant. sTM was positively associated with mean IMT (P for trend=0.001) but not with plaques. Finally, estrogen users had a lower sTM level than nonusers (difference 0.14 ng/ml, P=0.03). As HRT was associated with sTM and plaques, but not with IMT, while sTM was only associated with IMT, our hypothesis was not confirmed. This suggests that the possible beneficial effects of HRT on atherosclerosis may not go through the endothelial cell damage assessed by plasma thrombomodulin.