Albertine J. Oldehinkel

Cohort Profile: The Dutch ‘TRacking Adolescents’ Individual Lives’ Survey’; TRAILS

Mental disorders account for one-fifth of the total burden of disease in the Western world, 1 and, as such, should require due attention from the international epidemiological research community. Good quality research on the aetiology and course of psychopathology in the population is impossible without reliable and valid data from long-term longitudinal cohort studies. Research on psychopathology in adolescence is important both from a scientific point of view and from the point of view of prevention and public health policy. Adolescence is characterized by major biological, psychological and social challenges and opportunities, where interaction between the individual and environment is intense, and developmental pathways are set in motion or become established. 2–4 Furthermore, adolescent psychopathology can have important consequences for education, relationships and socioeconomic achievement in later life. 5–7 These characteristics of adolescence do not only set high demands for cohort studies aiming to capture the most salient aspects of developmental pathways, they also ensure a great gain in empirical knowledge and an invaluable source of information for public health policy from such studies. In order to fully benefit from this potential, a multidisciplinary approach is essential.

Adolescents' cortisol responses to awakening and social stress; Effects of gender, menstrual phase and oral contraceptives. The TRAILS study

Studies on the influence of sex hormones on cortisol responses to awakening and stress have mainly been conducted in adults, while reports on adolescents are scarce. We studied the effects of gender, menstrual cycle phase and oral contraceptive (OC) use on cortisol responses in a large sample of adolescents. Data come from TRAILS (TRacking Adolescents Individual Lives Survey), a prospective population study of Dutch adolescents. This study uses data of 644 adolescents (age 15-17 years, 54.7% boys) who participated in a laboratory session including a performance-related social stress task (public speaking and mental arithmetic). Free cortisol levels were assessed by multiple saliva samples, both after awakening and during the laboratory session. No significant effects of gender and menstrual phase on cortisol responses to awakening were found, while girls using OC displayed a slightly blunted response (F(1, 244)=5.30, p=.02). Cortisol responses to social stress were different for boys and free-cycling girls (F(3, 494)=9.73, p<.001), and OC users and free-cycling girls (F(3, 279)=15.12, p<.001). Unexpectedly, OC users showed no response at all but displayed linearly decreasing levels F(1, 279)=19.03, p<.001) of cortisol during the social stress test. We found no effect of menstrual cycle phase on cortisol responses to social stress (F(3, 157)=0.58, p=.55). The absence of a gender difference in the adolescents cortisol awakening response found in this study is consistent with previous reports. Our results further suggest that adolescent OC users display slightly blunted cortisol responses after awakening, and that gender differences in cortisol responses to social stress during adolescence are comparable to those described for adult populations, that is, stronger responses in men than in women. Whereas previous work in adults suggested blunted stress responses in OC users compared to men and free-cycling women, adolescent OC users showed no cortisol response. Effects of type of OC could not be studied because of low numbers of OC that were only progestin based.

Internalizing and externalizing problems in adolescence: general and dimension-specific effects of familial loadings and preadolescent temperament traits.

BACKGROUNDnWe investigated the links between familial loading, preadolescent temperament, and internalizing and externalizing problems in adolescence, hereby distinguishing effects on maladjustment in general versus dimension-specific effects on either internalizing or externalizing problems.nnnMETHODnIn a population-based sample of 2230 preadolescents (10-11 years) familial loading (parental lifetime psychopathology) and offspring temperament were assessed at baseline by parent report, and offspring psychopathology at 2.5-years follow-up by self-report, teacher report and parent report. We used purified measures of temperament and psychopathology and partialled out shared variance between internalizing and externalizing problems.nnnRESULTSnFamilial loading of internalizing psychopathology predicted offspring internalizing but not externalizing problems, whereas familial loading of externalizing psychopathology predicted offspring externalizing but not internalizing problems. Both familial loadings were associated with Frustration, low Effortful Control, and Fear. Frustration acted as a general risk factor predicting severity of maladjustment; low Effortful Control and Fear acted as dimension-specific risk factors that predicted a particular type of psychopathology; whereas Shyness, High-Intensity Pleasure, and Affiliation acted as direction markers that steered the conditional probability of internalizing versus externalizing problems, in the event of maladjustment. Temperament traits mediated one-third of the association between familial loading and psychopathology. Findings were robust across different composite measures of psychopathology, and applied to girls as well as boys.nnnCONCLUSIONSnWith regard to familial loading and temperament, it is important to distinguish general risk factors (Frustration) from dimension-specific risk factors (familial loadings, Effortful Control, Fear), and direction markers that act as pathoplastic factors (Shyness, High-Intensity Pleasure, Affiliation) from both types of risk factors. About one-third of familial loading effects on psychopathology in early adolescence are mediated by temperament.

Higher cortisol awakening response in young adolescents with persistent anxiety problems

Objective:u2002 The aims of the present study were to test the association between current anxiety problems and basal cortisol levels in a large population sample of young preadolescents, and to test if HPA‐axis activity differs between individuals with no, only current, or persistent anxiety problems.

Victimisation and suicide ideation in the TRAILS study: specific vulnerabilities of victims

BACKGROUNDnScientific studies have provided some support for a link between being a victim of bullying and suicide ideation. We examine whether (1) parental psychopathology and (2) feelings of rejection (at home and at school) exacerbate vulnerability to suicide ideation in victims of bullying (pure victims and bully-victims).nnnMETHODnData were from a population-based cohort study of Dutch children (n = 1526, mean age = 12.29 years). Using peer nominations, three groups were established: (1) victim only; (2) bully-victims (children who are victims and who also bully others); (3) uninvolved. Self-report data on suicide ideation were obtained using two items from the Youth Self-Report (Achenbach, 1991). Parental internalizing and externalizing disorders were assessed, as were self-reported feelings of rejection at home and social well-being among classmates.nnnRESULTSnThe association between victimization and suicide ideation was moderated by parental internalizing disorders (but not externalizing disorders) and feelings of rejection at home. Victims (but not bully-victims) with parents with internalizing disorders reported elevated levels of suicide ideation compared to children uninvolved in bullying. Victims feeling more rejected at home also reported more suicide ideation. There were no overall sex differences in suicide ideation. Surprisingly, bully-victims did not report higher levels of suicide ideation compared to children uninvolved in bullying.nnnCONCLUSIONSnParental internalizing disorders and feelings of rejection at home confer a specific vulnerability for suicide ideation among victims of bullying.

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.

Anxiety and depression are risk factors rather than consequences of functional somatic symptoms in a general population of adolescents: The TRAILS study

BACKGROUNDnIt 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.nnnMETHODSnFSS, 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.nnnRESULTSnTrait 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).nnnCONCLUSIONSnWhile 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.

Being Admired or Being Liked: Classroom Social Status and Depressive Problems in Early Adolescent Girls and Boys

This study investigates associations between depressive problems and classroom social status in a large population cohort of Dutch early adolescents (Nxa0=xa01046, age 13.52xa0±xa00.51, 52.4% girls). Depressive problems were assessed by parent and self-reports and classroom status by peer nominations. We assessed peer status with respect to both achievement-related (being a good learner, being good at sports, being good-looking) and affection-related (being liked, being disliked, being best friend) areas. In boys, depressive problems were most strongly associated with not being good at sports, while in girls the association was strongest for not being liked. The risk of a low status in one area could largely be compensated by a high status in another area.

Meta-analysis of genome-wide association studies of anxiety disorders

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 18u2009000 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.

Parental Overprotection Predicts the Development of Functional Somatic Symptoms in Young Adolescents

OBJECTIVEnTo examine whether parental overprotection contributes to the development of functional somatic symptoms (FSS) in young adolescents. In addition, we aimed to study whether this potential effect of parental overprotection is mediated by parenting distress and/or moderated by the adolescents sex.nnnSTUDY DESIGNnFSS were measured in 2230 adolescents (ages 10 to 12 years from the Tracking Adolescents Individual Lives Survey) by the Somatic Complaints subscale of the Youth Self Report at baseline and at follow-up 2 1/2 years later. Parental overprotection as perceived by the child was assessed by means of the EMBU-C (Swedish acronym for my memories of upbringing-child version). Parents completed the Parenting Stress Index. Linear regression analyses were performed adjusted for FSS at baseline and sex.nnnRESULTSnParental overprotection was a predictor of the development of FSS in young adolescents (beta = 0.055, P < .01). Stratified analyses revealed that maternal overprotection was a predictor of the development of FSS in girls (beta = 0.085, P < .02), whereas paternal overprotection was a predictor of the development of FSS in boys (beta = 0.072, P < .01). A small (5.7%) but significant mediating effect of maternal parenting stress in the relationship between parental overprotection and FSS was found.nnnCONCLUSIONSnParental overprotection may play a role in the development of FSS in young adolescents.