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Background: Person and environment-related childhood adverse events have been demonstrated to increase the risk of impaired mental health in later life differently for boys and girls. Altered hypothalamic pituitary adrenal (HPA)-axis functioning has been suggested as a key mechanism underlying this association. Cortisol and dehydroepiandrosterone (DHEA) are both output hormones of the HPA-axis. DHEA may have a protective function against long-term exposure to increased levels of cortisol, but has been little investigated in relation to childhood adversity. Objective: We aimed to test the associations between person-, and environment-related childhood adversity and levels of cortisol, DHEA and cortisol/DHEA ratio in adolescent boys and girls. Methods: A total of 215 Dutch adolescents participated in the study and filled out the 27-item Adverse Life Events Questionnaire for the assessment of childhood adversity, which was split up in separate scores for person-related and environment-related events. Cortisol and DHEA concentrations and cortisol/DHEA ratio were determined in proximal 3 cm long hair segments. Additionally, saliva samples were collected immediately and 30 minutes after waking up, at noon and at 8 pm. Multiple linear regression analyses were used to test associations between childhood adversity and cortisol and DHEA concentrations, for boys and girls separately, with age, BMI and pubertal development as covariates. Results: Data were available for 74 boys and 116 girls with a mean age of 15.7 years (SD = 2.0). Higher levels of person-related childhood adversity were associated with higher hair DHEA levels in girls and with higher hair cortisol levels in boys. A trend towards a significant association was observed between higher levels of environment-related childhood adversity and higher DHEA levels in boys. Neither person- nor environment related childhood adversity was associated with cortisol/DHEA ratio. A trend was observed for environment-related childhood adversity and lower daily cortisol output in boys. Conclusion: We found differential associations between childhood adversity and cortisol and DHEA levels in girls and boys, for respectively person-related and environment-related childhood adversity. Our findings suggest that different types of childhood adversity are not only linked to levels of cortisol, but also to DHEA concentrations, in a sex-specific manner, with possible future implications for mental health. [ABSTRACT FROM AUTHOR]

Dysregulated physiological stress reactivity has been suggested to impact the development of children and adolescents with important health consequences throughout the life span. Both environmental adversity and genetic predispositions can lead to physiological imbalances in stress systems, which in turn lead to developmental differences. We investigated genetic and environmental contributions to autonomic nervous system reactivity to a psychosocial stressor. Furthermore, we tested whether these effects were consistent with the differential susceptibility framework. Composite measures of adverse life events combined with socioeconomic status were constructed. Effects of these adversity scores in interaction with a polygenic score summarizing six genetic variants, which were hypothesized to work as susceptibility factors, were tested on autonomic nervous system measures as indexed by heart rate and heart rate variability. Results showed that carriers of more genetic variants and exposed to high adversity manifested enhanced heart rate variability reactivity to a psychosocial stressor compared to carriers of fewer genetic variants. Conversely, the stress procedure elicited a more moderate response in these individuals compared to carriers of fewer variants when adversity was low. [ABSTRACT FROM AUTHOR]

Aims To determine (1) the prospective associations of conduct problems during early adolescence with tobacco, alcohol and cannabis use in young adulthood and (2) to what extent these associations are due to overlapping genetic versus environmental influences. Design A prospective twin study using biometric twin modelling. Setting Finland. Participants A total of 1847 Finnish twins (943 males and 904 females) were interviewed in early adolescence, 73% of whom ( n = 1353, 640 males and 713 females) were retained in young adulthood. Measurements Symptom counts of conduct disorder (CD) criteria were obtained from a semi-structured clinical interview in early adolescence [age 14-15 years, mean = 14.2, standard deviation (SD) = 0.15]. Frequency of alcohol, tobacco and cannabis use was obtained from a semi-structured clinical interview in young adulthood (age 19.9-26.6 years, mean = 22.4, SD = 0.7). Findings We found modest to moderate phenotypical correlations ( r = 0.16-0.35) between early adolescent CD symptoms and substance use in young adulthood. In males, the phenotypical correlations of CD symptoms with all three substance use variables are explained largely by overlapping genetic influences. In females, overlapping shared environmental influences predominantly explain the phenotypical correlation between CD symptoms and tobacco and cannabis use. Conclusions Conduct disorder symptoms in early adolescence appear to moderately predict substance use in early adulthood. In males, genetic influences seem to be most important in explaining the relationship between conduct disorder symptoms and substance use whereas in females, shared environmental influences seem to be most important. [ABSTRACT FROM AUTHOR]

Aims To examine whether early onset of tobacco or alcohol use, and continued use of tobacco or alcohol in early adolescence, are related to a higher likelihood of developing a cannabis use disorder during adolescence. Design and setting Data were used from four consecutive assessment waves of the TRacking Adolescents' Individual Lives Survey ( TRAILS), a general Dutch population study. TRAILS is an ongoing longitudinal study that will follow the same group of adolescents from the ages of 10 to 24 years. Participants The sample consisted of 1108 (58% female) adolescents (mean ages at the four assessment waves are 11.09, 13.56, 16.27 and 19.05 years, respectively) Measurements Cannabis use disorders were assessed using the Composite International Diagnostic Interview 3.0 ( CIDI). Adolescent tobacco and alcohol use were assessed using self-report questionnaires. Findings Early-onset tobacco use [odds ratio ( OR) = 1.82, confidence interval ( CI) = 1.05-3.14, P < 0.05], but not early-onset alcohol use ( OR = 1.33, CI = 0.84-2.12, P > 0.05), was associated with a higher likelihood of developing a cannabis use disorder. Similarly, adolescents who reported continued use of tobacco ( OR = 2.47, CI = 1.02-5.98, P < 0.05), but not continued use of alcohol ( OR = 1.71, CI = 0.87-3.38, P > 0.05), were more likely to develop a cannabis use disorder. Conclusions Early-onset and continued tobacco use appear to predict the development of a cannabis use disorder in adolescence, whereas early onset and continued alcohol use do not. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims Hypothalamic-pituitary-adrenal (HPA) axis activity may prove a viable biomarker for identifying those susceptible to alcohol use disorders. The purpose of this study was to examine the relation of the age at which adolescents begin drinking with diurnal and stress cortisol. Design Adolescents' diurnal cortisol levels on a normal day and cortisol levels during a stress procedure were examined in relation to the age of onset of alcohol use. Setting and participants All adolescents (aged 14-20 years) were part of a general population study in the Netherlands ( n = 2286). Measurements Ten assessments of salivary cortisol taken on a normal day (diurnal cortisol), as well as during a social stress procedure (stress cortisol) were used as indicators of HPA axis activity. Findings The age at which the first alcoholic drink was consumed varied as a function of cortisol levels at the onset of as well as during the stress procedure. Those who began drinking at an earlier age showed lower cortisol levels at the onset of the stressful tasks ( r2 = 0.14, P < 0.001) and during the stressful tasks ( r2 = 0.10, P < 0.05), although not after the tasks (cortisol recovery). Effects were strongest for anticipatory pre-task cortisol levels. Differences in diurnal cortisol levels did not explain variance in the age at which adolescents had begun drinking. Conclusions Lessened activity of the hypothalamic-pituitary-adrenal axis at the onset of and during a stress procedure is present in adolescents who begin drinking at an early age. [ABSTRACT FROM AUTHOR]

Background: Adolescence is a critical developmental period regarding exposure to substances. Therefore, it is important to be able to identify those adolescents who are most vulnerable to substance abuse in the (near) future. The JOiN study was specifically designed to examine two endophenotypes of adolescent substance use in a normal risk (NR) and high risk (HR) sample of adolescents: (1) behavioural disinhibition, and (2) individual differences in stress sensitivity. Methods: The NR adolescents were part of a longitudinal general population study at the Erasmus Medical Center in Rotterdam, the Netherlands of children and adolescents initially aged 6 to 18 years old. Three assessment waves have been nearly completed, and data are available of N = 711 participants for stress sensitivity measures, and of a subsample of N = 110 for electroencephalography (EEG) measures. Added to this study, HR adolescents who had at least one parent with a substance use disorder and who were treated by an outpatient clinic of a primary addiction care provider were approached via their parent(s). In total, N = 83 adolescents formed this HR sample. NR and HR adolescents participated in standardized stress procedure and EEG procedures in our laboratory. Questionnaires were filled out on background variables, behavioural and emotional problems, and substance use, and a diagnostic interview was conducted with adolescents and parents to assess psychopathology symptoms. DNA was collected through saliva or blood samples. Discussion: The design of the JOiN study is optimal for examining the predictive role of endophenotypes of adolescent substance use. The combination of different methods, i.e. stress physiology, electrophysiology, genetics, and questionnaire data from several informants on a range of behaviours and environmental factors enables the investigation of the multifactorial nature of adolescent substance use. [ABSTRACT FROM AUTHOR]

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Abstract: Purpose: There is substantial research linking tobacco and alcohol use to subsequent cannabis use, yet the specificity of this relationship is still under debate. The aim of this study was to examine which substance use model—the gateway hypothesis, the common liability (CL) model and/or the route of administration model—best explains the relationship between early onset of tobacco and alcohol use and subsequent cannabis use initiation. Methods: We used data from 2,113 (51% female) Dutch adolescents who participated in three consecutive assessment waves (mean age: 11.09, 13.56, and 16.27 years, respectively) of the TRacking Adolescents'' Individual Lives Survey study. (Pre)adolescent cannabis, tobacco and alcohol use was assessed using the Youth Self-Report and a TRacking Adolescents'' Individual Lives Survey developed questionnaire. Results: We found that, during adolescence, early onset of tobacco use does not pose a significantly higher risk of initiating cannabis use than early onset alcohol use. Therefore, we can rule out the route of administration model. Moreover, we found that adolescents who reported early onset comorbid use of both tobacco and alcohol have a higher likelihood to initiate cannabis use than adolescents who have tried either tobacco or alcohol. The gateway hypothesis is not broad enough to explain this finding. Therefore, the CL model best predicts our findings. Conclusion: Future research on adolescent cannabis initiation should focus on testing the robustness of the CL model. Furthermore, identifying adolescents who use both tobacco and alcohol, before the age of 13, may help to curtail the onset of cannabis use. [Copyright &y& Elsevier]

The author comments on a study by Degenhardt and colleagues, on specific effect of adolescent cannabis use on anxiety - tentative explanations. The study helps answer the question if continued cannabis use in adolescence into adulthood is associated with major depression and/or anxiety disorders in adulthood, and looks at the need to understand more pathways towards mental health problems after continued cannabis use, since they can guide us to formulate intervention strategies at early stages.

The current study examined mean level and change in extraversion and neuroticism across adolescence in relation to physiological stress reactivity to social evaluation. Adolescents ( n = 327) from the Dutch general population reported on personality measures at five annual assessments. At age 17 years, adolescents participated in a psychosocial stress procedure characterized by social evaluation during which cortisol, heart rate, pre-ejection period (PEP) and heart rate variability were assessed. Dual latent growth curve models were fitted in which the intercepts (mean level) and slopes (change) of personality across adolescence predicted the intercepts (baseline) and slopes (reactivity) of the physiological stress measures. Most comparisons revealed no relation between personality and stress reactivity. Adolescents with higher mean level scores on extraversion did show lower cortisol reactivity. Adolescents with higher mean level neuroticism scores showed higher PEP reactivity. Our findings lend partial support for a relation between personality and physiological stress reactivity. [ABSTRACT FROM AUTHOR]

Abstract: Background: Few studies have investigated physiological stress (re)activity in relation to substance use, especially in adolescents. Using substances is one way to stimulate physiological arousal, therefore inherent hypo-arousal may be associated with substance use in adolescents. The purpose of this study was to examine the relation of autonomic nervous system (ANS) activity with alcohol and tobacco use in adolescents. Methods: ANS activity and perceived stress during a social stress procedure were examined in relation to substance use. 275 Dutch adolescents from a general population study provided complete data. Heart rate was recorded continuously during a pre-task rest period, a stressful task period and a post-task recovery period. Alcohol and tobacco use were self-reported. Results: Adolescents who consumed a medium and high number of alcoholic drinks per week (more than two) exhibited lower heart rates during the entire stress procedure as compared to those who consumed a low number of alcoholic drinks. Adolescents who smoked every day portrayed blunted heart rate reactivity to stress as compared to adolescents who smoked less frequently or not at all. Perceived stress was not related to alcohol or tobacco use. Conclusions: Overall lower heart rate in adolescents who drank more and blunted heart rate reactivity to stress in those who used tobacco every day may indicate inherent hypo-arousal of the ANS system in those vulnerable to use substances more often. These adolescents may actively seek out substances in order to achieve a more normalized state of arousal. [Copyright &y& Elsevier]

Abstract: Background: While temperamental characteristics have been related to the onset of cannabis use, it is not clear at what point(s) along the trajectory from early onset of tobacco use (EOT) to early onset of cannabis use (EOC) these characteristics exert their impact. This study examined if (1) temperamental characteristics predispose to EOT that on its turn predisposes to EOC, and (2) temperament moderates the importance of EOT on the progression to EOC. Methods: Data from 1848 (83%) participants in the TRacking Adolescents’ Individual Lives Survey (TRAILS), a prospective population study of Dutch adolescents, were analyzed. We used parent-reports on the Early Adolescent Temperament Questionnaire to assess the dimensions of high-intensity pleasure, frustration, effortful control, shyness and fearfulness at age 10–12. EOT and EOC were defined as use at least once before the ages of 12 and 13 years, respectively, assessed by means of self-reports. We performed mediation and moderation analyses in Mplus. Results: High levels of high-intensity pleasure predisposed to entrance in the trajectory from EOT to EOC. Once tobacco use had been initiated at early age, low levels of shyness and high levels of high-intensity pleasure increased the risk of progression to EOC. Conclusions: Besides a common liability for EOT and EOC based on temperament, the risk of transition from tobacco to cannabis use is modified by temperamental characteristics. Differences in interplay with other risk factors may explain the impact of temperament on distinct points along the substance use trajectory. [Copyright &y& Elsevier]