Hypothalamic-pituitary-adrenal axis responsivity during adolescence in relation to psychopathic personality traits later in life.

Psychopathic personality traits have been linked to low physiological arousal, particularly among high risk and forensic samples. A core indicator of physiological arousal is the activity of the hypothalamic-pituitary-adrenal (HPA) axis; however, findings of a link between HPA axis functioning and psychopathic personality traits have been inconsistent. Furthermore, given sex differences in both HPA axis responsivity and psychopathic personality traits, the association may be expected to differ between men and women. The aim of this study was to investigate the association between HPA axis responsivity in mid-adolescence and psychopathic personality traits in early adulthood and determine whether the association was moderated by sex. We examined this link in a general population sample of twins (N = 556). Adolescents participated in a psychosocial stress task during which samples of salivary cortisol were collected (11-15 years) and reported psychopathic personality traits using the Triarchic Psychopathy Measure (19-20 years). Multilevel linear regression models were estimated in which psychopathic personality traits (boldness, meanness and disinhibition), and their interactions with sex, were regressed on HPA axis responsivity. The study was pre-registered on the Open Science Framework (osf.io/gs2a8). Preliminary analyses showed that cortisol levels did not increase significantly during the stressor task but decreased during recovery. Results showed that there was no association between HPA axis responsivity in mid-adolescence and psychopathic personality traits in early adulthood. The associations were not moderated by sex. Findings suggest that HPA axis responsivity in mid-adolescence did not serve as a biological marker for psychopathic personality traits among young adults from the general population.

Classroom Disorder and Internalizing Problems Among Swedish Adolescents: Changes Between 1988 and 2011.

BACKGROUND: Internalizing problems have increased among Swedish adolescents. We examined whether classroom disorder was associated with internalizing problems and whether it explained the trends in internalizing problems. Furthermore, we examined whether school contextual factors were associated with internalizing problems and whether they moderated the association between classroom disorder and internalizing problems. METHODS: We used repeated cross-sectional survey data (1988-2011) among all 15- to 16-year-old students in Värmland, Sweden (N = 9491 boys, N = 9313 girls). School-level factors were the proportions of students with a low/average socioeconomic or an immigration background. RESULTS: Results from mixed effects models showed that classroom disorder was associated with internalizing problems across the years of investigation but did not explain the trends in internalizing problems. This association was moderated by the school-level proportion of students with a low/average socioeconomic background but not the school-level proportion of students with an immigration background. CONCLUSIONS: Students who perceived their classroom to be disorderly more often also reported more internalizing problems. Future studies are necessary to investigate other potential school factors that may explain the trends in internalizing problems.

Urbanicity, biological stress system functioning and mental health in adolescents.

Growing up in an urban area has been associated with an increased chance of mental health problems in adults, but less is known about this association in adolescents. We examined whether current urbanicity was associated with mental health problems directly and indirectly via biological stress system functioning. Participants (n = 323) were adolescents from the Dutch general population. Measures included home and laboratory assessments of autonomic nervous system and hypothalamic-pituitary-adrenal axis functioning, neighborhood-level urbanicity and socioeconomic status, and mother- and adolescent self-reported mental health problems. Structural equation models showed that urbanicity was not associated with mental health problems directly. Urbanicity was associated with acute autonomic nervous system and hypothalamic-pituitary-adrenal axis reactivity such that adolescents who lived in more urban areas showed blunted biological stress reactivity. Furthermore, there was some evidence for an indirect effect of urbanicity on mother-reported behavioral problems via acute autonomic nervous system reactivity. Urbanicity was not associated with overall autonomic nervous system and hypothalamic-pituitary-adrenal axis reactivity or basal hypothalamic-pituitary-adrenal axis functioning. Although we observed some evidence for associations between urbanicity, biological stress reactivity and mental health problems, most of the tested associations were not statistically significant. Measures of long-term biological stress system functioning may be more relevant to the study of broader environmental factors such as urbanicity.

A latent class analysis of changes in adolescent substance use between 1988 and 2011 in Sweden: associations with sex and psychosomatic problems.

AIMS: To characterize changes in patterns of adolescent substance use in Sweden between 1988 and 2011, and to assess whether sex and psychosomatic problems were associated with substance use and whether these associations changed over time. DESIGN: Secondary analysis of repeated cross-sectional survey data. Survey data were collected eight times and analyzed as four cohorts (1988-91, 1995-98, 2002-05 and 2008-11). SETTING AND PARTICIPANTS: The sample included all 15-16-year-olds in Värmland County, Sweden (n = 20 057). MEASUREMENTS: Binary-coded substance use measures included life-time use of alcohol and tobacco, getting drunk and past school year use of inhalants. An eight-item scale was used to assess psychosomatic problems. FINDINGS: A three-class model fitted the data best (i.e. non/low use, mainly alcohol use and polysubstance use). The patterns of substance use were different among cohorts; most notably, adolescents in the last cohort had lower odds of being included in the alcohol and polysubstance use classes rather than the non/low use class than in the earlier cohorts (all Ps < 0.001). Males had higher odds than females of being in the polysubstance use class rather than the non/low use class among the first three cohorts (all Ps < 0.001) but not the last. Sex was not associated with inclusion in the alcohol use class rather than the non/low use class. Adolescents who reported more psychosomatic problems had higher odds of being included in the alcohol and polysubstance use classes rather than the non/low use class (all Ps < 0.001). The associations of sex and psychosomatic problems with class inclusion did not change during the study period. CONCLUSIONS: Between 1988 and 2011, patterns of substance use among adolescents in Sweden shifted away from polysubstance use and alcohol use to non-use or low use. Associations between patterns of substance use and sex and psychosomatic problems remained largely consistent across the study period.

Mental Health Problems Among Adolescents in Sweden from 1995 to 2011: The Role of Immigrant Status and the Proportions of Immigrant Adolescents in Their Surrounding Community.

We compared the mental health of native and immigrant adolescents in Sweden from 1995 to 2011 and examined whether the municipality-level proportion of immigrant adolescents moderated the association between individual-level immigrant status and mental health. The sample (14,189 adolescents aged 15-16) was obtained from a repeated cross-sectional study conducted from 1995 to 2011. Adolescent self-report data (gender, immigrant status, economic situation, and mental health) and municipality-level data (proportion of immigrant adolescents) were used in multilevel linear regression analyses. Immigrant adolescents reported more mental health problems than their native Swedish peers. The long-term trend in mental health problems did not differ between the two groups. The association between individual immigrant status and mental health did not differ according to the municipality-level rate of immigrant adolescents. These findings highlight the need for public health attention to and efforts to address immigrant adolescents' mental health problems in Sweden.

Towards explaining time trends in adolescents' alcohol use: a multilevel analysis of Swedish data from 1988 to 2011.

BACKGROUND: Alcohol use has decreased among Swedish adolescents in the past few decades. We examined peer and parent factors (i.e. time spent with peers, time spent with parents and parental monitoring) that could contribute to explaining this trend by investigating their main effects and interaction effects with investigation years on alcohol use. We furthermore examined whether municipality-level socioeconomic conditions could contribute to explaining the trend. METHODS: We used data from a repeated cross-sectional study that took place eight times between 1988 and 2011. The study targeted all ninth grade students (15-16 years old) in Värmland County, Sweden. Adolescents (N = 22 257) reported their monthly alcohol use, time spent with peers and parents and parental monitoring. Municipality-level socioeconomic conditions were based on parent education levels. RESULTS: Logistic multilevel regression analyses showed that peer and parent factors and municipality-level socioeconomic conditions were associated with alcohol use among adolescents. The interaction effects between peer and parent factors and investigation years were not significant. The decreased trend in time spent with peers was associated with the decreased trend in frequency of alcohol use over time. CONCLUSIONS: The findings of the current study provide an indication that the decreased trend in alcohol use that has been observed in Swedish adolescents over the past few decades may be related to changes in adolescents' social interactions with peers.

Gene × Environment contributions to autonomic stress reactivity in youth.

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.

Stress Reactivity as a Prospective Predictor of Risky Substance Use During Adolescence.

OBJECTIVE: Youth who report risky substance use and who have a familial history of substance use disorders (SUDs) are at increased risk for developing SUDs themselves later in life. Physiological stress reactivity may be a potential biological mechanism underlying this increased risk. In the current study, we examined (a) whether physiological stress reactivity to a psychosocial stressor was prospectively related to risky substance use later in adolescence and (b) whether this relation was moderated by a familial history of SUDs. METHOD: Youth from the general population (n = 220) and the children of a parent/parents with an SUD (CPSUDs; n = 60) participated in a psychosocial stress procedure at Time 1. Cortisol and heart rate reactivity were measured during the procedure. Four years later, on average, risky substance use was self-reported (Time 2). RESULTS: Logistic regression analyses showed that youth who had lower cortisol reactivity at Time 1 were more likely to report risky substance use at Time 2. Heart rate reactivity was not related to risky substance use at Time 2, and the relation between stress reactivity and risky substance use was not more pronounced in CPSUDs compared with youth from the general population. These analyses were controlled for alcohol use at Time 1. CONCLUSIONS: The present findings suggest hyporeactivity of the hypothalamic-pituitary-adrenal axis in youth who are more likely to engage in risky substance use later in adolescence. These individuals may be inherently hypoaroused, which leads them to seek out substances in order to achieve a more normalized level of arousal.

Neuroticism and extraversion in relation to physiological stress reactivity during adolescence.

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.

Blunted Heart Rate Response as a Potential Endophenotype of Substance Use Disorders: Evidence from High-Risk Youth.

BACKGROUND: Children of parents with a substance use disorder (CPSUD) are at increased risk for developing problematic substance use later in life. Endophenotypes may help to clarify the mechanism behind this increased risk. However, substance use and externalizing symptoms may confound the relation between dysregulated physiological stress responding and familial risk for substance use disorders (SUDs). METHODS: We examined whether heart rate (HR) responses differed between CPSUDs and controls. Participants (aged 11-20 years) were CPSUDs (N = 75) and controls (N = 363), semi-matched on the basis of sex, socioeconomic status, and ethnicity. HR was measured continuously during a psychosocial stress procedure. Substance use and externalizing symptoms were self-reported and mother-reported, respectively. RESULTS: A piecewise, mixed-effects model was fit for HR across the stress procedure, with fixed effects for HR reactivity and HR recovery. CPSUDs showed a blunted HR recovery. CPSUDs reported drinking more frequently, were more likely to use tobacco daily, were more likely to report ever use of cannabis and used cannabis more frequently, and exhibited more externalizing symptoms. These variables did not confound the relation between familial risk for SUDs and a blunted HR recovery. CONCLUSION: Our findings suggest dysregulated autonomic nervous system (ANS) responding in CPSUDs and contribute to the accumulating evidence for ANS dysregulation as a potential endophenotype for SUDs.

Reasons for entering treatment reported by initially treatment-resistant patients with substance use disorders.

Many individuals with substance use disorders are resistant to entering formal treatment, despite the negative consequences that plague their own lives and the lives of concerned significant others (CSOs). Community Reinforcement and Family Training (CRAFT) has been developed as an effective strategy for helping family members who are concerned about the alcohol/drug use of a loved one who refuses to seek treatment. The present study explored reasons and feelings that played a part in these resistant individuals' (identified patients [IPs]) decision to begin treatment. Written statements and feelings of 36 initially treatment-refusing IPs, who were engaged into treatment via their CRAFT-trained CSOs, were examined upon entering treatment. Self-report forms assessed three complementary domains about entering treatment: (1) feelings about coming for treatment, (2) important reasons for entering treatment, and (3) reasons for entering treatment narratives. It was shown that the occurrences of self-reported positive emotions and statements that expressed a positive wish for change outweighed negative feelings and statements. Although conceivably these CRAFT-exposed IPs may have provided different responses than other treatment-seeking populations, the current study's strong IP reports of positive feelings, reasons, and narrative statements regarding treatment entry nonetheless address potential concerns that treatment-refusing IPs might only enter treatment if felt coerced by family members and while experiencing salient negative feelings overall.

Blunted feedback processing during risky decision making in adolescents with a parental history of substance use disorders.

Risky decision making, a hallmark phenotype of substance use disorders (SUD), is thought to be associated with deficient feedback processing. Whether these aberrations are present prior to SUD onset or reflect merely a consequence of chronic substance use on the brain remains unclear. The present study investigated whether blunted feedback processing during risky decision making reflects a biological predisposition to SUD. We assessed event-related potentials elicited by positive and negative feedback during performance of a modified version of the Balloon Analogue Risk Task (BART) among high-risk adolescents with a parental history of SUD (HR; n = 61) and normal-risk controls (NR; n = 91). HR males made significantly more risky and faster decisions during the BART than did NR controls. Moreover, HR adolescents showed significantly reduced P300 amplitudes in response to both positive and negative feedback as compared to NR controls. These differences were not secondary to prolonged substance use exposure. Results are discussed in terms of feedback-specific processes. Reduced P300 amplitudes in the BART may reflect poor processing of feedback at the level of overall salience, which may keep people from effectively predicting the probability of future gains and losses. Though conclusions are tentative, blunted feedback processing during risky decision making may represent a promising endophenotypic vulnerability marker for SUD.

Multifactorial determinants of target and novelty-evoked P300 amplitudes in children of addicted parents.

BACKGROUND: Although P300 amplitude reductions constitute a persistent finding in children of addicted parents, relatively little is known about the specificity of this finding. The major aim of this study was to investigate the association between parental rearing, adverse life events, stress-reactivity, substance use and psychopathology on the one hand, and P300 amplitude in response to both target and novel distracter stimuli on the other hand. Moreover, we assessed whether risk group status (i.e., having a parental history of Substance Use Disorders [SUD]) uniquely contributed to P300 amplitude variation above and beyond these other variables. METHODS: Event-related potentials were recorded in high-risk adolescents with a parental history of SUD (HR;n=80) and normal-risk controls (NR;n=100) while performing a visual Novelty Oddball paradigm. Stress-evoked cortisol levels were assessed and parenting, life adversities, substance use and psychopathology were examined by using self-reports. RESULTS: HR adolescents displayed smaller P300 amplitudes in response to novel- and to target stimuli than NR controls, while the latter only approached significance. Interestingly, the effect of having a parental history of SUD on target-P300 disappeared when all other variables were taken into account. Externalizing problem behavior was a powerful predictor of target-P300. In contrast, risk group status uniquely predicted novelty-P300 amplitude reductions above and beyond all other factors. CONCLUSION: Overall, the present findings suggest that the P300 amplitude reduction to novel stimuli might be a more specific endophenotype for SUD than the target-P300 amplitude. This pattern of results underscores the importance of conducting multifactorial assessments when examining important cognitive processes in at-risk adolescents.

Cortisol levels in children of parents with a substance use disorder.

BACKGROUND: Children of parents with a substance use disorder (CPSUDs) are at increased risk for the development of substance use disorders later in life, and therefore may manifest vulnerability markers for these disorders at a higher level than children from the general population. Our aim was to examine hypothalamic-pituitary-adrenal (HPA) axis activity as a potential vulnerability marker in CPSUDs as compared to healthy controls. We further examined whether having experienced more adverse life events (ALEs) accounted for differences in cortisol levels between CPSUDs and controls. METHODS: 83 CPSUDs were matched to 83 controls on the basis of age, sex and socioeconomic status. Salivary cortisol was assessed at four time points during a normal day and at six time points during a psychosocial stress procedure, during which perceived stress was also measured. We implemented piecewise multilevel growth curve modeling to examine group differences in diurnal and stress-evoked cortisol levels. RESULTS: Diurnal cortisol levels of CPSUDs did not differ from those of controls. Only stress-evoked cortisol levels at onset of the experiment were explained by group status, such that CPSUDs exhibited lower cortisol levels at onset of the stress procedure. CPSUDs reported experiencing significantly more ALEs, yet number of ALEs was not related to cortisol levels. CPSUDs furthermore reported less perceived stress than controls at onset of the procedure. CONCLUSIONS: HPA axis dysregulation may be a vulnerability marker for substance use disorders, as CPSUDs show blunted activation in anticipation of stress. These blunted cortisol levels were not the result of having experienced more stressful experiences during their lifetimes, thus might reflect an inborn vulnerability to substance use disorders.

Determinants of physiological and perceived physiological stress reactivity in children and adolescents.

AIMS: Abnormal physiological stress reactivity is increasingly investigated as a vulnerability marker for various physical and psychological health problems. However, studies are inconsistent in taking into account potential covariates that may influence the developing stress system. We systematically tested determinants (individual, developmental, environmental and substance use-related) of physiological and perceived physiological stress reactivity. We also examined the relation between physiological and perceived physiological stress reactivity. METHOD: In a stratified sample of 363 children (7-12 years) and 344 adolescents (13-20 years) from the general population, we examined cortisol, heart rate, respiratory sinus arrhythmia and perceived physiological stress reactivity to a psychosocial stress procedure. RESULTS: Using multivariate linear regression models, we found that individual, developmental, environmental and substance use-related factors were related to each of the stress response indices. These determinant factors were different for each of the stress reactivity indices, and different in children versus adolescents. Perceived physiological stress reactivity predicted cortisol reactivity in adolescents only. All other relations between perceived physiological and physiological stress reactivity were not significant. CONCLUSIONS: As physiological stress variables are often examined as vulnerability markers for the development of health problems, we maintain that it is essential that future studies take into consideration factors that may account for found relations. Our study provides an overview and indication of which variables should be considered in the investigation of the relation between physiological stress indices and illness.

Parental rearing behavior prospectively predicts adolescents' risky decision-making and feedback-related electrical brain activity.

The present study examined the role of parental rearing behavior in adolescents' risky decision-making and the brain's feedback processing mechanisms. Healthy adolescent participants (n = 110) completed the EMBU-C, a self-report questionnaire on perceived parental rearing behaviors between 2006 and 2008 (T1). Subsequently, after an average of 3.5 years, we assessed (a) risky decision-making during performance of the Balloon Analogue Risk Task (BART); (b) event-related brain potentials (ERPs) elicited by positive (gain) and negative feedback (loss) during the BART; and (c) self-reported substance use behavior (T2). Age-corrected regression analyses showed that parental rejection at T1 accounted for a unique and significant proportion of the variance in risk-taking during the BART; the more adolescents perceived their parents as rejecting, the more risky decisions were made. Higher levels of perceived emotional warmth predicted increased P300 amplitudes in response to positive feedback at T2. Moreover, these larger P300 amplitudes (gain) significantly predicted risky decision-making during the BART. Parental rearing behaviors during childhood thus seem to be significant predictors of both behavioral and electrophysiological indices of risky decision-making in adolescence several years later. This is in keeping with the notion that environmental factors such as parental rearing are important in explaining adolescents' risk-taking propensities.

Diminished error-related brain activity as a promising endophenotype for substance-use disorders: evidence from high-risk offspring.

One of the core features of individuals with a substance-use disorder (SUD) is the reduced ability to successfully process errors and monitor performance, as reflected by diminished error-related negativities (ERN). However, whether these error-related brain abnormalities are caused by chronic substance use or rather predates it remains unclear. The present study elucidated whether hypoactive performance monitoring represents an endophenotypic vulnerability marker for SUD by using a high-risk paradigm. We assessed the behavioral components of error-processing, as well as the amplitude of the ERN in the event-related brain potential (ERP) during performance of the Eriksen Flanker Task among high-risk adolescents of parents with a SUD (HR; n = 28) and normal-risk controls (NR; n = 40). Results revealed that HR offspring were characterized by a higher prevalence of internalizing symptoms and more frequent cannabis use, the latter having a significant influence on the ERN. Interestingly, risk group uniquely predicted the negativity amplitude in response to error trials above and beyond confounding variables. Moreover, we found evidence of smaller ERN amplitudes in (cannabis use-naïve) HR offspring, reflecting impaired early processing of error information and suboptimal performance monitoring, whereas no robust group differences were found for overall behavioral performance. This effect was independent of an overall reduction in brain activity. Taken together, although we cannot rule out alternative explanations, the results of our study may provide evidence for the idea that diminished error-processing represents a promising endophenotype for SUD that may indicate a vulnerability to the disorder.

Alcohol and tobacco use and heart rate reactivity to a psychosocial stressor in an adolescent population.

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.

Youth in the Netherlands study (JOiN): study design.

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.