The P300 event-related brain potential as a neurobiological endophenotype for substance use disorders: A meta-analytic investigation (Article)

2012-01-01T00:00:00Z

Endophenotypes are intermediate phenotypes on the putative causal pathway from genotype to phenotype and can aid in discovering the genetic etiology of a disorder. There are currently very few suitable endophenotypes available for substance use disorders (SUD). The amplitude of the P300 event-related brain potential is a possible candidate. The present study determined whether the P300 amplitude fulfils two fundamental criteria for an endophenotype: (1) an association with the disorder (disease marker), and (2) presence in unaffected biological relatives of those who have the disorder (vulnerability marker). For this purpose, two separate meta-analyses were performed. Meta-analysis 1 investigated the P300 amplitude in relation to SUD in 39 studies and Meta-analysis 2 investigated P300 amplitude in relation to a family history (FH+) of SUD in 35 studies. The findings indicate that a reduced P300 amplitude is significantly associated with SUD (d=0.51) and, though to a lesser extent, with a FH+ of SUD (d=0.28). As a disease maker, the association between reduced P300 amplitude and SUD is significantly larger for participants that were exclusively recruited from treatment facilities (d=0.67) than by other methods (i.e., community samples and family studies; d=0.45 and 0.32, respectively), and larger for abstinent SUD patients (d=0.71) than for current substance users (d=0.37). Furthermore, in contrast to FH+ males, a P300 amplitude reduction seems not to be present in FH+ females (d=-0.07). Taken together, these results suggest that P300 amplitude reduction can be both a useful disease and vulnerability marker and is a promising neurobiological endophenotype for SUD, though only in males. Implications and future directions are discussed.

Psychiatric comorbidities in autism spectrum disorders: Findings from a Danish Historic Birth Cohort (Article)

2011-12-01T00:00:00Z

Hypothalamic-pituitary-adrenal axis reactivity to social stress and adolescent cannabis use: The TRAILS study (Article)

2011-08-01T00:00:00Z

Aims To investigate the relationship of life-time and repeated cannabis use with hypothalamic-pituitary-adrenal (HPA) axis reactivity to social stress in a general population sample of adolescents. Design Adolescents who reported life-time or repeated cannabis use, life-time or repeated tobacco use and never use of either cannabis or tobacco were compared with respect to their HPA axis reactivity during the Groningen Social Stress Task (GSST), which was based on the Trier Social Stress Task. Setting A large prospective population study of Dutch adolescents [the TRacking Adolescents' Individual Lives Survey (TRAILS) study]. Participants A total of 591 adolescents (51% male) who participated in the GSST, which was an additional measurement during the third assessment wave. Measurements HPA axis stress-reactivity was indexed by four cortisol samples collected before, during and after the GSST. Furthermore, all adolescents in our study completed self-reported questionnaires on life-time and repeated cannabis and tobacco use. Models were adjusted for sex, recent alcohol use, experimental session risk status, socio-economic status, mood and time of the experimental session. Findings Life-time cannabis users had significantly lower stress-reactivity levels when compared to abstainers [odds ratio (OR)=0.68, confidence interval (CI)=0.55-0.85, P<0.01] and life-time tobacco users (OR=0.79, CI=0.64-0.98, P<0.05). In addition, repeated cannabis users also exhibited lower stress-reactivity levels when compared to life-time ever users of either tobacco or cannabis (OR=0.74, CI=0.53-0.98, P<0.05). Conclusions Lower hypothalamic-pituitary-adrenal-axis stress-reactivity in adolescents is related specifically to life-time and repeated cannabis use. © 2011 The Authors, Addiction

Risk indicators of anxiety throughout adolescence: The trails study (Article)

2011-06-01T00:00:00Z

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

Reduced cardiac autonomic flexibility associated with medically unexplained somatic complaints in the context of internalizing symptoms in a preadolescent population sample: The TRAILS study (Letter To Editor)

2010-12-01T00:00:00Z

Reduced autonomic flexibility as a predictor for future anxiety in girls from the general population: The TRAILS study (Article)

2010-09-01T00:00:00Z

The present study investigated whether autonomic flexibility predicted future anxiety levels in adolescent boys and girls. This study is part of the TRacking Adolescents' Individual Lives Survey (TRAILS), a prospective cohort study of Dutch adolescents. The current study included a subsample of 965 individuals. Measures of autonomic flexibility, i.e., heart rate (HR) and respiratory sinus arrhythmia (RSA), were determined during the first assessment wave (T1: participants 10–12 years old). Self-reported anxiety was assessed at the first and second assessment wave (T2: participants 12–14 years old). Possible gender differences and cooccurring depressive problems were examined. In girls, low RSA predicted anxiety levels 2 years later. In boys, no associations between HR and RSA and future anxiety were found. We conclude that in adolescent girls from the general population, signs of reduced autonomic flexibility (i.e., low RSA) predict future anxiety levels. Since the effect size was small, at this point, RSA reactivity alone cannot be used to identify individuals at risk for anxiety, but should be regarded as one factor within a large group of risk factors. However, if the present findings are replicated in clinical studies, intervention programmes – in the future – aimed at normalising autonomic functioning may be helpful.

Hypothalamic-pituitary-adrenal axis and smoking and drinking onset among adolescents: The longitudinal cohort TRacking Adolescents' Individual Lives Survey (TRAILS) (Article)

2009-11-01T00:00:00Z

Aims We examined within a prospective longitudinal study whether cortisol levels were associated with smoking or drinking behaviours, taking parental substance use into account. Design The influence of parental substance use on cortisol levels of their adolescent offspring at age 10-12 years was examined. Next, cortisol levels of adolescents who initiated smoking or drinking at the first data collection (age 10-12) were compared to non-users. Finally, we examined whether cortisol levels could predict new onset and frequency of smoking and drinking 2 years later. Setting and participants First and second assessment data of the TRacking Adolescents' Individual Lives Survey (TRAILS) were used, including 1768 Dutch adolescents aged 10-12 years, who were followed-up across a period of 2 years. Measurements Cortisol was measured in saliva samples at awakening, 30 minutes later, and at 8 p.m. at age 10-12. Self-reported substance use at age 10-12 and 13-14, and parental self-reported substance use were used. Findings Only maternal substance use was related to slightly lower adolescent cortisol levels at 8 p.m. Both maternal and paternal substance use were associated with adolescent smoking and drinking at age 13-14, although fathers' use only predicted the amount used and not the chance of ever use. Finally, higher cortisol levels were related moderately to current smoking and future frequency of smoking, but not to alcohol use. Conclusions In a general population, parental heavy substance use does not seem to affect cortisol levels consistently in their offspring. We found some evidence for higher, instead of lower, hypothalamic-pituitary-adrenal axis activity as a predictor of smoking in early adolescence.

The developmental course of anxiety symptoms during adolescence: The TRAILS study (Article)

2009-10-01T00:00:00Z

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.

Baseline cortisol measures and developmental pathways of anxiety in early adolescence (Article)

2009-09-01T00:00:00Z

Objective: This study investigated whether baseline cortisol measures predicted future anxiety, and compared cortisol values of groups with different developmental pathways of anxiety. Method: Cortisol levels were assessed in 1768 individuals (10-12 years). Anxiety levels were assessed at the same age and 2 years later. Results: Cortisol measures did not predict future anxiety levels. Individuals with persistent anxiety problems did not show higher morning cortisol levels than those with persistently low, decreasing, or increasing anxiety levels. Instead, individuals with persistently high anxiety levels showed significantly lower evening cortisol levels than all other individuals. Further, participants with increasing anxiety levels showed higher morning cortisol levels (area under the curve; AUC) than individuals with persistently low anxiety levels. Conclusion: The extent to which the HPA-axis - by itself - plays a role in the aetiology of anxiety is questionable. Interactions of the HPA-axis with other biological or environmental factors may be more important.

Roots of Anxiety: The role of cardiovascular regulation and cortisol in the development of anxiety in early adolecence (Doctoral Thesis)

2007-10-05T00:00:00Z

Since anxiety problems occur frequently, result in considerable suffering and impairment, and tend to persist over time, it is important to investigate putative underlying mechanisms. The aim of the present thesis was to extend the existing knowledge on the aetiology of anxiety by examining the role of two physiological stress response systems, the autonomic nervous system (ANS; consisting of the sympathetic and parasympathetic/vagal branche) and the hypothalamic-pituitaryadrenal (HPA)-axis, in the development of anxiety in early adolescence. The general idea is that some individuals are characterised by increased (re)activity of these two systems; they are more sensitive to stressors than others (so called ‘hyperaroused’). This increased sensitivity might put them at risk for future anxiety problems. In Chapter 1, the theoretical background and the main research questions were presented. The main research questions were: 1) Is anxiety associated with signs of hyperarousal, whereas depression is not? 2) Are high cortisol levels associated with high anxiety levels and is the persistence of anxiety problems associated with high cortisol levels? 3) Do measures of ANS (re)activity predict future anxiety levels, and are such associations different between boys and girls, and specific for anxiety, as apart from depression? 4) Do cortisol measures predict future anxiety levels, and are distinct developmental pathways of anxiety associated with different cortisol levels? 5) Do assymmetric activation patterns of ANS and HPA-axis activity predict future anxiety levels, are such associations more evident in individuals with high familial vulnerability, and different for boys and girls? To answer these questions the data of the first two assessment waves of TRAILS, a prospective cohort study of Dutch young adolescents, were used.

Testing the tripartite model in young adolescents: Is hyperarousal specific for anxiety and not depression? (Article)

2007-09-01T00:00:00Z

Background: To clarify the distinction between anxiety and depression, the tripartite model was introduced. According to this model, physiological hyperarousal (PH, i.e. autonomic hyperactivity) is specific for anxiety and not depression. Research on the relation between anxiety, depression and physiological measures representing arousal is lacking. Methods: Parent- and self-reported anxiety and depressive problems were assessed using the CBCL and RCADS. Heart rate (HR), heart rate variability in the low frequency (HRV LF) and respiratory sinus arrythmia (RSA) were used as indices for autonomic arousal. Results: Parent-reported anxiety was associated with low RSA in supine posture. This association was also found for self-reported anxiety problems, but only in boys. These findings point towards high arousal in anxiety. Self-reported depressive problems were associated with low HRV LF in standing posture and high RSA in supine posture in boys, pointing towards low arousal in depression. However, self-reported depressive problems were also associated with high HR in standing posture and with low HRV LF in supine posture in girls, suggesting high arousal in depression. Limitations: Although HRV LF in standing posture is primarily sympathetically mediated, and HRV LF in supine posture is primarily vagally mediated, the association between HRV LF and sympathetic versus vagal function is not exclusive. Thus, HRV LF measures are merely approaches of high or low arousal. Conclusions: Some evidence was found for hyperarousal in anxiety, but also for hyperarousal in depression. Apparently, the idea of hyperarousal in anxiety and not in depression is too simple to reflect the more complex reality.

Higher cortisol awakening response in young adolescents with persistent anxiety problems (Article)

2007-08-01T00:00:00Z

Objective: 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. Method: Cortisol levels of 10- to 12-year olds (n = 1768) from the general population were measured on three time points during the day. A self-report questionnaire (RCADS) was used to assess current anxiety, a parent-report questionnaire (TPBQ) to assess anxiety problems at age 4. Results: Associations between cortisol levels and current anxiety problems were not found. However, individuals with persistent anxiety problems had higher morning cortisol levels and a higher cortisol awakening response. Conclusion: Apparently, only persistent, and not current, anxiety problems are associated with higher HPA-axis activity. Alterations in HPA-axis activity might underlie persistent anxiety problems, or result from the stress accompanied by persistent anxiety problems.

Externalizing and internalizing problems in relation to autonomic function: A population-based study in preadolescents (Article)

2007-03-01T00:00:00Z

OBJECTIVE: To investigate whether externalizing and internalizing problems are related to lower and higher heart rate (HR), respectively, and to explore the relationship of these problems with respiratory sinus arrhythmia (RSA) and baroreflex sensitivity (BRS). Moreover, to study whether problems present at both preschool and preadolescent age show stronger associations with autonomic function than those that were not. METHOD: In a population cohort of 10- to 13-year-old children (N = 931; 11.6 ± 0.5 years; 47% boys), autonomic measurements in supine and standing position were performed at school. RSA and BRS were determined by spectral analysis. Current externalizing and internalizing problems were assessed by the Child Behavior Checklist and problems at age 4 to 5 retrospectively by the Preschool Behavior Questionnaire. RESULTS: At supine rest, current externalizing problems were associated with lower HR and higher RSA, but not with BRS and current internalizing problems with higher HR and lower RSA, but not with BRS. These results were specifically found in children with problems that were retrospectively reported to have been also present at preschool age. Standing-induced changes in autonomic parameters were unrelated to the behavioral dimensions. CONCLUSIONS: Externalizing and internalizing problems are associated with divergent autonomic patterns, suggesting autonomic underarousal and overarousal, respectively. Problems starting early in life may specifically account for this. This should be confirmed in prospective studies. Copyright 2007

Greaves-Lord, K.