Kirstin Greaves-Lord

The developmental course of anxiety symptoms during adolescence: The TRAILS study

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.

Higher cortisol awakening response in young adolescents with persistent anxiety problems

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.

The P300 event-related brain potential as a neurobiological endophenotype for substance use disorders: a meta-analytic investigation.

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.

The association of quality of social relations, symptom severity and intelligence with anxiety in children with autism spectrum disorders:

Limited quality of social relations, milder symptom severity and higher intelligence were shown to account for higher anxiety levels in autism spectrum disorders. The current study replicated and extended earlier findings by combining these three determinants of anxiety in autism spectrum disorders in one study. The sample consisted of 134 school-aged children with autism spectrum disorders, of whom 58 (43%) had a co-morbid anxiety disorder according to the Diagnostic Interview Schedule for Children–Parent version. In this sample, we tested associations between these determinants and anxiety univariately and multivariately to clarify the unique contribution of all determinants. Since we hypothesized that the association between limited quality of social relations and anxiety would be amplified by low symptom severity and/or high intelligence, we additionally tested for moderating effects. We found that higher anxiety levels were associated with a lower quality of social relations and lower symptom severity. In this mainly high-functioning sample, intelligence was not related to anxiety levels. No moderation effects were found. Since lower quality of social relations and lower symptom severity are associated with higher anxiety levels in children with autism spectrum disorders, therapeutic interventions aimed at reducing anxiety in autism spectrum disorders should pay attention to improving social relations, and presumably children with a lower symptom severity could benefit most from such interventions.

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.

Empirically based phenotypic profiles of children with pervasive developmental disorders: interpretation in the light of the DSM-5.

This study aimed to contribute to the Diagnostic and Statistical Manual (DSM) debates on the conceptualization of autism by investigating (1) whether empirically based distinct phenotypic profiles could be distinguished within a sample of mainly cognitively able children with pervasive developmental disorder (PDD), and (2) how profiles related to diagnoses and co-occurring behavioral and emotional problems. Six classes with distinct profiles were discerned. Three classes showed profiles not completely in line with the proposed DSM-5 conceptualization of autism. These classes included relatively many cognitively able individuals with PDD-not otherwise specified. However, profiles seemed to suit other diagnostic categories, such as social communication disorder. These alternative diagnoses could retain eligibility for services, and might adequately fit more specifically targeted interventions.

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.

Using the Child Behavior Checklist and the Teacher’s Report Form for identification of children with autism spectrum disorders:

This study evaluated the ability of the Child Behavior Checklist and the Teacher’s Report Form to identify children with autism spectrum disorders (ASD), using a sample of children with ASD (n = 458), referred children without ASD (n = 1109) and children from the general population (n = 999). A ten items ASD scale was constructed using half of the sample and the ability of this scale to discriminate between children with ASD and the other children was tested for the CBCL and the TRF separately and together in the other half of the sample. Using a cut-off score of 8 the combined CBCL/TRF ASD scale demonstrated high predictive values (NPV 95%, PPV 73%) in identifying children with ASD and children in the general population sample. This might be an acceptable percentage of false positives in general screening, considering the chance that these children might have other behavioural, emotional, and developmental problems which also need psychiatric evaluation. In the referred population, using a cut-off of 13, PPV was 49% and NPV was 85%. The high NPV indicates that in a referred population the scale is especially good at identifying children who do not need evaluation with a more ASD-specific instrument.

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.

Baseline cortisol measures and developmental pathways of anxiety in early adolescence

Objective:  This study investigated whether baseline cortisol measures predicted future anxiety, and compared cortisol values of groups with different developmental pathways of anxiety.