How Well Can we Diagnose Autism in Adults? Evaluating an Informant-based Interview: The Dutch Developmental, Dimensional and Diagnostic Interview - Adult Version (3Di-Adult).

The current study evaluated a brief, informant-based autism interview: the Developmental, Dimensional and Diagnostic Interview - Adult Version (3Di-Adult). Feasibility, reliability and validity of the Dutch 3Di-Adult was tested amongst autistic participants (n = 62) and a non-autistic comparison group (n = 30) in the Netherlands. The 3Di-Adult consists of two scales based on DSM-5 criteria: A scale 'Social communication and social interaction' and B scale 'Restricted, repetitive patterns of behavior, interests or activities'. ROC curves were used to determine cut-off scores for the A and the B scale, using an ASD diagnosis made by an independent clinician as the criterion. Mean administration time was 42 min. Internal consistency of the A scale (α = 0.92) and the B scale (α = 0.85) were good. Inter-rater reliability (ICCs = 0.99) and inter-rater agreement (ICCs ≥ 0.90) were promising. The 3Di-Adult showed good sensitivity (80.6%) and specificity (93.3%). Positive and negative predictive value were 96.2% and 70.0% respectively. Comparisons with the Autism-Spectrum Quotient-Short to investigate the convergent validity showed moderate, significant correlations with the 3Di-Adult in the total sample. Males, as compared to females, displayed significantly more autistic features on the 3Di-Adult. No relationship was found of the 3Di-Adult with education level, intelligence and age of the participants or informants. The feasibility and psychometric properties of the Dutch 3Di-Adult are promising, indicating that it can be a time-efficient, valid and reliable tool to use in diagnosing autism in adults according to DSM-5 criteria.

The ACCEPT-study: design of an RCT with an active treatment control condition to study the effectiveness of the Dutch version of PEERS® for adolescents with autism spectrum disorder.

BACKGROUND: Social skills interventions are commonly deployed for adolescents with autism spectrum disorder (ASD). Because effective and appropriate social skills are determined by cultural factors that differ throughout the world, the effectiveness of these interventions relies on a good cultural fit. Therefore, the ACCEPT study examines the effectiveness of the Dutch Program for the Education and Enrichment of Relational Skills (PEERS®) social skills intervention. METHODS/DESIGN: This study is a two-arm parallel group randomized controlled trial (RCT) in which adolescents are randomly assigned (after baseline assessment) to one of two group interventions (PEERS® vs. active control condition). In total, 150 adolescents are to be included, with multi-informant involvement of their parents and teachers. The ACCEPT study uses an active control condition (puberty psychoeducation group training, focussing on social-emotional development) and explores possible moderators and mediators in improving social skills. The primary outcome measure is the Contextual Assessment of Social Skills (CASS). The CASS assesses social skills performance in a face to face social interaction with an unfamiliar, typically developing peer, making this a valuable instrument to assess the social conversational skills targeted in PEERS®. In addition, to obtain a complete picture of social skills, self-, parent- and teacher-reported social skills are assessed using the Social Skills improvement System (SSiS-RS) and Social Responsiveness Scale (SRS-2). Secondary outcome measures (i.e. explorative mediators) include social knowledge, social cognition, social anxiety, social contacts and feelings of parenting competency of caregivers. Moreover, demographic and diagnostic measures are assessed as potential moderators of treatment effectiveness. Assessments of adolescents, parents, and teachers take place at baseline (week 0), intermediate (week 7), post intervention (week 14), and at follow-up (week 28). CONCLUSION: This is the first RCT on the effectiveness of the PEERS® parent-assisted curriculum which includes an active control condition. The outcome of social skills is assessed using observational assessments and multi-informant questionnaires. Additionally, factors related to social learning are assessed at several time points, which will enable us to explore potential mediators and moderators of treatment effect. TRAIL REGISTRATION: Dutch trail register NTR6255 (NL6117). Registered February 8th, 2017 - retrospectively registered.

Adult Manifestation of Milder Forms of Autism Spectrum Disorder; Autistic and Non-autistic Psychopathology.

We compared the presence of autistic and comorbid psychopathology and functional impairments in young adults who received a clinical diagnosis of Pervasive Developmental Disorders Not Otherwise Specified or Asperger's Disorder during childhood to that of a referred comparison group. While the Autism Spectrum Disorder group on average scored higher on a dimensional ASD self- and other-report measure than clinical controls, the majority did not exceed the ASD cutoff according to the Autism Diagnostic Observation Schedule. Part of the individuals with an ASD diagnosis in their youth no longer show behaviors that underscribe a clinical ASD diagnosis in adulthood, but have subtle difficulties in social functioning and a vulnerability for a range of other psychiatric disorders.

Urbanicity, hypothalamic-pituitary-adrenal axis functioning, and behavioral and emotional problems in children: a path analysis.

BACKGROUND: Urbanization is steadily increasing worldwide. Previous research indicated a higher incidence of mental health problems in more urban areas, however, very little is known regarding potential mechanisms underlying this association. We examined whether urbanicity was associated with mental health problems in children directly, and indirectly via hypothalamic-pituitary-adrenal (HPA)-axis functioning. METHODS: Utilizing data from two independent samples of children we examined the effects of current urbanicity (n = 306, ages seven to 12 years) and early childhood urbanicity (n = 141, followed from birth through age 7 years). Children's mothers reported on their mental health problems and their family's socioeconomic status. Salivary cortisol samples were collected during a psychosocial stress procedure to assess HPA axis reactivity to stress, and at home to assess basal HPA axis functioning. Neighborhood-level urbanicity and socioeconomic conditions were extracted from Statistics Netherlands. Path models were estimated using a bootstrapping procedure to detect indirect effects. RESULTS: We found no evidence for a direct effect of urbanicity on mental health problems, nor were there indirect effects of urbanicity through HPA axis functioning. Furthermore, we did not find evidence for an effect of urbanicity on HPA axis functioning or effects of HPA axis functioning on mental health problems. CONCLUSIONS: Possibly, the effects of urbanicity on HPA axis functioning and mental health do not manifest until adolescence. An alternative explanation is a buffering effect of high family socioeconomic status as the majority of children were from families with an average or high socioeconomic status. Further studies remain necessary to conclude that urbanicity does not affect children's mental health via HPA axis functioning.

The Stability of Comorbid Psychiatric Disorders: A 7 Year Follow Up of Children with Pervasive Developmental Disorder-Not Otherwise Specified.

The current study was a 7-year follow-up of 74 6-12 year old children with Pervasive Developmental Disorder-Not Otherwise Specified. We examined the rates and 7 year stability of comorbid psychiatric diagnoses as ascertained with the Diagnostic Interview Schedule for Children: Parent version at ages 6-12 and again at ages 12-20. Also, we examined childhood factors that predicted the stability of comorbid psychiatric disorders. The rate of comorbid psychiatric disorders dropped significantly from childhood (81 %) to adolescence (61 %). Higher levels of parent reported stereotyped behaviors and reduced social interest in childhood significantly predicted the stability of psychiatric comorbidity. Re-evaluation of psychiatric comorbidity should be considered in clinical practice, since several individuals shifted in comorbid diagnoses.

ASD Symptom Severity in Adolescence of Individuals Diagnosed with PDD-NOS in Childhood: Stability and the Relation with Psychiatric Comorbidity and Societal Participation.

The current 7-year follow-up study investigated: (1) the stability of ASD severity, and (2) associations of ASD severity in adolescence with (a) childhood and concurrent psychiatric comorbidity, and (b) concurrent societal functioning. The Autism Diagnostic Observation Schedule (ADOS) and the Diagnostic Interview Schedule for Children were administered in childhood (ages 6-12) and in adolescence (ages 12-20) to 72 individuals with a pervasive developmental disorder-not otherwise specified (PDD-NOS). ADOS calibrated severity scores showed a large stability (r = .51). Psychiatric comorbidity in childhood and adolescence were not associated with ASD severity in adolescence. Mental health care use (87 %) and special education needs were high (71 %). Reevaluation of ASD severity and psychiatric comorbidity later in life seem useful when PDD-NOS is diagnosed in childhood.

Neonatal levels of neurotrophic factors and risk of autism spectrum disorders.

OBJECTIVE: To examine levels of 3 neurotrophic factors (NTFs): Brain derived neurotrophic factor (BDNF), Neurotrophin-4 (NT-4), and transforming growth factor-ß (TGF-ß) in dried blood spot samples of neonates diagnosed with autism spectrum disorders (ASD) later in life and frequency-matched controls. METHOD: Biologic samples were retrieved from the Danish Newborn Screening Biobank. NTFs for 414 ASD cases and 820 controls were measured using Luminex technology. Associations were analyzed with continuous measures (Tobit regression) as well as dichotomized at the lower and upper 10th percentiles cutoff points derived from the controls' distributions (logistic regression). RESULTS: ASD cases were more likely to have BDNF levels falling in the lower 10th percentile (odds ratios [OR], 1.53 [95% confidence intervals (CI), 1.04-2.24], P-value = 0.03). Similar pattern was seen for TGF-ß in females with ASD (OR, 2.36 [95% CI, 1.05-5.33], P-value = 0.04). For NT-4, however, ASD cases diagnosed with ICD-10 only were less likely to have levels in upper 10th percentile compared with controls (OR, 0.22 [95% CI, 0.05-0.98], P-value = 0.05). CONCLUSION: Results cautiously indicate decreased NTFs levels during neonatal period in ASD. This may contribute to the pathophysiology of ASD through impairments of neuroplasticity. Further research is required to confirm our results and to examine the potential therapeutic effects of NTFs in ASD.

Risk indicators of anxiety throughout adolescence: the TRAILS study.

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

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. 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.

[Stress reactivity as an underlying mechanism of anxiety? Findings from the TRAILS study]. / Stressgevoeligheid als onderliggend mechanisme voor angstproblemen? Bevindingen uit de TRAILS-studie.

This short report provides an overview of the results of a recent Dutch study on the relation between anxiety and the reactivity of two important stress response systems: the autonomic nervous system and the hypothalamic-pituitary-adrenal axis. Future research will have to investigate the reactivity of both stress response systems in combination with several other important biological, psychological and social factors. In this way it should be possible to obtain more insight into the complex and interacting systems that underlie anxiety.

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. METHOD: Cortisol levels of 10- to 12-year olds (n = 1,768) 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.