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Many clinical trials repeatedly measure several longitudinal outcomes on patients. Patient follow-up can discontinue due to an outcome-dependent event, such as clinical diagnosis, death, or dropout. Joint modeling is a popular choice for the analysis of this type of data. Using example data from a prodromal Alzheimer's disease trial, we propose a new type of multivariate joint model in which longitudinal brain imaging outcomes and memory impairment ratings are allowed to be associated both with time to open-label medication and dropout, and where the brain imaging outcomes may also directly affect the memory impairment ratings. Existing joint models for multivariate longitudinal outcomes account for the correlation between the longitudinal outcomes through the random effects, often by assuming a multivariate normal distribution. However, for these models, it is difficult to interpret how the longitudinal outcomes affect each other. We model the dependence between the longitudinal outcomes differently so that a first longitudinal outcome affects a second one. Specifically, for each longitudinal outcome, we use a linear mixed-effects model to estimate its trajectory, where, for the second longitudinal outcome, we include the linear predictor of the first outcome as a time-varying covariate. This facilitates an easy and direct interpretation of the association between the longitudinal outcomes and provides a framework for latent mediation analysis to understand the underlying biological processes. For the trial considered here, we found that part of the intervention effect is mediated through hippocampal brain atrophy. The proposed joint models are fitted using a Bayesian framework via MCMC simulation.

Differential abundance analysis of infant 16S microbial sequencing data is complicated by challenging data properties, including high sparsity, extreme dispersion and the relative nature of the information contained within the data. In this study, we propose a pairwise ratio analysis that uses the compositional data analysis principle of subcompositional coherence and merges it with a beta-binomial regression model. The resulting method provides a flexible and easily interpretable approach to infant 16S sequencing data differential abundance analysis that does not require zero imputation. We evaluate the proposed method using infant 16S data from clinical trials and demonstrate that the proposed method has the power to detect differences, and demonstrate how its results can be used to gain insights. We further evaluate the method using data-inspired simulations and compare its power against related methods. Our results indicate that power is high for pairwise differential abundance analysis of taxon pairs that have a large abundance. In contrast, results for sparse taxon pairs show a decrease in power and substantial variability in method performance. While our method shows promising performance on well-measured subcompositions, we advise strong filtering steps in order to avoid excessive numbers of underpowered comparisons in practical applications.

To evaluate effects of attentional/ hyperactive (Att/Hi) and oppositional/ aggressive (Opp/Agg) behaviours of children at 14 and 21 months of age on parenting stress at 21 months. 107 children from the general population with low, intermediate, and high levels of disruptive behaviours at 14 months, as evaluated by parents on a 55-item checklist, participated. Parents completed the Child Behaviour Checklist 1.5-5 and the Dutch version of Parenting Stress Index (NOSI) at 21 months. Effects of problem behaviours were examined in a 2 (Att/Hi and Opp/Agg) by 2 (not high versus high) by 2 (14 and 21 months) multivariate design with parental stress as dependent variable. Oppositional/ aggressive behaviour at 14 months had a strong main effect on parenting stress, but not at 21 months. There was a significant interaction between parenting stress and Att/Hi behaviour at 14 and 21 months, indicating that increase in these behaviours over time was associated with parenting stress. Both Opp/Agg behaviour and an interaction between Att/Hi behaviour and parenting stress contributed to maternal role restriction and social isolation. Oppositional/ aggressive behaviour led to higher scores for parental competence and depression, whereas Att/Hi behaviour led to lower scores for attachment. Early Opp/Agg and Att/Hi behaviour had differential effects on parenting stress at 21 months. The increase in parenting stress associated with early Opp/Agg behaviour may be linked to overall feelings of parental competence, whereas the course of Att/Hi behaviour may be associated with increased demands on parent-child interactions and attachment. Our results have implications for development of early intervention programmes.

Item does not contain fulltext The Modified Checklist for Autism in Toddlers (M-CHAT) and the Early Screening of Autistic Traits (ESAT) were designed to screen for autism spectrum disorders in very young children. The aim of this study was to explore proportions of children that screened positive on the ESAT or the M-CHAT and to investigate if screening positive on the ESAT and M-CHAT is associated with clinical referral by 18 months and other aspects of children's development, health, and behavior. In this study, the mothers of 12,948 18-month-old children returned a questionnaire consisting of items from the ESAT and M-CHAT, plus questions about clinical and developmental characteristics. The M-CHAT identified more screen-positive children than the ESAT, but the ESAT was associated with more clinical referrals and tended to identify more children with medical, language, and behavioral problems. A post hoc analysis of combining the two instruments found this to be more effective than the individual instruments alone in identifying children referred to clinical services at 18 months. Further analysis at the level of single items is warranted to improve these screening instruments.

Background: To evaluate effects of attentional/ hyperactive (Att/Hi) and oppositional/ aggressive (Opp/Agg) behaviours of children at 14 and 21 months of age on parenting stress at 21 months. Method: 107 children from the general population with low, intermediate, and high levels of disruptive behaviours at 14 months, as evaluated by parents on a 55-item checklist, participated. Parents completed the Child Behaviour Checklist 1.5–5 and the Dutch version of Parenting Stress Index (NOSI) at 21 months. Effects of problem behaviours were examined in a 2 (Att/Hi and Opp/Agg) by 2 (not high versus high) by 2 (14 and 21 months) multivariate design with parental stress as dependent variable. Results: Oppositional/ aggressive behaviour at 14 months had a strong main effect on parenting stress, but not at 21 months. There was a significant interaction between parenting stress and Att/Hi behaviour at 14 and 21 months, indicating that increase in these behaviours over time was associated with parenting stress. Both Opp/Agg behaviour and an interaction between Att/Hi behaviour and parenting stress contributed to maternal role restriction and social isolation. Oppositional/ aggressive behaviour led to higher scores for parental competence and depression, whereas Att/Hi behaviour led to lower scores for attachment. Conclusions: Early Opp/Agg and Att/Hi behaviour had differential effects on parenting stress at 21 months. The increase in parenting stress associated with early Opp/Agg behaviour may be linked to overall feelings of parental competence, whereas the course of Att/Hi behaviour may be associated with increased demands on parent-child interactions and attachment. Our results have implications for development of early intervention programmes.

Contains fulltext : 98454.pdf (Publisher’s version ) (Closed access) The purpose of this study is to examine the relationship between parental religiosity, parental harmony on the subject of religiosity, and the mental health of pre-adolescents. In a community-based sample of 2,230 pre-adolescents (10-12 years), mental health problems were assessed using self-report (Youth Self-Report, YSR), parental report (Child Behavior Checklist, CBCL) as well as teacher report (Teacher Checklist for Psychopathology, TCP). Information about the religiosity of mother, the religiosity of father and religious harmony between the parents was obtained by parent report. The influence of maternal religiosity on internalizing symptoms depended on the religious harmony between parents. This was particularly apparent on the CBCL. Higher levels of internalizing symptoms were associated with parental religious disharmony when combined with passive maternal religiosity. Boys scored themselves as having more externalizing symptoms in case of religiously disharmonious parents. The levels of internalizing and externalizing symptoms in pre-adolescents were not influenced by parental religiosity. Religious disharmony between parents is a risk factor for internalizing problems when the mother is passive religious. Religious disharmony is a risk factor on its own for externalizing problems amongst boys. Parental religious activity and parental harmony play a role in the mental health of pre-adolescents. 01 mei 2011

Background: The Social Communication Questionnaire (SCQ) is a screening instrument with established validity against the Autism Diagnostic Interview-Revised (ADI-R) in children aged 4 years and older. Indices of diagnostic accuracy have been shown to be strong in school-aged samples; however, relatively little is known about the performance of the SCQ in toddlers at risk of autism spectrum disorder (ASD). Methods: This study replicates and extends previous research by Corsello et al. (2007) in a comparatively large (N = 208), substantially younger (20–40 months) sample of children at high risk of ASD. The usefulness of the SCQ as a second-level screening instrument with different cut-off scores was evaluated in relation to IQ, age, and type of ASD diagnosis. The use of the SCQ as compared to the ADI-R was evaluated against clinical diagnosis, both alone and in combination with the ADOS. Results: The SCQ with different cut-offs consistently showed an unsatisfactory balance between sensitivity and specificity in screening for ASD in high-risk toddlers, with only a few exceptions for specific age, IQ, or diagnostic groups. Even though the SCQ and ADI-R were highly correlated, diagnostic agreement with the best evidence clinical diagnosis was poor for both measures. The ADOS used alone consistently had the highest predictive value. For autism versus not-autism, the combined SCQ and ADOS performed as well as the ADOS alone and notably better than the combination ADI-R and ADOS. Conclusions: The SCQ is likely to result in a number of false-positive findings, particularly in children with autism symptomatology, and the balance between sensitivity and specificity is poor. The ADOS should be considered the most valid and reliable diagnostic instrument in these very young at-risk children. Keywords: SCQ, ADI-R, ADOS, review, validity, toddlers, autism. Abbreviations: SCQ: Social Communication Questionnaire; ADI-R: Autism Diagnostic Interview-Revised; ADOS: Autism Diagnostic Observation Schedule; ASD: autism spectrum disorder.

Contains fulltext : 88133.pdf (Publisher’s version ) (Closed access) Recently, Gotham et al. (2007) proposed revised algorithms for the Autism Diagnostic Observation Schedule (ADOS) with improved diagnostic validity. The aim of the current study was to replicate predictive validity, factor structure, and correlations with age and verbal and nonverbal IQ of the ADOS revised algorithms for Modules 1 and 2 in a large independent Dutch sample (N = 532). Results showed that the improvement of diagnostic validity was most apparent for autism, except in very young or low functioning children. Results for other autism spectrum disorders were less consistent. Overall, these findings support the use of the more homogeneous revised algorithms, with the use of similar items across developmental cells making it easier to compare ADOS scores within and between individuals. 01 juni 2010

Contains fulltext : 80152.pdf (Publisher’s version ) (Closed access) The perceptual pattern in autism has been related to either a specific localized processing deficit or a pathway-independent, complexity-specific anomaly. We examined auditory perception in autism using an auditory disembedding task that required spectral and temporal integration. 23 children with high-functioning-autism and 23 matched controls participated. Participants were presented with two-syllable words embedded in various auditory backgrounds (pink noise, moving ripple, amplitude-modulated pink noise, amplitude-modulated moving ripple) to assess speech-in-noise-reception thresholds. The gain in signal perception of pink noise with temporal dips relative to pink noise without temporal dips was smaller in children with autism (p = 0.008). Thus, the autism group was less able to integrate auditory information present in temporal dips in background sound, supporting the complexity-specific perceptual account. 9 p.

Contradictory findings on the relationship between hypothalamus-pituitary-adrenal (HPA)-axis activity and externalizing behavior problems could be due to studies not accounting for issues of comorbidity and gender. In a population-based cohort of 1768 (10- to 12-year-old) early adolescents, we used a person-oriented approach and a variable-oriented approach to investigate whether comorbidity with internalizing behavior problems and gender moderate the relationship between HPA-axis activity (cortisol awakening response and evening cortisol levels) and externalizing behavior problems. We found that: (1) in early adolescents with pure externalizing behavior problems, there was a particularly strong effect of gender, in that girls showed significantly higher total cortisol levels after awakening (AUC(G) levels) and a significantly higher cortisol awakening response (AUC(I) levels) than boys. (2) Girls with pure externalizing behavior problems showed a significantly higher cortisol awakening response (AUC(I) levels) than girls without behavior problems or girls with comorbid internalizing behavior problems. This effect was absent in boys. (3) Externalizing behavior problems, in contrast to internalizing behavior problems, were associated with higher evening cortisol levels. This effect might, however, result from girls with externalizing behavior problems showing the highest evening cortisol levels. Overall, we were unable to find the expected relationships between comorbidity and HPA-axis activity, and found girls with pure externalizing behavior problems to form a distinct group with regard to their HPA-axis activity. There is need for prospective longitudinal studies of externalizing behavior problems in boys and girls in relation to their HPA-axis activity. It would be useful to consider how other risk factors such as life events and family and parenting factors as well as genetic risks affect the complex relationship between externalizing behavior problems and HPA-axis activity.

Contains fulltext : 71472.pdf (Publisher’s version ) (Closed access) Play helps to develop social skills. Children with autism show deviances in their play behavior that may be associated with delays in their social development. In this study, we investigated manipulative, functional and symbolic play behavior of toddlers with and without autism (mean age: 26.45, SD 5.63). The results showed that the quality of interaction between the child and the caregiver was related to the development of play behavior. In particular, security of attachment was related to better play behavior. When the developmental level of the child is taken into account, the attachment relationship of the child with the caregiver at this young age is a better predictor of the level of play behavior than the child's disorder.

Contains fulltext : 69584.pdf (Publisher’s version ) (Closed access) Deficits in Joint Attention (JA) may be one of the earliest signs of Autism Spectrum Disorders (ASD). In this longitudinal study we investigated several types of JA behaviors at the age of 24 and 42 months, and their development over time. Eleven children with ASD, 10 children with other developmental disorders, and eight children without a developmental disorder participated. It was found that children with ASD showed significantly less JA at the age of 24 months. At this age, the various types of JA (Basic Joint Attention, Associated Joint Attention, Joint Visual Attention) were correlated with developmental level and number of autistic characteristics. However, at the age of 42 months, these associations were absent. Although children with ASD may show less JA at the age of 24 months compared to other groups of children, by the age of 42 months they reach about the same level of JA, except for joint visual attention. In fact, at both ages, children with ASD differed consistently only on JVA from the other groups. JVA may be a core component of an early screening device for ASD.

Children with autism are able to show secure attachment behaviours to their parents/caregivers. Most studies on attachment in children with autism used a (modified) Strange Situation Procedure (SSP) to examine attachment security. An advantage of the Attachment Q-Sort (AQS) over the SSP is that it can be attuned to the secure-base behaviour of children from special populations. In this study experts in the field of autism (both clinicians and researchers: N = 59) defined an AQS criterion sort for children with autism and tested its content validity. Separate criterion sorts were defined for the social subtypes aloof and active-but-odd, but the two criterion sorts could be combined into one AQS criterion sort for children with autism. It is concluded that with minor amendments the original Attachment Q-Sort is applicable in observing the attachment behaviour of children with autism.

Contains fulltext : 51958.pdf (Publisher’s version ) (Closed access) This study on sensitivity and attachment included 55 toddlers and their parents. Samples included children with autism spectrum disorder (ASD), mental retardation, language delay, and typical development. Children were diagnosed at 4 years of age. Two years before diagnosis, attachment was assessed with the Strange Situation procedure, and parental sensitivity and child involvement during free play were assessed with the Emotional Availability Scale. Parents of children with ASD were equally sensitive as parents of children without ASD, but their children showed more attachment disorganization and less child involvement. More sensitive parents had more secure children, but only in the group without ASD. Less severe autistic symptoms in the social domain predicted more attachment security. Autism challenges the validity of attachment theory.

Contains fulltext : 50178.pdf (Publisher’s version ) (Closed access) A two-stage protocol for screening for autistic spectrum disorders (ASD) was evaluated in a random population of 31,724 children aged 14-15 months. Children were first pre-screened by physicians at well-baby clinics using a 4-item screening instrument. Infants that screened positive were then evaluated during a 1.5-h home visit by a trained psychologist using a recently developed screening instrument, the 14-item Early Screening of Autistic Traits Questionnaire (ESAT). Children with 3 or more negative scores were considered to be at high-risk of developing ASD and were invited for further systematic psychiatric examination. Eighteen children with ASD were identified. The group of children with false positive results had related disorders, such as Language Disorder (N = 18) and Mental Retardation (N = 13).

Contains fulltext : 115433.pdf (Publisher’s version ) (Open Access) It is unclear whether symptoms of autism spectrum disorder (ASD) in young children in the population fit the three-factor structure of ASD as described in the DSM-IV, and cluster together in individual subjects. This study analysed questionnaire data on ASD symptoms filled in by mothers of 11,332 18-month-old children that was collected in the context of the Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health. Confirmatory Factor Analyses showed that the three-factor model had a significantly better fit then the two- and one-factor model of ASD symptoms. Latent class analysis revealed four homogeneous groups of children (classes) with different scores for Social Interaction and Communication at one hand and Stereotypies/Rigidity at the other hand.

Contains fulltext : 87982.pdf (Publisher’s version ) (Closed access) BACKGROUND: Few field trials exist on the impact of implementing guidelines for the early detection of autism spectrum disorders (ASD). The aims of the present study were to develop and evaluate a clinically relevant integrated early detection programme based on the two-stage screening approach of Filipek et al. (1999), and to expand the evidence base for this approach. METHODS: The integrated early detection programme encompassed: 1) training relevant professionals to recognise early signs of autism and to use the Early Screening of Autistic Traits Questionnaire (ESAT; Dietz, Swinkels et al., 2006; Swinkels, van Daalen, van Engeland, & Buitelaar, 2006), 2) using a specific referral protocol, and 3) building a multidisciplinary diagnostic team. The programme was evaluated in a controlled study involving children in two regions (N = 2793, range 0-11 years). The main outcome variables were a difference in mean age at ASD diagnosis and a difference in the proportion of children diagnosed before 36 months. RESULTS: ASD was diagnosed 21 months (95% CI 9.6, 32.4) earlier in the experimental region than in the control region during the follow-up period, with the mean age at ASD diagnosis decreasing by 19.5 months (95% CI 10.5, 28.5) from baseline in the experimental region. Children from the experimental region were 9.4 times (95% CI 2.1, 41.3) more likely than children from the control region to be diagnosed before age 36 months after correction for baseline measurements. Most of these early diagnosed children had narrowly defined autism with mental retardation. CONCLUSIONS: The integrated early detection programme appears to be clinically relevant and led to the earlier detection of ASD, mainly in children with a low IQ. 01 maart 2010

Contains fulltext : 89501.pdf (Publisher’s version ) (Closed access) This randomized controlled trial compared results obtained after 12 months of nonintensive parent training plus care-as-usual and care-as-usual alone. The training focused on stimulating joint attention and language skills and was based on the intervention described by Drew et al. (Eur Child Adolesc Psychiatr 11:266-272, 2002). Seventy-five toddlers with autism spectrum disorder (65 autism, 10 PDD-NOS, mean age = 34.4 months, SD = 6.2) were enrolled. Analyses were conducted on a final sample of 67 children (lost to follow-up = 8). No significant intervention effects were found for any of the primary (language), secondary (global clinical improvement), or mediating (child engagement, early precursors of social communication, or parental skills) outcome variables, suggesting that the 'Focus parent training' was not of additional value to the more general care-as-usual. 01 december 2010

Contains fulltext : 88620.pdf (Publisher’s version ) (Closed access) The aim was to investigate the contribution of familial risk to externalizing behaviors (FR-EXT), perceived parenting styles, and their interactions to the prediction of externalizing behaviors in preadolescents. Participants were preadolescents aged 10-12 years who participated in TRAILS, a large prospective population-based cohort study in the Netherlands (N = 2,230). Regression analyses were used to determine the relative contribution of FR-EXT and perceived parenting styles to parent and teacher ratings of externalizing behaviors. FR-EXT was based on lifetime parental externalizing psychopathology and the different parenting styles (emotional warmth, rejection, and overprotection) were based on the child's perspective. We also investigated whether different dimensions of perceived parenting styles had different effects on subdomains of externalizing behavior. We found main effects for FR-EXT (vs. no FR-EXT), emotional warmth, rejection, and overprotection that were fairly consistent across rater and outcome measures. More specific, emotional warmth was the most consistent predictor of all outcome measures, and rejection was a stronger predictor of aggression and delinquency than of inattention. Interaction effects were found for FR-EXT and perceived parental rejection and overprotection; other interactions between FR-EXT and parenting styles were not significant. Correlations between FR-EXT and perceived parenting styles were absent or very low and were without clinical significance. Predominantly main effects of FR-EXT and perceived parenting styles independently contribute to externalizing behaviors in preadolescents, suggesting FR-EXT and parenting styles to be two separate areas of causality. The relative lack of gene-environment interactions may be due to the epidemiological nature of the study, the preadolescent age of the subjects, the measurement level of parenting and the measurement level of FR-EXT, which might be a consequence of both genetic and environmental factors. 01 juli 2010

Contains fulltext : 80144.pdf (Publisher’s version ) (Closed access) To examine the inter-rater reliability and stability of autism spectrum disorder (ASD) diagnoses made at a very early age in children identified through a screening procedure around 14 months of age. In a prospective design, preschoolers were recruited from a screening study for ASD. The inter-rater reliability of the diagnosis of ASD was measured through an independent assessment of a randomly selected subsample of 38 patients by two other psychiatrists. The diagnoses at 23 months and 42 months of 131 patients, based on the clinical assessment and the diagnostic classifications of standardised instruments, were compared to evaluate stability of the diagnosis of ASD. Inter-rater reliability on a diagnosis of ASD versus non-ASD at 23 months was 87% with a weighted kappa of 0.74 (SE 0.11). The stability of the different diagnoses in the autism spectrum was 63% for autistic disorder, 54% for pervasive developmental disorder, not otherwise specified (PDD-NOS), and 91% for the whole category of ASD. Most diagnostic changes at 42 months were within the autism spectrum from autistic disorder to PDD-NOS and were mainly due to diminished symptom severity. Children who moved outside the ASD category at 42 months made significantly larger gains in cognitive and language skills than children with a stable ASD diagnosis. In conclusion, the inter-rater reliability and stability of the diagnoses of ASD established at 23 months in this population-based sample of very young children are good.

Contains fulltext : 81679.pdf (Publisher’s version ) (Closed access) Several instruments have been developed to screen for autism spectrum disorders (ASD) in high-risk populations. However, few studies compare different instruments in one sample. Data were gathered from the Early Screening of Autistic Traits Questionnaire, Social Communication Questionnaire, Communication and Symbolic Behavior Scales-Developmental Profile, Infant-Toddler Checklist and key items of the Checklist for Autism in Toddlers in 238 children (mean age = 29.6 months, SD = 6.4) at risk for ASD. Discriminative properties are compared in the whole sample and in two age groups separately (8-24 months and 25-44 months). No instrument or individual item shows satisfying power in discriminating ASD from non-ASD, but pros and cons of instruments and items are discussed and directions for future research are proposed.

Contains fulltext : 80710.pdf (Publisher’s version ) (Closed access) BACKGROUND: Accumulating evidence indicates that there is a rich and varied interplay between persons and their environments, which strongly suggests that this involves gene-environment correlations and interactions. We investigated whether familial risk (FR) to externalizing behaviors and prenatal and perinatal risk factors, separately or in interaction with each other, predicted externalizing behaviors. METHODS: The subjects were 10- to 12-year-old preadolescents who were taking part in TRAILS, a large prospective population-based cohort study (N = 2,230). Regression analyses were used to determine the relative contribution of FR and prenatal and perinatal risks to parent and teacher ratings of inattention, hyperactivity/impulsivity aggression, and delinquency. RESULTS: Regression models explained between 6 and 11% of the variance of externalizing behaviors. We found main effects of FR (vs. no FR), macrosomia (birth weight > 4,500 g), maternal prenatal smoking (MPS), pregnancy and delivery complications (PDCs), and gender that were rather consistent across rater and outcome measures. For some outcome measures, the effect of MPS and PDCs depended on the presence of FR. These included both positive and negative interaction effects. Correlations between FR and prenatal and perinatal risks were significant but rather low. CONCLUSIONS: Both main effects and interaction effects of FR and prenatal and perinatal risks contributed to externalizing behaviors in preadolescents, but all effects were of small size. Further research including use of candidate gene polymorphisms is necessary to identify the underlying neurobiological mechanisms of these main and interaction effects.

Contains fulltext : 70260.pdf (Publisher’s version ) (Closed access) Behavioral genetic studies imply that salient environmental influences operate within families, making siblings in a family different rather than similar. This study is the first one to examine differential sibling experiences (as measured with the Sibling Inventory of Differential Experience) and its effect on behavioral outcomes within ADHD families. Subjects were 45 Dutch ADHD probands and their unaffected siblings (n = 45) aged 10-18 years. ADHD probands and their unaffected siblings reported differences in sibling interaction, parental treatment, and peer characteristics. These nonshared environmental influences were related to both the severity of ADHD symptoms as well as to comorbid problem behaviors. These findings suggest that environmental influences that operate within ADHD families appear relevant to the severity of problem behaviors of ADHD children and their siblings.

Contains fulltext : 71211.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To study the correlation between symptoms of ADHD in adults, obtained with different methods and from different sources. METHOD: Information was obtained from 120 adults with ADHD, their partners, and their parents, using the ADHD Rating Scale, the Conners' Adult ADHD Rating Scales (CAARS), the Brown Attention-Deficit Disorder Scale (BADDS), and the structured interview Diagnostic Interview Schedule-IV, section L (DIS-L). RESULTS: All self-report rating scales can be used to assess ADHD symptoms in clinical samples of adults. The BADDS and the ADHD Rating Scale proved best in predicting the clinical diagnosis. The DSM-IV factors, originally developed for children, achieve lower patient-informant agreement than the other factors. CONCLUSION: Adults with ADHD appear to be the best informants with regard to their symptoms but tend to underreport the severity of their symptoms. Informant report may be used to get additional information on symptoms and impairment.

Kanner introduceerde het syndroom early infantile autism in de kinderpsychiatrie. Hij omschreef het syndroom uitgaande van een groep van 11 kinderen in het tijdschrift The Nervous Child in 1943 (Kanner, 1943). Daarna zijn er op basis van de ervaringen van clinici en wetenschappers criteria geformuleerd. Bij een classificatie Autistische Stoornis moet er sprake zijn van problemen op het gebied van de sociale interactie, de verbale en non-verbale communicatie en de aanwezigheid van repetitief en stereotiep gedrag. Huidige criteria voor deze stoornis zijn omschreven in de DSM-IV (American Psychiatric Association, 1994) en de ICD-10 (World Health Organization, 1992), twee classificatiesystemen die op dit punt sterk overeenkomen. Voor de classificatie van autisme moeten zes of meer criteria aanwezig zijn waarvan ten minste twee op de dimensie van sociale interactie en minstens een op elk van de twee andere dimensies.

Contradictory findings on the relationship between hypothalamus-pituitary-adrenal (HPA)-axis activity and externalizing behavior problems could be due to studies not accounting for issues of comorbidity and gender. In a population-based cohort of 1768 (10- to 12-year-old) early adolescents, we used a person-oriented approach and a variable-oriented approach to investigate whether comorbidity with internalizing behavior problems and gender moderate the relationship between HPA-axis activity (cortisol awakening response and evening cortisol levels) and externalizing behavior problems. We found that: (1) in early adolescents with pure externalizing behavior problems, there was a particularly strong effect of gender, in that girls showed significantly higher total cortisol levels after awakening (AUC(G) levels) and a significantly higher cortisol awakening response (AUC(I) levels) than boys. (2) Girls with pure externalizing behavior problems showed a significantly higher cortisol awakening response (AUC(I) levels) than girls without behavior problems or girls with comorbid internalizing behavior problems. This effect was absent in boys. (3) Externalizing behavior problems, in contrast to internalizing behavior problems, were associated with higher evening cortisol levels. This effect might, however, result from girls with externalizing behavior problems showing the highest evening cortisol levels. Overall, we were unable to find the expected relationships between comorbidity and HPA-axis activity, and found girls with pure externalizing behavior problems to form a distinct group with regard to their HPA-axis activity. There is need for prospective longitudinal studies of externalizing behavior problems in boys and girls in relation to their HPA-axis activity. It would be useful to consider how other risk factors such as life events and family and parenting factors as well as genetic risks affect the complex relationship between externalizing behavior problems and HPA-axis activity.

Contains fulltext : 53399.pdf (Publisher’s version ) (Closed access) Children with Autism Spectrum Disorder (ASD) have severe and pervasive impairments in the development of social interaction, which may affect the attachment relationship with their parents and may have an impact on parenting. In the current investigation 89 families with young children (mean age 26.5 months) were involved, who were diagnosed as ASD, mentally retarded (MR), or language delayed (LD), or part of a non-clinical comparison group. Attachment security was observed with the Brief Attachment Screening Questionnaire, and several parental self-report questionnaires assessed the parenting style, parental efficacy, parental experiences of daily hassles, social support, and psychological problems. Children with ASD were rated as less secure compared to the other clinical and normal comparison groups. Parents of non-clinical children reported higher levels of authoritative parenting than parents in the ASD group and in the total clinical group, and they also received less social support. Parents of children with ASD coped remarkably well with the challenges of raising a child with ASD.

Contains fulltext : 51957.pdf (Publisher’s version ) (Closed access) OBJECTIVES: To examine the prevalence of parents' compliance with follow-up measurements after their child tested positive at a screening to assess problems in social development, as well as to find demographic, screening-related, and child-specific factors associated with parental compliance. DESIGN: Two-stage screening design. SETTING: Utrecht, the Netherlands. PARTICIPANTS: A random population of 31,724 children were screened at well-baby clinics at age 14 to 15 months (screen 1). Three hundred sixty-four children underwent screen 2 (255 children who scored positive at screen 1 [population screening] and 109 children younger than 36 months who were identified by surveillance because of suspected problems in their social development). Main Exposure A 2-stage screening was applied. MAIN OUTCOME MEASURES: Compliance with recommendations of having either a second screening (after screen 1) or clinical evaluation (after screen 2). RESULTS: Of 370 children who tested positive at screen 1, parents of 255 children (69%) complied with screen 2. Three groups were distinguished after screen 2 (n = 173): early compliance (clinical evaluation within 6 months) (68%), late compliance (clinical evaluation after 6 months) (14%), and noncompliance (no clinical evaluation) (18%). Late compliance and noncompliance were more common in parents of younger children and children who were identified via population screening. Parents of children with either relatively high cognitive skills and/or low scores on screening measures were less inclined to comply. CONCLUSIONS: Study results suggest higher effectiveness of surveillance over population screening. Screening may well be applied as a second step after surveillance to identify children who need further clinical evaluation.

Contains fulltext : 52011.pdf (Publisher’s version ) (Closed access) Joint attention is often referred to as a triadic relation between self, other and object. Young children with autism show deficiencies in the use of joint attention behaviors. Individual differences may be expected, and they may be determined by the children's cognitive development or the characteristics of the relationship of the child with the caregiver. Although most joint attention skills develop under the age of three, most studies of joint attention in children with autism involved children older than 3 years of age, due to difficulties in diagnosing autism under this age. In this study we investigated joint attention behaviors of 78 young children (mean age 25.7 months, SD 6.1) with autism spectrum disorders (n = 20), other developmental delays (n = 18), and typically developing children (n = 40). Following the pertinent literature and confirmed by factor analysis, two types of joint attention behaviors were distinguished, Basic Joint Attention (BJA) and Associated Joint Attention (AJA). We found that cognitive delays and autistic symptoms-but not attachment insecurity or disorganization-were related to less joint attention. Already at the age of 2 years, children with more autistic symptoms show less joint attention, even after controlling for developmental level.

Contains fulltext : 52867.pdf (Publisher’s version ) (Closed access) Data on the growth of the head in the first year of life in children with autism spectrum disorders are inconsistent. We measured head circumference and body length during the first year of life, and determined whether the head grew in proportion to body length. This is a case-control study nested in a population-based screening study of autism spectrum disorders. Longitudinal data for head circumference and body length of 53 children with autism spectrum disorders were compared with those of a control group and population norms, using univariate and multilevel statistical modeling. Growth of body length was accelerated, but growth of head circumference was normal in children with autism spectrum disorders compared with controls in the first year of life. The rate of macrocephaly we detected in the first year of life in our sample, 11.3%, fits within the 95% confidence intervals of macrocephaly rates in previous studies. Our findings suggest that autism spectrum disorder is due to a dysregulation of growth in general, rather than to a dysregulation of neuronal growth in the brain. It is unclear whether this early, disproportionate growth of children with autism spectrum disorders is specific to the disorder, and whether this growth could serve as a biomarker to delineate more homogeneous subtypes of autism spectrum disorders.

Contains fulltext : 52172.pdf (Publisher’s version ) (Closed access)

Contains fulltext : 50179.pdf (Publisher’s version ) (Closed access) This article describes the development of a screening instrument for young children. Screening items were tested first in a non-selected population of children aged 8-20 months (n = 478). Then, parents of children with clinically diagnosed ASD (n = 153, average age 87 months) or ADHD (n = 76, average age 112 months) were asked to score the items retrospectively for when their child was 14 months old. A 14-item screening instrument, Early Screening of Autistic Traits (ESAT) which had maximal sensitivity and specificity for ASD was developed. The sensitivity of the ESAT was checked in an independent sample of 34 children aged 16-48 months clinically diagnosed with ASD. A 4-item version appears to be a promising prescreening instrument.

Contains fulltext : 136250.pdf (Publisher’s version ) (Open Access) BACKGROUND: Little is known about the stability of behavioural and developmental problems as children develop from infants to toddlers in the general population. Therefore, we investigated behavioural profiles at two time points and determined whether behaviours are stable during early development. METHODS: Parents of 4,237 children completed questionnaires with 62 items about externalizing, internalizing, and social-communicative behaviour when the children were 14-15 and 36-37 months old. Factor mixture modelling identified five homogeneous profiles at both time points: three with relatively normal behaviour or with mild/moderate problems, one with clear communication and interaction problems, and another with pronounced negative and demanding behaviour. RESULTS: More than 85% of infants with normal behaviour or mild problems at 14-15 months were reported to behave relatively typically as toddlers at 36-37 months. A similar percentage of infants with moderate communication problems outgrew their problems by the time they were toddlers. However, infants with severe problems had mild to severe problems as toddlers, and did not show completely normal behaviour. Improvement over time occurred more often in children with negative and demanding behaviour than in children with communication and interaction problems. The former showed less homotypic continuity than the latter. CONCLUSIONS: Negative and demanding behaviour is more often transient and a less specific predictor of problems in toddlerhood than communication and interaction problems.

Frequencies and sequential patterns of behaviour elements in pure hyperactive (N = 12), pure aggressive (N = 13), combined hyperactive/aggressive (N = 15) and control children (N = 10) were recorded in a semistructured playroom session and subsequently compared. The samples were age- and IQ-matched. In an overall MANOVA a significant main effect for hyperactivity but not for aggression was found. The hyperactive children were characterized particularly by differences in squirming and changes in sitting. The sequential patterning of their behaviour revealed weaker temporal contingencies between their behaviour and the conversational speech of the experimenter than in the case of the nonhyperactive (aggressive and control) children. This may be explained by deficits in social attention in the hyperactive groups. Language: en

Contains fulltext : 89698.pdf (Publisher’s version ) (Closed access) It is unclear whether subclinical autistic traits at very young age are transient or stable, and have clinical relevance. This study investigated the relationship between early subclinical autistic traits and the occurrence of later developmental and behavioural problems as well as problems in cognitive and language functioning. Parents of infants aged 14-15 months from the general population completed the Early Screening of Autistic Traits Questionnaire (ESAT). Three groups of children with high, moderate, and low ESAT-scores (total n = 103) were selected. Follow-up assessments included the CBCL 1(1/2)-5 at age 3 years, and the SCQ, the ADI-R, the ADOS-G, an on-verbal intelligence test, and language tests for comprehension and production at age 4-5 years. None of the children met criteria for autism spectrum disorder at follow-up. Children with high ESAT-scores at 14-15 months showed significantly more internalizing and externalizing problems at age 3 years and scored significantly lower on language tests at age 4-5 years than children with moderate or low ESAT-scores. Further, significantly more children with high ESAT-scores (14/26, 53.8%) than with moderate and low ESAT-scores (5/36, 13.9% and 1/41, 2.4%, respectively) were in the high-risk/clinical range on one or more outcome domains (autistic symptoms, behavioural problems, cognitive and language abilities). Subclinical autistic traits at 14-15 months predict later behavioural problems and delays in cognitive and language functioning rather than later ASD-diagnoses. The theoretical implications of the findings lie in the pivotal role of early social and communication skills for the development of self-regulation of emotions and impulses. The practical implications bear on the early recognition of children at risk for behavioural problems and for language and cognitive problems. 01 augustus 2010

Contains fulltext : 70165.pdf (Publisher’s version ) (Closed access) Deficits in the perception of social stimuli may contribute to the characteristic impairments in social interaction in high functioning autism (HFA). Although the cortical processing of voice is abnormal in HFA, it is unclear whether this gives rise to impairments in the perception of voice gender. About 20 children with HFA and 20 matched controls were presented with voice fragments that were parametrically morphed in gender. No differences were found in the perception of gender between the two groups of participants, but response times differed significantly. The results suggest that the perception of voice gender is not impaired in HFA, which is consistent with behavioral findings of an unimpaired voice-based identification of age and identity by individuals with autism. The differences in response times suggest that individuals with HFA use different perceptual approaches from those used by typically developing individuals.