Mark-Peter Steenhuis’s research while affiliated with University of Groningen and other places

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. 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. 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. 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.

The authors recently developed an Internet version of the Diagnostic Interview Schedule for Children-Version 4 (DISC-IV), parent version (D. Shaffer, P. Fisher, C. P. Lucas, M. K. Dulcan, & M. E. Schwab-Stone, 2000), with the main purpose of using it at home without an interviewer. This offers many advantages (e.g., extended applicability, fast communication, reduction of costs) but requires thorough study of correspondence between diagnostic outcomes of the interview and self-administered Internet versions. This is the 1st study to report on Internet administration of the DISC-IV. Using the attention-deficit/hyperactivity disorder (ADHD) section, the authors investigated whether the 2 versions yielded the same diagnostic outcome. Parents (N = 120) of patients visiting a child and adolescent psychiatry outpatient clinic were randomly divided into 4 groups, each completing 1 test and about 2 weeks later another according to 1 of these patterns: Internet-interview, interview-Internet, interview-interview, and Internet-Internet. Correspondence between the Internet and interview versions at the level of symptom scores was excellent, and correspondence with respect to the presence/absence of ADHD was good. Although highly comparable diagnostic outcomes between self-administration through the Internet and interviewer administration were found, further study using other DISC-IV modules is required.

This pilot study examined the effects of atomoxetine on attention-deficit/hyperactivity disorder (ADHD) symptoms and autistic features in children with pervasive developmental disorders (PDD). Twelve children (aged 6-14 years) with PDD accompanied by ADHD symptoms entered a 10-week open-label study with atomoxetine (1.19 +/- 0.41 mg/kg/day). Response was assessed by using parent and clinician rating scales with change in the ADHD-Rating Scale (ADHDRS) as primary outcome measure. Atomoxetine reduced ADHD-symptoms as measured by the ADHDRS (44% decrease vs. baseline, p < 0.003), the Conners' Parent Rating Scale-R:S (CPRS-R) (25% in the subscale "Cognitive Problems," p < 0.028; 32% in "Hyperactivity," p < 0.030; and 23% in "ADHD index," p < 0.023). We found a reduction of 21% (p = 0.071) for changes in the subscale "Hyperactivity" of the Aberrant Behavior Checklist (ABC). No change was found in any of the other ABC subscales, nor in the subscale "Oppositional" of the CPRS-R. Five patients (42%) discontinued because of side effects. Gastrointestinal symptoms, irritability, sleep problems, and fatigue were the most frequent side effects. These preliminary findings indicate that atomoxetine may be a promising new agent in the treatment of ADHD symptoms in children with PDD. However, children with PDD may have a higher vulnerability for some of the known side-effects of atomoxetine.

The short-term benefit of risperidone in ameliorating severe disruptive behavior in pediatric patients with autism spectrum disorders is well established; however, only one placebo-controlled, long-term study of efficacy is available. Thirty-six children with an autism spectrum disorder (5-17 years old) accompanied by severe tantrums, aggression, or self-injurious behavior, started 8-week open-label treatment with risperidone. Responders (n = 26) continued treatment for another 16 weeks, followed by a double-blind discontinuation (n = 24; two patients discontinued treatment because of weight gain) consisting of either 3 weeks of taper and 5 weeks of placebo only or continuing use of risperidone. Relapse was defined as a significant deterioration of symptoms based on clinical judgment and a parent questionnaire. Risperidone was superior to placebo in preventing relapse: this occurred in 3 of 12 patients continuing on risperidone versus 8 of 12 who switched to placebo (p = .049). Weight gain, increased appetite, anxiety, and fatigue were the most frequently reported side effects. This study indicates the effectiveness of risperidone during a period of several months, reducing disruptive behavior in about half of the children with autism spectrum disorders. The results provide a rationale for the continuing use of risperidone beyond 6 months, although considerable weight gain can limit the use of this agent.

Cross-sectional data and case studies suggest a temporal relationship between fluctuations in tic severity and preceding infections. In this study, we aimed to examine this possible relationship in a prospective longitudinal design. Two groups of tic disorder patients were included, a pediatric group between 7 and 15 years of age (n = 20), and an adult group over 15 years of age (n = 41). During a 24-week period, participants were asked to fill out weekly self questionnaires regarding the presence of tic exacerbations and the experience of the common cold. In addition, 6 throat swabs were taken at monthly intervals and cultured for streptococci; also, 3 serial serum assessments of streptococcal antibodies were performed at 8-week intervals. In the pediatric group, our results indicated a strong association between the self report of a common cold and a symptom exacerbation 4 weeks later (Odds ratio = 4.685; p = 0.001). In the adult group, we found no association between reports of common cold and tic exacerbations. Association with streptococcal infections could not be determined owing to the limited number of observed streptococcal infections. Thus, this study points to a hitherto unknown association of common viral infections with tic exacerbations in children, which may support the involvement of immune dysregulation in tic disorders.

The aim of this study was to investigate social and behavioral problems related to attention-deficit hyperactivity disorder (ADHD), obsessions and compulsions, and tic severity in children with a tic disorder. Parents of 58 children with a tic disorder with and without different forms of ADHD completed the Child Behavior Checklist (CBCL) and the Children's Social Behavior Questionnaire. Patients with a tic disorder with primarily hyperactive-impulsive ADHD had the highest questionnaire scores, patients with primarily inattentive ADHD had medium scores, and patients without ADHD had the lowest scores. On most subscales, significant part correlations with ADHD severity, but not tic severity, were obtained. Severity of obsessions and compulsions was independently correlated with the CBCL Thought Problems subscale but not with most other subscales. There was no significant correlation between tic severity and ADHD severity. Thus, in patients with a tic disorder, the presence and severity of ADHD are the main predictors of associated behavioral and social problems.

Clinical experience suggests an association between stressful life events and fluctuations in symptom severity of tic disorder patients. The aim of the present study was to examine this possible relationship in a prospective longitudinal design. Two groups of patients with tic disorder according to the research criteria of the Tourette Syndrome Classification Study Group were included in this study (Sept. 2001 through March 2002): a pediatric group aged from 7 through 16 years (N = 25) and an adult group aged 18 years and older (N = 32). During a 12-week period, participants were asked weekly to fill out questionnaires regarding the occurrence of small life events and self ratings of tic severity. Twenty-four of 25 patients in the pediatric group completed the study, and 28 of 32 patients in the adult group completed the study and reported at least 1 life event. In the adult group as a whole, we found a weak but statistically significant correlation between negative small life events and tic severity during the same week (r = 0.268, p <.001). However, only a minority of individual pediatric (21%) and adult (18%) patients demonstrated significant relationships between the frequency of small life events and tic severity in the same week or 1 week later (p </=.05), with undesirable small life events positively associated with tic severity in some patients and negatively associated with tic severity in other patients. Contrary to traditional views, in general, life events do not account for changes in tic severity. Only in a minority of tic disorder patients do fluctuations in symptom severity appear to be associated with possibly stressful small life events.

To study the influence of increased familial risk for attention-deficit/hyperactivity disorder (ADHD) on brain morphology. Volumetric cerebral measures based on whole brain magnetic resonance imaging scans from 30 boys with ADHD, 30 of their unaffected siblings, and 30 matched controls were compared. Both subjects with ADHD and their unaffected siblings displayed reductions in right prefrontal gray matter and left occipital gray and white matter of up to 9.1% (p < 0.05). Right cerebellar volume was reduced by 4.9% in subjects with ADHD (p = 0.026) but not in their unaffected siblings (p = 0.308). A 4.0% reduction in intracranial volume was found in subjects with ADHD (p = 0.031), while a trend was observed in their unaffected siblings (p = 0.068). The volumetric reductions in cortical gray and white matter in subjects with ADHD are also present in their unaffected siblings, suggesting that they are related to an increased familial risk for the disorder. In contrast, the cerebellum is unaffected in siblings, suggesting that the reduction in volume observed in subjects with ADHD may be more directly related to the pathophysiology of this disorder.

Objective: One of the most powerful medications that have very broad aspects of clinical application are the selective serotonin reuptake inhibitors (SSRI). We use SSRI as a first choice agents in treatment of depression, obsessive-compulsive disorders and some anxiety disordes. Objective: To analyze the outcome of treatment of adolescent depresion with SSRI’s, considering the age group, disorder categories, response to treatment and side effects. Methods: A retrospective epidemiological investigation was conducted by means of medical records for all adolescent treated with sertraline during six months period at the Department of Child and Adolescent Psychiatry in Belgrade. The clinical response to treatment was rated by Beck Depression Inventory and Hamilton Depression Rating Scale. Results: 5 boys and 10 girls (mean age 15.7) were treated with sertraline during the first episode of depression; administred doses were 50–75 mg per day. 86% of patients improved, 10% droped out because of economic reasons, and 4% experienced side affects (nausea, vomiting, headache). Conclusion: Sertraline is potent, safe and effective in the treatment of young people with first episode of depression.

Elevated D8/17 expression on B lymphocytes is a known susceptibility marker of rheumatic fever. Previous studies have reported higher than usual D8/17 expression on B lymphocytes of patients with tic disorders. The purpose of this study was to assess D8/17 expression on B lymphocytes of tic disorder patients by using an objective method in which no operator variability was involved. D8/17 expression on B lymphocytes was assessed with flow cytometry by using an immunoglobulin M (IgM) monoclonal D8/17-specific antibody in an unselected group of Dutch patients with tic disorders (N=33) and healthy volunteers (N=20). Binding of this monoclonal antibody was compared with binding of an irrelevant IgM monoclonal antibody, and the shift in mean fluorescence intensity of the D8/17-specific antibody compared to that of the irrelevant IgM monoclonal antibody was used as a measure of D8/17 overexpression. For the patients, Yale Global Tic Severity Scale scores were used to assess disease severity. D8/17 overexpression in the patient group (mean=16.8 arbitrary units, SD=30.5) was significantly higher than in the comparison group (mean=3.2, SD=3.0). A significant minority of the patients (N=13, 39.4%), however, had levels of D8/17 overexpression within the range of that of the healthy comparison subjects. Flow cytometric analysis did not indicate a separate subpopulation of D8/17-positive B cells. These data confirm the utility of D8/17 B cell overexpression as a peripheral blood marker in patients with tic disorders and are compatible with a streptococcus-related pathogenesis for at least a subgroup of patients with tic disorders.