Biomedical subjects

Ruud B Minderaa

Publications and source records attributed to Ruud B Minderaa.

At least 19 recordsLinked to original sources

PubMed2007

Prolactin release in children treated with risperidone: impact and role of CYP2D6 metabolism.

OBJECTIVE: Little is known about the role of CYP2D6 polymorphism in risperidone-induced prolactin release in children. METHOD: Twenty-five children (aged 5-15 years) with pervasive developmental disorders were genotyped for CYP2D6 polymorphisms. Serum prolactin, risperidone, and 9-hydroxyrisperidone were assessed at baseline and after 8 weeks of risperidone treatment (mean dosage, 0.06 +/- 0.03 mg/kg/d). After 24 weeks of treatment, prolactin was measured in a subsample of 15 children. Adverse effects were evaluated using a clinician-rated survey. RESULTS: Mean +/- SD prolactin levels increased from 7.8 +/- 8.0 ng/mL at baseline to 33.2 +/- 12.8 ng/mL at week 8 (P < 0.001), with a slight decrease to 28.8 +/- 13.6 ng/mL at week 24. At week 8, serum prolactin level was positively correlated with dose per kilogram (r = 0.648, P < 0.001), number of functional CYP2D6 genes (J = 2.117, P = 0.034), and serum 9-hydroxyrisperidone concentration (r = 0.664, P = 0.001) and was negatively correlated with the risperidone/9-hydroxyrisperidone ratio (r = -0.571, P = 0.004) but not with risperidone concentration (r = -0.243, P = 0.264) nor age (r = 0.072, P = 0.733). Prolactin elevation was not associated with adverse effects. CONCLUSIONS: Low-to-intermediate doses of risperidone induced a 4-fold prolactin increase in children without a clear development of tolerance up to 6 months. CYP2D6 ultrarapid metabolism may be a risk factor for more pronounced prolactin elevation.

Adolescent↗

PubMed2006

The effects of memory load and stimulus relevance on the EEG during a visual selective memory search task: an ERP and ERD/ERS study.

OBJECTIVE: Psychophysiological correlates of selective attention and working memory were investigated in a group of 18 healthy children using a visually presented selective memory search task. METHODS: Subjects had to memorize one (load1) or 3 (load3) letters (memory set) and search for these among a recognition set consisting of 4 letters only if the letters appeared in the correct (relevant) color. Event-related potentials (ERPs) as well as alpha and theta event-related synchronization and desynchronization (ERD/ERS) were derived from the EEG that was recorded during the task. RESULTS: In the ERP to the memory set, a prolonged load-related positivity was found. In response to the recognition set, effects of relevance were manifested in an early frontal positivity and a later frontal negativity. Effects of load were found in a search-related negativity within the attended category and a suppression of the P3-amplitude. Theta ERS was most pronounced for the most difficult task condition during the recognition set, whereas alpha ERD showed a load-effect only during memorization. CONCLUSIONS: The manipulation of stimulus relevance and memory load affected both ERP components and ERD/ERS. SIGNIFICANCE: The present paradigm may supply a useful method for studying processes of selective attention and working memory and can be used to examine group differences between healthy controls and children showing psychopathology.

Attention↗

PubMed2006

Parents report on stimulant-treated children in the Netherlands: initiation of treatment and follow-up care.

OBJECTIVES: The aim of this study was to describe current practices around initiation and follow-up care of stimulant treatment among stimulant-treated children in a nationwide survey among parents. METHODS: A total of 115 pharmacies detected current stimulant users <16 years old in their pharmacy information system and sent parents a questionnaire regarding their child's stimulant treatment. RESULTS: Parents returned 924 of 1,307 questionnaires (71%). The median age of the stimulant users was 10 years and 85% were boys. In all, 91% were diagnosed with attention-deficit/hyperactivity disorder (ADHD). In 77% of the cases, the child or parents received other therapies besides stimulants-21% received psychotropic co-medication, with melatonin (11%) and antipsychotics (7%) being mentioned most frequently. Stimulant use was primarily initiated by child psychiatrists (51%) and pediatricians (32%), but most children received repeat prescriptions from general practitioners (61%). Of these 924 children, 19% did not receive any follow-up care, and transfer of prescribing responsibility increased the risk of not receiving follow-up care. The 732 children (79%) who were monitored visited a physician approximately twice a year. During follow-up visits, pediatricians performed physical check ups significantly more often. CONCLUSION: Stimulant treatment in The Netherlands is initiated mainly by specialists such as child psychiatrists and pediatricians. In the current study, follow-up care for stimulant-treated children in The Netherlands appeared to be poor, suggesting an urgent need for improvement.

Adolescent↗

PubMed2006

Neuropsychological effects of risperidone in children with pervasive developmental disorders: a blinded discontinuation study.

OBJECTIVE: Little is known about the neuropsychological effects of risperidone in children with pervasive developmental disorders. METHOD: Twenty-four children (aged 5-17 years) with pervasive developmental disorders and co-morbid disruptive behavior who responded favorably to open-label treatment with risperidone as part of a previously described controlled discontinuation study completed two different computerized attention tasks at baseline, weeks 4, 8, and 24 of open-label treatment, and, at 8 weeks after random assignment to either placebo or risperidone. The primary efficacy measures were response latencies to visually presented stimuli requiring two different types of attention-controlled processing, i.e., focused and divided attention. RESULTS: About half of the clinical responders did not produce valid performance measures. These could be shown to be of younger mental age and less adaptive as measured by the Vineland Behavior Scales. For the valid task performers divided attention (serial search in working memory) was shown to regress in the placebo group (n = 7), while in the risperidone group (n = 7) there was further improvement. No such group difference was found for focused attention. CONCLUSIONS: The study suggests a beneficial effect of risperidone after several months of treatment, enhancing divided attention in children with pervasive developmental disorders.

Adolescent↗

PubMed2006

Atomoxetine for attention-deficit/hyperactivity disorder symptoms in children with pervasive developmental disorders: a pilot study.

OBJECTIVE: 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). METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

Adolescent↗

PubMed2006

Structural equation analysis of a hypothesised symptom model in the autism spectrum.

BACKGROUND: Several studies showed a different symptom structure underlying the spectrum of autistic-like disorders from the behaviour triad as mentioned in the DSM-IV. In the present study, a hypothesised symptom model for autism was constructed, based on earlier explorative findings, and was put to a confirmatory test. METHOD: Items from the Autism Diagnostic Interview-Revised (ADI-R) were used to examine the goodness of fit of the DSM-IV model, the hypothesised symptom model, and two additional models for autism. All models were tested in a group of 255 verbal and nonverbal individuals with minor to severe autistic symptomatology. RESULTS: The DSM-IV model encountered estimation problems. Conversely, the hypothesised symptom model had no such problems and proved to have a better fit to the sample data than the two additional models for autism. However, some of the observed variables were weak indicators of the three latent factors in the model. CONCLUSIONS: The hypothesised symptom model appeared to be a plausible model in a group of individuals with a broad range of autistic behaviours and levels of functioning. Nevertheless, the stability of the model needs further examination in a larger group of individuals with disorders in the autism spectrum, and with varying degrees of intellectual functioning.

Autistic Disorder↗

PubMed2006

Pervasive developmental disorder, behavior problems, and psychotropic drug use in children and adolescents with mental retardation.

OBJECTIVE: This study investigated the interrelationship between psychopharmacotherapy in general and the use of specific psychotropic drugs and pervasive developmental disorder and other behavior problems in children and adolescents with mental retardation. METHODS: A total of 862 participants 4 to 18 years of age, including all levels of mental retardation, were recruited through facilities for children with mental retardation in Friesland, The Netherlands. Information on medication was collected through parent interviews. Behavior problems were investigated with a standardized parent questionnaire (Developmental Behavior Checklist). A pervasive developmental disorder classification was based on the Pervasive Developmental Disorder in Mental Retardation Scale, completed by psychologists or teachers. Logistic regression analysis was used to investigate the relationship between the use of psychotropic drugs and pervasive developmental disorder and other behavioral problems, in the presence of possible confounders. RESULTS: One of 10 participants used psychotropic medication. The main factors associated with psychotropic drug use were pervasive developmental disorder and disruptive behavior. The level of functioning was also associated. Self-absorbed behavior was statistically significantly associated with clonidine use and disruptive behavior with stimulant use. Pervasive developmental disorder and communication problems were the main factors associated with the use of antipsychotic drugs. Age also played a role, whereas gender, living situation, and level of mental retardation did not. CONCLUSIONS: Antipsychotic drugs were associated with pervasive developmental disorder, whereas clonidine and stimulants were associated with self-absorbed and disruptive behavior, respectively. Although clonidine and risperidone are not registered for the problems reported and the other nonstimulants were only sometimes used on-label, their use was associated with specific psychiatric or behavioral problems.

Adolescent↗

PubMed2005

Automated on-line solid-phase extraction coupled with HPLC for measurement of 5-hydroxyindole-3-acetic acid in urine.

BACKGROUND: Quantification of 5-hydroxyindole-3-acetic acid (5-HIAA) in urine is useful in diagnosing and monitoring of patients with carcinoid tumors and in the study of serotonin (5-hydroxytryptamine) metabolism in various disorders. We describe an automated method that incorporates on-line solid-phase extraction (SPE) and HPLC to measure urinary 5-HIAA. METHODS: Automated prepurification of urine was accomplished with HySphere-resin GP SPE cartridges containing strong hydrophobic polystyrene resin. The analyte (5-HIAA) and internal standard [5-hydroxyindole-3-carboxylic acid (5-HICA)] were eluted from the SPE cartridge, separated by reversed-phase HPLC, and detected fluorometrically with a total cycle time of 20 min. Urinary excretion of 5-HIAA was measured in a group of patients with known and suspected carcinoid tumors (n=63) and in 20 patients with autism. RESULTS: The internal standard (5-HICA) and 5-HIAA were recovered in high yields (87.2%-114%). Within- and between-series CVs for the measurement of 5-HIAA in urine ranged from 1.2% to 3.9% and 3.2% to 7.6%, respectively. For urine samples from patients with known or suspected carcinoid tumors, results obtained by the automated method were highly correlated (r=0.988) with those from an established manual extraction method. For samples from autistic patients, urinary excretion of 5-HIAA was similar to that reported for healthy individuals. CONCLUSION: This SPE-HPLC method demonstrated lower imprecision and time per analysis than the manual solvent extraction method.

Autistic Disorder↗

PubMed2005

A comparison of central coherence skills between adolescents with an intellectual disability with and without comorbid autism spectrum disorder.

Central coherence theory hypothesizes individuals with autism process information in a detail-focused fashion. The present study examined whether adolescents with an intellectual disability and comorbid autism spectrum disorder showed a weaker central coherence than age- and IQ-matched controls. The central coherence skills of 43 adolescents from schools for students with severe learning problems were examined with two cognitive tasks. In these two tasks, detail-focused processing is beneficial to global processing to perform the tasks accurately and quickly. The group with autism spectrum disorder performed better than the control group. Adolescents with an intellectual disability and with comorbid autism spectrum disorder have a weaker central coherence than age- and IQ-matched controls. Partial support was also given for variability in weak central coherence within the autism spectrum.

Adolescent↗

PubMed2005

Serotonin transporter intron 2 polymorphism associated with rigid-compulsive behaviors in Dutch individuals with pervasive developmental disorder.

Two putatively functional polymorphisms of the serotonin transporter gene (HTT, SLC6A4) were examined for associations with risk for pervasive developmental disorders (PDDs) and specific autism phenotypes. Dutch patients diagnosed with PDD (N = 125, age range 5-20 years, DSM-IV-TR based criteria, ADI-R and ADOS behavioral assessments) and their parents (N = 230) were genotyped for promoter ins/del (5-HTTLPR) and intron 2 variable number of tandem repeats (VNTR) alleles. Using the transmission disequilibrium test (TDT), no disorder-specific preferential transmission of promoter (long and short) or intron 2 (10- and 12-repeat) alleles was observed. However, multivariate analysis of continuous autism-related behavioral measures revealed that subjects with intron 2 12/12 genotype were significantly more impaired in the rigid-compulsive domain (P = 0.008). Quantitative TDT (QTDT) analysis also showed significant association of the intron 2 VNTR 12-repeat allele with rigid-compulsive behavior (P = 0.015). These results suggest that intron 2 VNTR alleles or nearby polymorphisms in linkage disequilibrium may play a role in specific aspects of the behavioral phenotype of autism.

Adolescent↗

PubMed2005

Deficits in motor control processes involved in production of graphic movements of children with attention-deficit-hyperactivity disorder.

This study aimed to investigate whether two distinct motor control processes, i.e. motor planning and parameter setting, were impaired in children with attention-deficit-hyperactivity disorder (ADHD). An experiment was designed in which children copied figures of increasing complexity under increasing accuracy levels on a digitizer. Sixteen children with ADHD (11 males, 5 females; mean age 8 y 4 mo, SD 1 y 1 mo) and 16 comparison children, without impairment, matched for age and sex participated. ADHD was diagnosed by a psychiatrist following the criteria of the DSM-V. Only children with IQ scores greater than 80 were included. Across all graphic tasks, children with ADHD made slower, inaccurate strokes with relatively high axial pen force compared with the comparison group. No evidence was found for a deficit in motor planning, but parameter setting appeared to be deficient as the ADHD group made less accurate strokes when accuracy demands increased.

Adolescent↗

PubMed2005

Tic disorders and obsessive-compulsive disorder: is autoimmunity involved?

The precise cause of tic disorders and paediatric obsessive-compulsive disorder (OCD) is unknown. In addition to genetic factors, autoimmunity may play a role, possibly as a sequela of preceding streptococcal throat infections in susceptible children. Here we review the most recent findings, from July 2003 onwards, with regard to a possible relationship between tics/OCD and autoimmunity. Evidence about an intriguing correlation between streptococcal infections and tic disorders and OCD is accumulating. Specific criteria have been outlined for paediatric autoimmune disorders associated with streptococcal infections (PANDAS), but autoimmunity may also be involved in tic disorders and/or OCD in general. Anti-basal ganglia auto-antibodies are an important potential indicator of autoimmunity. Although the lack of a standardized methodology makes comparisons of findings difficult, new data has emerged pointing to the possible involvement of specific auto-antigens. Earlier findings of increased D8/17 B cell expression as a putative susceptibility marker could not be replicated, possibly due to instability of the D8/17-binding antibody. Although PANDAS patients have been reported to improve after therapeutic plasma exchange, and antibiotics may prevent symptom exacerbations, immune-based treatments should not be routinely given. In future studies, demonstrating the pathogenetic significance of anti-basal ganglia antibodies in animals is a major challenge to draw any firm conclusions about a role for autoimmunity. Future longitudinal studies should be aimed at assessing the precise relationship between symptom exacerbations, infections, and immune parameters, possibly along with gene expression profiles.

Animals↗

PubMed2005

Association of common cold with exacerbations in pediatric but not adult patients with tic disorder: a prospective longitudinal study.

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.

Adolescent↗

PubMed2005

Long-term effects of risperidone in children with autism spectrum disorders: a placebo discontinuation study.

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

Adolescent↗

PubMed2004

Gender differences in the relation between social support, problems in parent-offspring communication, and depression and anxiety.

Gender differences in the buffer-effect of social support in the relation between stressful circumstances and the development of depression and anxiety disorders are widely assumed, but few studies address this three-way interaction between gender, stress, and support. Data in the present study came from the baseline assessment of the Adolescents at Risk for Anxiety and Depression (ARIADNE) study in 502 adolescent and young-adult children of 356 parents in the Netherlands with a depression, panic disorder and/or obsessive-compulsive disorder. Results indicate that the daughters benefit more from social support than the sons when problems in parent-offspring communication are high, but that this effect holds only for depression symptoms and particularly in relation to problems in father-offspring communication. Social support does not seem to play a role in the development of anxiety.

Adolescent↗

PubMed2004

Magnetic resonance imaging of boys with attention-deficit/hyperactivity disorder and their unaffected siblings.

OBJECTIVE: To study the influence of increased familial risk for attention-deficit/hyperactivity disorder (ADHD) on brain morphology. METHOD: 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. RESULTS: 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). CONCLUSIONS: 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.

Adolescent↗

PubMed2004

Platelet serotonin levels in pervasive developmental disorders and mental retardation: diagnostic group differences, within-group distribution, and behavioral correlates.

OBJECTIVE: To investigate group differences, the within-group distributions, and the clinical correlates of platelet serotonin (5-HT) levels in pervasive developmental disorders (PDD). METHOD: Platelet 5-HT levels were measured in Dutch children and young adults, recruited from 2001 through 2003, with PDD (autism, Asperger's, and PDD-not otherwise specified [PDD-NOS]; n = 81) or with mental retardation (MR; n = 54) but without PDD, and in normal controls (n = 60). The distribution of platelet 5-HT levels was assessed using mixture-modeling analyses. Relationships between platelet 5-HT levels and a full range of demographic, clinical, and behavioral variables were examined. RESULTS: Group mean (+/- SD) platelet 5-HT levels (nmol/10 platelets) were significantly higher in the autistic (4.51 +/- 1.61, n = 33) and PDD-NOS (4.90 +/- 1.54, n = 43) groups compared to the MR (3.48 +/- 1.33, n = 54) or the normal control (3.58 +/- 1.08, n = 60) groups (F4,190 = 9.35, p <.001). Platelet 5-HT values in the combined PDD group showed a bimodal distribution, and an empirical cutpoint for hyperserotonemia was determined. None of the behavioral variables examined was significantly associated with platelet 5-HT levels. CONCLUSIONS: The platelet hyperserotonemia of autism was replicated in Dutch subjects. Platelet 5-HT levels were also increased in PDD-NOS, while no elevation was seen in MR. Platelet 5-HT levels appeared to be bimodally distributed in the PDD group, with an apparent hyperserotonemic subgroup.

Adolescent↗

PubMed2004

Relative contribution of attention-deficit hyperactivity disorder, obsessive-compulsive disorder, and tic severity to social and behavioral problems 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.

Adolescent↗