Paternal influences on treatment outcome of behavioral parent training in children with attention-deficit/hyperactivity disorder.

This study aims to explore the influence of paternal variables on outcome of behavioral parent training (BPT) in children with attention-deficit/hyperactivity disorder (ADHD). 83 referred, school-aged children with ADHD were randomly assigned to BPT plus ongoing routine clinical care (RCC) or RCC alone. Treatment outcome was based on parent-reported ADHD symptoms and behavioral problems. Moderator variables included paternal ADHD symptoms, depressive symptoms, and parenting self-efficacy. We conducted repeated measures analyses of variance (ANOVA) for all variables, and then analyzed the direction of interaction effects by repeated measures ANOVA in high and low scoring subgroups. Paternal ADHD symptoms and parenting self-efficacy played a moderating role in decreasing behavioral problems, but not in decreasing ADHD symptoms. Paternal depressive symptoms did not moderate either treatment outcome. BPT is most beneficial in reducing children's behavioral problems when their fathers have high levels of ADHD symptoms or high-parenting self-efficacy.

Response time variability and response inhibition predict affective problems in adolescent girls, not in boys: the TRAILS study.

The present study examines the relationship between neurocognitive functioning and affective problems through adolescence, in a cross-sectional and longitudinal perspective. Baseline response speed, response speed variability, response inhibition, attentional flexibility and working memory were assessed in a cohort of 2,179 adolescents (age 10-12 years) from the TRacking Adolescents' Individual Lives Survey (TRAILS). Affective problems were measured with the DSM-oriented Affective Problems scale of the Youth Self Report at wave 1 (baseline assessment), wave 2 (after 2.5 years) and wave 3 (after 5 years). Cross-sectionally, baseline response speed, response time variability, response inhibition and working memory were associated with baseline affective problems in girls, but not in boys. Longitudinally, enhanced response time variability predicted affective problems after 2.5 and 5 years in girls, but not in boys. Decreased response inhibition predicted affective problems after 5 years follow-up in girls, and again not in boys. The results are discussed in light of recent insights in gender differences in adolescence and state-trait issues in depression.

Minor neurological dysfunction in children with autism spectrum disorder.

AIM: The aim of this study was to improve the understanding of brain function in children with autism spectrum disorder (ASD) in relation to minor neurological dysfunctions (MNDs). METHOD: We studied MNDs in 122 children (93 males, 29 females; mean age 8 y 1 mo, SD 2 y 6 mo) who, among a total cohort of 705 children (513 males, 192 females; mean age 9 y, SD 2 y 0.5 mo) referred to a regional outpatient non-academic psychiatric centre in the Netherlands, were diagnosed with ASD after an extensive multidisciplinary psychiatric assessment. Children with clear neurological abnormalities (e.g. cerebral palsy or spina bifida) were excluded from the study. MNDs were assessed in all 705 children using the Touwen examination method. Special attention was paid to the severity and type of MND. Data of the children with ASD were compared with neurological morbidity data of children with other psychiatric disorders and with children in the general population, who were born at Groningen University Hospital between 1975 and 1978. RESULTS: Seventy-four percent of the children with ASD showed complex MNDs compared with 52% of the children with other psychiatric disorders and 6% of the reference group (χ(2) =18.0, p<0.001; χ(2) =937.5, p<0.001 respectively). Specific dysfunctions frequently encountered in ASD were dysfunctional posture and muscle tone, fine manipulative disability, dyscoordination, and excessive associated movements. CONCLUSION: These findings suggest a contribution of dysfunctional supraspinal networks involving multiple parts of the brain in the pathogenesis of ASD. This is consistent with findings from neuroimaging studies, and highlights the importance of neurological examinations in paediatric psychiatric assessments.

The DRD4 gene and severity of tics and comorbid symptoms: main effects and interactions with delivery complications.

In this study, we investigated the role of the dopamine receptor D4 (DRD4) 48-base pairs (bp) variable number of tandem repeats (VNTR) and perinatal adversities regarding severity of tics and comorbid symptoms in children with tic disorders. We genotyped 110 children with tics with regard to the 48-bp VNTR and assessed presence of prenatal smoking exposure, and pregnancy and delivery complications by parent questionnaires. We examined associations between 2, 3, 4, and 7 repeat (R) alleles and severity of tics and comorbid obsessive-compulsive, depressive, anxious, and autistic symptoms. Through linear regressions, we investigated whether perinatal adversities and the 2R, 3R, 4R, and 7R alleles would interact with severity ratings of tics or comorbid symptoms as outcome. Presence of a 2R allele was related to more severe obsessive-compulsive symptoms, and presence of a 3R allele to increased severity of autistic features. Pregnancy complications were associated with decreased obsessive-compulsive symptom severity, and prenatal smoking exposure to more severe depressive and autistic symptoms. In children without a 3R allele delivery complications were associated with more severe tics, but in children with a 3R variant an inverse relation between delivery complications and tic severity was found. Moreover, the relation between delivery complications and internalizing symptom severity appeared to be most pronounced in children with a 2R allele. In conclusion, this study provides evidence for a role of the 48-bp VNTR in the etiology of tic and associated disorders, and for interactions with delivery complications regarding severity of tics and co-occurring internalizing symptoms.

Perinatal risk factors interacting with catechol O-methyltransferase and the serotonin transporter gene predict ASD symptoms in children with ADHD.

BACKGROUND: Symptoms of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) often co-occur. Given the previously found familiality of ASD symptoms in children with ADHD, addressing these symptoms may be useful for genetic association studies, especially for candidate gene findings that have not been consistently replicated for ADHD. METHODS: We studied the association of the catechol O-methyltransferase (COMT) Val158Met polymorphism and the serotonin transporter (SLC6A4/SERT/5-HTT) 5-HTTLPR insertion/deletion polymorphism with ASD symptoms in children with ADHD, and whether these polymorphisms would interact with pre- and perinatal risk factors, i.e., maternal smoking during pregnancy and low birth weight. Analyses were performed using linear regression in 207 Dutch participants with combined type ADHD of the International Multicenter ADHD Genetics (IMAGE) study, and repeated in an independent ADHD sample (n =439) selected from the TRracking Adolescents' Individual Lives Survey (TRAILS). Dependent variables were the total and subscale scores of the Children's Social Behavior Questionnaire (CSBQ). RESULTS: No significant main effects of COMT Val158Met, 5-HTTLPR, maternal smoking during pregnancy and low birth weight on ASD symptoms were found. However, the COMT Val/Val genotype interacted with maternal smoking during pregnancy in increasing stereotyped behavior in the IMAGE sample (p =.008); this interaction reached significance in the TRAILS sample after correction for confounders (p =.02). In the IMAGE sample, the 5-HTTLPR S/S genotype interacted with maternal smoking during pregnancy, increasing problems in social interaction (p =.02), and also interacted with low birth weight, increasing rigid behavior (p =.03). Findings for 5-HTTLPR in the TRAILS sample were similar, albeit for related CSBQ subscales. CONCLUSIONS: These findings suggest gene-environment interaction effects on ASD symptoms in children with ADHD.

Urinary excretion of 5-hydroxyindoleacetic acid, serotonin and 6-sulphatoxymelatonin in normoserotonemic and hyperserotonemic autistic individuals.

OBJECTIVE: A substantial proportion of individuals with autism have elevated levels of platelet serotonin (5-HT). We examined whether platelet hyperserotonemia is associated with increased gut 5-HT synthesis, altered 5-HT catabolism or altered melatonin production. METHODS: Urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) and 5-HT was compared in 10 normoserotonemic and 10 hyperserotonemic age-matched autistic individuals. The relationship of urinary 6-sulfatoxymelatonin (6-SM) excretion to platelet 5-HT, and to urinary 5-HT and 5-HIAA excretion, was also examined. RESULTS: In the hyperserotonemic group, significant increases at trend level in urinary excretion of 5-HIAA (p = 0.061) and 5-HT (p = 0.071) and a significant decrease for 6-SM were found (p = 0.027). The urinary 5-HIAA:5-HT ratio was similar in the normo- versus the hyperserotonemic groups. CONCLUSIONS: The catabolism of 5-HT does not differ in the groups, but greater exposure of the platelet to 5-HT cannot be ruled out as a cause of the platelet hyperserotonemia of autism. Although only trend level significant, the data point to a need for larger studies to examine more thoroughly the relationships between platelet hyperserotonemia, gut 5-HT synthesis and melatonin production.

Behavioral parent training as an adjunct to routine care in children with attention-deficit/hyperactivity disorder: moderators of treatment response.

OBJECTIVE: To investigate predictors and moderators of outcome of behavioral parent training (BPT) as adjunct to ongoing routine clinical care (RCC), versus RCC alone. METHODS: We randomly assigned 94 referred children (4-12 years) with attention-deficit/hyperactivity disorder (ADHD) to BPT plus RCC or RCC alone. Outcome was based on parent-reported behavioral problems and ADHD symptoms. Predictor/moderator variables included children's IQ, age, and comorbidity profile, and maternal ADHD, depression, and parenting self-efficacy. RESULTS: Superior BPT treatment effects on behavioral problems and ADHD symptoms were present in children with no or single-type comorbidity-anxiety/depression or oppositional defiant disorder (ODD)/conduct disorder (CD)-and when mothers had high parenting self-efficacy, but absent in children with broad comorbidity (anxiety/depression and ODD/CD) and when mothers had low parenting self-efficacy. In older children ADHD symptoms tended to decrease more through BPT than in younger children. CONCLUSIONS: Adjunctive BPT is most useful when mothers have high parenting self-efficacy and in children with no or single-type comorbidity.

Co-morbidity and patterns of care in stimulant-treated children with ADHD in the Netherlands.

This study aimed at investigating the use of psychosocial interventions and psychotropic co-medication among stimulant-treated children with attention-deficit hyperactivity disorder (ADHD) in relation to the presence of psychiatric co-morbidity. Stimulant users younger than 16 years were identified in 115 pharmacies and a questionnaire was sent to their stimulant prescribing physician. Of 773 questionnaires sent out, 556 were returned and were suitable for analysis (72%). The results are based on 510 questionnaires concerning stimulant-treated children for whom a diagnosis of ADHD was reported. Of the 510 children diagnosed with ADHD, 31% had also received one or more other psychiatric diagnoses, mainly pervasive developmental disorder or oppositional defiant disorder/conduct disorder. We found an association between the presence of co-morbidity and the use of psychosocial interventions for the child (P < 0.001) and the parents (P < 0.001). In the ADHD-only group, 26% did not receive any form of additional interventions, while psychosocial interventions varied from 8 to 18% in children with ADHD and psychiatric co-morbidity. The presence of diagnostic co-morbidity was also associated with the use of psychotropic co-medication (overall, P = 0.012) and antipsychotics (P < 0.001). Stimulant-treated youths with ADHD and psychiatric co-morbidity received more psychosocial interventions and psychotropic co-medication than children with ADHD-only. The type of psychosocial interventions and psychotropic co-medication received by the children and their parents, depended on the specific co-morbid psychiatric disorder being present.

Symptom diagnostics based on clinical records: a tool for scientific research in child psychiatry?

INTRODUCTION: Child psychiatric diagnoses are generally based on a clinical examination and not on standardized questionnaires. The present study assessed whether symptom diagnostics based on clinical records facilitates the use of non-standardized clinical material for research. METHOD: Six hundred and eighty-five children, referred to a third level child psychiatric centre in the Netherlands, were, after extensive multidisciplinary examination, classified according to the multi-axial classification scheme for psychiatric disorders in childhood and adolescence (MAC-ICD-9). By two raters 44 behavioural symptoms were scored based on the clinical records of these children. Interrater agreement on symptoms in 50 records was performed. Principal components analysis on symptom scores of all children was performed; factor scores were related with MAC-ICD-9 classifications. RESULTS: Interrater reliability for behavioural symptoms was excellent (kappa = 0.88). Many children with psychiatric problems suffer from a large number of behavioural symptoms. Factor scores of the symptoms revealed recognizable and well interpretable entities and indicated overlap in symptomatology and comorbidity. CONCLUSION: A symptom-based diagnostic approach based on extensive clinical patient files may provide a special dimension to improve the reliability of psychiatric classification.

Effectiveness of an emotion regulation group training for adolescents--a randomized controlled pilot study.

Emotion Regulation Training (ERT) was developed for adolescents with symptoms of borderline personality disorder (BPD) and emotion dysregulation. ERT is an adaptation of the Systems Training for Emotional Predictability and Problem Solving (STEPPS) programme. This paper describes the background of the programme, and gives an outline of the treatment programme. The effectiveness of ERT was examined in a randomized controlled pilot study with 43 youth (aged 14-19 years) in five mental health centres in the Netherlands. Subjects were assessed before and after random assignment to ERT plus treatment as usual (TAU) (n = 23) or to TAU alone (n = 20). Outcome measures included assessment of BPD symptoms, locus of control, and internalizing and externalizing behaviour. Both groups showed equal reductions in BPD symptoms over time. The group receiving ERT plus TAU (and not the TAU-only group) had a significant increase in internal locus of control: ERT participants reported more sense of control over their own mood swings, and attributed changes in mood swings not only to external factors. The study was complicated by a high attrition. The implications of the findings are discussed, including the difficulties inherent in treating and researching an adolescent population, and the need for researchers to develop age-appropriate assessments.

Distinct information processing characteristics in dyslexia and ADHD during a covert orienting task: an event-related potential study.

OBJECTIVE: A visuo-spatial orienting task was used to investigate the individual and joint contribution of the presence of dyslexia and attention-deficit hyperactivity disorder (ADHD) to information processing. METHODS: Sixteen control, 17 dyslexic, 16 ADHD, and 15 comorbid adults performed the task, comprising a valid, invalid, and no-cue condition. Performance measures were errors and reaction time (RT). A negative potential in response to cues and targets (N2), and a positive potential in response to targets (P3) were derived from the EEG. A 2x2 design was used with the factors dyslexic/non-dyslexic, and ADHD/non-ADHD. RESULTS: Dyslexic participants demonstrated a smaller cue-related N2, yet a greater target-related N2 in the valid condition. ADHD participants were discriminated by the P3 difference between the invalid and valid conditions. Comorbids differed from ADHD mainly in invalid-valid RT, and were similar to dyslexics in target N2 processing. CONCLUSIONS: Dyslexics were impaired in early information processing, and participants with ADHD differed for later processing stages. SIGNIFICANCE: This is the first ERP study of attentional processes in dyslexia to incorporate an ADHD and a comorbid group. Its results may contribute to differentiation of these clinical groups.

Error and feedback processing in children with ADHD and children with Autistic Spectrum Disorder: an EEG event-related potential study.

OBJECTIVE: Performance monitoring was investigated in typically developing (TD) children, children with Autistic Spectrum Disorder (ASD), and Methylphenidate (Mph)-treated and medication-free children with Attention Deficit Hyperactivity Disorder (ADHD). METHODS: Subjects performed a feedback-based learning task. Event-related Potentials (ERPs) time locked to responses and feedback were derived from the EEG. RESULTS: Compared to the TD and ASD groups, the medication-free ADHD group showed a decreased response-locked Error Related Negativity (ERN) and error Positivity (Pe), particularly as learning progressed throughout the task. Compared to the medication-free ADHD group, the Methylphenidate-treated group showed a normalised Pe. All clinical groups showed or tended to show a decreased feedback-locked late positive potential to negative feedback. CONCLUSIONS: The ERPs suggest that medication-free children with ADHD, but not with ASD, have a diminished capacity to monitor their error responses when they are learning by performance feedback. This capacity partially 'normalises' in Mph-treated children with ADHD. Both children with ADHD and children with ASD are suggested being compromised in affective feedback processing. SIGNIFICANCE: This study shows that measuring ERPs of error and feedback processing is a useful method for (1) dissociating ADHD from ASD and (2) elucidating medication effects in ADHD on component processes of performance monitoring.

Attention-deficit/hyperactivity disorder and social dysfunctioning.

Attention-deficit/hyperactivity disorder (ADHD) is associated with functional impairments in different areas of daily life. One such area is social functioning. The purpose of this paper is to critically review research on social dysfunctioning in children with ADHD. Children with ADHD often have conflicts with adults and peers, and suffer from unpopularity, rejection by peers, and a lack of friendships, in part as a consequence of their ADHD symptoms. Comorbid oppositional defiant or conduct disorder aggravates these impairments. In some cases the inadequate social behavior of children with ADHD may be phenomenologically and etiologically related to pervasive developmental disorders (PDD). However, the causes and consequences of PDD symptoms in ADHD are understudied. Also, the relative contributions of ADHD, on the one hand, and comorbid disorders, on the other, to the course of social impairments are unknown. Social dysfunctioning in children with ADHD appears to increase their risk of later psychopathology other than ADHD. Thus far effective treatment for social dysfunctioning is lacking. Future research should address the exact nature and long-term consequences of social dysfunctioning in children with ADHD, and focus on development of effective treatment strategies.

Risk of emotional disorder in offspring of depressed parents: gender differences in the effect of a second emotionally affected parent.

In offspring of depressed parents a second parent with emotional problems is likely to increase risk of emotional disorder. This effect may however differ between sons and daughters and between offspring of depressed fathers and offspring of depressed mothers. In adolescent and young-adult offspring of parents with major depressive disorder, this study examined the effects of a second affected parent, offspring gender, gender of the depressed parent and their interactions on risk of depression and anxiety disorder. We found that daughters had a higher risk of depression and anxiety than sons and that offspring of depressed mothers had a higher risk of anxiety than offspring of depressed fathers. In addition to these main effects, we found an interaction between parent and offspring gender inasmuch that sons of depressed fathers had the lowest risk of depression and anxiety relative to the other groups. A second affected parent tended to increase risk of depression and significantly increased risk of anxiety. However, this effect of a second affected parent on offspring anxiety was most prominent in daughters when the second affected parent was the father, whereas risk in sons did not increase if the father was affected as well. Our results indicate that paternal and maternal depression similarly and additively increase daughters' risk of emotional disorder, but that sons' risk only increases with maternal depression. Intergenerational transmission of emotional disorder seems strongest when the female gender is involved, either in the form of a daughter or a depressed mother.

Use of antipsychotic drugs among Dutch youths between 1997 and 2005.

OBJECTIVE: The authors examined prevalence, incidence, and duration of antipsychotic drug use in the northern and eastern regions of the Netherlands between 1997 and 2005 among youths in regard to age, gender, and class of drug. METHODS: Prescription drug dispensing data were collected from community pharmacies in the northern Netherlands (www.iadb.nl). Prevalence, incidence, and duration of use were studied among roughly 100,000 youths ranging in age from infancy to age 19 years, calculated by age group (zero to four years, five to nine years, ten to 14 years, and 15 to 19 years), for boys and girls, and for first- and second-generation antipsychotics. Duration of use was compared between youths who started antipsychotic treatment in 1998-1999 and those who started in 2001-2002. RESULTS: From 1997 to 2005, prevalence increased from 3.0 to 6.8 per thousand. Prevalence was highest among ten-year-olds to 14-year-olds (11 per thousand), especially among boys (17 per thousand). The increased prevalence was mainly attributable to an increased use of second-generation antipsychotics and to a longer duration of use. Median duration of use doubled from .8 year in 1998-1999 to 1.6 years in 2001-2002. CONCLUSIONS: Second-generation antipsychotic drugs were increasingly prescribed, and for longer periods of time, to younger children, probably because of new indications. This practice increases the exposure of a young population to (partly unknown) risks.

Effectiveness of behavioral parent training for children with ADHD in routine clinical practice: a randomized controlled study.

OBJECTIVE: To investigate the effectiveness of behavioral parent training (BPT) as adjunct to routine clinical care (RCC). METHOD: After a first phase of RCC, 94 children with attention-deficit/hyperactivity disorder (ADHD) ages 4-12, all referred to a Dutch outpatient mental health clinic, were randomly assigned to 5 months of BPT plus concurrent RCC (n = 47) or to 5 months of RCC (n = 47) alone. BPT consisted of 12 sessions in group format; RCC included family support and pharmacotherapy when appropriate. Exclusionary criteria were minimized, and children with and without medication could participate. Parent-reported behavioral problems, ADHD symptoms, internalizing problems, and parenting stress were assessed before and after treatment. Follow-up assessment of the BPT + RCC group was completed 25 weeks post-BPT intervention. Repeated-measures analyses of variance were carried out on an intention-to-treat basis. RESULTS: Both groups showed improvements over time on all measures. BPT + RCC was superior to RCC alone in reducing behavioral (p = .017) and internalizing (p = .042) problems. No outcome differences were found in ADHD symptoms (p = .161) and parenting stress (p = .643). These results were equal for children with and without medication. Children allocated to RCC alone received more polypharmaceutical treatment. CONCLUSIONS: Adjunctive BPT enhances the effectiveness of routine treatment of children with ADHD, particularly in decreasing behavioral and internalizing problems, but not in reducing ADHD symptoms or parenting stress. Furthermore, adjunctive BPT may limit the prescription of polypharmaceutical treatment.

Physiological correlates of learning by performance feedback in children: a study of EEG event-related potentials and evoked heart rate.

In this study we measured event-related potentials (ERPs) and evoked heart rate (EHR) to investigate performance monitoring in 10-12-year-old children. The children received feedback on their performance while conducting a probabilistic learning task. Error-related ERP components time-locked to the response increased in amplitude when the children had learned the task, whereas the feedback-locked components decreased. Concerning EHR, there was a general reduction in feedback-related heart rate deceleration when the children had learned. Moreover, a prolonged heart rate deceleration was observed at negative feedback onset in comparison to positive feedback, which shifted in timing when the task progressed. Together, the ERP and EHR-measures suggest a shift from external to internal monitoring when the children are learning by performance feedback. The data suggest that error- and feedback-related EHR deceleration is a reflection of the same error monitoring system that is responsible for the emergence of the error-related negativity (ERN).

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.

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.