[Medication for ADHD and the risk of cardiovascular mortality].
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Amphetamine↗
Biomedical subjects
J K Buitelaar
Publications and source records attributed to J K Buitelaar.
[Hereditary factors in attention deficit hyperactivity disorder].
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by concentration problems, hyperactivity and impulsivity. Disturbances in dopamine and/or noradrenalin neurotransmission are probably the underlying pathophysiological mechanisms of ADHD. Around 80% of variants of the phenotype can be ascribed to hereditary factors. There are various chromosomal loci containing ADHD genes. They partially overlap the loci found in linkage studies on dyslexia and autism. It seems likely that a number of genetic variants, each with a small effect size, in combination with gene-environment interactions predispose to ADHD. There is a high degree of phenotypical heterogeneity among people with ADHD. Finding endophenotypes may improve the power of genetic studies. Endophenotypes are specific expressions of the underlying pathophysiology, intermediate between gene and phenotype. Neuro-imaging studies in children with ADHD have indicated abnormalities in frontostriatal, temporal and cerebellar volume. Unaffected brothers and sisters show the same cerebral abnormalities, but not the cerebellar abnormalities. These brain abnormalities together with specific neuropsychological features could be ADHD endophenotypes.
Attention Deficit Disorder with Hyperactivity↗
Children with unexplained chronic pain: substantial impairment in everyday life.
AIMS: To describe and quantify impairment in an outpatient population of children with chronic pain of unknown origin (UCP). METHODS: A total of 149 children who presented with pain of at least three months' duration and without a satisfactory explanation at presentation were studied. Number of somatic complaints (Children's Somatisation Inventory, CSI), pain intensity (VAS, 0-10 cm), functional disability (Child Health Questionnaire (CHQ-CF) and clinical history), and general health perceptions (CHQ) were determined. RESULTS: Mean age of the children was 11.8 years; 73% were girls. Overall, 72% suffered impairment in sports activities, 51% reported absence from school, 40% experienced limitations in social functioning, and 34% had problems with sleeping. Mean number of somatic symptoms differed significantly between boys (8.4) and girls (10.7). The CHQ-CF scores for physical functioning, role/social functioning, and general health perceptions were 76.4, 70.7, and 57.5, respectively, indicating substantial impairment on all domains. The mean pain intensity was 4.7 for current and 7.1 for worst pain. Children solely evaluated by a general practitioner prior to referral reported less, though still substantial, impairment. Low general health perceptions, impaired role/social functioning, high pain intensity, and having headache or musculoskeletal pain were independent predictors of having significant impairment. CONCLUSIONS: Referred children with UCP show substantial impairment on multiple domains in daily life.
Activities of Daily Living↗
ADHD: strategies to unravel its genetic architecture.
Attention deficit/hyperactivity disorder (ADHD) is a common and impairing neuropsychiatric disorder with onset at preschool age and strong persistence over time. Its validity as a psychiatric disorder has been established according to Robins and Guze criteria. Genetic factors predominate in the etiology of ADHD. This paper summarizes the current status of genetic research into ADHD, and describes eight factors that complicate research into genetically complex disorders as ADHD. These factors are that multiple genes of small main effects are involved rather than main genes, the relevant phenotype is unknown, presence of clinical heterogeneity, presence of genetic heterogeneity, gene-environment correlation, gene-environment interaction, importance of endophenotypes, and importance of developmental factors. The further unraveling of the genetic architecture of ADHD will depend to a large extent on how well these complicating factors are handled or even used.
Attention Deficit Disorder with Hyperactivity↗
A psychometric evaluation of the social skills rating system in children with attention deficit hyperactivity disorder.
The social skills rating system (SSRS) was developed to assess social skills of children, as observed by multiple raters (teacher, parent, child). Studies of the SSRS have been conducted with handicapped, mentally retarded and learning disabled children. No studies have reported the psychometric properties of the SSRS in a clinical ADHD sample. This is important, because deficient social functioning is associated with ADHD. The present study assesses the psychometric properties of the teacher, parent and child versions of the SSRS in children with ADHD (n = 123), and normal controls (n = 239). Also, the social skills of children with ADHD, as rated on the SSRS were examined. Results support the factor structure and internal consistency of the original SSRS-teacher version. Moreover, support was found for 3 out of 4 scales of the SSRS-parent version. The factor structure of the SSRS-child version could not be replicated. An explanatory factor analysis on the SSRS-child version yielded two factors. Evidence was found for discriminative ability of the SSRS between normal controls and children with ADHD. Finally, informant agreement between raters was found to be poor.
Attention Deficit Disorder with Hyperactivity↗
Determinants of salivary cortisol levels in 10-12 year old children; a population-based study of individual differences.
The hypothalamic-pituitary-adrenal (HPA)-axis is a central component of the body's neuroendocrine response to stress. Its major end-product cortisol has profound effects on mood and behavior. Although it has often been suggested, it remains unknown whether differences in HPA-axis physiology are part of an individual's vulnerability to psychopathology, and constitute a causal factor in its development. In order to study the contribution of HPA-axis physiology to the development of psychopathology, we measured HPA-axis physiology in a community-cohort of 1768 10-12 year-old children. The aims of the here presented study were twofold: (1) to obtain data on HPA-axis function in a large cohort of pre- and early-adolescent children, both in terms of total hormonal output and in terms of the dynamics of cortisol secretion (by means of the cortisol awakening response); and (2) to study potential confounders of the cortisol-psychopathology relationship in this age group, such as season of sampling, age, gender, pubertal development, perinatal variables and BMI. We found a wide interindividual variability in HPA-axis function. An increase in cortisol in the first 30 min after awakening was present in 70.7% of children, but the increase appears lower in children than in adults. In addition, this study suggests that season of sampling and gender may act as potential confounders in the cortisol-psychopathology relationship. We will follow these children longitudinally for the development of psychopathology in the period from childhood into adulthood. This period covers adolescence, which is a critical time for the appearance and development of psychiatric disorders.
Aging↗
Stopping and changing in adults with ADHD.
BACKGROUND: A lack of inhibitory control has been suggested to be the core deficit in children with attention deficit hyperactivity disorder (ADHD). This means that a primary deficit in behavioral inhibition mediates a cascade of secondary deficits in other executive functions, such as arousal regulation. Clinical observations have revealed that with increasing age symptoms of hyperactivity and impulsivity decline at a higher rate than those of inattention. This might imply that a deficit in attention rather than a lack of inhibitory control is the major feature in adult ADHD. METHOD: To study whether an attentional or inhibitory deficit predominates, the stop-signal task and the stop-change task were presented to 24 adults with ADHD combined subtype and 24 controls. RESULTS: Relative to controls, the stop-signal reaction time (SSRT) was significantly more prolonged than the go-stimulus reaction time (RT) in patients with ADHD. This disproportionate elongation of the SSRT was comparable across tasks, even though the stop-change task exerted more complex (or at least different) demands on the inhibitory system than the stop-signal task. ADHD patients had a higher proportion of choice errors, possibly reflecting more premature responses. Specifically in the stop-change task, patients had more variable choice responses and made more inappropriate change responses, which may also reflect enhanced impulsivity. CONCLUSIONS: The results support a core deficit in behavioral inhibition in adults with ADHD. We further suggest that there is more evidence for a critical role of deficient inhibitory control in adults than in children with ADHD.
Adolescent↗
Internalizing and externalizing problems in adolescence: general and dimension-specific effects of familial loadings and preadolescent temperament traits.
BACKGROUND: We investigated the links between familial loading, preadolescent temperament, and internalizing and externalizing problems in adolescence, hereby distinguishing effects on maladjustment in general versus dimension-specific effects on either internalizing or externalizing problems. METHOD: In a population-based sample of 2230 preadolescents (10-11 years) familial loading (parental lifetime psychopathology) and offspring temperament were assessed at baseline by parent report, and offspring psychopathology at 2.5-years follow-up by self-report, teacher report and parent report. We used purified measures of temperament and psychopathology and partialled out shared variance between internalizing and externalizing problems. RESULTS: Familial loading of internalizing psychopathology predicted offspring internalizing but not externalizing problems, whereas familial loading of externalizing psychopathology predicted offspring externalizing but not internalizing problems. Both familial loadings were associated with Frustration, low Effortful Control, and Fear. Frustration acted as a general risk factor predicting severity of maladjustment; low Effortful Control and Fear acted as dimension-specific risk factors that predicted a particular type of psychopathology; whereas Shyness, High-Intensity Pleasure, and Affiliation acted as direction markers that steered the conditional probability of internalizing versus externalizing problems, in the event of maladjustment. Temperament traits mediated one-third of the association between familial loading and psychopathology. Findings were robust across different composite measures of psychopathology, and applied to girls as well as boys. CONCLUSIONS: With regard to familial loading and temperament, it is important to distinguish general risk factors (Frustration) from dimension-specific risk factors (familial loadings, Effortful Control, Fear), and direction markers that act as pathoplastic factors (Shyness, High-Intensity Pleasure, Affiliation) from both types of risk factors. About one-third of familial loading effects on psychopathology in early adolescence are mediated by temperament.
Adolescent↗
Differential effects of DRD4 and DAT1 genotype on fronto-striatal gray matter volumes in a sample of subjects with attention deficit hyperactivity disorder, their unaffected siblings, and controls.
Genetic influences on behavior are complex and, as such, the effect of any single gene is likely to be modest. Neuroimaging measures may serve as a biological intermediate phenotype to investigate the effect of genes on human behavior. In particular, it is possible to constrain investigations by prior knowledge of gene characteristics and by including samples of subjects where the distribution of phenotypic variance is both wide and under heritable influences. Here, we use this approach to show a dissociation between the effects of two dopamine genes that are differentially expressed in the brain. We show that the DAT1 gene, a gene expressed predominantly in the basal ganglia, preferentially influences caudate volume, whereas the DRD4 gene, a gene expressed predominantly in the prefrontal cortex, preferentially influences prefrontal gray matter volume in a sample of subjects including subjects with ADHD, their unaffected siblings, and healthy controls. This demonstrates that, by constraining our investigations by prior knowledge of gene expression, including samples in which the distribution of phenotypic variance is wide and under heritable influences, and by using intermediate phenotypes, such as neuroimaging, we may begin to map out the pathways by which genes influence behavior.
Adolescent↗
Efficacy and safety of methylphenidate in 45 adults with attention-deficit/hyperactivity disorder. A randomized placebo-controlled double-blind cross-over trial.
BACKGROUND: Data on the efficacy and safety of methylphenidate in adults with attention deficit/ hyperactivity disorder (ADHD) are lacking in Europe. This study was undertaken to report on the efficacy and safety of methylphenidate in an adult out-patient population with ADHD, and to compare results with US data. METHOD: A double-blind randomized cross-over trial comparing methylphenidate and placebo in 45 adults with ADHD with childhood onset was performed in a dose-titration design. Methylphenidate was titrated from 0.5 mg/kg per day in week 1 up to 1.0 mg/kg per day in week 3. RESULTS: Response rates using methylphenidate varied between 38 and 51%, and using placebo between 7 and 18% (p<0.05), depending on outcome measure used. Although the overall percentage of subjects having any side effect on both methylphenidate and placebo was rather high, side effects on methylphenidate over and above those on placebo were few and mild. CONCLUSIONS: Methylphenidate proves to be an effective and well tolerated treatment for symptoms of ADHD in adults in the short term. Future research should study the long-term response and clarify the impact of gender, co-morbidity, socio-economic status and IQ on response rates in adults with ADHD.
Adult↗
Effects of methylphenidate, desipramine, and L-dopa on attention and inhibition in children with Attention Deficit Hyperactivity Disorder.
The objective of this study was to investigate the effects of methylphenidate (MPH) on attention and inhibition in children with Attention Deficit Hyperactivity Disorder (ADHD) and to establish what the relative contributions of the noradrenergic and dopaminergic systems to this effect were. In addition to MPH, two other drugs were administered in order to affect both transmitter systems more selectively, L-dopa (dopamine (DA) agonist) and desipramine (DMI) (noradrenaline (NA) re-uptake inhibitor). Sixteen children with ADHD performed a stop-task, a laboratory task that measures the ability to inhibit an ongoing action, in a double-blind randomized within-subjects design. Each child received an acute clinical dose of MPH, DMI, L-dopa, and placebo; measures of performance and plasma were determined. The results indicated that inhibition performance was improved under DMI but not under MPH or L-dopa. The response-time to the stop-signal was marginally shortened after intake of DMI. MPH decreased omission and choice-errors and caused faster reaction times to the trials without the stop-tone. No effects of L-dopa whatsoever were noted. Prolactin levels were increased and 5-HIAA levels were lowered under DMI relative to placebo. It is suggested that the effects of MPH on attention are due to a combination of noradrenergic and dopaminergic mechanisms. The improved inhibition under DMI could be serotonergically mediated.
Attention↗
['It is not in our heads'. The management and psychiatric referral of children with somatically-unexplained abdominal pain].
Two patients, girls aged 9 and 10 years, were admitted to the paediatric ward due to somatically-unexplained debilitating abdominal pain. Both they and their parents expressed resistance to psychiatric examination before and after admission. After conversations with a psychiatrist and an activation programme, one of the girls recovered and the other family broke the medical contact after having enforced a lot of somatic investigations; when followed up, they stated that the complaints had disappeared. The management of somatically-unexplained abdominal pain in children is not always easy. It is essential to introduce the psychiatrist as an expert in treating the consequences of the complaints rather than an expert in searching for psychiatric causes. Associated impaired functioning is a sign of severe symptoms, which require referral to a psychiatrist or a psychologist.
Abdominal Pain↗
A whole-genome scan in 164 Dutch sib pairs with attention-deficit/hyperactivity disorder: suggestive evidence for linkage on chromosomes 7p and 15q.
A genome scan was performed on 164 Dutch affected sib pairs (ASPs) with attention-deficit/hyperactivity disorder (ADHD). All subjects were white and of Dutch descent and were phenotyped according to criteria set out in the Diagnostic and Statistical Manual Of Mental Disorders, 4th edition. Initially, a narrow phenotype was defined, in which all the sib pairs met the full ADHD criteria (117 ASPs). In a broad phenotype, additional sib pairs were included, in which one child had an autistic-spectrum disorder but also met the full ADHD criteria (164 ASPs). A set of 402 polymorphic microsatellite markers with an average intermarker distance of 10 cM was genotyped and analyzed using the Mapmaker/sibs program. Regions with multipoint maximum likelihood scores (MLSs) >1.5 in both phenotypes were fine mapped with additional markers. This genome scan indicated several regions of interest, two of which showed suggestive evidence for linkage. The most promising chromosome region was located at 15q, with an MLS of 3.54 under the broad phenotype definition. This region was previously implicated in reading disability and autism. In addition, MLSs of 3.04 and 2.05 were found for chromosome regions 7p and 9q in the narrow phenotype. Except for a region on chromosome 5, no overlap was found with regions mentioned in the only other independent genome scan in ADHD reported to date.
Adolescent↗
Fetal behaviour does not differ between boys and girls.
INTRODUCTION: Little is known about sex differences in human fetal heart and behaviour. PATIENTS AND METHODS: One hundred twenty-three nulliparous healthy women carrying a male (n=56) or female (n=67) fetus participated in this study. All pregnancies remained uncomplicated and delivery was uneventful. Ultrasound observation of fetal general movements (GM) was performed for 1 h at 15-17 (T1) and 27-28 (T2) weeks of gestation and for 2 h at 37-39 weeks (T3). Fetal heart rate (FHR) monitoring occurred simultaneously with fetal ultrasound observations at T2 and T3. The incidence of GM (percentage of time), FHR and its variability, and the incidences of fetal heart rate patterns (HRP) A-D and behavioural states 1F-4F were compared between boys and girls. RESULTS: There were no significant differences between males and females in the distribution of HRP A-D, overall behavioural state distribution, and basal FHR, FHR variability or the presence of GM during quiet and active sleep (or during HRP A and HRP B, respectively). A TimeXSex interaction effect for GM assessed for total record length and a higher %GM in male fetuses at term age were the only significant findings. However, these observations lost statistical significance after adjustment for the effects of fetal wakefulness, which occurred to a higher extent in male than in female fetuses. CONCLUSION: Our data do not provide evidence for a difference in fetal functional development or maturation between the two sexes.
Adolescent↗
Conduct disorder: guidelines for investigating efficacy of pharmacological intervention.
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Adolescent↗
Attention deficit hyperactivity disorder: guidelines for investigating efficacy of pharmacological intervention.
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Adolescent↗
[Favourable effect of a standard elimination diet on the behavior of young children with attention deficit hyperactivity disorder (ADHD): a pilot study].
OBJECTIVE: To determine whether a standard elimination diet can decrease the ADHD-symptoms in a heterogeneous group of young children with ADHD. DESIGN: Open, descriptive. METHOD: 40 children, 36 boys and 4 girls, aged 3-7 (average 4.8 years), who met the DSM-IV-criteria for ADHD, followed their usual diet for two weeks and thereafter for two weeks an elimination diet, based on the few foods diet (rice, turkey, pear and lettuce). The behaviour of the child was evaluated at study entry, after the baseline period and at the end of the diet. Parents completed the 10-item Conners list, the ADHD Rating Scale and a physical complaints list. The teachers completed the 10-item Conners list and the ADHD Rating Scale twice, at the beginning and at the end of the diet. RESULTS: According to the parent-ratings, 25 children (62%) showed an improvement in behaviour of at least 50% on both the Conners list and the ADHD Rating Scale at the end of the elimination diet. Nine children (23%) withdrew from the study because the parents were unable to stick to the diet or because the child fell ill. Among the 15 children with both parent and teacher ratings, 10 responded both at home and in school. CONCLUSION: In young children with ADHD an elimination diet can lead to a statistically significant decrease in symptoms.
Attention Deficit Disorder with Hyperactivity↗
Prenatal maternal stress: effects on pregnancy and the (unborn) child.
BACKGROUND: Animal experiments have convincingly demonstrated that prenatal maternal stress affects pregnancy outcome and results in early programming of brain functions with permanent changes in neuroendocrine regulation and behaviour in offspring. AIM: To evaluate the existing evidence of comparable effects of prenatal stress on human pregnancy and child development. STUDY DESIGN: Data sources used included a computerized literature search of PUBMED (1966-2001); Psychlit (1987-2001); and manual search of bibliographies of pertinent articles. RESULTS: Recent well-controlled human studies indicate that pregnant women with high stress and anxiety levels are at increased risk for spontaneous abortion and preterm labour and for having a malformed or growth-retarded baby (reduced head circumference in particular). Evidence of long-term functional disorders after prenatal exposure to stress is limited, but retrospective studies and two prospective studies support the possibility of such effects. A comprehensive model of putative interrelationships between maternal, placental, and fetal factors is presented. CONCLUSIONS: Apart from the well-known negative effects of biomedical risks, maternal psychological factors may significantly contribute to pregnancy complications and unfavourable development of the (unborn) child. These problems might be reduced by specific stress reduction in high anxious pregnant women, although much more research is needed.
Adult↗