Polygenic association between attention-deficit/hyperactivity disorder liability and cognitive impairments.

Background: A recent genome-wide association study (GWAS) identified 12 independent loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). Polygenic risk scores (PRS), derived from the GWAS, can be used to assess genetic overlap between ADHD and other traits. Using ADHD samples from several international sites, we derived PRS for ADHD from the recent GWAS to test whether genetic variants that contribute to ADHD also influence two cognitive functions that show strong association with ADHD: attention regulation and response inhibition, captured by reaction time variability (RTV) and commission errors (CE).

Differential utility of teacher and parent-teacher combined information in the assessment of Attention Deficit/Hyperactivity Disorder symptoms.

Background: Consistent research findings indicate that parents and teachers observe genuinely different Attention Deficit/Hyperactivity Disorder (ADHD) behaviours in their respective settings.

Objective: To evaluate the utility of information provided by teacher informant assessments (INFAs) of ADHD symptoms, and the implications of aggregation algorithms in combing parents' information, i.e.

Is the endorsement of the Attention Deficit Hyperactivity Disorder symptom criteria ratings influenced by informant assessment, gender, age, and co-occurring disorders? A measurement invariance study.

Objectives: This study aims to ascertain whether the differences of prevalence and severity of attention deficit hyperactivity disorder (ADHD) are true or whether children are perceived and rated differently by parent and teacher informant assessments (INFAs) according to gender, age, and co-occurring disorders, even at equal levels of latent ADHD traits.

Methods: Use of latent trait models (for binary responses) to evaluate measurement invariance in children with ADHD and their siblings from the International Multicenter ADHD Gene data.

Results: Substantial measurement noninvariance between parent and teacher INFAs was detected for seven out of nine inattention (IA) and six out of nine hyperactivity/impulsivity (HI) items; the correlations between parent and teacher INFAs for six IA and four HI items were not significantly different from zero, which suggests that parent and teacher INFAs are essentially rating different kinds of behaviours expressed in different settings, instead of measurement bias.

Familiality of Co-existing ADHD and Tic Disorders: Evidence from a Large Sibling Study.

Background: The association of attention-deficit/hyperactivity disorder (ADHD) and tic disorder (TD) is frequent and clinically important. Very few and inconclusive attempts have been made to clarify if and how the combination of ADHD+TD runs in families.

Aim: To determine the first time in a large-scale ADHD sample whether ADHD+TD increases the risk of ADHD+TD in siblings and, also the first time, if this is independent of their psychopathological vulnerability in general.

Are all the 18 DSM-IV and DSM-5 criteria equally useful for diagnosing ADHD and predicting comorbid conduct problems?

In view of ICD-11 revision, we evaluate whether the 18 DSM-IV diagnostic items retained by DSM-5 could be further improved (i) in predicting ADHD 'caseness' and 'impairment' and (ii) discriminating ADHD without CD (ADHD - CD) cases from ADHD with CD (ADHD + CD) cases. In a multi-centre study sample consisting of 1497 ADHD probands and 291 unaffected subjects, 18 diagnostic items were examined for redundancy; then each item was evaluated for association with caseness, impairment and CD status using Classical Test Theory, Item-Response Theory and logistic regression methods. First, all 18 DSM-IV items contributed significantly and independently to the clinical diagnosis of ADHD.

Angiogenic, neurotrophic, and inflammatory system SNPs moderate the association between birth weight and ADHD symptom severity.

Low birth weight is associated with increased risk for Attention-Deficit/Hyperactivity Disorder (ADHD); however, the etiological underpinnings of this relationship remain unclear. This study investigated if genetic variants in angiogenic, dopaminergic, neurotrophic, kynurenine, and cytokine-related biological pathways moderate the relationship between birth weight and ADHD symptom severity. A total of 398 youth from two multi-site, family-based studies of ADHD were included in the analysis.

Somatic and mental health service use of children and adolescents in Germany (KiGGS-study).

Only a limited number of national surveys have investigated both somatic and mental health service use in children and adolescents. The current study aimed to assess service use in Germany as based on at least a single contact with a somatic (pediatrician, general practitioner, nonmedical practitioner) and/or mental health (psychiatrist, psychologist, youth welfare) care specialist within the last 12 months. Questionnaire responses of 6,475 children and adolescents aged 11.

Candidate genetic pathways for attention-deficit/hyperactivity disorder (ADHD) show association to hyperactive/impulsive symptoms in children with ADHD.

Objective: Because multiple genes with small effect sizes are assumed to play a role in attention-deficit/hyperactivity disorder (ADHD) etiology, considering multiple variants within the same analysis likely increases the total explained phenotypic variance, thereby boosting the power of genetic studies. This study investigated whether pathway-based analysis could bring scientists closer to unraveling the biology of ADHD.

Method: The pathway was described as a predefined gene selection based on a well-established database or literature data.

Stimulant treatment for attention-deficit hyperactivity disorder and risk of developing substance use disorder.

Background: Attention-deficit hyperactivity disorder (ADHD) is linked to increased risk for substance use disorders and nicotine dependence.

Aims: To examine the effects of stimulant treatment on subsequent risk for substance use disorder and nicotine dependence in a prospective longitudinal ADHD case-control study.

Method: At baseline we assessed ADHD, conduct disorder and oppositional defiant disorder.

High loading of polygenic risk for ADHD in children with comorbid aggression.

OBJECTIVE Although attention deficit hyperactivity disorder (ADHD) is highly heritable, genome-wide association studies (GWAS) have not yet identified any common genetic variants that contribute to risk. There is evidence that aggression or conduct disorder in children with ADHD indexes higher genetic loading and clinical severity. The authors examine whether common genetic variants considered en masse as polygenic scores for ADHD are especially enriched in children with comorbid conduct disorder.

Substance use disorders in adolescents with attention deficit hyperactivity disorder: a 4-year follow-up study.

Aim: To examine the relationship between a childhood diagnosis of attention deficit hyperactivity disorder (ADHD) with or without oppositional defiant disorder (ODD)/conduct disorder (CD) and the development of later alcohol/drug use disorder [psychoactive substance use disorder (PSUD)] and nicotine dependence in a large European sample of ADHD probands, their siblings and healthy control subjects.

Participants, Design And Setting: Subjects (n = 1017) were participants in the Belgian, Dutch and German part of the International Multicenter ADHD Genetics (IMAGE) study. IMAGE families were identified through ADHD probands aged 5-17 years attending out-patient clinics, and control subjects from the same geographic areas.

Neuropsychological correlates of emotional lability in children with ADHD.

Background: Emotional lability (EL) is commonly seen in patients with attention-deficit/hyperactivity disorder (ADHD). The reasons for this association remain currently unknown. To address this question, we examined the relationship between ADHD and EL symptoms, and performance on a range of neuropsychological tasks to clarify whether EL symptoms are predicted by particular cognitive and/or motivational dysfunctions and whether these associations are mediated by the presence of ADHD symptoms.

German validation of the conners adult ADHD rating scale-self-report: confirmation of factor structure in a large sample of participants with ADHD.

Objective: The Conners Adult ADHD Rating Scales (CAARS) assess symptoms specific to adults that are frequently used and have been translated into German. The current study tests the factor structure of the CAARS in a large sample of German adults with ADHD and compares the means of the CAARS subscales with those of healthy German controls.

Method: CAARS were completed by 466 participants with ADHD and 851 healthy control participants.

Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a common, heritable neuropsychiatric disorder of unknown etiology. We performed a whole-genome copy number variation (CNV) study on 1,013 cases with ADHD and 4,105 healthy children of European ancestry using 550,000 SNPs. We evaluated statistically significant findings in multiple independent cohorts, with a total of 2,493 cases with ADHD and 9,222 controls of European ancestry, using matched platforms.

The hierarchical factor model of ADHD: invariant across age and national groupings?

Objective: To examine the factor structure of attention-deficit/hyperactivity disorder (ADHD) in a clinical sample of 1,373 children and adolescents with ADHD and their 1,772 unselected siblings recruited from different countries across a large age range. Hierarchical and correlated factor analytic models were compared separately in the ADHD and sibling samples, across three different instruments and across parent and teacher informants. Specific consideration was given to factorial invariance analyses across different ages and different countries in the ADHD sample.

An exploration of the associations of pregnancy and perinatal features with cytokines and tryptophan/kynurenine metabolism in children with attention-deficit hyperactivity disorder (ADHD).

Intra-individual variability of the characteristics of children with attention-deficit hyperactivity (ADHD) may reflect compromised glial energy supply in the synapse. We reported recently that while serum levels of a glial marker, the cytokine S100B, were not seriously altered, levels of other cytokines and tryptophan metabolites were related to symptoms, attention and variability. Here, we explore with a regression analysis whether levels of these substances were associated with features of the index pregnancy of potential aetiological significance.

A functional variant of the serotonin transporter gene (SLC6A4) moderates impulsive choice in attention-deficit/hyperactivity disorder boys and siblings.

Background: Impulsive drive for immediate reward (IDIR) and delay aversion are dissociable elements of the preference for immediate over delayed rewards seen in attention-deficit/hyperactivity disorder (ADHD). We hypothesized that IDIR would be associated with dopamine regulating genes and delay aversion would be associated with serotonin-regulating genes.

Methods: Impulsive drive for immediate reward and delay aversion were measured in 459 male children and adolescents (328 ADHD and 131 unaffected siblings) with a laboratory choice task.

The impact of study design and diagnostic approach in a large multi-centre ADHD study: Part 2: Dimensional measures of psychopathology and intelligence.

Background: The International Multi-centre ADHD Genetics (IMAGE) project with 11 participating centres from 7 European countries and Israel has collected a large behavioural and genetic database for present and future research. Behavioural data were collected from 1068 probands with ADHD and 1446 unselected siblings. The aim was to describe and analyse questionnaire data and IQ measures from all probands and siblings.

The impact of study design and diagnostic approach in a large multi-centre ADHD study. Part 1: ADHD symptom patterns.

Background: The International Multi-centre ADHD Genetics (IMAGE) project with 11 participating centres from 7 European countries and Israel has collected a large behavioural and genetic database for present and future research. Behavioural data were collected from 1068 probands with the combined type of attention deficit/hyperactivity disorder (ADHD-CT) and 1446 'unselected' siblings. The aim was to analyse the IMAGE sample with respect to demographic features (gender, age, family status, and recruiting centres) and psychopathological characteristics (diagnostic subtype, symptom frequencies, age at symptom detection, and comorbidities).

Genome-wide association study of motor coordination problems in ADHD identifies genes for brain and muscle function.

Objectives: Motor coordination problems are frequent in children with attention deficit/hyperactivity disorder (ADHD). We performed a genome-wide association study to identify genes contributing to motor coordination problems, hypothesizing that the presence of such problems in children with ADHD may identify a sample of reduced genetic heterogeneity.

Methods: Children with ADHD from the International Multicentre ADHD Genetic (IMAGE) study were evaluated with the Parental Account of Children's Symptoms.

The ATXN1 and TRIM31 genes are related to intelligence in an ADHD background: evidence from a large collaborative study totaling 4,963 subjects.

Intelligence is a highly heritable trait for which it has proven difficult to identify the actual genes. In the past decade, five whole-genome linkage scans have suggested genomic regions important to human intelligence; however, so far none of the responsible genes or variants in those regions have been identified. Apart from these regions, a handful of candidate genes have been identified, although most of these are in need of replication.