Screening instruments for early detection of autism spectrum disorder in Spanish speaking communities.

BACKGROUND: Since autism detection protocols rely primarily on parental accounts of early symptoms, the use by Spanish-speaking populations of screening tools developed in a different language and socio-cultural context (usually English) might hamper the success of early detection programs. METHOD: A systematic search in four databases was completed, identifying 59 tools used for ASD detection. Of these, only nine tools had been applied in Spanish-speaking populations, and of those, only five can be considered specific tools for the early detection of autism. RESULTS: Sensitivity detecting autism was generally lower in the Spanish versions of the reviewed instruments, while specificity tended to be equal to or higher than that reported in the original screeners. CONCLUSIONS: Heterogeneity and poor methodological rigor of the studies conducted to date emphasize an urgent need for a concerted effort to develop reliable and valid instruments for the early detection of autism in Spanish-speaking populations worldwide.

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 sample was genotyped for the 5HTT (SLC6A4) promoter serotonin-transporter-linked polymorphic region polymorphism and a DAT1 (SLC6A3) 40-base pair variable number tandem repeat located in the 3'-untranslated region of the gene. RESULTS: There was no effect of dopamine transporter (DAT)1 on IDIR. As predicted, serotonin-transporter-linked polymorphic region s-allele carriers were more delay averse. This effect was driven by the s/l genotype in the ADHD group. These results were not altered by taking account of the rs25531 A/G single nucleotide polymorphism and were independent of age, IQ, and oppositional defiant disorder symptoms. CONCLUSIONS: The results support the genetic distinctiveness of IDIR and delay aversion in ADHD and implicate serotonin function in delay aversion. Possible explanations of the heterosis effect in the ADHD cases are presented.

Performance variability, impulsivity errors and the impact of incentives as gender-independent endophenotypes for ADHD.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is one of the most common and highly heritable child psychiatric disorders. There is strong evidence that children with ADHD show slower and more variable responses in tasks such as Go/Nogo tapping aspects of executive functions like sustained attention and response control which may be modulated by motivational factors and/or state-regulation processes. The aim of this study was (1) to determine if these executive functions may constitute an endophenotype for ADHD; (2) to investigate for the first time whether known modulators of these executive functions may also be familial; and (3) to explore whether gender has an impact on these measures. METHODS: Two hundred and five children with ADHD combined type, 173 nonaffected biological siblings and 53 controls with no known family history of ADHD were examined using a Go/Nogo task in the framework of a multi-centre study. Performance-measures and modulating effects of event-rate and incentives were examined. Shared familial effects on these measures were assessed, and the influence of gender was tested. RESULTS: Children with ADHD responded more slowly and variably than nonaffected siblings or controls. Nonaffected siblings showed intermediate scores for reaction-time variability, false alarms and omission errors under fast and slow event-rates. A slower event-rate did not lead to reduced performance specific to ADHD. In the incentive condition, mean reaction-times speeded up and became less variable only in children with ADHD and their nonaffected siblings, while accuracy was improved in all groups. Males responded faster, but also committed more false alarms. There were no interactions of group by gender. CONCLUSIONS: Reaction-time variability and accuracy parameters could be useful neuropsychological endophenotypes for ADHD. Performance-modulating effects of incentives suggested a familially driven motivational dysfunction which may play an important role on etiologic pathways and treatment approaches for ADHD. The effects of gender were independent of familial effects or ADHD-status, which in turn suggests that the proposed endophenotypes are independent of gender.

Delay and reward choice in ADHD: an experimental test of the role of delay aversion.

Children with attention deficit/hyperactivity disorder (ADHD) choose smaller sooner (SS) over larger later (LL) rewards more than controls. Here we assess the contributions of impulsive drive for immediate rewards (IDIR) and delay aversion (DAv) to this pattern. We also explore the characteristics of, and the degree of familiality in, ADHD SS responders. We had 360 ADHD probands; 349 siblings and 112 controls (aged between 6 to 17 years) chose between SS (1 point after 2 s) and LL reward (2 points after 30 s) outcomes on the Maudsley Index of Delay Aversion (Kuntsi, Oosterlaan, & Stevenson, 2001): Under one condition SS choice led to less overall trial delay under another it did not. ADHD participants chose SS more than controls under both conditions. This effect was larger when SS choice reduced trial delay. ADHD SS responders were younger, had lower IQ, more conduct disorder and had siblings who were more likely to be SS responders themselves. The results support a dual component model in which both IDIR and DAv contribute to SS choice in ADHD. SS choice may be a marker of an ADHD motivational subtype.

Autism symptoms in Attention-Deficit/Hyperactivity Disorder: a familial trait which correlates with conduct, oppositional defiant, language and motor disorders.

It is hypothesised that autism symptoms are present in Attention-Deficit/Hyperactivity Disorder (ADHD), are familial and index subtypes of ADHD. Autism symptoms were compared in 821 ADHD probands, 1050 siblings and 149 controls. Shared familiality of autism symptoms and ADHD was calculated using DeFries-Fulker analysis. Autism symptoms were higher in probands than siblings or controls, and higher in male siblings than male controls. Autism symptoms were familial, partly shared with familiality of ADHD in males. Latent class analysis using SCQ-score yielded five classes; Class 1(31%) had few autism symptoms and low comorbidity; Classes 2-4 were intermediate; Class 5(7%) had high autism symptoms and comorbidity. Thus autism symptoms in ADHD represent a familial trait associated with increased neurodevelopmental and oppositional/conduct disorders.

Linkage to chromosome 1p36 for attention-deficit/hyperactivity disorder traits in school and home settings.

BACKGROUND: Limited success has been achieved through previous attention-deficit/hyperactivity disorder (ADHD) linkage scans, which were all designed to map genes underlying the dichotomous phenotype. The International Multi-centre ADHD Genetics (IMAGE) project performed a whole genome linkage scan specifically designed to map ADHD quantitative trait loci (QTL). METHODS: A set of 1094 single selected Caucasian ADHD nuclear families was genotyped on a highly accurate and informative single nucleotide polymorphism (SNP) panel. Two quantitative traits measuring the children's symptoms in home and school settings were collected and standardized according to a population sample of 8000 children to reflect the developmental nature and gender prevalence difference of ADHD. Univariate linkage test was performed on both traits and their mean score. RESULTS: A significant common linkage locus was found at chromosome 1p36 with a locus-specific heritability of 5.1% and a genomewide empirical p < .04. Setting-specific suggestive linkage signals were also found: logarithm of odds (LOD) = 2.2 at 9p23 for home trait and LOD = 2.6 at 11q21 for school trait. CONCLUSIONS: These results indicate that given large samples with proper phenotypic measures, searching for ADHD genes with a QTL strategy is an important alternative to using the clinical diagnosis. The fact that our linkage region 1p36 overlaps with the dyslexia QTL DYX8 further suggests it is potentially a pleiotropic locus for ADHD and dyslexia.

DSM-IV combined type ADHD shows familial association with sibling trait scores: a sampling strategy for QTL linkage.

Attention deficit hyperactivity disorder (ADHD) is a discrete clinical syndrome characterized by the triad of inattention, hyperactivity, and impulsivity in the context of marked impairments. Molecular genetic studies have been successful in identifying genetic variants associated with ADHD, particularly with DSM-IV inattentive and combined subtypes. Quantitative trait locus (QTL) approaches to linkage and association mapping have yet to be widely used in ADHD research, although twin studies investigating individual differences suggest that genetic liability for ADHD is continuously distributed throughout the population, underscoring the applicability of quantitative dimensional approaches. To investigate the appropriateness of QTL approaches, we tested the familial association between 894 probands with a research diagnosis of DSM-IV ADHD combined type and continuous trait measures among 1,135 of their siblings unselected for phenotype. The sibling recurrence rate for ADHD combined subtype was 12.7%, yielding a sibling recurrence risk ratio (lambda(sib)) of 9.0. Estimated sibling correlations around 0.2-0.3 are similar to those estimated from the analysis of fraternal twins in population twin samples. We further show that there are no threshold effects on the sibling risk for ADHD among the ADHD probands; and that both affected and unaffected siblings contributed to the association with ADHD trait scores. In conclusion, these data confirm the main requirement for QTL mapping of ADHD by demonstrating that narrowly defined DSM-IV combined type probands show familial association with dimensional ADHD symptom scores amongst their siblings.