Differential association between MAOA, ADHD and neuropsychological functioning in boys and girls

Contains fulltext : 70148.pdf (publisher's version ) (Closed access)Attention-deficit/hyperactivity disorder (ADHD) is more common in boys than in girls. It has been hypothesized that this sex difference might be related to genes on the X-chromosome, like Monoamine Oxidase A (MAOA). Almost all studies on the role of MAOA in ADHD have focused predominantly on boys, making it unknown whether MAOA also has an effect on ADHD in girls, and few studies have investigated the relationship between MAOA and neuropsychological functioning, yet this may provide insight into the pathways leading from genotype to phenotype. The current study set out to examine the relationship between MAOA, ADHD, and neuropsychological functioning in both boys (265 boys with ADHD and 89 male non-affected siblings) and girls (85 girls with ADHD and 106 female non-affected siblings). A haplotype was used based on three single nucleotide polymorphisms (SNPs) (rs12843268, rs3027400, and rs1137070). Two haplotypes (GGC and ATT) captured 97% of the genetic variance in the investigated MAOA SNPs. The ATT haplotype was more common in non-affected siblings (P = 0.025), conferring a protective effect for ADHD in both boys and girls. The target and direction of the MAOA effect on neuropsychological functioning was different in boys and girls: The ATT haplotype was associated with poorer motor control in boys (P = 0.002), but with better visuo-spatial working memory in girls (P = 0.01). These findings suggest that the genetic and neuropsychological mechanisms underlying ADHD may be different in boys and girls and underline the importance of taking into account sex effects when studying ADHD

About breaking barriers, the risk paradox, and other twists

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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 settingSubjects (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. After a follow-up period (mean: 4.4 years) this subsample was re-assessed at a mean age of 16.4 years. Measurements PSUD and nicotine dependence were assessed using the Diagnostic Interview Schedule for Children, Alcohol Use Disorders Identification Test, Drug Abuse Screening Test and Fagerstrom test for Nicotine Dependence. Findings The ADHD sample was at higher risk of developing PSUD [hazard ratio (HR)=1.77, 95% confidence interval (CI)=1.05-3.00] and nicotine dependence (HR=8.61, 95% CI=2.44-30.34) than healthy controls. The rates of these disorders were highest for ADHD youth who also had CD, but could not be accounted for by this comorbidity. We did not find an increased risk of developing PSUD (HR=1.18, 95% CI=0.62-2.27) or nicotine dependence (HR=1.89, 95% CI=0.46-7.77) among unaffected siblings of ADHD youth. Conclusions A childhood diagnosis of attention deficit hyperactivity disorder is a risk factor for psychoactive substance use disorder and nicotine dependence in adolescence and comorbid conduct disorder, but not oppositional defiant disorder, further increases the risk of developing psychoactive substance use disorder and nicotine dependence

A review and analysis of the relationship between neuropsychological measures and DAT1 in ADHD

Contains fulltext : 69105.pdf (publisher's version ) (Closed access)Meta-analyses indicate that the gene coding for the dopamine transporter (DAT1 or SLC6A3) is associated with an increased risk for ADHD. The mechanisms of this gene for ADHD are unclear. We systematically reviewed studies linking the VNTR in the 3' UTR of the DAT1 to neurophysiological and neuropsychological measures. In addition, a broad set of executive/cognitive and motor tests was administered to 350 children (5-11 years) and adolescents (11-19 years) with ADHD and 195 non-affected siblings. Two VNTRs (in intron 8 and the 3' UTR) and four SNPs (two 5' and two 3') in DAT1 were genotyped. The effect of the polymorphisms on neuropsychological functioning was studied. The review indicated that the majority of studies did not find a relation between DAT1 and neurophysiological or neuropsychological measures. In our sample, several of the polymorphisms of DAT1 were associated with ADHD and ADHD was associated with impaired neuropsychological functioning. However, none of the DAT1 polymorphisms was convincingly associated with neuropsychological dysfunctioning. This suggests that the effect of DAT1 on ADHD was not mediated by neuropsychological performance. However, since DAT1 is mainly expressed in the striatum and not the prefrontal cortex, it may influence striatum-related functions (such as delay aversion) more heavily than prefrontal related functions (such as executive functions). Associations of DAT1 with ADHD were only found in adolescents, which may suggest that DAT1 mainly exerts its effect in adolescence, and/or that having a more persistent form of ADHD may mark a more severe or homogeneous genetic form of the disorder

De arbeidsongeschiktheidsverzekering: tussen publiek en privaat. Een beschrijving, analyse en waardering van de belangrijkste wijzigingen in het Nederlandse arbeidsongeschiktheidsstelsel tussen 1980 en 2010

Het Nederlandse arbeidsongeschiktheidsstelsel bestaat uit wettelijke regelingen, zoals de loondoorbetaling bij ziekte op grond van het Burgerlijk Wetboek en de Wet Werk en inkomen naar arbeidsvermogen, én uit cao-regelingen die een bovenwettelijke aanvulling verstrekken. De laatste dertig jaar zijn de wettelijke regelingen vaak en grondig herzien. In reactie daarop hebben sociale partners hun cao-regelingen aangepast. In deze studie worden de belangrijkste wijzigingen onderzocht die zich tussen 1980 en 2010 hebben voorgedaan in de personele en materiële werkingssfeer, de financiering en de uitvoering van de hiervoor bedoelde regelingen. Daarbij staat de vraag centraal hoe die wijzigingen en de daaraan ten grondslag liggende overwegingen, kunnen worden gewaardeerd. Dat geschiedt op basis van vijf criteria: mate van keuzevrijheid, mate van inkomensbescherming, mate van solidariteit, aantal arbeidsongeschikten en totale kosten. Verder wordt onderzocht welke alternatieven er bestaan voor het huidige arbeidsongeschiktheidsstelsel. Ook die alternatieven worden gewaardeerd op basis van de vijf hiervoor genoemde criteria. Op deze manier wordt de bestaande kennis over de grondslagen van het huidige arbeidsongeschiktheidsstelsel verdiept. Waarom is het stelsel ingericht zoals het is ingericht? Wat zijn de voor- en nadelen van dit stelsel? Meer concreet wordt ingegaan op de noodzaak of wenselijkheid van een verzekeringsplicht voor werknemers, de optimale verhouding tussen publieke en private inkomensbescherming, de spanning tussen rechtvaardigheid en doelmatigheid bij de financiering van de uitkeringslasten, de effectiviteit van financiële prikkels en de doelmatigheid van de uitvoering.Hervorming Sociale Regelgevin

Structural brain imaging correlates of ASD and ADHD across the lifespan:a hypothesis-generating review on developmental ASD-ADHD subtypes

Contains fulltext : 169832.pdf (publisher's version ) (Open Access)We hypothesize that it is plausible that biologically distinct developmental ASD-ADHD subtypes are present, each characterized by a distinct time of onset of symptoms, progression and combination of symptoms. The aim of the present narrative review was to explore if structural brain imaging studies may shed light on key brain areas that are linked to both ASD and ADHD symptoms and undergo significant changes during development. These findings may possibly pinpoint to brain mechanisms underlying differential developmental ASD-ADHD subtypes. To this end we brought together the literature on ASD and ADHD structural brain imaging symptoms and particularly highlight the adolescent years and beyond. Findings indicate that the vast majority of existing MRI studies has been cross-sectional and conducted in children, and sometimes did include adolescents as well, but without explicitly documenting on this age group. MRI studies documenting on age effects in adults with ASD and/or ADHD are rare, and if age is taken into account, only linear effects are examined. Data from various studies suggest that a crucial distinctive feature underlying different developmental ASD-ADHD subtypes may be the differential developmental thinning patterns of the anterior cingulate cortex and related connections towards other prefrontal regions. These regions are crucial for the development of cognitive/effortful control and socio-emotional functioning, with impairments in these features as key to both ASD and ADHD

A polygenic risk score analysis of ASD and ADHD across emotion recognition subtypes

This study investigated the genetic components of ADHD and ASD by examining the cross-disorder trait of emotion recognition problems. The genetic burden for ADHD and ASD on previously identified emotion recognition factors (speed and accuracy of visual and auditory emotion recognition) and classes (Class 1: Average visual, impulsive auditory; Class 2: Average-strong visual & auditory; Class 3: Impulsive & imprecise visual, average auditory; Class 4: Weak visual & auditory) was assessed using ASD and ADHD polygenic risk scores (PRS). Our sample contained 552 participants: 74 with ADHD, 85 with ASD, 60 with ASD + ADHD, 177 unaffected siblings of ADHD or ASD probands, and 156 controls. ADHD- and ASD-PRS, calculated from the latest ADHD and ASD GWAS meta-analyses, were analyzed across these emotion recognition factors and classes using linear mixed models. Unexpectedly, the analysis of emotion recognition factors showed higher ASD-PRS to be associated with faster visual emotion recognition. The categorical analysis of emotion recognition classes showed ASD-PRS to be reduced in Class 3 compared to the other classes (p value threshold [pT] = 1, p = .021). A dimensional analysis identified a high ADHD-PRS reduced the probability of being assigned to the Class 1 or Class 3 (pT = .05, p = .028 and p = .044, respectively). Though these nominally significant results did not pass FDR correction, they potentially indicate different indirect causative chains from genetics via emotion recognition to ADHD and ASD, which need to be verified in future research

Cognitive correlates of attention-deficit hyperactivity disorder in children and adolescents with high intellectual ability

Background There is an ongoing debate as to whether attention-deficit hyperactivity disorder (ADHD) in highly intelligent individuals has a similar presentation as in average intelligent individuals. The aim of this study was to examine the cognitive correlates of ADHD in highly intelligent children and adolescents with ADHD. Method Two independent samples (N = 204 and N = 84) of (1) high intelligence quotient (IQ) (IQ >= 120) children and adolescents with ADHD were used, carefully matched on age, gender, ADHD severity, and IQ with (2) control participants with high intelligence, (3) participants with ADHD with an average intelligence (IQ 90-110), and (4) control participants with an average intelligence. These samples were selected from the Dutch node of the International Multicenter ADHD Genetics (NeuroIMAGE) and Tracking Adolescents' Individual Lives Survey (TRAILS) cohorts, respectively, in which a large battery of cognitive tasks was administered. Linear mixed models were used to examine the main effects of ADHD and IQ and their interaction on cognitive performance. Results ADHD-control group differences were not moderated by IQ; mostly equally large ADHD-control differences in cognitive performance were found for high versus average intelligent groups. The small moderating effects found mostly indicated somewhat milder cognitive problems in highly intelligent individuals with ADHD. Overall, highly intelligent children and adolescents with ADHD performed at the level of the average intelligent control children. Conclusions Our findings indicate the cognitive profile of ADHD is similar in highly versus average intelligent individuals with ADHD, although ADHD-related cognitive deficits may be easily overlooked in the high intelligence population when compared to the typical (i.e., average intelligent) control group

Does the cognitive architecture of simplex and multiplex ASD families differ?

Contains fulltext : 167741.pdf (publisher's version ) (Open Access)Children with an autism spectrum disorder (ASD) and their unaffected siblings from 54 simplex (SPX, one individual in the family affected) and 59 multiplex (MPX, two or more individuals affected) families, and 124 controls were assessed on intelligence, social cognition and executive functions. SPX and MPX ASD probands displayed similar cognitive profiles, but within-family contrasts were highest in SPX families, suggesting SPX-MPX stratification may help parse etiological heterogeneity of ASD. Unaffected siblings (regardless SPX or MPX) were mostly unimpaired, suggesting that cognitive problems may be part of the defining features of ASD, rather than being an endophenotypic trait. Except for affective prosody, which appeared to be the most sensitive cognitive marker for detecting familial risk for ASD