Attention Deficit Hyperactivity Disorder Traits Research Articles

The affective temperament traits and pregnancy-related depression in mothers may constitute risk factors for their children with attention deficit and hyperactivity disorder

We investigated whether the affective temperaments of mothers and maternal depression before and during the index pregnancy are related to the development of Attention-Deficit Hyperactivity Disorder (ADHD) in their children. One hundred and twenty children were screened for the diagnosis of ADHD. After exclusion and inclusion criteria were applied for children and their mothers, we compared the mothers of children with (n = 63) and without ADHD (n = 60) in terms of affective temperament traits, depression before and during the index pregnancy, and some environmental risk factors. The rate of boys were significantly higher among children with ADHD compared to healthy controls. The mothers of children with ADHD had significantly lower education levels, more cigarette consumption during pregnancy, and more depression rates before the pregnancy than those of healthy children. Male gender (p = .002), Hamilton Depression Rating Scale (HDRS) (p = .002), cyclothymic (p = .022), irritable (p = .035) and anxious temperament scores (p = .016) significantly predicted the association between the mothers and their children with ADHD. Our findings might suggest that male child gender, the severity of depression at index pregnancy, higher cyclothymic, irritable, and anxious temperament scores in mothers may constitute as important risk factors for the development of ADHD in their children.Impact statementWhat is already known on this subject? Although the effects of maternal depression on ADHD were extensively investigated, the relationship between affective temperament traits of mothers and ADHD in their children has not been sufficiently examined. To investigate the roles of maternal affective temperament traits and pregnancy-related depression on offspring ADHD would help us to understand the etiopathogenic bases of ADHD.What do the results of this study add? Cyclothymic, irritable and anxious temperaments of mothers were significantly associated with the offspring ADHD after adjusting for the gender, maternal smoking, prepartum and antenatal depression.What are the implications of these findings for clinical practice and/or further research? These findings might demonstrate that some maternal affective temperaments and depression during pregnancy are suggestive of an inherited predisposition to ADHD in offsprings. Longitudinal studies are required to demonstrate the relationship between maternal affective temperament features and the development of affective illness in children with ADHD.

Coordination difficulties, IQ and psychopathology in children with high-risk copy number variants.

The prevalence and impact of motor coordination difficulties in children with copy number variants associated with neurodevelopmental disorders (ND-CNVs) remains unknown. This study aims to advance understanding of motor coordination difficulties in children with ND-CNVs and establish relationships between intelligence quotient (IQ) and psychopathology. 169 children with an ND-CNV (67% male, median age = 8.88 years, range 6.02-14.81) and 72 closest-in-age unaffected siblings (controls; 55% male, median age = 10.41 years, s.d. = 3.04, range 5.89-14.75) were assessed with the Developmental Coordination Disorder Questionnaire, alongside psychiatric interviews and standardised assessments of IQ. The children with ND-CNVs had poorer coordination ability (b = 28.98, p < 0.001) and 91% of children with an ND-CNV screened positive for suspected developmental coordination disorder, compared to 19% of controls (OR = 42.53, p < 0.001). There was no difference in coordination ability between ND-CNV genotypes (F = 1.47, p = 0.184). Poorer coordination in children with ND-CNV was associated with more attention deficit hyperactivity disorder (ADHD) (β = -0.18, p = 0.021) and autism spectrum disorder trait (β = -0.46, p < 0.001) symptoms, along with lower full-scale (ß = 0.21, p = 0.011), performance (β = -0.20, p = 0.015) and verbal IQ (β = 0.17, p = 0.036). Mediation analysis indicated that coordination ability was a full mediator of anxiety symptoms (69% mediated, p = 0.012), and a partial mediator of ADHD (51%, p = 0.001) and autism spectrum disorder trait symptoms (66%, p < 0.001) as well as full scale IQ (40%, p = 0.002), performance IQ (40%, p = 0.005) and verbal IQ (38%, p = 0.006) scores. The findings indicate that poor motor coordination is highly prevalent and closely linked to risk of mental health disorder and lower intellectual function in children with ND-CNVs. Future research should explore whether early interventions for poor coordination ability could ameliorate neurodevelopmental risk.

Association of maternal developmental disorder traits with child maltreatment

Abstract Objective Maternal mental disorders are known risk factors for child mistreatment. However, little is known about the involvement of maternal developmental disorder traits. The aim of this study was to examine maternal traits related to Pervasive Developmental Disorder (PDD) and Attention Deficit Hyperactivity Disorder (ADHD), and their possible association with child maltreatment. Methods Maternal PDD and ADHD were assessed through a self-administered questionnaire (N = 846) during mid-pregnancy using the Pervasive Developmental Disorders Autism Society Japan Rating Scale (PARS) and Adult ADHD Self-Report Scale (ASRS). The mothers completed another questionnaire on child mistreatment when the offspring was approximately 18 months of age. The associations between maternal PDD and ADHD traits and child maltreatment score were analyzed using linear regression models adjusted for covariates. Results Mothers who exhibited stronger PDD traits showed significantly higher child maltreatment score, even after adjustment for maternal characteristics at baseline and ADHD traits. At the same time, ADHD traits were significantly associated with child maltreatment after adjustment of covariates, although the association became non-significant after adjustment of PDD traits. Conclusions Mothers who showed PDD and ADHD traits during pregnancy were more likely to maltreat their children. It is essential to educate mothers with such traits with appropriate, easy-to-follow childcare instructions, preferably in simple language combined with pictorial aids. Key messages Maternal developmental disorder traits are risk factor of child maltreatment. Specific parenting training intervention for mothers with developmental disorders are needed.

Executive functioning and neurodevelopmental disorders in early childhood: a prospective population-based study

BackgroundExecutive functioning deficits are common in children with neurodevelopmental disorders. However, prior research mainly focused on clinical populations employing cross-sectional designs, impeding conclusions on temporal neurodevelopmental pathways. Here, we examined the prospective association of executive functioning with subsequent autism spectrum disorder (ASD) traits and attention-deficit/hyperactivity disorder (ADHD) traits.MethodsThis study included young children from the Generation R Study, a general population birth cohort. The Brief Rating Inventory of Executive Function-Preschool Version was used to assess parent-reported behavioral executive functioning when the children were 4 years old. ASD traits were assessed at age 6 (n = 3938) using the parent-reported Social Responsiveness Scale. The Teacher Report Form was used to assess ADHD traits at age 7 (n = 2749). Children with high scores were screened to determine possible clinical ASD or ADHD diagnoses. We were able to confirm an ASD diagnosis for n = 56 children by retrieving their medical records and established an ADHD diagnosis for n = 194 children using the Diagnostic Interview Schedule for Children-Young Child version (DISC-YC). Data were analyzed using hierarchical linear and logistic regressions.ResultsImpaired executive functioning was associated with more ASD and ADHD traits across informants (for ASD traits and diagnoses: β = 0.33, 95% CI [0.30–0.37]; OR = 2.69, 95% CI [1.92–3.77], respectively; for ADHD traits and diagnoses: β = 0.12, 95% CI [0.07–0.16]; OR = 2.32, 95% CI [1.89–2.85], respectively). Deficits in all subdomains were associated with higher levels of ASD traits, whereas only impaired inhibition, working memory, and planning/organization were associated with more ADHD traits.ConclusionsThe findings of the current study suggest a graded association of executive functioning difficulties along the continuum of ASD and ADHD and that problems in executive functioning may be a precursor of ASD and ADHD traits from an early age onwards.

Prenatal and childhood phthalate exposure and attention deficit hyperactivity disorder traits in child temperament: A 12-year follow-up birth cohort study

Temperamental tendencies may form the basis of personality development, and specific personality constellations are associated with increased incidences of behavioural problems. Phthalic acid ester (PAE) has been associated with symptoms of attention deficit hyperactivity disorder (ADHD) in cross-sectional studies. We hypothesised that early-life exposure to PAE affects the temperaments of children, particularly ADHD traits. In this study, we analysed the temperament evaluations completed at least once by maternal–infant pairs (n = 208) when the child was aged 2, 5, and/or 11 years between 2000 and 2012. We measured seven PAE metabolites in the urine of the mothers during pregnancy and their children using liquid chromatography-electrospray ionisation-tandem mass spectrometry. These metabolites included mono-methyl phthalate, mono-ethyl phthalate, mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), and three metabolites of di (2-ethylhexyl) phthalate. The phthalate metabolite levels in pregnant women were significantly associated with a decreased threshold of responsiveness (coefficients from −0.21 to −0.46) and increased distractibility (coefficients from 0.23 to 0.46) in pre-school children. After adjustment for maternal exposure, the phthalate metabolite concentrations of the children exhibited significantly increased odds ratios (ORs) with respect to the ADHD symptom traits. Specifically, mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), the sum of the DEHP metabolites, and MBzP yielded ORs and 95% confidence intervals of 2.98 (1.05–8.48), 3.28 (1.15–9.35), and 9.12 (1.07–78.06), respectively, for every log10 creatinine unit (g/g creatinine) increase. Thus, early-life phthalate exposure was found to be associated with the behavioural characteristics of children, particularly temperamental traits associated with ADHD.

Association of Genetic and Environmental Risks for Attention-Deficit/Hyperactivity Disorder With Hypomanic Symptoms in Youths

Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder are highly comorbid, with significantly associated symptoms. The mechanisms that account for their co-occurrence are not known. To examine the degree to which genetic and environmental risk factors for ADHD traits, across childhood and adolescence, are associated with adolescent hypomanic symptoms. This study used data on 13 532 twin pairs from the Child and Adolescent Twin Study in Sweden, a prospective, longitudinal twin study. Their parents provided ADHD data when children were 9 or 12 years of age. Of those who reached 15 years of age, 3784 participated. Of those who reached 18 years of age, 3013 participated. The study was performed from December 20, 2017, to December 5, 2018. Data analysis was performed at the Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm, Sweden, from March 1, 2018, to October 31, 2018. Attention-deficit/hyperactivity disorder traits and hypomanic symptoms were assessed using parent-rated instruments. Associations between ADHD and adolescent hypomanic symptoms across childhood and adolescence were investigated using generalized estimating equations. Multivariate twin models were used to examine the extent to which genetic and environmental risk factors for ADHD were associated with hypomania. Among 3784 15-year-old twin pairs and 3013 18-year-old twin pairs, ADHD and hypomanic symptoms were significantly associated (age 15 years: β = 0.30; 95% CI, 0.24-0.34; P < .001; age 18 years: β = 0.19; 95% CI, 0.16-0.22; P < .001), especially for the hyperactivity-impulsivity ADHD symptom domain (age 15 years: β = 0.53; 95% CI, 0.46-0.60; P < .001; age 18 years: β = 0.36; 95% CI, 0.30-0.42; P < .001) compared with the inattention domain (age 15 years: β = 0.40; 95% CI, 0.34-0.47; P < .001; age 18 years: β = 0.24; 95% CI, 0.19-0.29; P < .001). Between 13% and 29% of the genetic risk factors for hypomania were also associated with ADHD, with higher estimates detected for symptoms of hyperactivity-impulsivity (10%-25%) compared with inattention (6%-16%). Environmental factors played a negligible role in the associations. Genetic factors unique to adolescent hypomania were associated with 25% to 42% of its variance, suggesting some etiologic distinction between these forms of psychopathology. More than a quarter of the genetic risk factors for adolescent hypomanic traits were also associated with ADHD symptoms in childhood and adolescence, with hypomania-specific genetic risk factors detected. These findings suggest that ADHD and hypomanic symptoms are associated with shared genetic factors, which should be the focus of further research.

Adolescents’ experiences of being diagnosed with attention deficit hyperactivity disorder: a phenomenological study conducted in Sweden

ObjectivesTo explore adolescents’ experiences of being diagnosed with Attention deficit hyperactivity disorder (ADHD).DesignQualitative interview study, using a phenomenological framework and analysis.SettingThe children’s clinic of a specialised out-care hospital located in...

Organophosphate pesticide metabolite concentrations in urine during pregnancy and offspring attention-deficit hyperactivity disorder and autistic traits

BackgroundPrenatal exposure to organophosphate (OP) pesticides has been associated with altered neuronal cell development and behavioral changes in animal offspring. However, the few studies investigating the association between prenatal OP pesticide exposure and neurodevelopmental outcomes such as Attention-Deficit Hyperactivity Disorder (ADHD) and autistic traits in children produced mixed findings. ObjectiveThe objective of the present study was to examine whether maternal urinary concentrations of OP pesticide metabolites are associated with ADHD and autistic traits in children participating in the Generation R Study, a population-based birth cohort from Rotterdam, the Netherlands. MethodMaternal concentrations of 6 dialkylphosphates (DAPs) were measured using gas chromatography coupled with tandem mass spectrometry in urine samples collected at <18 weeks, 18‐25 weeks, and > 25 weeks of gestation in 784 mother-child pairs. DAP metabolite concentrations were expressed as molar concentrations divided by creatinine levels and log10 transformed. ADHD traits were measured at ages 3, 6, and 10 years using the Child Behavior Checklist (CBCL) (n = 781) and autistic traits were measured at age 6 years using the Social Responsiveness Scale (SRS) (n = 622). First, regression models were fit for the averaged prenatal exposure across pregnancy. Second, we investigated associations for each collection phase separately, and applied a mutually adjusted model in which the effect of prenatal DAP concentrations from each time period on ADHD and autistic traits were jointly estimated. All associations were adjusted for relevant confounders. ResultsMedian DAP metabolite concentration was 309 nmol/g creatinine at <18 weeks, 316 nmol/g creatinine at 18–25 weeks, and 308 nmol/g creatinine at >25 weeks of gestation. Overall, DAP metabolite concentrations were not associated with ADHD traits. For instance, a log10 increase in averaged total DAP concentrations across gestation was not associated with a lower ADHD score (-0.03 per SD 95 CI: −0.28 to 0.23). Similarly, no associations between maternal DAP concentrations and autistic traits were detected. ConclusionsIn this study of maternal urinary DAP metabolite concentrations during pregnancy, we did not observe associations with ADHD and autistic traits in children. These are important null observations because of the relatively high background DAP concentrations across pregnancy, the relatively large sample size, and the 10-year follow-up of the offspring. Given the measurement error inherent in our OP pesticide exposure biomarkers, future studies using more urine samples are needed to accurately measure OP pesticide exposure over pregnancy in relation to ADHD and autistic traits.

Lower Attentional Skills predict increased exploratory foraging patterns

When engaged in a search task, one needs to arbitrate between exploring and exploiting the environment to optimize the outcome. Many intrinsic, task and environmental factors are known to influence the exploration/exploitation balance. Here, in a non clinical population, we show that the level of inattention (assessed as a trait) is one such factor: children with higher scores on an ADHD (Attention Deficit/Hyperactivity Disorder) questionnaire exhibited longer transitions between consecutively retrieved items, in both a visual and a semantic search task. These more frequent exploration behaviours were associated with differential performance patterns: children with higher levels of ADHD traits performed better in semantic search, while their performance was unaffected in visual search. Our results contribute to the growing literature suggesting that ADHD should not be simply conceived as a pure deficit of attention, but also as a specific cognitive strategy that may prove beneficial in some contexts.

Inattention and task switching performance: the role of predictability, working memory load and goal neglect

Inattention is a symptom of many clinical disorders including attention deficit hyperactivity disorder (ADHD) and is thought to be primarily related to limitations in working memory. In two studies, we investigated the implications of inattention for task switching performance. In study one, we measured task switching performance using predictable and unpredictable conditions in adults who self-rated inattention and other ADHD-related tendencies. Tasks required proactive control and reactive control, respectively, under both high and low working memory loads. Results revealed that inattentive, but not hyperactive/impulsive traits, predicted switch costs when switching was predictable and working memory load was high. None of the ADHD traits were related to unpredictable switch costs. Study two was designed to: (1) de-confound the role of proactive control and the need to keep track of task order in the predictable task switching paradigm; (2) investigate whether goal neglect, an impairment related to working memory, could explain the relationship between inattention and predictable task switching. Results revealed that neither predictability nor the need to keep track of the task order led to the association between switch costs and inattention, but instead it was the tendency for those high in inattention to neglect preparatory proactive control, especially when reactive control options were available.

Maternal urinary concentrations of pyrethroid and chlorpyrifos metabolites and attention deficit hyperactivity disorder (ADHD) symptoms in 2-4-year-old children from the Odense Child Cohort

BackgroundPyrethroids and chlorpyrifos are widely used insecticides, but the potential impact of prenatal exposure on child neurodevelopment has only been addressed in few longitudinal studies. ObjectivesTo investigate associations between prenatal exposure to pyrethroids and chlorpyrifos and traits of ADHD in 2-4-year-old children. MethodsMetabolites of chlorpyrifos and pyrethroids were measured in maternal urine collected at gestational week 28 among 1207 women from the Odense Child Cohort. Of these, 948 completed the Child Behavior Check List for ages 1.5–5 years (CBCL: 1½-5). Negative binomial and logistic regression models were used to estimate relative differences in ADHD problem scores (CBCL: 1½-5 subscale) expressed as the ratio of expected scores between exposure groups and the odds (OR) of scoring equal to or above the 90th percentile in relation to maternal urinary metabolite concentrations (continuous ln2-transformed or categorized into tertiles). The analyses were adjusted for maternal education level, parental psychiatric diagnosis, child age and sex. ResultsThe chlorpyrifos metabolite, 3,5,6-trichloro-2-pyridinol (TCPY), the generic pyrethroid metabolite, 3-phenoxybenzoic acid (3-PBA), and the metabolite of trans-isomers of permethrin, cypermethrin, and cyfluthrin, trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (trans-DCCA), were detected in 90%, 94%, and 11%, respectively, of the urine samples. Each doubling in maternel 3-PBA concentration was associated with a 3% increase in the ADHD score (Ratio: 1.03 (95% CI: 1.00,1.07)) and a 13% higher odds of having a ADHD score ≥ the 90th percentile (OR: 1.13 (1.04,1.38)). Similar associations were seen for 3-PBA as categorical variable (p-trend=0.052 in negative binimoal regression, p-trend=0.007 in logistic regression). Furthermore, concurrent concentrations of 3-PBA and TCPY above their medians were associated with higher ADHD score (Ratio: 1.20 (1.04, 1.38)) and higher odds of scoring ≥ the 90th percentile (OR: 1.98 (1.26, 3.11)). Maternal trans-DCCA above the detection level increased the odds of ADHD symptoms (OR: 1.76 (1.08, 2.86)). The associations were not modified by sex. ConclusionsPrenatal exposure to pyrethroids was associated with ADHD related traits at 2–4 years of age. Considering the widespread use of pyrethroids these results are of concern.

KCNJ6 variants modulate reward-related brain processes and impact executive functions in attention-deficit/hyperactivity disorder.

KCNJ6, encoding a potassium channel subunit, regulates the excitability of dopaminergic neurons and is expressed in attention-deficit/hyperactivity disorder (ADHD)-relevant brain regions. As a potential ADHD risk gene, KCNJ6, therefore, may contribute to the endophenotypic variation of the disorder. The impact of two SNPs, rs7275707 and rs6517442, both located in the transcriptional control region of KCNJ6, on reporter gene expression was explored in cultured cells. The KCNJ6 variants were then tested for association with ADHD and personality traits in a family-based sample (165 affected children) and an adult case-control sample (450 patients, 426 controls). Furthermore, the genotypic influence on performance in an n-back task and a cued continuous performance test (cCPT) was investigated by electroencephalography recordings. Finally, rs6517442 function was assessed by a reward anticipation paradigm using functional magnetic resonance imaging. Different haplotypes of rs7275707 and rs6517442 significantly influenced KCNJ6 gene expression proving their functional relevance on the molecular level. In the family-based children sample rs7275707 was associated with ADHD (p = .038). Moreover, rs7275707 showed association with the personality trait of Reward Dependence (p = .031). In the ADHD group, both rs7275707 and rs6517442 influenced the Go-centroid location in the cCPT and the N200 amplitude in the n-back task. Furthermore, ventral striatal activation was impacted by rs6517442 during reward anticipation. Our data indicate that functional variants of KCNJ6 influence brain activity during reward-related and executive processes supporting the view of a differential, age-dependent modulatory impact of dopamine-related brain processes in ADHD risk.

Are Sluggish Cognitive Tempo, ADHD, and Oppositional Defiant Disorder Trait- or State-Like Constructs from Prekindergarten to Fourth Grade?

The objective was to determine the proportion of trait (consistency across occasions) and occasion-specific variance in sluggish cognitive tempo (SCT), attention deficit/hyperactivity disorder (ADHD)–inattention (IN), ADHD–hyperactivity/impulsivity (HI), and oppositional defiant disorder (ODD) symptom ratings. A single trait factor-multiple state factors model was applied to parent ratings of SCT, ADHD-IN, ADHD-HI, and ODD symptoms for 978 children (50% female) across prekindergarten (M = 4.90 years), kindergarten (M = 6.27 years), 1st-grade (M = 7.42 years), 2nd-grade (M = 8.45 years), and 4th-grade (M = 10.45 years) assessments. For the prekindergarten assessment, SCT, ADHD-IN, ADHD-HI, and ODD contained more occasion-specific than trait variance (54%, 64%, 56%, and 55% occasion-specific variance, respectively). In contrast, SCT, ADHD-IN, ADHD-HI, and ODD contained more trait than occasion-specific variance for the kindergarten through 4th-grade assessments (62%–72%, 65%–68%, 71%–75%, and 60%–69% trait variance, respectively). SCT, ADHD-IN, ADHD-HI, and ODD are slightly to moderately more state-like than trait-like during the prekindergarten developmental period but are more stable traits than fluctuating states from kindergarten to 4th grade. Findings indicate that, particularly after children start formal schooling, these psychopathology dimensions are primarily stable traits; implications for assessment are discussed.

The Functional Brain Organization of an Individual Allows Prediction of Measures of Social Abilities Transdiagnostically in Autism and Attention-Deficit/Hyperactivity Disorder

BackgroundAutism spectrum disorder and attention-deficit/hyperactivity disorder (ADHD) are associated with complex changes as revealed by functional magnetic resonance imaging. To date, neuroimaging-based models are not able to characterize individuals with sufficient sensitivity and specificity. Further, although evidence shows that ADHD traits occur in individuals with autism spectrum disorder, and autism spectrum disorder traits in individuals with ADHD, the neurofunctional basis of the overlap is undefined. MethodsUsing individuals from the Autism Brain Imaging Data Exchange and ADHD-200, we apply a data-driven, subject-level approach, connectome-based predictive modeling, to resting-state functional magnetic resonance imaging data to identify brain–behavior associations that are predictive of symptom severity. We examine cross-diagnostic commonalities and differences. ResultsUsing leave-one-subject-out and split-half analyses, we define networks that predict Social Responsiveness Scale, Autism Diagnostic Observation Schedule, and ADHD Rating Scale scores and confirm that these networks generalize to novel subjects. Networks share minimal overlap of edges (<2%) but some common regions of high hubness (Brodmann areas 10, 11, and 21, cerebellum, and thalamus). Further, predicted Social Responsiveness Scale scores for individuals with ADHD are linked to ADHD symptoms, supporting the hypothesis that brain organization relevant to autism spectrum disorder severity shares a component associated with attention in ADHD. Predictive connections and high-hubness regions are found within a wide range of brain areas and across conventional networks. ConclusionsAn individual's functional connectivity profile contains information that supports dimensional, nonbinary classification in autism spectrum disorder and ADHD. Furthermore, we can determine disorder-specific and shared neurofunctional pathology using our method.

Genetic and environmental aetiologies of associations between dispositional mindfulness and ADHD traits: a population-based twin study

To get additional insight into the phenotype of attentional problems, we examined to what extent genetic and environmental factors explain covariation between lack of dispositional mindfulness and attention-deficit/hyperactivity disorder (ADHD) traits in youth, and explored the incremental validity of these constructs in predicting life satisfaction. We used data from a UK population-representative sample of adolescent twins (N = 1092 pairs) on lack of dispositional mindfulness [Mindful Attention Awareness Scale (MAAS)], ADHD traits [Conners’ Parent Rating Scale-Revised (CPRS-R): inattentive (INATT) and hyperactivity/impulsivity (HYP/IMP) symptom dimensions] and life satisfaction (Students’ Life Satisfaction Scale). Twin model fitting analyses were conducted. Phenotypic correlations (rp) between MAAS and CPRS-R (INATT: rp = 0.18, HYP/IMP: rp = 0.13) were small, but significant and largely explained by shared genes for INATT (% rp INATT–MAAS due to genes: 93%, genetic correlation rA = 0.37) and HYP/IMP (% rp HYP/IMP–MAAS due to genes: 81%; genetic correlation rA = 0.21) with no significant contribution of environmental factors. MAAS, INATT and HYP/IMP significantly and independently predicted life satisfaction. Lack of dispositional mindfulness, assessed as self-reported perceived lapses of attention (MAAS), taps into an aspect of attentional functioning that is phenotypically and genetically distinct from parent-rated ADHD traits. The clinically relevant incremental validity of both scales implicates that MAAS could be used to explore the underlying mechanisms of an aspect of attentional functioning that uniquely affects life satisfaction and is not captured by DSM-based ADHD scales. Further future research could identify if lack of dispositional mindfulness and high ADHD traits can be targeted by different therapeutic approaches resulting in different effects on life satisfaction.

Spit For Science: Using Kids From The Community To Uncover The Genomics of Childhood Psychiatric Disorders

BackgroundMost common disorders, including Attention-Deficit Hyperactivity Disorder (ADHD) and Obsessive-Compulsive Disorder (OCD), are likely extremes of traits that are widely distributed in the general population. People are more or less restless, inattentive, impulsive, obsessional and compulsive; only the extreme of these traits demarcate a clinical diagnosis. Thus, quantitative psychiatric traits, which often share polygenic risk with their relevant diagnosis, will help us discover genes for disorders. Quantitative cognitive traits that might mediate part of the genetic risk of psychiatric disorders (i.e., cognitive endophenotypes) are often less heterogeneous than a diagnosis which could help reduce noise to improve power for gene discovery. Based on these alternative approaches, we designed the Spit for Science study to examine the genomics of childhood psychiatric disorders using behavioural traits and a cognitive endophenotype relevant to ADHD and OCD in a large population-based sample of youth. MethodsSpit for Science is a sample of 17,263 children (6-17 years of age) seen at a local science museum with measures of psychiatric traits and DNA from saliva. Quantitative data on ADHD traits using the Strengths and Weaknesses of ADHD and Normal Behavior (SWAN) scale, obsessive-compulsive (OC) traits using the Toronto Obsessive-Compulsive scale (TOCS) and response inhibition using the Stop-Signal task was collected. We genotyped unrelated Caucasians (n=5,636) using Illumina HumanCoreExome beadchips. For common variant analyses, we conducted standard quality control and used hypothesis-driven genome-wide association analyses (GWAS-HD) to test biological hypotheses for each trait. For the GWAS-HD, permutation tests were used to test the whole gene set for association with each trait respectively. Copy number variants (CNVs) were called using three algorithms and only CNV calls detected by two algorithms and at least 10kb in size were retained. We examined CNV burden for each trait individually. ResultsWe have identified the first genome-wide finding for OC traits (rs7856850; p = 2.9 x 10-8, β = 0.13) replicated in an independent sample of youth screened for OCD. Genes involved in central nervous system development were significantly associated with both OC traits and response inhibition. Polygenic risk score analyses are forthcoming. ADHD traits were associated with increased CNV deletions while response inhibition was associated with more CNV duplications and longer CNV deletions. DiscussionSeveral promising findings have emerged from the Spit for Science study. We identified the first genome-wide finding for OC traits, identified a biological pathway involved in both OC traits and response inhibition, and demonstrated the relationship between rare CNVs with ADHD traits and response inhibition. Results to date demonstrate the feasibility, power and utility of using quantitative-trait based and cognitive endophenotype approaches in community samples to help uncover the underlying genetic architecture of psychiatric disorders.

The Manifestation Of Genetic Risk For Attention Deficit Hyperactivity Disorder In Females And Males In The General Population

Attention Deficit Hyperactivity Disorder (ADHD) is a common, heritable childhood disorder that is more commonly diagnosed in males than females. Several family and molecular genetic studies suggest that females may require a higher burden of genetic risk to manifest the disorder, however the evidence for this effect is mixed and requires replication. Another possibility for the discrepancy in prevalence rate by sex is that females at high genetic risk for ADHD are routinely under-diagnosed with ADHD and instead this genetic risk manifests itself in other ways, e.g. through other diagnoses. To address these possibilities, we utilised Swedish whole population registry data and data on a subset of Swedish twins who were genotyped. In a sample of N=21,784 individuals, we found evidence that full siblings of females with diagnosed ADHD are at higher risk for an ADHD diagnosis than siblings of diagnosed males [OR=1.14 (1.11-1.18), p=1.5E-15]. However, we found no difference in ADHD polygenic risk scores (PRS) between males and females with traits of ADHD [N=1,226, OR=0.98 (0.87-1.11), p=0.70] or related neurodevelopmental disorders [N=2,719, OR=1.04 (0.96-1.13), p=0.32]. On the other hand, females diagnosed with anxiety had higher ADHD PRS than males with anxiety [N=265, OR=1.49 (1.13-1.98), p=0.0048], suggesting that genetic risk for ADHD may manifest differently in females. A replication of these analyses in a second sample will also be presented. The results of this study provide additional evidence for an increased genetic burden of ADHD risk in females diagnosed with ADHD and their relatives, although it would appear that common genetic variants may not play a substantial role. On the other hand, common variants related to ADHD appear to predispose females more than males to anxiety, which may partly explain the lower prevalence of ADHD seen in females.

M2 - ANALYZING THE ROLE OF COMMON EXOMIC VARIANTS ON MODULATING ADHD BEHAVIORS USING A BEHAVIORAL DYNAMIC APPROACH

Background Attention-Deficit/Hyperactivity Disorder (ADHD) is the most common behavioural disorder in school-aged children (3–6%). ADHD is characterized by developmentally inappropriate levels of attention, motor hyperactivity/impulsivity, or both. ADHD is a multifactorial highly heritable disorder, but its genetic underpinnings remain very difficult to unravel. This is mainly due to its multilayered phenotypic presentations (combination of several cognitive, emotional and motor traits), multiple environmental determinants and its complex genetic architecture. Our research group has been dissecting these various dimensions through a pharmaco-behavioural genetic study of ADHD while systematically collecting highly relevant environmental factors. Methods This unbiased and systematic approach will be deployed in two phases. First, we are using 179 children diagnosed with ADHD aged between 6–12 years and their parents to identify common exomic SNPs that are associated with ADHD or behavioural traits that are relevant for ADHD. This genotyping has already been completed through collaboration with the international ADHD genetic consortium. Preliminary results of this genotyping and its quality control indicate that there are over 20 000 eligible SNPs that can be analysed. In the second phase, 100 SNPs were selected according to a specific algorithm being developed (including criteria such as consistent association with ADHD across various behavioural relevant traits, functional relevance based on the role of the SNP in gene function or expression, the role of the gene in functional neural networks…) to be replicated in an independent sample of over 500 patients and their parents which are currently available in our laboratory. Results Preliminary results of this genotyping and its quality control indicate that there are over 20,000 eligible SNPs that can be analysed. In the second phase, 100 SNPs were selected according to a specific algorithm being developed (including criteria such as consistent association with ADHD across various behavioural relevant traits, functional relevance based on the role of the SNP in gene function or expression, the role of the gene in functional neural networks…). Discussion To our knowledge, this is the largest study attempting to unravel the genetic architecture of ADHD combining highly enriched behavioural dimensions of ADHD, pharmacological probes and a two-pronged whole exomic exploratory and a confirmatory steps. It is expected that this highly sophisticated approach will enable us to better understand the genetic of ADHD and its phenotypic variability.

Genetics of Attention Deficit Hyperactivity Disorder Across The Lifespan

Overall Abstract Attention Deficit Hyperactivity Disorder (ADHD) is the most commonly diagnosed childhood-onset neuropsychiatric condition, with impairing symptoms persisting into adulthood in the majority of cases. ADHD-diagnosed children, adolescents and adults share similar clinical features, co-morbidities and failures in major life domains. These associated problems increase the burden of disease and, consequently, global impairment, resistance to treatment and costs of illness. As most genetic studies on ADHD so far have been focusing on its childhood form only, there is limited knowledge about the genetics of ADHD at different ages, in clinical subgroups and across comorbid conditions. This symposium will present recent advances in our understanding of the genetics of ADHD and its major comorbid conditions across the lifespan. Speakers will address ADHD traits from a dimensional perspective using quantitative measures from national twin registry data, as well as unpublished genome wide molecular genetic data collected from large international multi-center clinical samples at different age groups. In this integrated symposium hosted by the International Multi-center persistent ADHD Collaboration (IMpACT), we will first present an updated review on ADHD heritability across the lifespan (presentation 1). We will then present a new international genome-wide association study of the adult form of ADHD (presentation 2), address genetic aspects of ADHD co-morbidity with adult obesity (presentation 3), and finally explore genetic correlations between ADHD dimensions in childhood and neuropsychiatric phenotypes in adulthood (presentation 4). As we gather more knowledge about ADHD, it is becoming clear that a full understanding of the disorder requires research from a lifetime perspective, integrating data from adults and children, using clinical samples as well as population registry data. Combination of different research traditions into a joint symposium will aid the exchange of information and future development of this important field.

Genetic and environmental contribution to the overlap between ADHD and ASD trait dimensions in young adults: a twin study.

Traits of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are strongly associated in children and adolescents, largely due to genetic factors. Less is known about the phenotypic and aetiological overlap between ADHD and ASD traits in adults. We studied 6866 individuals aged 20-28 years from the Swedish Study of Young Adult Twins. Inattention (IA) and hyperactivity/impulsivity (HI) were assessed using the WHO Adult ADHD Self-Report Scale-V1.1. Repetitive and restricted behaviours (RRB) and social interaction and communication (SIC) were assessed using the Autism-Tics, ADHD, and other Comorbidities inventory. We used structural equation modelling to decompose covariance between these ADHD and ASD trait dimensions into genetic and shared/non-shared environmental components. At the phenotypic level, IA was similarly correlated with RRB (r = 0.33; 95% Confidence Interval (CI) 0.31-0.36) and with SIC (r = 0.32; 95% CI 0.29-0.34), whereas HI was more strongly associated with RRB (r = 0.38; 95% CI 0.35-0.40) than with SIC (r = 0.24; 95% CI 0.21-0.26). Genetic and non-shared environmental effects accounted for similar proportions of the phenotypic correlations, whereas shared environmental effects were of minimal importance. The highest genetic correlation was between HI and RRB (r = 0.56; 95% 0.46-0.65), and the lowest was between HI and SIC (r = 0.33; 95% CI 0.23-0.43). We found evidence for dimension-specific phenotypic and aetiological overlap between ADHD and ASD traits in adults. Future studies investigating mechanisms underlying comorbidity between ADHD and ASD may benefit from exploring several symptom-dimensions, rather than considering only broad diagnostic categories.