Attention Deficit Hyperactivity Disorder Traits Research Articles

Reward and Punishment Sensitivity are Associated with Cross-disorder Traits

Reversal learning deficits following reward and punishment processing are observed across disruptive behaviors (DB) and attention-deficit/hyperactivity disorder (ADHD), and have been associated with callous-unemotional (CU) traits. However, it remains unknown to what extent these altered reinforcement sensitivities are linked to the co-occurrence of oppositional traits, ADHD symptoms, and CU traits. Reward and punishment sensitivity and perseverative behavior were therefore derived from a probabilistic reversal learning task to investigate reinforcement sensitivity in participants with DB (n=183, ODD=62, CD=10, combined=57, age-range 8-18), ADHD (n=144, age-range 11-28), and controls (n=191, age-range 8-26). The SNAP-IV and Conners rating scales were used to assess oppositional and ADHD traits. The Inventory of CU traits was used to assess CU traits. Decreased reward sensitivity was associated with ADHD symptom severity (p=0.018) if corrected for oppositional symptoms. ADHD symptomatology interacted with oppositional behavior on perseveration (p=0.019), with the former aggravating the effect of oppositional behavior on perseveration and vice versa. Within a pooled sample, reversal learning alterations were associated with the severity of ADHD symptoms, underpinned by hyposensitivity to reward and increased perseveration. These results show ADHD traits, as opposed to oppositional behavior and CU traits, is associated with decreased reward-based learning in adolescents and adults.

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

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). The discovery GWAS included 19 099 ADHD cases and 34 194 control participants. The combined target sample included 845 people with ADHD (age: 8-40 years). RTV and CE were available from reaction time and response inhibition tasks. ADHD PRS were calculated from the GWAS using a leave-one-study-out approach. Regression analyses were run to investigate whether ADHD PRS were associated with CE and RTV. Results across sites were combined via random effect meta-analyses. When combining the studies in meta-analyses, results were significant for RTV (R2 = 0.011, β = 0.088, p = 0.02) but not for CE (R2 = 0.011, β = 0.013, p = 0.732). No significant association was found between ADHD PRS and RTV or CE in any sample individually (p > 0.10). We detected a significant association between PRS for ADHD and RTV (but not CE) in individuals with ADHD, suggesting that common genetic risk variants for ADHD influence attention regulation.

Testing the evolutionary advantage theory of attention-deficit/hyperactivity disorder traits.

To reconcile the strong secular persistence of attention-deficit/hyperactivity disorder (ADHD) despite its impairing effects, ADHD traits have been postulated to offer an evolutionary advantage. It has been proposed that such advantages should in particular be observable under time-critical, novel, and resource-depleted conditions requiring response-readiness and high levels of scanning and exploration/foraging. Our objective was to provide the first behavioral test of this hypothesis. Schoolchildren from the general population with no/few (n = 56), mild (n = 50), moderate (n = 48), and severe (n = 48) ADHD traits, defined according to their ADHD-Rating Scale IV (ADHD-RS-IV) total score, participated in an exploratory foraging and response-readiness laboratory test. Here, children searched for coins hidden in locations of varying obscurity in an unfamiliar room for 1min. Test-performance (number of coins found) adjusted for age, sex, and estimated IQ was analyzed categorically using multiple linear regression analyses and dimensionally by fitting a regression model including the ADHD-RS-IV score as a continuous measure. There were no differences in the mean number of coins between the No/Few (Mean = 7.82), Mild (Mean = 7.76), Moderate (Mean = 7.58), and Severe (Mean = 7.88) groups [F(3,195) = 0.24, p = 0.871]. Furthermore, excluding children with functional impairment, adjusting for verbal working memory and response inhibition, and stratifying for sex did not change these findings. Finally, continuous ADHD traits were not found to be related to test-performance [F(3,195) = 0.73, p = 0.536]. While our results do generally not support the evolutionary advantage theory (i.e., ADHD traits neither conferred an advantage nor a disadvantage), this does not disprove that ADHD traits may have offered advantages via other mechanisms.

Behavioural and neural markers of tactile sensory processing in infants at elevated likelihood of autism spectrum disorder and/or attention deficit hyperactivity disorder

BackgroundsAtypicalities in tactile processing are reported in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) but it remains unknown if they precede and associate with the traits of these disorders emerging in childhood. We investigated behavioural and neural markers of tactile sensory processing in infants at elevated likelihood of ASD and/or ADHD compared to infants at typical likelihood of the disorders. Further, we assessed the specificity of associations between infant markers and later ASD or ADHD traits.MethodsNinety-one 10-month-old infants participated in the study (n = 44 infants at elevated likelihood of ASD; n = 20 infants at elevated likelihood of ADHD; n = 9 infants at elevated likelihood of ASD and ADHD; n = 18 infants at typical likelihood of the disorders). Behavioural and EEG responses to pairs of tactile stimuli were experimentally recorded and concurrent parental reports of tactile responsiveness were collected. ASD and ADHD traits were measured at 24 months through standardized assessment (ADOS-2) and parental report (ECBQ), respectively.ResultsThere was no effect of infants’ likelihood status on behavioural markers of tactile sensory processing. Conversely, increased ASD likelihood associated with reduced neural repetition suppression to tactile input. Reduced neural repetition suppression at 10 months significantly predicted ASD (but not ADHD) traits at 24 months across the entire sample. Elevated tactile sensory seeking at 10 months moderated the relationship between early reduced neural repetition suppression and later ASD traits.ConclusionsReduced tactile neural repetition suppression is an early marker of later ASD traits in infants at elevated likelihood of ASD or ADHD, suggesting that a common pathway to later ASD traits exists despite different familial backgrounds. Elevated tactile sensory seeking may act as a protective factor, mitigating the relationship between early tactile neural repetition suppression and later ASD traits.

Trait-Based Dimensions Discriminating Adults with Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD) and, Co-occurring ADHD/ASD.

This study assessed the co-occurrence of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in newly diagnosed adults of normal intelligence and the contribution of trait-based dimensions deriving from the Barkley Adult ADHD Rating Scale-IV (BAARS-IV), the Autism-Spectrum Quotient (AQ), and the Empathy Quotient (EQ) to the differentiation of patients with ADHD, ASD, and ADHD/ASD. A total of 16.1% of patients with ADHD received a co-occurring ASD diagnosis, while 33.3% of patients with ASD received an ADHD diagnosis. Subjects with ADHD or ADHD/ASD had higher scores in all ADHD traits compared to ASD subjects. Compared to the ADHD group, the ASD group had AQ scores that were significantly greater, except for attention to detail. ADHD/ASD co-occurrence significantly increased the score of attention to detail. The total EQ score was greater in the ADHD group. In the stepwise logistic regression analyses, past hyperactivity, current inattention and impulsivity, attention switching, communication, imagination, and total EQ score discriminated ADHD patients from ASD patients. Attention to detail, imagination, and total EQ score discriminated ADHD cases from ADHD/ASD cases, while past hyperactivity and current impulsivity discriminated ASD subjects from ADHD/ASD subjects. Our findings highlight the importance of particular trait-based dimensions when discriminating adults with ADHD, ASD, and co-occurring ADHD/ASD.

Increased visual bias in children with developmental coordination disorder: Evidence from a visual-tactile temporal order judgment task.

Previous studies have suggested that children with developmental coordination disorder (DCD) rely heavily on vision to perform movements, which may contribute to their clumsy movements. However, few studies have objectively and quantitatively investigated the perceptual biases of children with DCD. A visual-tactile temporal order judgment (TOJ) task was used to measure and compare the perceptual biases of 19 children with DCD and 19 age- and sex-matched typically developing children. The point of subjective equality, which demonstrates when "visual first" and "tactile first" judgment probabilities are equal (50%), obtained by analyzing the results of the visual-tactile TOJ task, was used as an indicator of perceptual biases. Further, variables (age and manual dexterity in all participants; motor function, autism spectrum disorder and attention-deficit hyperactivity disorder traits, and depressive symptoms in children with DCD) associated with perceptual biases were examined with correlation analysis. Children with DCD had significantly stronger visual bias than typically developing children. Overall correlation analysis showed that increased visual bias was significantly correlated with poor manual dexterity. Children with DCD had a strong visual bias, which was associated with poor manual dexterity.

Subgrouping children and adolescents with disruptive behaviors: symptom profiles and the role of callous-unemotional traits.

Disruptive behavior during childhood and adolescence is heterogeneous and associated with several psychiatric disorders. The identification of more homogeneous subgroups might help identify different underlying pathways and tailor treatment strategies. Children and adolescents (aged 8-18) with disruptive behaviors (N = 121) and healthy controls (N = 100) were included in a European multi-center cognition and brain imaging study. They were assessed via a battery of standardized semi-structured interviews and questionnaires. K-means cluster-model analysis was carried out to identify subgroups within the group with disruptive behaviors, based on clinical symptom profiles, callous-unemotional (CU) traits, and proactive and reactive aggression. The resulting subgroups were then compared to healthy controls with regard to these clinical variables. Three distinct subgroups were found within the group with disruptive behaviors. The High CU Traits subgroup presented elevated scores for CU traits, proactive aggression and conduct disorder (CD) symptoms, as well as a higher proportion of comorbidities (CD + oppositional defiant disorder + attention deficit hyperactivity disorder (ADHD). The ADHD and Affective Dysregulation subgroup showed elevated scores for internalizing and ADHD symptoms, as well as a higher proportion of females. The Low Severity subgroup had relatively low levels of psychopathology and aggressive behavior compared to the other two subgroups. The High CU Traits subgroup displayed more antisocial behaviors than the Low Severity subgroup, but did not differ when compared to the ADHD and Affective Dysregulation subgroup. All three subgroups differed significantly from the healthy controls in all the variables analyzed. The present study extends previous findings on subgrouping children and adolescents with disruptive behaviors using a multidimensional approach and describes levels of anxiety, affective problems, ADHD, proactive aggression and CU traits as key factors that differentiate conclusively between subgroups.

Brief Report: Associations Between Cognitive Control Processes and Traits of Autism Spectrum Disorder (ASD), attention-Deficit/Hyperactivity Disorder (ADHD) and Anxiety in Children at Elevated and Typical Familial Likelihood for ASD.

Shared difficulties with cognitive control may play a role in co-occurring mental health problems frequently observed in autistic children. We investigated how different cognitive control processes (inhibitory control, conflict resolution, cognitive flexibility) associated with traits of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD) and anxiety in 7-year-old children at elevated (n = 44) and typical (n = 37) familial likelihood for ASD. Poor inhibitory control was associated with higher ADHD traits. Better inhibitory control and poorer cognitive flexibility predicted higher anxiety traits. Cognitive control processes were not associated dimensionally with autistic traits, though better conflict resolution predicted greater likelihood of meeting diagnostic criteria for ASD in categorical analysis. These findings suggest that different cognitive control alterations are associated with ASD, ADHD and anxiety.

Look duration at the face as a developmental endophenotype: elucidating pathways to autism and ADHD.

Identifying developmental endophenotypes on the pathway between genetics and behavior is critical to uncovering the mechanisms underlying neurodevelopmental conditions. In this proof-of-principle study, we explored whether early disruptions in visual attention are a unique or shared candidate endophenotype of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). We calculated the duration of the longest look (i.e., peak look) to faces in an array-based eye-tracking task for 335 14-month-old infants with and without first-degree relatives with ASD and/or ADHD. We leveraged parent-report and genotype data available for a proportion of these infants to evaluate the relation of looking behavior to familial (n = 285) and genetic liability (using polygenic scores, n = 185) as well as ASD and ADHD-relevant temperament traits at 2 years of age (shyness and inhibitory control, respectively, n = 272) and ASD and ADHD clinical traits at 6 years of age (n = 94).Results showed that longer peak looks at the face were associated with elevated polygenic scores for ADHD (β = 0.078, p = .023), but not ASD (β = 0.002, p = .944), and with elevated ADHD traits in mid-childhood (F(1,88) = 6.401, p = .013, $\eta _p^2$=0.068; ASD: F (1,88) = 3.218, p = .076), but not in toddlerhood (ps > 0.2). This pattern of results did not emerge when considering mean peak look duration across face and nonface stimuli. Thus, alterations in attention to faces during spontaneous visual exploration may be more consistent with a developmental endophenotype of ADHD than ASD. Our work shows that dissecting paths to neurodevelopmental conditions requires longitudinal data incorporating polygenic contribution, early neurocognitive function, and clinical phenotypic variation.

The relationship between sensory processing sensitivity and attention deficit hyperactivity disorder traits: A spectrum approach

The aim of the present study was to examine the relationship between sensory processing sensitivity (SPS) and symptoms of Attention Deficit Hyperactivity Disorder (ADHD) in adults. The Highly Sensitive Person Scale (HSPS) scale and the Adult ADHD Self-Report Scale (ASRS) were administered to a non-clinical group of 274 participants recruited from a university volunteers list. We found a highly significant positive correlation between number of self-reported ADHD traits and sensory sensitivity. Furthermore, ADHD traits and age were predictors of SPS and exploratory factor analysis revealed a factor that combined ADHD traits and items from the HSPS. The psychometric properties of the HSPS were also examined supporting the unidimensional nature of the concept. To our knowledge, this is the first study to identify a positive relationship between HSPS and ADHD traits in the general population. Our results further support recent findings suggesting abnormal sensory processing in ADHD.

The Dynamic Properties of a Brain Network During Spatial Working Memory Tasks in College Students With ADHD Traits.

This study investigated deficits of spatial working memory in college students with attention-deficit/hyperactivity disorder (ADHD) traits using event-related potentials (ERPs) and the spatial 2-back task. We also computed sensory-level activity using EEG data and investigated theta and alpha neural oscillations, phase-locking values (PLV), and brain networks. Based on the scores from the Adult ADHD Self-Report Scale (ASRS) and Conners’ Adult ADHD Rating Scales (CAARS), an ADHD-trait group (n = 40) and a normal control group (n = 41) were selected. Participants were required to respond to whether the presented stimulus was at the same location as that presented two trials earlier. The ADHD-trait group showed significantly slower response times than the control group in the spatial 2-back task. In terms of spectrum, the ADHD-trait group showed significantly reduced theta power than the control group. In contrast, the ADHD-trait group exhibited an increased alpha power compared to the control group with the 250–1000 ms interval after stimulus onset. In terms of the PLV, the ADHD-trait group showed significantly weaker theta phase synchrony and fewer connection numbers in frontal-occipital areas than the control group. In terms of the theta brain network, the ADHD-trait group showed a significantly lower clustering coefficient and longer characteristic path length than the control group for the theta band. The present results indicate that college students with ADHD traits have deficits in spatial working memory and that these abnormal activities in neural oscillation, functional connectivity, and the network may contribute to spatial working memory deficits.

Deficits of sustained attention in pediatric obsessive-compulsive disorder comorbid with Tic disorders

BackgroundPediatric obsessive-compulsive disorder (OCD) and Tourette syndrome/chronic tics (tic disorders, TD), are associated with attention-deficit hyperactivity disorder (ADHD). Deficits in sustained attention are a core deficit in ADHD which can be captured by continuous performance tests (CPT). CPT data are used to examine deficits in sustained attention in youth with OCD, TD or both, and OCD symptom factors, to characterize the deficits in sustained attention in OCD and TD, testing the hypothesis whether comorbid OCD + TD is distinct from OCD only or TD only. MethodsA clinical registry of youth with OCD and/or TD included data on sustained attention, obtained with the Conner's CPT Test II (CPT-II). The CPT-II spans six time-blocks, capturing values for the capacity for sustained attention. The main outcome measure is the variability in the standard error (SE) of reaction time (RT) for correct responses (RT-SE), which is considered a core ADHD trait. Higher RT-SE values reflect a lack of uniformity in responses and is considered to reflect a deficit in sustained attention. Using generalized linear models (GLM), RT-SE is measured over the six time-blocks in three groups: OCD only, TD only and OCD + TS, with sex and age groups as moderators. Clinical ADHD diagnoses were contrasted between diagnostic groups while OCD dimensions (contamination-washing, aggressive-somatic, sexual-religious, counting-checking-repeating and hoarding) were tested for their effect on sustained attention. ResultsDeficits in sustained attention are significantly greater in the comorbid OCD + TD compared to OCD only and TD only, with the greatest differences apparent in blocks 5 and 6 (p < .001). While sex does not moderate sustained attention deficits, the higher RT-SE in blocks 5 and 6 is only seen in the younger age group (7–11 years), but not in adolescents (12–17 years). As expected, clinical ADHD is more prevalent in youth with comorbid OCD + TS (67%) compared to OCD only (21%) or TD only (33%) (p = .0002). The hoarding group, characterized by more frequent clinical ADHD diagnoses, has higher RT-SE for time blocks 3,4,5,6 compared to non-hoarders. Participants with contamination-washing symptoms, characterized by more prevalent anxiety disorders, have higher RT-SE than those with no contamination-washing symptoms for time block 4. ConclusionDeficits in sustained attention are associated with comorbid OCD + TD compared OCD only or TD only, evident only in a younger age group. Sustained attention deficits are also more common in youth with ADHD, OCD hoarding and OCD contamination-washing symptoms. In summary, sustained attention deficits are intrinsic to the comorbid OCD + TD group, suggesting a compounded developmental insult specific to sustained attention which tends to resolve by adolescence. A mechanistic commonality to sustained attention, tic disorders and OCD-related extinction learning may be aberrant oscillatory brain phenomena.

Self-compassion and Perceived Criticism in Adults with Attention Deficit Hyperactivity Disorder (ADHD)

ObjectivesAttention deficit hyperactivity disorder (ADHD) is associated with increased criticism from others. To date, there is little research considering the consequences of how others respond to people with ADHD. Self-compassion is a positive way of relating to oneself during difficulty. Here, we investigate whether levels of self-compassion differ between people with and without ADHD, and whether perceived criticism mediates any differences in self-compassion between people with and without ADHD.MethodsA cross-sectional design was used to conduct natural group comparisons. A sample of 1203 adults (46% with a self-reported ADHD diagnosis) recruited via social media, online forums and posters completed online self-report measures of diagnostic status, ADHD traits, self-compassion and perceived criticism. Between-group comparisons of self-compassion and perceived criticism were conducted on participants grouped by diagnosis, then grouped by ADHD trait severity. Perceived criticism was tested as a mediator variable between ADHD diagnosis and self-compassion.ResultsAdults with an ADHD diagnosis showed significantly lower self-compassion and higher perceived criticism than the participants without ADHD. Participants high in ADHD traits but without a diagnosis had significantly similar levels of self-compassion to the diagnosed group. Mediation analysis found that higher perceived criticism partially explained the relationship between ADHD diagnosis and self-compassion, even after accounting for co-occurring mood disorder diagnosis.ConclusionsAdults with ADHD are less self-compassionate than adults without ADHD. This is partially explained by the higher level of criticism they perceive from others.

Autistic traits in young adults who gamble.

Little is known about the relationship between autistic traits and addictive behaviors such as problem gambling. Thus, the present study examined clinical characteristics and multiple facets of cognition in young adults who gamble and have autistic traits. A total of 102 young adults who gamble were recruited from two Mid-Western university communities in the United States using media advertisements. Autistic traits were examined using the brief Autism-Spectrum Quotient (AQ-10). Clinician rating scales, questionnaires, and cognitive tests were completed. Relationships between AQ10 scores and demographic, gambling symptom, and neurocognitive measures were evaluated. Autistic traits were correlated with disordered gambling symptoms, attention-deficit/hyperactivity disorder (ADHD) symptoms, trait impulsivity, and some types of obsessive-compulsive symptoms. In regression, ADHD no longer significantly related to autistic traits once disordered gambling symptoms were accounted for; whereas the link between autistic traits and disordered gambling symptoms was robust even controlling for ADHD. These data suggest a particularly strong relationship between autistic traits and problem gambling symptoms, as well as certain aspects of impulsivity and compulsivity. The link between ADHD and autistic traits in some prior studies may have been attributable to disordered gambling symptoms, which was likely not screened for, and since individuals may endorse ADHD instruments due to other impulsive/compulsive symptom types (eg, gambling). The contribution of autistic traits to the emergence and chronicity of disordered gambling now requires further scrutiny, not only in community samples (such as this) but also in clinical settings.

Maternal Iodine Status During Pregnancy Is Not Consistently Associated with Attention-Deficit Hyperactivity Disorder or Autistic Traits in Children

ABSTRACTBackgroundSevere iodine deficiency during pregnancy can cause intellectual disability, presumably through inadequate placental transfer of maternal thyroid hormone to the fetus. The association between mild-to-moderate iodine deficiency and child neurodevelopmental problems is not well understood.ObjectivesWe investigated the association of maternal iodine status during pregnancy with child attention-deficit hyperactivity disorder (ADHD) and autistic traits.MethodsThis was a collaborative study of 3 population-based birth cohorts: Generation R (n = 1634), INfancia y Medio Ambiente (n = 1293), and the Avon Longitudinal Study of Parents and Children (n = 2619). Exclusion criteria were multiple fetuses, fertility treatment, thyroid-interfering medication use, and pre-existing thyroid disease. The mean age of assessment in the cohorts was between 4.4 and 7.7 y for ADHD symptoms and 4.5 and 7.6 y for autistic traits. We studied the association of the urinary iodine-to-creatinine ratio (UI/Creat) <150 μg/g—in all mother–child pairs, and in those with a urinary-iodine measurement at ≤18 weeks and ≤14 weeks of gestation—with the risk of ADHD or a high autistic-trait score (≥93rd percentile cutoff), using logistic regression. The cohort-specific effect estimates were combined by random-effects meta-analyses. We also investigated whether UI/Creat modified the associations of maternal free thyroxine (FT4) or thyroid-stimulating hormone concentrations with ADHD or autistic traits.ResultsUI/Creat <150 μg/g was not associated with ADHD (OR: 1.2; 95% CI: 0.7, 2.2; P = 0.56) or with a high autistic-trait score (OR: 0.8; 95% CI: 0.6, 1.1; P = 0.22). UI/Creat <150 μg/g in early pregnancy (i.e., ≤18 weeks or ≤14 weeks of gestation) was not associated with a higher risk of behavioral problems. The association between a higher FT4 and a greater risk of ADHD (OR: 1.3; 95% CI: 1.0, 1.6; P = 0.017) was not modified by iodine status.ConclusionsThere is no consistent evidence to support an association of mild-to-moderate iodine deficiency during pregnancy with child ADHD or autistic traits.

Attention deficit hyperactivity symptoms predict problematic mobile phone use

Attention-deficit-hyperactivity disorder (ADHD) is the most commonly diagnosed childhood disorder characterised by inattention, hyperactivity/impulsivity, or both. Some of the key traits of ADHD have previously been linked to addictive and problematic behaviours. The aim of the present study was to examine the relationship between problematic mobile phone use, smartphone addiction risk and ADHD symptoms in an adult population. A sample of 273 healthy adult volunteers completed the Adult ADHD Self-Report Scale (ASRS), the Mobile Phone Problem Usage Scale (MPPUS), and the Smartphone Addiction Scale (SAS). A significant positive correlation was found between the ASRS and both scales. More specifically, inattention symptoms and age predicted smartphone addiction risk and problematic mobile phone use. Our results suggest that there is a positive relationship between ADHD traits and problematic mobile phone use. In particular, younger adults with higher level of inattention symptoms could be at higher risk of developing smartphone addiction. The implication of our findings for theoretical frameworks of problematic mobile phone use and clinical practice are discussed.

Shared genetic background between children and adults with attention deficit/hyperactivity disorder

Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by age-inappropriate symptoms of inattention, impulsivity, and hyperactivity that persist into adulthood in the majority of the diagnosed children. Despite several risk factors during childhood predicting the persistence of ADHD symptoms into adulthood, the genetic architecture underlying the trajectory of ADHD over time is still unclear. We set out to study the contribution of common genetic variants to the risk for ADHD across the lifespan by conducting meta-analyses of genome-wide association studies on persistent ADHD in adults and ADHD in childhood separately and jointly, and by comparing the genetic background between them in a total sample of 17,149 cases and 32,411 controls. Our results show nine new independent loci and support a shared contribution of common genetic variants to ADHD in children and adults. No subgroup heterogeneity was observed among children, while this group consists of future remitting and persistent individuals. We report similar patterns of genetic correlation of ADHD with other ADHD-related datasets and different traits and disorders among adults, children, and when combining both groups. These findings confirm that persistent ADHD in adults is a neurodevelopmental disorder and extend the existing hypothesis of a shared genetic architecture underlying ADHD and different traits to a lifespan perspective.

Genome-Wide DNA Methylation Patterns in Persistent Attention-Deficit/Hyperactivity Disorder and in Association With Impulsive and Callous Traits.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that often persists into adulthood. ADHD and related personality traits, such as impulsivity and callousness, are caused by genetic and environmental factors and their interplay. Epigenetic modifications of DNA, including methylation, are thought to mediate between such factors and behavior and may behave as biomarkers for disorders. Here, we set out to study DNA methylation in persistent ADHD and related traits. We performed epigenome-wide association studies (EWASs) on peripheral whole blood from participants in the NeuroIMAGE study (age range 12–23 years). We compared participants with persistent ADHD (n = 35) with healthy controls (n = 19) and with participants with remittent ADHD (n = 19). Additionally, we performed EWASs of impulsive and callous traits derived from the Conners Parent Rating Scale and the Callous-Unemotional Inventory, respectively, across all participants. For every EWAS, the linear regression model analyzed included covariates for age, sex, smoking scores, and surrogate variables reflecting blood cell type composition and genetic background. We observed no epigenome-wide significant differences in single CpG site methylation between participants with persistent ADHD and healthy controls or participants with remittent ADHD. However, epigenome-wide analysis of differentially methylated regions provided significant findings showing that hypermethylated regions in the APOB and LPAR5 genes were associated with ADHD persistence compared to ADHD remittance (p = 1.68 * 10−24 and p = 9.06 * 10−7, respectively); both genes are involved in cholesterol signaling. Both findings appeared to be linked to genetic variation in cis. We found neither significant epigenome-wide single CpG sites nor regions associated with impulsive and callous traits; the top-hits from these analyses were annotated to genes involved in neurotransmitter release and the regulation of the biological clock. No link to genetic variation was observed for these findings, which thus might reflect environmental influences. In conclusion, in this pilot study with a small sample size, we observed several DNA-methylation–disorder/trait associations of potential significance for ADHD and the related behavioral traits. Although we do not wish to draw conclusions before replication in larger, independent samples, cholesterol signaling and metabolism may be of relevance for the onset and/or persistence of ADHD.

Autistic and Attention Deficit/Hyperactivity Disorder Traits Are Associated with Suboptimal Performance among Japanese University Students.

Introduction: Recent estimates suggest that there is a substantial number of Japanese students with developmental disabilities. This study aimed to examine potential associations between autistic, autistic subcomponents, and attention deficit/hyperactivity disorder (ADHD) traits with student performance (as measured by presenteeism) and class attendance among Japanese university students. Methods: Participants comprised 721 students from different regions of Japan who completed a self-administered internet survey. Autistic and ADHD traits were measured using an abridged version of the autism spectrum quotient (AQ-Short) and adult ADHD self-report scale (ASRS). Presenteeism, which is an indicator of student performance, was assessed using the modified World Health Organization Health and Work Performance Questionnaire. Class attendance during the past year was self-reported by participants. Results: Students with high levels of autistic traits and high levels of ADHD traits were significantly more likely to report poor student performance (odds ratio [OR] = 3.07, 95% confidence interval [95% CI]: 1.90–4.96; and OR = 2.13, 95% CI: 1.32–3.42, respectively). Regarding autistic trait subcomponents, students with high levels of preference for routine (OR = 2.39, 95% CI: 1.38–4.13) and high levels of difficulties with social skills (OR = 1.81, 95% CI: 1.03–3.18) were also significantly more likely to report poor student performance. There were borderline significant associations between traits of attention-switching difficulties and poor student performance (OR = 1.78, 95% CI: 1.00–3.15). Regarding ADHD trait subcomponents, students with high levels of inattention (OR = 2.88, 95% CI: 1.32–6.26) were also significantly more likely to report poor student performance. Students with both high levels of autistic traits and high levels of ADHD traits were more likely to report poor student performance than those with high levels of only one trait type. There were, however, no statistically significant associations between these traits and low class attendance risk. Conclusions: Sickness presenteeism was significantly associated with high levels of both autistic traits and ADHD traits among Japanese university students.

Prenatal androgens and autistic, attention deficit hyperactivity disorder, and disruptive behavior disorders traits

Objective: Androgen exposure is hypothesized to play a role in the development of autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and disruptive behavior disorders/DBDs (oppositional defiant disorder/ODD and conduct disorder/CD). The aim of this cross-sectional study was to investigate ASD, ADHD, and DBD (ODD and CD) traits in children and adolescents with congenital adrenal hyperplasia (CAH), a natural cause of prenatal androgen excess in females. Methods: Forty-five children and adolescents (27 girls, mean age 11.1±3; 18 boys, mean age 10.8±3.6) with CAH and their unaffected siblings (16 girls, mean age 11.4±3.9; 14 boys, mean age 12.6±4.2) were included in the study. Parents completed the Social Communication Questionnaire, to measure ASD symptoms; and the Turgay DSM-IV-Based Child and Adolescent Disruptive Behavioral Disorders Screening and Rating Scale to assess ADHD and DBD traits. Results: In this study, boys but not girls with CAH showed higher autistic traits. There was no significant difference between either girls or boys with CAH and their unaffected counterparts with respect to inattention or hyperactivity symptoms. Boys with CAH showed more ODD symptoms than the unaffected boys. There was a trend for boys to have more CD symptoms compared to unaffected boys. Conclusions: Our study does not support the hypothesis that prenatal androgen exposure is associated with ASD, ADHD or DBDs. Postnatal/circulating androgen levels, higher testosterone/cortisol ratio, lower basal cortisol or dysregulation in HPA axis might be related to higher autistic traits or increased DBDs symptoms found in boys with CAH. Further investigations with larger groups are needed to clarify these associations.