The familial co-aggregation of ASD and ADHD: a register-based cohort study.

Autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur. The presence of a genetic link between ASD and ADHD symptoms is supported by twin studies, but the genetic overlap between clinically ascertained ASD and ADHD remains largely unclear. We therefore investigated how ASD and ADHD co-aggregate in individuals and in families to test for the presence of a shared genetic liability and examined potential differences between low- and high-functioning ASD in the link with ADHD. We studied 1 899 654 individuals born in Sweden between 1987 and 2006. Logistic regression was used to estimate the association between clinically ascertained ASD and ADHD in individuals and in families. Stratified estimates were obtained for ASD with (low-functioning) and without (high-functioning) intellectual disability. Individuals with ASD were at higher risk of having ADHD compared with individuals who did not have ASD (odds ratio (OR)=22.33, 95% confidence interval (CI): 21.77-22.92). The association was stronger for high-functioning than for low-functioning ASD. Relatives of individuals with ASD were at higher risk of ADHD compared with relatives of individuals without ASD. The association was stronger in monozygotic twins (OR=17.77, 95% CI: 9.80-32.22) than in dizygotic twins (OR=4.33, 95% CI: 3.21-5.85) and full siblings (OR=4.59, 95% CI: 4.39-4.80). Individuals with ASD and their relatives are at increased risk of ADHD. The pattern of association across different types of relatives supports the existence of genetic overlap between clinically ascertained ASD and ADHD, suggesting that genomic studies might have underestimated this overlap.

Association of preterm birth with ADHD-like cognitive impairments and additional subtle impairments in attention and arousal malleability.

BACKGROUND: Whilst preterm-born individuals have an increased risk of developing attention-deficit/hyperactivity disorder (ADHD), and are reported to have ADHD-like attention and arousal impairments, direct group comparisons are scarce. METHODS: We directly compared preterm-born adolescents (n = 186) to term-born adolescents with ADHD (n = 69), and term-born controls (n = 135), aged 11-23, on cognitive-performance, event-related potential and skin conductance level (SCL) measures associated with attention and arousal. The measures are from baseline and fast-incentive conditions of a four-choice reaction time task, previously shown to discriminate between the individuals with ADHD and controls. We aimed to establish whether preterm-born adolescents show: (a) identical cognitive-neurophysiological impairments to term-born adolescents with ADHD (b) possible additional impairments, and whether (c) the observed impairments correlate with ADHD symptom scores. RESULTS: The preterm group, like the term-born ADHD group, showed increased mean reaction time (MRT) and reaction time variability (RTV) in the baseline condition, and attenuated contingent negative variation (CNV) amplitude (response preparation) in the fast-incentive condition. The preterm group, only, did not show significant within-group adjustments in P3 amplitude (attention allocation) and SCL (peripheral arousal). Dimensional analyses showed that ADHD symptoms scores correlated significantly with MRT, RTV and CNV amplitude only. CONCLUSIONS: We find impairments in cognition and brain function in preterm-born adolescents that are linked to increased ADHD symptoms, as well as further impairments, in lack of malleability in neurophysiological processes. Our findings indicate that such impairments extend at least to adolescence. Future studies should extend these investigations into adulthood.

Characteristics of prisoners with intellectual disabilities.

BACKGROUND: Previous studies have found high rates of intellectual disabilities (ID) in prison. However, little is understood about prisoners with ID. This study aimed to identify prisoners with ID and compare their characteristics with prisoners without neurodevelopmental disorders with regard to demographic profile, mental health, suicide risk and offences. METHOD: This was a descriptive, cross-sectional study carried out using face-to-face interviews with 240 participants in a London Category C prison. Standardised tools were used to assess prisoners for ID and mental disorder. RESULTS: The study identified 18 prisoners as having ID. Participants with ID were less likely to be from a black or minority ethnic background, be over 35 years of age or have any qualifications. They were more likely to have been single, homeless or unemployed before coming into prison. Prisoners with ID were significantly more likely to have mental health problems and 25% had thought about suicide in the last month and 63% had attempted suicide in the past. Prisoners with ID were also more likely to be housed in the vulnerable prisoners' wing and significantly more likely to have committed robbery than other prisoners. CONCLUSIONS: The findings confirm the presence of significant numbers of people with ID with high levels of mental illness in a male prison. Services across the CJS are required for this group, specifically, there is a need for raised awareness among those working in prison about ID and improved skills to recognise offenders with ID and address major gaps in current healthcare provision in prison.

Callous-unemotional traits moderate executive function in children with ASD and ADHD: A pilot event-related potential study.

Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are associated with varied executive function (EF) difficulties. Callous-unemotional (CU) traits, a proposed antecedent of adult psychopathy, are often associated with intact or enhanced EF. Here we test whether CU traits may therefore modulate EF in ASD and ADHD, in which EF is typically impaired. We collected CU traits and measured event-related potentials (ERPs) that index EF during a cued-continuous performance test (CPT-OX) in boys with ASD, ADHD, comorbid ASD+ADHD and typical controls. We examined attentional orienting at cues (Cue-P3), inhibitory processing at non-targets (NoGo-P3) and conflict monitoring between target and non-target trials (Go-N2 vs. NoGo-N2). In children with ASD, higher CU traits were associated with an enhanced increase in N2 amplitude in NoGo trials compared to Go trials, which suggests relatively superior conflict monitoring and a potential cognitive strength associated with CU traits. The results emphasise the importance of considering the effects of co-occurring traits in the assessment of heterogeneity of EF profiles in neurodevelopmental disorders.

Effects of stimulants and atomoxetine on emotional lability in adults: A systematic review and meta-analysis.

BACKGROUND: Emotional lability (EL) is an associated feature of attention-deficit/hyperactivity disorder (ADHD) in adults, contributing to functional impairment. Yet the effect of pharmacological treatments for ADHD on EL symptoms is unknown. We conducted a systematic review and meta-analysis to examine the effects of stimulants and atomoxetine on symptoms of EL and compare these with the effects on core ADHD symptoms. METHODS: A systematic search was conducted on the databases Embase, PsychInfo, and Ovid Medline® and the clinicaltrials.gov website. We included randomised, double-blind, placebo-controlled trials of stimulants and atomoxetine in adults aged 18-60 years, with any mental health diagnosis characterised by emotional or mood instability, with at least one outcome measure of EL. All identified trials were on adults with ADHD. A random-effects meta-analysis with standardised mean difference and 95% confidence intervals was used to investigate the effect size on EL and compare this to the effect on core ADHD symptoms. RESULTS: Of the 3,864 publications identified, nine trials met the inclusion criteria for the meta-analysis. Stimulants and atomoxetine led to large mean weighted effect-sizes for on ADHD symptoms (n=9, SMD=-0.8, 95% CI:-1.07 to -0.53). EL outcomes showed more moderate but definite effects (n=9, SMD=-0.41, 95% CI:-0.57 to -0.25). CONCLUSIONS: In this meta-analysis, stimulants and atomoxetine were moderately effective for EL symptoms, while effect size on core ADHD symptoms was twice as large. Methodological issues may partially explain the difference in effect size. Reduced average effect size could also reflect heterogeneity of EL with ADHD pharmacotherapy responsive and non-responsive sub-types. Our findings indicate that EL may be less responsive than ADHD symptoms overall, perhaps indicating the need for adjunctive psychotherapy in some cases. To clarify these questions, our findings need replication in studies selecting subjects for high EL and targeting EL as the primary outcome.

Exome chip analyses in adult attention deficit hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable childhood-onset neuropsychiatric condition, often persisting into adulthood. The genetic architecture of ADHD, particularly in adults, is largely unknown. We performed an exome-wide scan of adult ADHD using the Illumina Human Exome Bead Chip, which interrogates over 250 000 common and rare variants. Participants were recruited by the International Multicenter persistent ADHD CollaboraTion (IMpACT). Statistical analyses were divided into 3 steps: (1) gene-level analysis of rare variants (minor allele frequency (MAF)<1%); (2) single marker association tests of common variants (MAF⩾1%), with replication of the top signals; and (3) pathway analyses. In total, 9365 individuals (1846 cases and 7519 controls) were examined. Replication of the most associated common variants was attempted in 9847 individuals (2077 cases and 7770 controls) using fixed-effects inverse variance meta-analysis. With a Bonferroni-corrected significance level of 1.82E-06, our analyses of rare coding variants revealed four study-wide significant loci: 6q22.1 locus (P=4.46E-08), where NT5DC1 and COL10A1 reside; the SEC23IP locus (P=6.47E-07); the PSD locus (P=7.58E-08) and ZCCHC4 locus (P=1.79E-06). No genome-wide significant association was observed among the common variants. The strongest signal was noted at rs9325032 in PPP2R2B (odds ratio=0.81, P=1.61E-05). Taken together, our data add to the growing evidence of general signal transduction molecules (NT5DC1, PSD, SEC23IP and ZCCHC4) having an important role in the etiology of ADHD. Although the biological implications of these findings need to be further explored, they highlight the possible role of cellular communication as a potential core component in the development of both adult and childhood forms of ADHD.

Predicting the diagnosis of autism in adults using the Autism-Spectrum Quotient (AQ) questionnaire.

BACKGROUND: Many adults with autism spectrum disorder (ASD) remain undiagnosed. Specialist assessment clinics enable the detection of these cases, but such services are often overstretched. It has been proposed that unnecessary referrals to these services could be reduced by prioritizing individuals who score highly on the Autism-Spectrum Quotient (AQ), a self-report questionnaire measure of autistic traits. However, the ability of the AQ to predict who will go on to receive a diagnosis of ASD in adults is unclear. METHOD: We studied 476 adults, seen consecutively at a national ASD diagnostic referral service for suspected ASD. We tested AQ scores as predictors of ASD diagnosis made by expert clinicians according to International Classification of Diseases (ICD)-10 criteria, informed by the Autism Diagnostic Observation Schedule-Generic (ADOS-G) and Autism Diagnostic Interview-Revised (ADI-R) assessments. RESULTS: Of the participants, 73% received a clinical diagnosis of ASD. Self-report AQ scores did not significantly predict receipt of a diagnosis. While AQ scores provided high sensitivity of 0.77 [95% confidence interval (CI) 0.72-0.82] and positive predictive value of 0.76 (95% CI 0.70-0.80), the specificity of 0.29 (95% CI 0.20-0.38) and negative predictive value of 0.36 (95% CI 0.22-0.40) were low. Thus, 64% of those who scored below the AQ cut-off were 'false negatives' who did in fact have ASD. Co-morbidity data revealed that generalized anxiety disorder may 'mimic' ASD and inflate AQ scores, leading to false positives. CONCLUSIONS: The AQ's utility for screening referrals was limited in this sample. Recommendations supporting the AQ's role in the assessment of adult ASD, e.g. UK NICE guidelines, may need to be reconsidered.

Six-year follow-up study of combined type ADHD from childhood to young adulthood: Predictors of functional impairment and comorbid symptoms.

BACKGROUND: ADHD in childhood is associated with development of negative psychosocial and behavioural outcomes in adults. Yet, relatively little is known about which childhood and adulthood factors are predictive of these outcomes and could be targets for effective interventions. To date follow-up studies have largely used clinical samples from the United States with children ascertained at baseline using broad criteria for ADHD including all clinical subtypes or the use of DSM III criteria. AIMS: To identify child and adult predictors of comorbid and psychosocial comorbid outcomes in ADHD in a UK sample of children with DSM-IV combined type ADHD. METHOD: One hundred and eighteen adolescents and young adults diagnosed with DSM-IV combined type ADHD in childhood were followed for an average of 6years. Comorbid mental health problems, drug and alcohol use and police contact were compared for those with persistent ADHD, sub-threshold ADHD and population norms taken from the Adult Psychiatric Morbidity Study 2007. Predictors included ADHD symptomology and gender. RESULTS: Persistent ADHD was associated with greater levels of anger, fatigue, sleep problems and anxiety compared to sub-threshold ADHD. Comorbid mental health problems were predicted by current symptoms of hyperactivity-impulsivity, but not by childhood ADHD severity. Both persistent and sub-threshold ADHD was associated with higher levels of drug use and police contact compared to population norms. CONCLUSIONS: Young adults with a childhood diagnosis of ADHD showed increased rates of comorbid mental health problems, which were predicted by current levels of ADHD symptoms. This suggests the importance of the continuing treatment of ADHD throughout the transitional years and into adulthood. Drug use and police contact were more common in ADHD but were not predicted by ADHD severity in this sample.

Diagnostic accuracy of a brief screening tool for attention deficit hyperactivity disorder in UK prison inmates.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is overrepresented in prison, making it imperative to identify a screening tool that can be quickly applied to efficiently detect the disorder. We explored the discrimination ability of a widely used ADHD screen, the Barkley Adult ADHD Rating Scale (BAARS-IV), against a clinical diagnostic interview. A brief version of the screen was then developed in order to simplify its use in the prison context, and maximize its diagnostic properties. METHOD: A cross-sectional study of 390 male prison inmates was performed in the UK, all participants were screened and interviewed via the Diagnostic Interview for ADHD in Adults 2.0 (DIVA-2). RESULTS: A total of 47 (12.1%) inmates screened positive for ADHD using the full BAARS-IV, and 96 (24.6%) were clinically diagnosed, for a sensitivity of 37.9 and a specificity of 96.3. Our models identified the six items that most predicted ADHD diagnosis, with adjusted odds ratios ranging from 2.66 to 4.58. Sensitivity, specificity and accuracy were 0.82, 0.84 and 0.84, respectively, for the developed brief scale, and 0.71, 0.85 and 0.81 for its validation. Weighted probability scores produced an area under the curve of 0.89 for development, and 0.82 for validation of the brief scale. CONCLUSIONS: The original BAARS-IV performed poorly at identifying prison inmates with ADHD. Our developed brief scale substantially improved diagnostic accuracy. The brief screening instrument has great potential to be used as an accurate and resource-effective tool to screen young people and adults for likely ADHD in the criminal justice system.

Characteristics of prisoners with neurodevelopmental disorders and difficulties.

BACKGROUND: Previous studies have found high rates of attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and intellectual disability (ID) within the criminal justice system (CJS). However, little is understood about prisoners with neurodevelopmental disorders and difficulties (NDD) or their needs. This study aimed to identify prisoners with NDD and compare their characteristics with prisoners without NDD on a range of socio-demographic and social functioning measures. METHOD: This was a descriptive, cross-sectional study carried out using face-to-face interviews with 240 participants in a London Category C prison. Standardised tools were used to assess prisoners for ADHD, ASD and ID. RESULTS: The study identified 87 prisoners who screened positive for one or more type of NDD. Participants with NDD were significantly younger and more likely to be single [(odds ratio) OR = 2.1], homeless (OR = 3.4) or unemployed (OR = 2.6) before they came into prison. They also had poorer educational achievements that those without NDD. Over 80% of those with NDD had a previous conviction or imprisonment. CONCLUSIONS: The findings confirm the presence of significant numbers of people with NDD in a male prison. Services across the CJS are required for this group; specifically, there is a need for raised awareness among those working in the CJS to improve the recognition of offenders with NDD. Services in the community need to work with individuals with NDD who are at risk of offending, targeting those who are homeless, unemployed and have poor employment opportunities.

Disorder-specific and shared neurophysiological impairments of attention and inhibition in women with attention-deficit/hyperactivity disorder and women with bipolar disorder.

BACKGROUND: In adults, attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) have certain overlapping symptoms, which can lead to uncertainty regarding the boundaries of the two disorders. Despite evidence of cognitive impairments in both disorders separately, such as in attentional and inhibitory processes, data on direct comparisons across ADHD and BD on cognitive-neurophysiological measures are as yet limited. METHOD: We directly compared cognitive performance and event-related potential measures from a cued continuous performance test in 20 women with ADHD, 20 women with BD (currently euthymic) and 20 control women. RESULTS: The NoGo-N2 was attenuated in women with BD, reflecting reduced conflict monitoring, compared with women with ADHD and controls (both p < 0.05). Both ADHD and BD groups showed a reduced NoGo-P3, reflecting inhibitory control, compared with controls (both p < 0.05). In addition, the contingent negative variation was significantly reduced in the ADHD group (p = 0.05), with a trend in the BD group (p = 0.07), compared with controls. CONCLUSIONS: These findings indicate potential disorder-specific (conflict monitoring) and overlapping (inhibitory control, and potentially response preparation) neurophysiological impairments in women with ADHD and women with BD. The identified neurophysiological parameters further our understanding of neurophysiological impairments in women with ADHD and BD, and are candidate biomarkers that may aid in the identification of the diagnostic boundaries of the two disorders.

The effects of atomoxetine on emotional control in adults with ADHD: An integrated analysis of multicenter studies.

PURPOSE: To investigate the effects of atomoxetine on emotional control in adults with ADHD. METHODS: We performed an integrated analysis using individual patient data pooled from three Eli Lilly-sponsored studies. An integrated analysis can be viewed as a meta-analysis of individual patient-level data, rather than study-level summary data. RESULTS: Two populations were identified: a large sample of patients with pre-treatment baseline data (the "overall population"; n=2846); and a subset of these patients with placebo-controlled efficacy data from baseline to 10 or 12 weeks after initiating treatment (the "placebo-controlled population"; n=829). At baseline, in the overall population, ∼50% of ADHD patients had BRIEF-AS (Behavior Rating Inventory of Executive Function-Adult Version Self-Report) Emotional control subscores between 21 and 30, compared with ∼10% of normative subjects in the BRIEF-A manual. At endpoint, in the placebo-controlled population, atomoxetine led to a small (effect size 0.19) but significant (P=0.013) treatment effect for emotional control. The effect size was 0.32 in patients with BRIEF-AS Emotional control scores>20 at baseline. Improvements in emotional control correlated with improvements in the core ADHD symptoms and quality-of-life. DISCUSSION: As deficient emotional control is associated with impaired social, educational and occupational functioning over and above that explained by core ADHD symptoms alone, improvements in emotional control may be clinically relevant. CONCLUSION: At baseline, adults with ADHD were more likely to have impaired emotional control than normative subjects. In the adult ADHD patients, atomoxetine treatment was associated with improvements in emotional control, as well as in core ADHD symptoms and quality-of-life.

Impairments, diagnosis and treatments associated with attention-deficit/hyperactivity disorder (ADHD) in UK adults: results from the lifetime impairment survey.

AIM: The Lifetime Impairment Survey assessed how ADHD impairs everyday life, identifying areas most affected. METHODS: This opinion-based survey evaluated experiences, diagnosis and treatment of lifetime impairment in adults with (n=89) and without (n=94) ADHD. Groups were compared using impairment and symptoms scales; higher scores indicate greater impairment. RESULTS: Mean (standard deviation) age at diagnosis was 18.2 (11.5) years; 47.1% were taking prescription medication for ADHD. Adults with ADHD reported greater impairments than those without for all scales (p<0.001) except the involvement scale. CONCLUSION: Greater impairments in adults with than without ADHD suggest a continued impact throughout their daily lives.

Everyday emotional experience of adults with attention deficit hyperactivity disorder: evidence for reactive and endogenous emotional lability.

BACKGROUND: Emotional lability (EL), characterized by negative emotional traits and emotional instability, is frequently reported in children and adults with attention deficit hyperactivity disorder (ADHD). However, EL is primarily assessed using retrospective self-report, which is subject to reporting bias and does not consider the potential influence of positive and negative everyday experiences. METHOD: Ambulatory assessment was carried out in 41 men with ADHD without co-morbidity, current medication or substance abuse, and 47 healthy control participants. Reports of negative and positive emotions (irritability, frustration, anger, happiness, excitement) and the occurrence of bad and good events were completed eight times daily during a working week. Group differences in emotional intensity and instability were investigated using multilevel models, and explored in relation to bad and good events and the Affective Lability Scale - Short Form (ALS-SF), an EL questionnaire. RESULTS: The ADHD group reported significantly more frequent bad events, heightened intensity and instability of irritability and frustration, and greater intensity of anger. The results for positive emotions were equivocal or negative. Bad events significantly contributed to the intensity and instability of negative emotions, and showed a stronger influence in the ADHD group. However, covariation for their effect did not eliminate group differences. Small-to-moderate correlations were seen between intensity and instability of negative emotions and the ALS-SF. CONCLUSIONS: Adults with ADHD report heightened intensity and instability of negative emotions in daily life. The results suggest two components of EL in ADHD: a reactive component responsive to bad events and an endogenous component, independent of negative everyday events.

Glutamate/glutamine and neuronal integrity in adults with ADHD: a proton MRS study.

There is increasing evidence that abnormalities in glutamate signalling may contribute to the pathophysiology of attention-deficit hyperactivity disorder (ADHD). Proton magnetic resonance spectroscopy ([1H]MRS) can be used to measure glutamate, and also its metabolite glutamine, in vivo. However, few studies have investigated glutamate in the brain of adults with ADHD naive to stimulant medication. Therefore, we used [1H]MRS to measure the combined signal of glutamate and glutamine (Glu+Gln; abbreviated as Glx) along with other neurometabolites such as creatine (Cr), N-acetylaspartate (NAA) and choline. Data were acquired from three brain regions, including two implicated in ADHD-the basal ganglia (caudate/striatum) and the dorsolateral prefrontal cortex (DLPFC)-and one 'control' region-the medial parietal cortex. We compared 40 adults with ADHD, of whom 24 were naive for ADHD medication, whereas 16 were currently on stimulants, against 20 age, sex and IQ-matched healthy controls. We found that compared with controls, adult ADHD participants had a significantly lower concentration of Glx, Cr and NAA in the basal ganglia and Cr in the DLPFC, after correction for multiple comparisons. There were no differences between stimulant-treated and treatment-naive ADHD participants. In people with untreated ADHD, lower basal ganglia Glx was significantly associated with more severe symptoms of inattention. There were no significant differences in the parietal 'control' region. We suggest that subcortical glutamate and glutamine have a modulatory role in ADHD adults; and that differences in glutamate-glutamine levels are not explained by use of stimulant medication.

Daily life impairments associated with self-reported childhood/adolescent attention-deficit/hyperactivity disorder and experiences of diagnosis and treatment: results from the European Lifetime Impairment Survey.

The Lifetime Impairment Survey assessed impairment and symptoms of attention-deficit/hyperactivity disorder (ADHD) in children/adolescents from six European countries. Parents/caregivers of children/adolescents aged<20 years with ADHD (ADHD group; n = 535) and without ADHD (control group; n=424) participated in an online survey. History of ADHD diagnosis was self-reported. ADHD and control groups were compared using impairment and symptom scales; higher scores indicate greater impairment. Mean (SD) age at ADHD diagnosis was 7.0 (2.8) years, following consultation of 2.7 (2.6) doctors over 20.4 (23.9) months. Parents/caregivers (64%; 344/535) reported frustration with some aspect of the diagnostic procedure; 74% (222/298) were satisfied with their child's current medication. ADHD had a negative impact on children/adolescents in all aspects of life investigated. The ADHD group had a higher mean (SD) school impairment score (2.7 [0.7]) compared with the control group (2.1 [0.7]; P<0.001) and were more likely to be in the bottom of their class (P<0.001). These data provide insights into impairments associated with ADHD in childhood/adolescence, and identify areas for improvement in its management and treatment.

Attention and inhibition in children with ASD, ADHD and co-morbid ASD + ADHD: an event-related potential study.

BACKGROUND: Substantial overlap has been reported between attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Deficits in executive function (EF) are characteristic of both disorders but these impairments have not been compared directly across pure and co-morbid cases using event-related potentials (ERPs). METHOD: Behavioural parameters and ERPs were recorded during a flankered cued-continuous performance test (CPT-OX) administered to 8-13-year-old boys with ASD (n = 19), ADHD (n = 18), co-morbid ASD + ADHD (n = 29) and typically developing controls (TD; n = 26). Preparatory processing (contingent negative variation, CNV) and attentional orienting (Cue-P3) at cues, response execution at targets (Go-P3), inhibitory processing at non-targets (NoGo-P3) and conflict monitoring between target and non-target trials (Go-N2 v. NoGo-N2) were examined. RESULTS: Categorical diagnoses and quantitative trait measures indicated that participants with ADHD (ADHD/ASD + ADHD) made more omission errors and exhibited increased reaction-time (RT) variability and reduced amplitude of the Cue-P3 and NoGo-P3 compared to TD/ASD participants. Participants with ASD (ASD/ ASD + ADHD) demonstrated reduced N2 enhancement from Go to NoGo trials compared to TD/ADHD participants. Participants with ASD-only displayed enhanced CNV amplitude compared to ASD + ADHD and TD participants. CONCLUSIONS: Children with ADHD show deficits in attentional orienting and inhibitory control whereas children with ASD show abnormalities in conflict monitoring and response preparation. Children with co-morbid ASD + ADHD present as an additive co-occurrence with deficits of both disorders, although non-additive effects are suggested for response preparation. Measuring ERPs that index attention and inhibition is useful in disentangling cognitive markers of ASD and ADHD and elucidating the basis of co-occurring ASD + ADHD to guide clinical assessment.

Different heritabilities but shared etiological influences for parent, teacher and self-ratings of ADHD symptoms: an adolescent twin study.

BACKGROUND: Parent and teacher ratings of attention deficit hyperactivity disorder (ADHD) symptoms yield high estimates of heritability whereas self-ratings typically yield lower estimates. To understand why, the present study examined the etiological overlap between parent, teacher and self-ratings of ADHD symptoms in a population-based sample of 11-12-year-old twins. Method Participants were from the Twins Early Development Study (TEDS). ADHD symptoms were assessed using the Strengths and Difficulties Questionnaire (SDQ) hyperactivity scale completed by parents, teachers and children. Structural equation modeling was used to examine genetic and environmental contributions to phenotypic variance/covariance. RESULTS: The broad-sense heritability of ADHD symptoms was 82% for parent ratings, 60% for teacher ratings and 48% for self-ratings. Post-hoc analyses revealed significantly higher heritability for same-teacher than different-teacher ratings of ADHD (76% v. 49%). A common pathway model best explained the relationship between different informant ratings, with common genetic influences accounting for 84% of the covariance between parent, teacher and self-rated ADHD symptoms. The remaining variance was explained by rater-specific genetic and non-shared environmental influences. CONCLUSIONS: Despite different heritabilities, there were shared genetic influences for parent, teacher and self-ratings of ADHD symptoms, indicating that different informants rated some of the same aspects of behavior. The low heritability estimated for self-ratings and different-teacher ratings may reflect increased measurement error when different informants rate each twin from a pair, and/or greater non-shared environmental influences. Future studies into the genetic influences on ADHD should incorporate informant data in addition to self-ratings to capture a pervasive, heritable component of ADHD symptomatology.

Genetic analysis of reaction time variability: room for improvement?

BACKGROUND: Increased reaction time variability (RTV) on cognitive tasks requiring a speeded response is characteristic of several psychiatric disorders. In attention deficit hyperactivity disorder (ADHD), the association with RTV is strong phenotypically and genetically, yet high RTV is not a stable impairment but shows ADHD-sensitive improvement under certain conditions, such as those with rewards. The state regulation theory proposed that the RTV difference score, which captures change from baseline to a rewarded or fast condition, specifically measures 'state regulation'. By contrast, the interpretation of RTV baseline (slow, unrewarded) scores is debated. We aimed to investigate directly the degree of phenotypic and etiological overlap between RTV baseline and RTV difference scores. Method We conducted genetic model fitting analyses on go/no-go and fast task RTV data, across task conditions manipulating rewards and event rate, from a population-based twin sample (n=1314) and an ADHD and control sibling-pair sample (n=1265). RESULTS: Phenotypic and genetic/familial correlations were consistently high (0.72-0.98) between RTV baseline and difference scores, across tasks, manipulations and samples. By contrast, correlations were low between RTV in the manipulated condition and difference scores. A comparison across two different go/no-go task RTV difference scores (slow-fast/slow-incentive) showed high phenotypic and genetic/familial overlap (r = 0.75-0.83). CONCLUSIONS: Our finding that RTV difference scores measure largely the same etiological process as RTV under baseline condition supports theories emphasizing the malleability of the observed high RTV. Given the statistical shortcomings of difference scores, we recommend the use of RTV baseline scores for most analyses, including genetic analyses.

Developmental associations between traits of autism spectrum disorder and attention deficit hyperactivity disorder: a genetically informative, longitudinal twin study.

BACKGROUND: Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), and associated subclinical traits, regularly co-occur with one another. However, the aetiology of their co-occurrence remains poorly understood. This paper provides the first genetically informative, longitudinal analysis of the interaction between traits of ASD and ADHD, and explores their genetic and environmental overlap. METHOD: Parents of approximately 5000 twin pairs completed questionnaires assessing traits of ASD and ADHD when twins were aged 8 and 12 years. Cross-lagged longitudinal modelling explored their developmental association, enabling a consideration of phenotypic-driven processes. Overlapping aetiological influences on traits at age 12 years were explored using bivariate twin modelling. RESULTS: Traits of ADHD at age 8 years were more strongly predictive of traits of ASD at 12 years than traits of ASD at 8 years were of traits of ADHD at 12 years. Analysis of traits by subscales assessing specific symptom domains suggested that communication difficulties were most strongly associated with traits of ADHD. Bivariate modelling suggested moderate genetic overlap on traits in males (genetic correlation = 0.41), and a modest degree of overlap in females (genetic correlation = 0.23) at age 12 years. CONCLUSIONS: Traits of ADHD at age 8 years significantly influence traits of ASD at age 12 years, after controlling for their initial relationship at age 8 years. In particular, early ADHD traits influenced later communication difficulties. These findings demonstrate the dynamic nature of co-occurring traits across development. In addition, these findings add to a growing body of literature suggesting that traits of ASD and ADHD may arise via similar aetiological processes.