Search

Background and aims: Studies have indicated that maternal prenatal substance use may be associated with offspring attention deficit hyperactivity disorder (ADHD) via intrauterine effects. We measured associations between prenatal smoking, alcohol and caffeine consumption with childhood ADHD symptoms accounting for shared familial factors. Design: First, we used a negative control design comparing maternal and paternal substance use. Three models were used for negative control analyses: unadjusted (without confounders), adjusted (including confounders) and mutually adjusted (including confounders and partner's substance use). The results were meta-analysed across the cohorts. Secondly, we used polygenic risk scores (PRS) as proxies for exposures. Maternal PRS for smoking, alcohol and coffee consumption were regressed against ADHD symptoms. We triangulated the results across the two approaches to infer causality. Setting: We used data from three longitudinal pregnancy cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC) in the United Kingdom, Generation R study (GenR) in the Netherlands and Norwegian Mother, Father and Child Cohort study (MoBa) in Norway. Participants: Phenotype data available for children were: N ALSPAC = 5455–7751; N GENR = 1537–3119; N MOBA = 28 053–42 206. Genotype data available for mothers was: N ALSPAC = 7074; N MOBA = 14 583. Measurements: A measure of offspring ADHD symptoms at age 7–8 years was derived by dichotomizing scores from questionnaires and parental self-reported prenatal substance use was measured at the second pregnancy trimester. Findings: The pooled estimate for maternal prenatal substance use showed an association with total ADHD symptoms [odds ratio (OR) SMOKING = 1.11, 95% confidence interval (CI) = 1.00–1.23; OR ALCOHOL = 1.27, 95% CI = 1.08–1.49; OR CAFFEINE = 1.05, 95% CI = 1.00–1.11], while not for fathers (OR SMOKING = 1.03, 95% CI = 0.95–1.13; OR ALCOHOL = 0.83, 95% CI = 0.47–1.48; OR CAFFEINE = 1.02, 95% CI = 0.97–1.07). However, maternal associations did not persist in sensitivity analyses (substance use before pregnancy, adjustment for maternal ADHD symptoms in MoBa). The PRS analyses were inconclusive for an association in ALSPAC or MoBa. Conclusions: There appears to be no causal intrauterine effect of maternal prenatal substance use on offspring attention deficit hyperactivity disorder symptoms.

Contains fulltext : 219447.pdf (Publisher’s version ) (Open Access) Attention-deficit/hyperactivity disorder (ADHD) is a severely impairing neurodevelopmental disorder with a prevalence of 5% in children and adolescents and of 2.5% in adults. Comorbid conditions in ADHD play a key role in symptom progression, disorder course and outcome. ADHD is associated with a significantly increased risk for substance use, abuse and dependence. ADHD and cannabis use are partly determined by genetic factors; the heritability of ADHD is estimated at 70-80% and of cannabis use initiation at 40-48%. In this study, we used summary statistics from the largest available meta-analyses of genome-wide association studies (GWAS) of ADHD (n = 53,293) and lifetime cannabis use (n = 32,330) to gain insights into the genetic overlap and causal relationship of these two traits. We estimated their genetic correlation to be r2 = 0.29 (P = 1.63 x 10-5) and identified four new genome-wide significant loci in a cross-trait analysis: two in a single variant association analysis (rs145108385, P = 3.30 x 10-8 and rs4259397, P = 4.52 x 10-8) and two in a gene-based association analysis (WDPCP, P = 9.67 x 10-7 and ZNF251, P = 1.62 x 10-6). Using a two-sample Mendelian randomization approach we found support that ADHD is causal for lifetime cannabis use, with an odds ratio of 7.9 for cannabis use in individuals with ADHD in comparison to individuals without ADHD (95% CI (3.72, 15.51), P = 5.88 x 10-5). These results substantiate the temporal relationship between ADHD and future cannabis use and reinforce the need to consider substance misuse in the context of ADHD in clinical interventions. 11 p.

Child maltreatment has consistently been found to be associated with attention deficit/hyperactivity disorder (ADHD). However, the robustness of this association and the direction of the link between maltreatment and ADHD remain unclear. We used data from the Environmental Risk (E-Risk) Longitudinal Twin Study, a cohort of 2232 British twins, to investigate the associations between exposure to abuse/neglect and ADHD in childhood and in young adulthood, and to test their robustness and specificity. We also aimed to test longitudinal associations between abuse/neglect and ADHD from childhood to young adulthood, controlling for confounders. Results indicated strong associations between abuse/neglect and ADHD in childhood and also in young adulthood. In childhood, the association was concentrated among children with comorbid conduct disorder. Longitudinal analyses showed that childhood ADHD predicted abuse/neglect in later years. This association was again concentrated among individuals with comorbid conduct disorder. Abuse/neglect in childhood was not associated with later ADHD in young adulthood after adjusting for childhood ADHD. Our study does not provide support of a causal link between child abuse/neglect and adult ADHD but highlights the possibility of a long-term effect of disruptive behaviors on the risk for experiencing abuse/neglect. These findings emphasize the need for clinicians treating people with ADHD, especially those with comorbid conduct disorder, to be aware of their increased risk for experiencing abuse/neglect. Interventions aimed at reducing risks of abuse/neglect should also focus on the environment of individuals with disruptive behaviors.

BackgroundThe results of twin and sibling studies suggest that executive functioning is a prime candidate endophenotype in attention deficit hyperactivity disorder (ADHD). However, studies have not assessed the co-segregation of executive function (EF) deficits from parents to offspring directly, and it is unclear whether executive functioning is an ADHD endophenotype in adolescents, given the substantial changes in prefrontal lobe functioning, EF and ADHD symptoms during adolescence.MethodWe recruited 259 ADHD and 98 control families with an offspring average age of 17.3 years. All participants were assessed for ADHD and EF [inhibition, verbal (VWM) and visuospatial working memory (VsWM)]. Data were analysed using generalized estimating equations (GEEs).ResultsParental ADHD was associated with offspring ADHD and parental EF was associated with offspring EF but there were no cross-associations (parental ADHD was not associated with offspring EF or vice versa). Similar results were found when siblings were compared. EF deficits were only found in affected adolescents and not in their unaffected siblings or (un)affected parents.ConclusionsThe core EFs proposed to be aetiologically related to ADHD, that is working memory and inhibition, seem to be aetiologically independent of ADHD in adolescence. EF deficits documented in childhood in unaffected siblings were no longer present in adolescence, suggesting that children ‘grow out’ of early EF deficits. This is the first study to document ADHD and EF in a large family sample with adolescent offspring. The results suggest that, after childhood, the majority of influences on ADHD are independent from those on EF. This has potential implications for current aetiological models of causality in ADHD.

Background Attention-Deficit-Hyperactivity-Disorder (ADHD) is, with a prevalence of 5 %, a highly common childhood disorder, and has severe impact on the lives of youngsters and their families. Medication is often the treatment of choice, as it currently is most effective. However, medication has only short-term effects, treatment adherence is often low and most importantly; medication has serious side effects. Therefore, there is a need for other interventions for youngsters with ADHD. Mindfulness training is emerging as a potentially effective training for children and adolescents with ADHD. The aim of this study is to compare the (cost) effectiveness of mindfulness training to the (cost) effectiveness of methylphenidate in children with ADHD on measures of attention and hyperactivity/impulsivity. Methods/design A multicenter randomized controlled trial with 2 follow-up measurements will be used to measure the effects of mindfulness training versus the effects of methylphenidate. Participants will be youngsters (aged 9 to 18) of both sexes diagnosed with ADHD, referred to urban and rural mental healthcare centers. We aim to include 120 families. The mindfulness training, using the MYmind protocol, will be conducted in small groups, and consists of 8 weekly 1.5-h sessions. Youngsters learn to focus and enhance their attention, awareness, and self-control by doing mindfulness exercises. Parents will follow a parallel mindful parenting training in which they learn to be fully present in the here and now with their child in a non-judgmental way, to take care of themselves, and to respond rather than react to difficult behavior of their child. Short-acting methylphenidate will be administered individually and monitored by a child psychiatrist. Assessments will take place at pre-test, post-test, and at follow-up 1 and 2 (respectively 4 and 10 months after the start of treatment). Informants are parents, children, teachers, and researchers. Discussion This study will inform mental health care professionals and health insurance companies about the clinical and cost effectiveness of mindfulness training for children and adolescents with ADHD and their parents compared to the effectiveness of methylphenidate. Limitations and several types of bias that are anticipated for this study are discussed. Trial registration Dutch Trial Register: NTR4206. Registered 11 October 2013.

Objectives. Several pharmacological and genetic studies support the involvement of the dopamine neurotransmitter system in the aetiology of attention-defihyperactivity disorder (ADHD). Based on this information we evaluated the contribution to ADHD of nine genes involved in dopaminergic neurotransmission ( DRD1, DRD2, DRD3, DRD4, DRD5, DAT1, TH, DBH and COMT ). Methods. We genotyped a total of 61 tagging single nucleotide polymorphisms (SNPs) in a sample of 533 ADHD patients (322 children and 211 adults), 533 sex-matched unrelated controls and additional 196 nuclear ADHD families from Spain. Results. The single- and multiple-marker analysis in both population and family-based approaches provided preliminary evidence for the contribution of DRD1 to combined-type ADHD in children ( P � 8.8e-04; OR � 1.50 (1.18 – 1.90) and P � 0.0061; OR � 1.73 (1.23 – 2.45)) but not in adults. Subsequently, we tested positive results for replication in an independent sample of 353 German families with combined-type ADHD children and replicated the initial association between DRD1 and childhood ADHD ( P � 8.4e-05; OR � 3.67 (2.04 – 6.63)). Conclusions: The replication of the association between DRD1 and ADHD in two European cohorts highlights the validity of our fi nding and supports the involvement of DRD1 in childhood ADHD.

BackgroundTwin and sibling studies have identified specific cognitive phenotypes that may mediate the association between genes and the clinical symptoms of attention deficit hyperactivity disorder (ADHD). ADHD is also associated with lower IQ scores. We aimed to investigate whether the familial association between measures of cognitive performance and the clinical diagnosis of ADHD is mediated through shared familial influences with IQ.MethodMultivariate familial models were run on data from 1265 individuals aged 6–18 years, comprising 920 participants from ADHD sibling pairs and 345 control participants. Cognitive assessments included a four-choice reaction time (RT) task, a go/no-go task, a choice–delay task and an IQ assessment. The analyses focused on the cognitive variables of mean RT (MRT), RT variability (RTV), commission errors (CE), omission errors (OE) and choice impulsivity (CI).ResultsSignificant familial association (rF) was confirmed between cognitive performance and both ADHD (rF=0.41–0.71) and IQ (rF=−0.25 to −0.49). The association between ADHD and cognitive performance was largely independent (80–87%) of any contribution from etiological factors shared with IQ. The exception was for CI, where 49% of the overlap could be accounted for by the familial variance underlying IQ.ConclusionsThe aetiological factors underlying lower IQ in ADHD seem to be distinct from those between ADHD and RT/error measures. This suggests that lower IQ does not account for the key cognitive impairments observed in ADHD. The results have implications for molecular genetic studies designed to identify genes involved in ADHD.

Contains fulltext : 154452.pdf (Publisher’s version ) (Closed access) Background A developmental improvement of symptoms in Attention-Deficit/Hyperactivity Disorder (ADHD) is frequently reported, but the underlying neurobiological substrate has not been identified. The aim of this study was to determine whether white matter microstructure is related to developmental improvement of ADHD symptoms. Methods A cross-sectional Magnetic Resonance Imaging (MRI) analysis was embedded in a prospective follow-up of an adolescent cohort of ADHD and control subjects (NeuroIMAGE). Mean age at baseline was 11.9 years, mean interval of follow-up was 5.9 years. About 75.3% of the original cohort was retained successfully. Data of 101 participants with ADHD combined type at baseline and 40 healthy controls were analysed. ADHD symptoms were measured with semistructured, investigator-based interviews and Conners' questionnaires, on the basis of DSM-IV criteria. Fractional anisotropy (FA) and mean diffusivity (MD) indices of white matter microstructure were measured using whole brain diffusion tensor imaging at follow-up only. In a dimensional analysis FA and MD were related to change in ADHD symptoms. To link this analysis to DSM-IV diagnoses, a post hoc categorical group analysis was conducted comparing participants with persistent (n = 59) versus remittent (n = 42) ADHD and controls. Results Over time, participants with ADHD showed improvement mainly in hyperactive/impulsive symptoms. This improvement was associated with lower FA and higher MD values in the left corticospinal tract at follow-up. Findings of the dimensional and the categorical analysis strongly converged. Changes in inattentive symptoms over time were minimal and not related to white matter microstructure. Conclusions The corticospinal tract is important in the control of voluntary movements, suggesting the importance of the motor system in the persistence of hyperactive/impulsive symptoms.

PubMedID: 18437277 The aim of this study was to determine the frequency of adult attention deficit hyperactivity disorder (ADHD) comorbidity with lifetime bipolar disorder, and the influence of this comorbidity on various demographic and clinical variables in patients. Patients (n = 159) with a previous diagnosis of bipolar disorder (79 female, 80 male) were included in this study. All patients were interviewed for the presence of current adult and childhood ADHD diagnosis and other axis I psychiatric disorder comorbidities using the structured clinical interview for DSM-IV (SCID) and the Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version (K-SADS-PL). The subjects also completed a Wender Utah rating scale (WURS-25) and a Current Symptoms Scale for ADHD symptoms. In particular, patients' clinical characteristics, the age of onset of bipolar disorder, and the number of episodes were noted. Twenty-six of the 159 bipolar patients (16.3%) were diagnosed with adult ADHD, while another subgroup of patients (n = 17, 10.7%) received a diagnosis of childhood ADHD but did not fulfill criteria for adult ADHD. Both of these two subgroups (patients with adult ADHD, and patients with only childhood ADHD) had an earlier age of onset of the disease and a higher number of previous total affective or depressive episodes than those without any lifetime ADHD comorbidity. However only bipolar patients with adult ADHD comorbidity had higher lifetime comorbidity rates for axis I psychiatric disorders, such as panic disorder and alcohol abuse/dependence, compared to patients without lifetime ADHD. Bipolar patients with comorbid adult ADHD did not differ from bipolar patients with comorbid childhood ADHD in terms of any demographic or clinical variables except for adult ADHD scale scores. In conclusion, ADHD is a common comorbidity in bipolar patients, and it adversely affects the course of the disease and disrupts the social adjustment of the patients. Regular monitoring of ADHD will help to prevent problems and complications that could arise in the course of the disease, particularly in patients with early onset bipolar disorder. © 2008 Springer.

Objective: The aim of this review was to gain insight into the relationship between Attention deficit hyperactivity disorder (ADHD) and risky performance in gambling tasks and to identify any potential alternate explanatory factors.Methods: PsycINFO, PubMed, and Web of Knowledge were searched for relevant literature comparing individuals with ADHD to normal controls (NCs) in relation to their risky performance on a gambling task. In total, fourteen studies in children/adolescents and eleven studies in adults were included in the review.Results: Half of the studies looking at children/adolescents with ADHD found evidence that they run more risks on gambling tasks when compared to NCs. Only a minority of the studies on adults with ADHD reported aberrant risky behavior. The effect sizes ranged from small to large for both age groups and the outcome pattern did not differ between studies that applied an implicit or explicit gambling task. Two studies demonstrated that comorbid oppositional defiant disorder (ODD) and conduct disorder (CD) increased risky behavior in ADHD. Limited and/or inconsistent evidence was found that comorbid internalizing disorders (IDs), ADHD subtype, methylphenidate use, and different forms of reward influenced the outcomes.Conclusion: The evidence for increased risky performance of individuals with ADHD on gambling tasks is mixed, but is stronger for children/adolescents with ADHD than for adults with ADHD, which may point to developmental changes in reward and/or penalty sensitivity or a publication bias for positive findings in children/adolescents. The literature suggests that comorbid ODD/CD is a risk factor in ADHD for increased risky behavior. Comorbid IDs, ADHD subtype, methylphenidate use, and the form of reward received may affect risky performance in gambling tasks; however, these factors need further examination. Finally, the implications of the findings for ADHD models and the ecological validity of gambling tasks are discussed.