Heritability Of Attention-deficit/hyperactivity Disorder Research Articles

A twin study of genetic and environmental contributions to attention-deficit/hyperactivity disorder over time.

Attention-deficit/hyperactivity disorder (ADHD) is an increasingly commonly diagnosed neurodevelopmental condition. One possibility is that this reflects a genuine increase in the prevalence of ADHD due to secular environmental changes, yet this hypothesis remains untested. We therefore investigated whether the genetic and environmental variance underlying ADHD, and traits of ADHD, has changed over time. We identified twins born from 1982 to 2008 from the Swedish Twin Registry (STR). We linked the STR with the Swedish National Patient Register and Prescribed Drug Register to identify diagnoses of ADHD and prescriptions of ADHD medication for these twins. We also utilized data collected from participants in the Child and Adolescent Twin Study in Sweden (CATSS), born from 1992 to 2008. Their parents completed a structured ADHD screening tool, which was used to measure traits of ADHD and assign broad screening diagnoses of ADHD. We used the classical twin design to test whether the degree to which variation in these measures was influenced by genetic and environmental variation changed over time. We included 22,678 twin pairs from the STR and 15,036 pairs from CATSS. The heritability of ADHD in the STR ranged from 66% to 86% over time, although these fluctuations were not statistically significant. We observed a modest increase in variance in ADHD traits, from 0.98 to 1.09. This was driven by small increases in the underlying genetic and environmental variance, with heritability estimated as 64%-65%. No statistically significant changes in variance in screening diagnoses were observed. The relative contribution of genetic and environmental factors to ADHD has remained stable over time, despite its increasing prevalence. Thus, changes in the underlying etiology of ADHD over time are unlikely to explain the increase in ADHD diagnoses.

The Heritability of ADHD in Children of ADHD Parents: A Post-hoc Analysis of Longitudinal Data

Objective: A growing literature suggests attention-deficit/hyperactivity disorder (ADHD) is a heritable disorder. We evaluated children at risk for ADHD by virtue of having parents with ADHD and compared them with children of parents without ADHD to assess the degree of heritability of ADHD. Method: The sample for this study was derived from three longitudinal studies that tracked families with various disorders, including ADHD. Children were stratified based on presence of parental ADHD, and clinical assessments were taken to evaluate presence of ADHD and related psychiatric and functional outcomes in children. Results: Children with parental ADHD had significantly more full or subthreshold psychiatric disorders (including ADHD) as well as functional impairments compared to children without parental ADHD. Conclusion: Our findings suggest that offspring of parents with ADHD are at significant risk for ADHD and its associated psychiatric, cognitive, and educational impairments. These findings aid in identifying early manifestations of ADHD in young children at risk.

Upside down: dissecting impulsivity in attention-deficit hyperactivity disorder through genotype-phenotype association analyses

IntroductionBetter evaluation and understanding of the core symptoms have key importance both in clinical practice and the research of attention-deficit hyperactivity disorder (ADHD). One hallmark neurocognitive feature of ADHD is impaired inhibition, related to impulsivity. Given the high heritability of ADHD, the assessment of genetic background of impaired inhibition may contribute to our knowledge about the genetic background of the disorder.ObjectivesIn our study we investigated whether different forms of impulsivity (attentive, motor, and nonplanning) and polymorphisms in genes of the noradrenergic, serotonergic, and dopaminergic neurotransmission, i.e. dopamine transporter-1 (DAT1), cathecoloamin-O-metiltransferase (COMT), and serotonin receptor-1B (HTR1B genes show association.Methods208 aADHD patients diagnosed according to DSM-5 criteria from a clinical sample and 142 individuals from a population sample who screened positive for aADHD were included in the study. DNA samples were genotyped for the HTR-1B gene rs1321041 and the COMT gene rs4680 SNPs, moreover the DAT-1 VNTR polymorphism. Dimensional variables for impulsivity were compared between genotypes with the Generalized Linear Model procedure corrected for sex and age, using the PLINK 1.9 statistical software.ResultsThe 9 repeat polymorphism in DAT1 was associated with the severity of hyperactivity, moreover, all impulsivity factors. The A allele in COMT was associated with hyperactivity and better motor inhibition activity. In carriers of the G allele in HTR1B we detected significantly higher inattention scores and increased reaction time.ConclusionsOur results support the putative role of the investigated genetic polymorphisms in the etiology of impulsivity. Nevertheless, these polymorphisms demonstrate a heterogeneous associations.DisclosureNo significant relationships.

Genetics in the ADHD Clinic: How Can Genetic Testing Support the Current Clinical Practice?

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a childhood prevalence of 5%. In about two-thirds of the cases, ADHD symptoms persist into adulthood and often cause significant functional impairment. Based on the results of family and twin studies, the estimated heritability of ADHD approximates 80%, suggests a significant genetic component in the etiological background of the disorder; however, the potential genetic effects on disease risk, symptom severity, and persistence are unclear. This article provides a brief review of the genome-wide and candidate gene association studies with a focus on the clinical aspects, summarizing findings of ADHD disease risk, ADHD core symptoms as dimensional traits, and other traits frequently associated with ADHD, which may contribute to the susceptibility to other comorbid psychiatric disorders. Furthermore, neuropsychological impairment and measures from neuroimaging and electrophysiological paradigms, emerging as potential biomarkers, also provide a prominent target for molecular genetic studies, since they lie in the pathway from genes to behavior; therefore, they can contribute to the understanding of the underlying neurobiological mechanisms and the interindividual heterogeneity of clinical symptoms. Beyond the aforementioned aspects, throughout the review, we also give a brief summary of the genetic results, including polygenic risk scores that can potentially predict individual response to different treatment options and may offer a possibility for personalized treatment for the therapy of ADHD in the future.

Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder

Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder often comorbid with disruptive behavior disorders (DBDs). Here, we report a GWAS meta-analysis of ADHD comorbid with DBDs (ADHD + DBDs) including 3802 cases and 31,305 controls. We identify three genome-wide significant loci on chromosomes 1, 7, and 11. A meta-analysis including a Chinese cohort supports that the locus on chromosome 11 is a strong risk locus for ADHD + DBDs across European and Chinese ancestries (rs7118422, P = 3.15×10−10, OR = 1.17). We find a higher SNP heritability for ADHD + DBDs (h2SNP = 0.34) when compared to ADHD without DBDs (h2SNP = 0.20), high genetic correlations between ADHD + DBDs and aggressive (rg = 0.81) and anti-social behaviors (rg = 0.82), and an increased burden (polygenic score) of variants associated with ADHD and aggression in ADHD + DBDs compared to ADHD without DBDs. Our results suggest an increased load of common risk variants in ADHD + DBDs compared to ADHD without DBDs, which in part can be explained by variants associated with aggressive behavior.

Resilience Factors That Modify Genetic Risk for ADHD Matter for Later Life Emotional and Cognitive Health Outcomes

Having features of Attention Deficit Hyperactivity Disorder (ADHD) is associated with challenges with emotional regulation and cognitive function. Heritability for ADHD in adults is estimated to be 30%. The degree to which genetic risk for ADHD can be modified by protective factors, such as strong personal relationships and pursuing more education, to result in better emotional and cognitive outcomes at later ages is not well understood. We evaluated these relationships in a population-representative sample of older adults in the U.S. Health and Retirement Study, with 9,003 European Americans (EA; 57% women, age M=68.6, SD=10.4), and 1,622 African Americans (AA; 63% women, age M=64.4, SD=9.5). Outcomes included validated scales for psychological resilience, life satisfaction, depressive symptoms (DepSx), cognitive functioning, and impairment, assessed between 2008-2012. A genetic risk score for ADHD (GRS-ADHD) was calculated from a genomewide-scan, using a mixed ancestry sample. We used multivariable linear and logistic regression models, adjusted for age, gender, and genetic ancestry. We found a protective effect such that stronger personal relationships in adulthood reduced the inverse relationship between the GRS-ADHD and resilience and life satisfaction in later age (interaction p’s<.004 in EAs), but not with DepSx. In contrast, strong parental relationships in childhood attenuated the association between the GRS-ADHD and later life DepSx (interaction p’s<.007 in EAs and AAs) only. Education did not modify, but mediated the main effect of the GRS-ADHD on cognitive abilities and impairment in EAs and AAs. Findings have implications for later age health for those at greater genetic risk for ADHD.

Recent advances in understanding of attention deficit hyperactivity disorder (ADHD): how genetics are shaping our conceptualization of this disorder.

Attention deficit hyperactivity disorder (ADHD) is a clinically defined disorder, and inattention and hyperactivity/impulsivity are its main symptom domains. The presentation, lifelong continuation and treatment response of ADHD symptoms, however, is highly heterogeneous. To better define, diagnose, treat and prevent ADHD, it is essential that we understand the biological processes underlying all of these elements. In this review, given the high heritability of ADHD, we discuss how and why genetics can foster such progress. We examine what genetics have taught us so far with regard to ADHD definition, classification, clinical presentation, diagnosis and treatment. Finally, we offer a prospect of what genetic studies on ADHD may bring in the future.

Recent advances in understanding of attention deficit hyperactivity disorder (ADHD): how genetics are shaping our conceptualization of this disorder

Attention deficit hyperactivity disorder (ADHD) is a clinically defined disorder, and inattention and hyperactivity/impulsivity are its main symptom domains. The presentation, lifelong continuation and treatment response of ADHD symptoms, however, is highly heterogeneous. To better define, diagnose, treat and prevent ADHD, it is essential that we understand the biological processes underlying all of these elements. In this review, given the high heritability of ADHD, we discuss how and why genetics can foster such progress. We examine what genetics have taught us so far with regard to ADHD definition, classification, clinical presentation, diagnosis and treatment. Finally, we offer a prospect of what genetic studies on ADHD may bring in the future.

Functional EEG connectivity is a neuromarker for adult attention deficit hyperactivity disorder symptoms

ObjectiveAltered brain functional connectivity has been shown in youth with attention-deficit/hyperactivity disorder (ADHD). However, relatively little is known about functional connectivity in adult ADHD, and how it is linked with the heritability of ADHD. MethodsWe measured eyes-open and eyes-closed resting electroencephalography (EEG) from 38 adults with ADHD, 45 1st degree relatives of people with ADHD and 51 healthy controls. Functional connectivity among all scalp channels was calculated using a weighted phase lag index for delta, theta, alpha, beta and gamma frequency bands. A machine learning analysis using penalized linear regression was used to identify if connectivity features (10,080 connectivity pairs) could predict ADHD symptoms. Furthermore, we examined if EEG connectivity could accurately classify participants into ADHD, 1st degree relatives and/or control groups. ResultsHyperactive symptoms were best predicted by eyes-open EEG connectivity in delta, beta and gamma bands. Inattentive symptoms were predicted by eyes-open EEG connectivity in delta, alpha and gamma bands, and eyes-closed EEG connectivity in delta and gamma bands. EEG connectivity features did not reliably classify participants into groups. ConclusionsEEG connectivity may represent a neuromarker for ADHD symptoms. SignificanceEEG connectivity may help elucidate the neural basis of adult ADHD symptoms.

Genetic risk factors and gene-environment interactions in adult and childhood attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable neurodevelopmental disorder. In recent years, genetic studies have revealed several risk gene variants associated with ADHD; however, these variants could only be partly replicated and are responsible for only a fraction of the whole heritability of ADHD estimated from family and twin studies. One factor that could potentially explain the 'missing heritability' of ADHD is that childhood and adult or persistent ADHD could be genetically distinct subtypes, which therefore need to be analyzed separately. Another approach to identify this missing heritability could be combining the investigation of both common and rare gene risk variants as well as polygenic risk scores. Finally, environmental factors are also thought to play an important role in the etiology of ADHD, acting either independently of the genetic background or more likely in gene-environment interactions. Environmental factors might additionally convey their influence by epigenetic mechanisms, which are relatively underexplored in ADHD. The aforementioned mechanisms might also influence the response of patients with ADHD to stimulant and other ADHD medication. We conducted a selective review with a focus on risk genes of childhood and adult ADHD, gene-environment interactions, and pharmacogenetics studies on medication response in childhood and adult ADHD.

Attention-deficit/hyperactivity disorder and lifetime cannabis use: genetic overlap and causality.

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 × 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 × 10-8 and rs4259397, P = 4.52 × 10-8) and two in a gene-based association analysis (WDPCP, P = 9.67 × 10-7 and ZNF251, P = 1.62 × 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 × 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.

Heritability of Attention-Deficit Hyperactivity Disorder Across The Lifespan

Attention-Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder affecting around 5-10% of children and 2.5-5% of adults worldwide. Research addressing the heritability of ADHD have yielded inconsistent findings, with studies in children suggesting higher heritability (75–90%) compared to studies in adults (30–50% )(Brikell, Kuja-Halkola, and Larsson 2015). To review the role of rater effects on the observed differences in heritability between children and adults, and to address the role of genetic and environmental influences on stability and change of ADHD over the life-span, we conducted a literature review of cross-sectional and longitudinal studies addressing the heritability of ADHD across ages, or in adulthood. We identified quantitative genetic studies published up until May 2017 by searching the NCBI's PubMed database using a combination of the keywords heritability, attention-deficit hyperactivity disorder, attention problems, ADHD, adult, genetic, self-report, twin, longitudinal and family studies.Based on the reviewed cross-sectional studies, the heritability of self-rated ADHD symptoms in adults ranged between 30%-44% and the heritability of self-rated symptoms in adolescent between 34%-54%. Cross-sectional studies including multiple informants showed that heritability estimates based on ratings from different informants (i.e., self-ratings and different parents/teachers rating each twin in a pair) consistently yield lower heritability estimates compared to studies based on ratings from a single informant. This effect appears to be independent of age. One study using cross-informant data in adults (combined parent and self-ratings) and two studies using register based clinical diagnoses in twin and family data reported the heritability of ADHD in adults to be 70–80%. The reviewed longitudinal twin studies suggest that stability in ADHD is largely due to genetic factors. In addition, longitudinal studies also provide evidence that new genetic effects for ADHD come online at different developmental stages and that these genetic factors are partly independent of those contributing to baseline symptoms. We identified one study assessing late-onset adult ADHD, which reported the heritability of both self-reported and co-informant (mother or co-twin) reported clinically relevant ADHD at age 18 to be around 35%.Together, the reviewed cross-sectional studies suggest that the reported lower heritability of ADHD in adults is likely to be at least partly explained by the switch from relying one rater (parent/teacher) in childhood, to relying on self-ratings (where each twin rates themselves) of ADHD symptoms in adulthood. When rater effects are addressed using cross-informant data or clinical diagnoses, the heritability of ADHD in adulthood appears to be comparable to the heritability of ADHD in childhood. Longitudinal studies show evidence for the role of genetic factors in both the stability and change in ADHD across ages. Emerging evidence suggest that the genes implicated in the onset of childhood ADHD are in part distinct from those associated with the developmental course of ADHD. Such findings raise new questions as to whether the heterogeneity in heritability estimates of ADHD across ages may be related to differential developmental trajectories of ADHD.

Biological Mechanisms of ADHD

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inappropriate levels of inattention, hyperactivity and impulsivity. Recent developments in neuroimaging and functional brain studies have revealed volumetric reductions and decreased neural activities in the frontal lobe, basal ganglia, limbic system, and cerebellum. Based on these findings, impairment of executive function and the reward system, reffered to as the dual pathway model, and dysfunction of the default mode network have been proposed as biological changes underlying ADHD. Bio-pharmacological studies have shown dysfunctions in catecholamine- regulated neurotransmission, especially dysfunction of dopamine transporters, which the therapeutic drug of methylphenidate is thought to modulate. Agrowing body of genetic research suggests the high heritability of ADHD and several candidate genes relating to dopamine synthesis and transmission have been identified. Epigenetic modification is also garnering much attention in ADHD research and the mutual effects of environmental factors and genetic polymorphism have been reported. Despite such accumulative findings, how genes, the environment, and brain functioning interact and relate to create the symptoms of ADHD are still unknown and more research is needed to uncover the biological mechanisms of ADHD.

Rare DNA variants in the brain-derived neurotrophic factor gene increase risk for attention-deficit hyperactivity disorder: a next-generation sequencing study

Attention-deficit hyperactivity disorder (ADHD) is a prevalent and highly heritable disorder of childhood with negative lifetime outcomes. Although candidate gene and genome-wide association studies have identified promising common variant signals, these explain only a fraction of the heritability of ADHD. The observation that rare structural variants confer substantial risk to psychiatric disorders suggests that rare variants might explain a portion of the missing heritability for ADHD. Here we believe we performed the first large-scale next-generation targeted sequencing study of ADHD in 152 child and adolescent cases and 188 controls across an a priori set of 117 genes. A multi-marker gene-level analysis of rare (<1% frequency) single-nucleotide variants (SNVs) revealed that the gene encoding brain-derived neurotrophic factor (BDNF) was associated with ADHD at Bonferroni corrected levels. Sanger sequencing confirmed the existence of all novel rare BDNF variants. Our results implicate BDNF as a genetic risk factor for ADHD, potentially by virtue of its critical role in neurodevelopment and synaptic plasticity.

Heritability of attention-deficit hyperactivity disorder in adults.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Symptoms often persist into adulthood, with a prevalence of 2.5-5% in adult populations. Twin studies in childhood consistently report high heritabilities of 70-80%, while studies in adult samples show only moderate heritability of 30-40% when estimated from self-ratings. This review summarizes the available research on the heritability of ADHD in adults. Three key findings are outlined: (i) self-ratings lead to relatively low heritability estimates of ADHD, independent of age and whether ratings refer to current or retrospective symptoms; (ii) studies relying on different informants to rate each twin within a pair (i.e., self-ratings and different parents/teachers rating each twin in a pair) consistently yield lower heritability estimates than studies relying on ratings from a single informant; (iii) studies using cross-informant data via either combined parent and self-ratings or clinical diagnoses information suggest that the heritability of ADHD in adults could be as high as 70-80%. Together, the reviewed studies suggest that the previously reported low heritability of ADHD in adults is unlikely to reflect a true developmental change. Instead, the drop in heritability is better explained by rater effects related to a switch from using one rater for both twins in a pair (parent/teacher) in childhood, to relying on self-ratings (where each twin rates themselves) of ADHD symptoms in adulthood. When rater effects are addressed using cross-informant approaches, the heritability of ADHD in adults appears to be comparable to the heritability of ADHD in childhood. © 2015 Wiley Periodicals, Inc.

Neuropsychological and dimensional behavioral trait profiles in Costa Rican ADHD sib pairs: Potential intermediate phenotypes for genetic studies.

Attention deficit hyperactivity disorder (ADHD) is associated with substantial functional impairment in children and in adults. Many individuals with ADHD have clear neurocognitive deficits, including problems with visual attention, processing speed, and set shifting. ADHD is etiologically complex, and although genetic factors play a role in its development, much of the genetic contribution to ADHD remains unidentified. We conducted clinical and neuropsychological assessments of 294 individuals (269 with ADHD) from 163 families (48 multigenerational families created using genealogical reconstruction, 78 affected sib pair families, and 37 trios) from the Central Valley of Costa Rica (CVCR). We used principal components analysis (PCA) to group neurocognitive and behavioral variables using the subscales of the Child Behavior Checklist (CBCL) and 15 neuropsychological measures, and created quantitative traits for heritability analyses. We identified seven cognitive and two behavioral domains. Individuals with ADHD were significantly more impaired than their unaffected siblings on most behavioral and cognitive domains. The verbal IQ domain had the highest heritability (92%), followed by auditory attention (87%), visual processing speed and problem solving (85%), and externalizing symptoms (81%). The quantitative traits identified here have high heritabilities, similar to the reported heritability of ADHD (70-90%), and may represent appropriate alternative phenotypes for genetic studies. The use of multigenerational families from a genetically isolated population may facilitate the identification of ADHD risk genes in the face of phenotypic and genetic heterogeneity.

Understanding attention deficit disorder: a neuroscience prospective.

Today’s ready access to electronic devices and the internet often substitute for social interaction. Such situation, if it starts in early childhood, in certain vulnerable individuals, who crave immediate rewards, can decrease the ability to maintain prolonged attention (1) and tolerate delayed gratification, thus reinforcing future addictive behaviors (2). Once established, these behaviors, such as attention deficit hyperactivity disorder (ADHD), may persist into adulthood. ADHD is one of the most common reasons for referring children to mental health facilities. Generally, parents seek professional help for their children after the school suggests that their child has difficulties. These difficulties may be related to academic performance, behavior, or both. Research data support the idea that children with attention deficit disorder often come from families with attention deficit in one or both parents (3). Very recent data indicate a significant genetic predisposition for this disorder. Seventy percent of children who have this disorder will have the disorder as teenagers, and about 40%-60% will still have the disorder as adults, and although genetic studies have not isolated a gene for ADHD, there may be several genes contributing to the vulnerability for developing this disorder. For example, twin studies have shown a significant heritability for ADHD (4) as high as 76%. In addition, the parents and siblings of children with ADHD have an ADHD diagnostic probability 4-5 times higher than the general population, and boys are more vulnerable than girls (5). Based on these data, it might appear that ADHD is easily diagnosed and, thus, simple to treat, but we still must question the methods and criteria used for diagnosing ADHD. Currently, clinical interviews and collateral histories from parents and teachers drive the standards. Only occasionally do we use objective assessments, such as continuous performance tasks and neuropsychological assessments, to evaluate whether or not a child can sustain attention, and whether their deficits lie in either or both auditory and visual domains. Various factors may play a role in sustaining attention. These may include: motivation, concurrent anxiety, lack of sleep, low blood glucose, medication, and family collaboration (6). Clinicians consider and evaluate three major symptom groups for diagnosing ADHD: inattention, hyperactivity, and impulsivity. Each category describes particular symptoms; for example, inattention may involve an inability to finish tasks, organize, and sustain efforts as well as forgetfulness and distractibility. Hyperactivity is defined as being fidgety, inability to sit still, and motoric hyperactivity – excessive running, climbing, and moving. Impulsivity involves excessive talking, answering without thinking, inability to wait one’s turn, interrupting, and so on. Both the DSM IV and the ICD 10 provide guidelines for the frequency and duration of the symptoms in these diagnostic categories, and both generally agree on the necessary number of symptoms before someone receives the diagnosis of ADHD. Nevertheless, it should be noted that these symptoms may be defined and scored by individuals that are untrained in this process. Therefore, we need to question the reliability and validity of such unidimensional data.

The heritability of clinically diagnosed attention deficit hyperactivity disorder across the lifespan

No prior twin study has explored the heritability of clinically diagnosed attention deficit hyperactivity disorder (ADHD). Such studies are needed to resolve conflicting results regarding the importance of genetic effects for ADHD in adults. We aimed to estimate the relative contribution of genetic and environmental influences for clinically diagnosed ADHD across the lifespan with a specific focus on ADHD in adults. Information on zygosity and sex was obtained from 59514 twins born between 1959 and 2001 included in the nationwide population-based Swedish Twin Registry. Clinical data for ADHD diagnoses (i.e. stimulant or non-stimulant medication for ADHD) were obtained from the Swedish Prescribed Drug Register (PDR) and from the National Patient Register (i.e. ICD-10 diagnosis of ADHD). Twin methods were applied to clinical data of ADHD diagnoses using structural equation modeling with monozygotic (MZ) and dizygotic (DZ) twins. The best-fitting model revealed a high heritability of ADHD [0.88, 95% confidence interval (CI) 0.83-0.92] for the entire sample. However, shared environmental effects were non-significant and of minimal importance. The heritability of ADHD in adults was also substantial (0.72, 95% CI 0.56-0.84). This study shows that the heritability of clinically diagnosed ADHD is high across the lifespan. Our finding of high heritability for clinically diagnosed ADHD in adults indicates that the previous reports of low heritability are best explained by rater effects, and that gene-identification studies of ADHD in adults need to consider pervasiveness (e.g. multiple raters) and developmentally (e.g. childhood-onset criteria) informative data.

Paternal ADHD symptoms and child conduct problems: is father involvement always beneficial?

Maternal psychopathology robustly predicts poor developmental and treatment outcomes for children with attention-deficit/hyperactivity disorder (ADHD). Despite the high heritability of ADHD, few studies have examined associations between paternal ADHD symptoms and child adjustment, and none have also considered degree of paternal involvement in childrearing. Identification of modifiable risk factors for child conduct problems is particularly important in this population given the serious adverse outcomes resulting from this comorbidity. This cross-sectional study examined the extent to which paternal involvement in childrearing moderated the association between paternal ADHD symptoms and child conduct problems among 37 children with ADHD and their biological fathers. Neither paternal ADHD symptoms nor involvement was independently associated with child conduct problems. However, the interaction between paternal ADHD symptoms and involvement was significant, such that paternal ADHD symptoms were positively associated with child conduct problems only when fathers were highly involved in childrearing. The presence of adult ADHD symptoms may determine whether father involvement in childrearing has a positive or detrimental influence on comorbid child conduct problems.

The relationship between the presence of ADHD and certain candidate gene polymorphisms in a Turkish sample

Due to the high heritability of attention-deficit hyperactivity disorder (ADHD), parents of children with ADHD appear to represent a good sample group for investigating the genetics of the disorder. The aim of this study was to investigate the association between ADHD and six polymorphisms in five candidate genes [5-HT2A (rs6311), NET1 (rs2242447), COMT (rs4818), NTF3 (rs6332), SNAP-25 (rs3746544) and (rs1051312)]. We included 228 parents of children diagnosed with ADHD and 109 healthy parents as the control group. The polymorphisms were genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) assays and analyzed using the chi-square test and the multinomial logit model. SNAP-25 (rs3746544) polymorphism was associated with loading for ADHD, while 5-HT2A (rs6311) and NET1 (rs2242447) polymorphisms were associated with ADHD. On the other hand, there was no significant association between the SNAP-25 (rs1051312), NTF3 (rs6332), or COMT (rs4818) gene polymorphisms and ADHD.In addition, we found that even if variation in the SNAP-25 gene alone does not affect the phenotype, it may nevertheless lead to the emergence of a clinical ADHD picture in the presence of other genetic factors. Our findings suggest that a combination of NET1 (rs2242447) and SNAP-25 (rs3746544) is a risk factor for ADHD. Problems associated with the noradrenergic and serotonergic systems and SNAP-25 may play a role, both alone and in interaction with one another, in the pathophysiological mechanisms of ADHD.