Etiology Of Attention Deficit Hyperactivity Disorder Research Articles

Candidate system analysis in ADHD: Evaluation of nine genes involved in dopaminergic neurotransmission identifies association with DRD1

Objectives. Several pharmacological and genetic studies support the involvement of the dopamine neurotransmitter system in the aetiology of attention-deficit hyperactivity 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 finding and supports the involvement of DRD1 in childhood ADHD.

Differential expression of prostaglandin D2 synthase (PTGDS) in patients with attention deficit–hyperactivity disorder and bipolar disorder

As marker genes for bipolar disorder (BP) and attention deficit hyperactivity disorder (ADHD) are not fully identified, we carried out a complete genome analysis to search for genes differentially expressed in ADHD and BP. We recruited 39 patients (30 ADHD, 9 BP), aged 7 to 23 years. For evaluation of the psychiatric diagnosis, we used a semi-structured interview based on the K-SADS-PL (DSM-IV). RNA was extracted from peripheral blood and analyzed with the GeneChip® Human Genome U133-Plus 2.0 (Affymetrix). For the validation of differentially expressed genes, real-time PCR was used. Hybridization and subsequent statistical analysis found 502 probe-sets with significant differences in expression in ADHD and BP patients. Of these, 82 had highly significant differences. Neuregulin (NRG1), cathepsins B and D (CTSB, CTSD) and prostaglandin-D2-synthase (PTGDS) were chosen for semi-quantitative mRNA determination. The expression of PTGDS was statistically increased in ADHD relative to BP patients (p=0.01). We found no such differential expression with NRG1, CTSB and CTSD genes (p>0.05). The gene coding for PTGDS was found to be more expressed in patients with ADHD relative to patients with BP, indicating a possible link with the differential etiology of ADHD. The experimental approach we have used is, at least in part, validated by the detection of proteins directly concerned with brain functions, and shows a possible way forward for studies of the connection between brain function genes and psychiatric disorders. Confirmation of our findings requires a larger sample of patients with clearly-defined phenotypes.

Genome-Wide Analysis of Copy Number Variants in Attention Deficit Hyperactivity Disorder: The Role of Rare Variants and Duplications at 15q13.3

Objective:Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable psychiatric disorder. Because of its multifactorial etiology, however, identifying the genes involved has been difficult. The authors followed up on recent findings suggesting that rare copy number variants (CNVs) may be important for ADHD etiology.Method:The authors performed a genome-wide analysis of large, rare CNVs (<1% population frequency) in children with ADHD (N=896) and comparison subjects (N=2,455) from the IMAGE II Consortium.Results:The authors observed 1,562 individually rare CNVs >100 kb in size, which segregated into 912 independent loci. Overall, the rate of rare CNVs >100 kb was 1.15 times higher in ADHD case subjects relative to comparison subjects, with duplications spanning known genes showing a 1.2-fold enrichment. In accordance with a previous study, rare CNVs >500 kb showed the greatest enrichment (1.28-fold). CNVs identified in ADHD case subjects were significantly enriched for loci implicated in autism and in schizophrenia. Duplications spanning the CHRNA7 gene at chromosome 15q13.3 were associated with ADHD in single-locus analysis. This finding was consistently replicated in an additional 2,242 ADHD case subjects and 8,552 comparison subjects from four independent cohorts from the United Kingdom, the United States, and Canada. Presence of the duplication at 15q13.3 appeared to be associated with comorbid conduct disorder.Conclusions:These findings support the enrichment of large, rare CNVs in ADHD and implicate duplications at 15q13.3 as a novel risk factor for ADHD. With a frequency of 0.6% in the populations investigated and a relatively large effect size (odds ratio=2.22, 95% confidence interval=1.5–3.6), this locus could be an important contributor to ADHD etiology.

The Brazilian contribution to Attention-Deficit/Hyperactivity Disorder molecular genetics in children and adolescents

Attention-Deficit/Hyperactivity Disorder (ADHD) is a common psychiatric condition of children worldwide. This disorder is defined by a combination of symptoms of inattention and hyperactivity/impulsivity. Diagnosis is based on a sufficient number of symptoms causing impairment in these two domains determining several problems in personal and academic life. Although genetic and environmental factors are important in ADHD etiology, how these factors influence the brain and consequently behavior is still under debate. It seems to be consensus that a frontosubcortical dysfunction is responsible, at least in part, for the ADHD phenotype spectrum. The main results from association and pharmacogenetic studies performed in Brazil are discussed. The investigations performed so far on ADHD genetics in Brazil and elsewhere are far from conclusive. New plausible biological hypotheses linked to neurotransmission and neurodevelopment, as well as new analytic approaches are needed to fully disclose the genetic component of the disorder.

Depressive symptoms as a side effect of the sustained release form of methylphenidate in a 7-year-old boy with attention-deficit hyperactivity disorder

Hyperkinetic disorder or attention-deficit hyperactivity disorder (ADHD) is a clinical entity consisting of a cluster of symptoms including hyperactivity, attention disorder and impulse control disorder group. In the context of ADHD etiology we may say that genetic, clinical and imaging studies point out a disruption of the brain dopamine system, which is corroborated by the clinical effectiveness of stimulant drugs, which increase extracellular dopamine in the brain. Basically, it is a biological and not psychological disorder, which is important both for the comprehension and therapeutical approach to this problem. Today, the best recommended approach regarding children with ADHD is a combination of two therapeutic modalities: pharmacotherapy and behavioral treatment. The first-choice drugs for this disorder belong to the group of sympathomimetics--psychostimulants and atomoxetine (more recently). As the first-choice therapy, methylphenydate in sustained release form has numerous advantages. Like all drugs, methylphenidate has its unwanted side effects. Most common are: loss of appetite, weight loss, sleeping disorders, irritability, headache. These side effects are well-known and documented in the literature. By analysing the available literature we have found cases of psychiatric side effects such as: psychosis, mania, visual hallucinations, agitation, suicidal ideas. We have not found examples of ADHD in children who use increased dosage of sustained release of methylphenidate leading to depressive symptomatology. On the other side, methylphenidate may be prescribed for off-label use in treatment-resistant cases of depression. The case of a 7-year-old boy diagnosed with ADHD was on a minimal dose of sustained release form of methylphenidate. After initial titration of the drug, i.e. after raising the dose to the next level the boy developed clinical signs of depression. The treatment was ceased and depressive symptoms were withdrawed. Manifestation of depressive symptomatology after dose increasement of sustained release form of methylphenidate in a 7-year-old boy with ADHD represents an uncommon side effect. Precise drug activity mechanisms responsible for the appearance of these symptoms remains to be explained.

Editorial: Seeking a new characterisation of learning disorders

Editorial: Seeking a new characterisation of learning disorders

Animal models to guide clinical drug development in ADHD: lost in translation?

We review strategies for developing animal models for examining and selecting compounds with potential therapeutic benefit in attention-deficit hyperactivity disorder (ADHD). ADHD is a behavioural disorder of unknown aetiology and pathophysiology. Current understanding suggests that genetic factors play an important role in the aetiology of ADHD. The involvement of dopaminergic and noradrenergic systems in the pathophysiology of ADHD is probable. We review the clinical features of ADHD including inattention, hyperactivity and impulsivity and how these are operationalized for laboratory study. Measures of temporal discounting (but not premature responding) appear to predict known drug effects well (treatment validity). Open-field measures of overactivity commonly used do not have treatment validity in human populations. A number of animal models have been proposed that simulate the symptoms of ADHD. The most commonly used are the spontaneously hypertensive rat (SHR) and the 6-hydroxydopamine-lesioned (6-OHDA) animals. To date, however, the SHR lacks treatment validity, and the effects of drugs on symptoms of impulsivity and inattention have not been studied extensively in 6-OHDA-lesioned animals. At the present stage of development, there are no in vivo models of proven effectiveness for examining and selecting compounds with potential therapeutic benefit in ADHD. However, temporal discounting is an emerging theme in theories of ADHD, and there is good evidence of increased value of delayed reward following treatment with stimulant drugs. Therefore, operant behaviour paradigms that measure the effects of drugs in situations of delayed reinforcement, whether in normal rats or selected models, show promise for the future.

A lifetime of attention-deficit/hyperactivity disorder: diagnostic challenges, treatment and neurobiological mechanisms

Attention-deficit/hyperactivity disorder (ADHD) is a common, early-onset and enduring neuropsychiatric disorder characterized by developmentally inappropriate deficits in attention, hyperactivity, increased impulsivity and emotional dysregulation, resulting in impairments in multiple domains of personal and professional life. ADHD has long been considered a disorder of childhood that resolves gradually with maturation during adolescence; however, this view was contested by systematic follow-up studies documenting the persistence of ADHD across the lifespan. In this article, we present converging evidence from clinical and genetic studies arguing for a remarkable perseverance of ADHD-related symptomatology, taking into account the disorder’s variable and changing phenotype moderated by a high rate of comorbidity throughout the lifecycle. We also cover findings highlighting alterations in structural and functional neuroanatomy based on neuropsychological, psychophysiological and brain imaging approaches, and discuss options for deficit-focused pharmacological and psychotherapeutic interventions at different stages of life. In addition, we develop a fusion model of disease risk underlying the pathway to ADHD etiology. Finally, we argue for large-scale, systematic studies to explore factors predicting the long-term outcome of the disease and the possibilities to exploit those predictors with more personalized treatment strategies to enhance remittance and/or coping.

Update on Environmental Risk Factors for Attention-Deficit/Hyperactivity Disorder

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurobehavioral disorder affecting 5% to 10% of children. Although considered to be a highly familial disorder, ADHD heritability estimates of 60% to 80% highlight the considerable role that environmental factors may still play in disorder susceptibility. Proposed ADHD environmental risk factors include prenatal substance exposures, heavy metal and chemical exposures, nutritional factors, and lifestyle/psychosocial factors. This paper reviews the literature published in 2010 investigating the association between environmental risk factors and ADHD or related symptomatology. Sources of risk factor exposure and the proposed mechanism by which each exposure is linked to ADHD-related neurobehavioral changes are also reported. Methodologic limitations of the current literature are discussed, and guidelines for future study are proposed. An improved understanding of the role that environmental factors play in ADHD etiology is critical to future ADHD prevention efforts.

DIRAS2 is Associated with Adult ADHD, Related Traits, and Co-Morbid Disorders

Several linkage analyses implicated the chromosome 9q22 region in attention deficit/hyperactivity disorder (ADHD), a neurodevelopmental disease with remarkable persistence into adulthood. This locus contains the brain-expressed GTP-binding RAS-like 2 gene (DIRAS2) thought to regulate neurogenesis. As DIRAS2 is a positional and functional ADHD candidate gene, we conducted an association study in 600 patients suffering from adult ADHD (aADHD) and 420 controls. Replication samples consisted of 1035 aADHD patients and 1381 controls, as well as 166 families with a child affected from childhood ADHD. Given the high degree of co-morbidity with ADHD, we also investigated patients suffering from bipolar disorder (BD) (n=336) or personality disorders (PDs) (n=622). Twelve single-nucleotide polymorphisms (SNPs) covering the structural gene and the transcriptional control region of DIRAS2 were analyzed. Four SNPs and two haplotype blocks showed evidence of association with ADHD, with nominal p-values ranging from p=0.006 to p=0.05. In the adult replication samples, we obtained a consistent effect of rs1412005 and of a risk haplotype containing the promoter region (p=0.026). Meta-analysis resulted in a significant common OR of 1.12 (p=0.04) for rs1412005 and confirmed association with the promoter risk haplotype (OR=1.45, p=0.0003). Subsequent analysis in nuclear families with childhood ADHD again showed an association of the promoter haplotype block (p=0.02). rs1412005 also increased risk toward BD (p=0.026) and cluster B PD (p=0.031). Additional SNPs showed association with personality scores (p=0.008-0.048). Converging lines of evidence implicate genetic variance in the promoter region of DIRAS2 in the etiology of ADHD and co-morbid impulsive disorders.

ADHD, Lead, and PCBs: Eubig et al. Respond

In response to Brondum’s comments we would like to reiterate that the main purpose of our review (Eubig et al. 2010) was to examine the parallels between cognitive domains affected in children with attention deficit/hyperactivity disorder (ADHD) and domains shown to be affected in human and animal studies of developmental exposure to lead and polychlorinated biphenyls (PCBs), two environmental contaminants for which a relatively large body of literature exists. In doing so we hoped to explore the possible role of exposure to environmental contaminants in the variable phenotypic expression of ADHD, and to stimulate interest in further research in this area. In our review, we did not seek to identify individual behavioral tests or functional domains that could serve as surrogates for ADHD diagnosis. Nor did we make the case that developmental lead and PCB exposure are responsible for the rise in ADHD diagnoses in recent years. To the contrary, in our section on other environmental contaminants we specifically highlighted the fact that PCB and lead exposures are declining, whereas exposures to other chemicals—including brominated flame retardants, bisphenol A, phthalates, polyfluoroalkylated compounds and certain pesticides—are increasing. We note that studies of the potential role of these emerging contaminants in the etiology of ADHD are equally, if not more, important than further studies of lead and PCBs. In addition, there is a clear difference between exploring contaminants as potential contributors to ADHD risk as opposed to causing ADHD. Examining our Table 6 (Eubig et al. 2010), which showed a comparison of the strength of the evidence for cognitive domains affected in ADHD with domains affected in developmental lead and PCB exposure, should convince the reader that these three conditions are similar but not the same. Brondum seems to miss this point in implying that our review is without value because the studies that evaluated the association between lead and a diagnosis of ADHD, which comprise a relatively small part of our review, are flawed in his opinion. No one is debating whether parental psychopathology should be considered as a possible confounding factor in studies that examine the association of contaminant exposure with specific neurobehavioral diagnoses, including ADHD. Braun et al. (2007) acquiesced to that point in a reply to the first of several letters to the editor by Brondum (2007) on the same topic. However, Braun et al. (2007) noted that including such information is not always possible when, for example, the use of National Health and Nutrition Examination Survey (NHANES) data or other constraints on study design do not allow it. Although we agree that failure to control for parental psychopathology is a weakness in many of the published studies reporting an association between childhood lead exposure and a diagnosis of ADHD, we believe that the consistency of the association across several published studies using different study designs adds to the weight of evidence that this is a real association and not a spurious effect due to uncontrolled confounding. We hope that this reply clarifies the goals of our review for those faced with the challenge of assessing the neurobehavioral effects of emerging contaminants and their possible contribution to the phenotypic expression of ADHD or other neurodevelopmental disorders.

Twin study on transplacental-acquired antibodies and attention deficit/hyperactivity disorder — A pilot study

Objective We hypothesize that maternal transplacentally acquired antibodies may cause Attention Deficit/Hyperactivity Disorder (ADHD) symptoms years after birth, and tested the hypothesis in twins discordant for ADHD symptoms. Method In a pre-screened sample of 7793 same sex twin pair's (4–18 years) questionnaire data on hyperactivity and inattention was collected. Blood samples taken 5 days after birth from 190 ADHD-score discordant pairs (15% MZ) were analyzed for antibodies. Results Pneumococcus Polysaccaride 14 (PnPs14) was present in the ADHD high scoring twin more often than in the lower scoring twin ( P = 0.04). Conclusion Although the study provides no strong support for the hypothesis, infection or immunological factors may be one among several causes of ADHD. The genetic control obtained in a twin design may reduce the exposure contrast and a larger sample is needed to further explore the role of PnPs14 in the etiology of ADHD.

Integrated Genome-Wide Association Study Findings: Identification of a Neurodevelopmental Network for Attention Deficit Hyperactivity Disorder

Attention deficit hyperactivity disorder (ADHD) is a highly heritable neuropsychiatric disorder. In the present study, the authors investigated the presence of genomic convergence in the top findings of the five published genome-wide association studies (GWASs) of ADHD. The authors carried out bioinformatics pathway analyses, using the Ingenuity and BiNGO tools, as well as a systematic literature analysis of 85 genes from the five published GWASs containing single nucleotide polymorphisms associated with ADHD at a p value <0.0001. Findings revealed that 45 of the 85 top-ranked ADHD candidate genes encode proteins that fit into a neurodevelopmental network involved in directed neurite outgrowth. Data on copy number variations in patients with ADHD and data from animal studies provide further support for the involvement of this network in ADHD etiology. Several network proteins are also directly modulated by stimulants, the most commonly used psychopharmacological treatment for ADHD. The authors have identified a protein network for ADHD that contributes to our understanding of the molecular basis of the disorder. In addition, the data suggest new candidate genes for ADHD and provide clues to future research into psychopharmacological ADHD treatments.

The effects of physical activity on attention deficit hyperactivity disorder symptoms: The evidence

Evidence supports the beneficial effects of physical activity (PA) on cognitive performance and suggests that effects might be particularly large for children. However, limited research has explored PA as a means of managing behavioral symptoms and improving cognitive performance of children with attention deficit hyperactivity disorder (ADHD). The etiology of ADHD and the putative mechanisms for the effects of PA on cognitive performance suggest that PA might be especially important for this population. Objective The purpose of this paper is to review the literature regarding the potential of PA for ADHD symptom management, particularly in regard to behavioral and cognitive symptoms. Methods Literature was reviewed for published and unpublished research specifically examining the effects of PA on cognitive and/or behavioral symptoms of ADHD. Additionally, potential mechanisms were addressed. Results Albeit limited, current research generally supports the potential for acute and chronic PA to mitigate ADHD symptoms. Conclusion Given the generally supportive extant literature and the challenges that face children with ADHD, future research exploring the potential of PA with this population is advocated.

Attention-Deficit/Hyperactivity Disorder: A Shift Toward Resilience?

Children with attention-deficit/hyperactivity disorder (ADHD) present a concern across clinical, academic, and social domains. However, a subset of these children does fairly well symptomatically and functionally. This article employs a resilience framework to organize the research on factors that promote favorable outcomes in ADHD. A PubMed search was conducted using key words: resilience and ADHD. Of particular interest were articles focusing on modifiable protective factors, such as parenting and pharmacotherapy. There is consensus that genetics strongly contributes to the etiology of ADHD. Parental, peer, and environmental factors may interact with genes to moderate the developmental expression of ADHD. Pharmacotherapy research reveals that medications exert positive effects of modest magnitude in academic achievement, social functioning and quality of life. However, there is insufficient evidence to determine whether treatment can modify developmental outcomes. Efforts to strengthen family support along with access to health and educational resources may also optimize outcomes.

Theta power as an intermediate phenotype of ADHD

Event Abstract Back to Event Theta power as an intermediate phenotype of ADHD Gráinne McLoughlin1*, Jason Palmer2, Fruhling Rijsdijk3 and Scott Makeig2 1 Institute of Psychiatry, King's College London, United Kingdom 2 SCCN, University of California San Diego, United States 3 King’s College London, United Kingdom Theta power has been consistently associated with attention deficit hyperactivity disorder (ADHD) and is heritable and thus may be a possible endophenotype of the disorder. The term endophenotype (EPT) has been used extensively in recent genetic research into the aetiology of psychiatric disorders. EPTs must be genetically and phenotypically associated with the disorder, and are proposed to be closer to the site of gene action. However, conventional definitions of EPTs do not discriminate between a ‘liability-index’ (LI) and a ‘mediational’ (ME) model. The LI model specifies that a common set of genes increase risk both for the disorder and for the EPT. The ME model makes the stronger assumption that the causal pathway from genes to disorder passes through EPT. In this study, we aimed to use multivariate twin modeling to compare the LI model and the ME model for theta power in the etiology of ADHD. We collected EEG data in a sample of 69 male twin pairs (13 – 15 years) in two resting conditions, with three tasks in between. Theta power was identified using adaptive mixture independent component analysis (AMICA). AMICA indicated similar states in both resting conditions, which reduced measurement error and allowed more accurate estimations of the genetic architecture. Theta power in the two conditions was highly correlated (r = .90). Structural equation modeling of the data, which segregates the genetic and environmental variance, indicated that theta power is highly heritable (80%) and shares genetic overlap with ADHD (40%). Further, the ME model fitted the data better than the LI model, which indicates that theta activity mediates genetic influences on ADHD. Theta power is therefore important in the etiology of ADHD and may be a useful target for intervention. Funding: National Institute of Health Research, Royal Society. Keywords: EPT, Neuropsychiatry Conference: XI International Conference on Cognitive Neuroscience (ICON XI), Palma, Mallorca, Spain, 25 Sep - 29 Sep, 2011. Presentation Type: Poster Presentation Topic: Poster Sessions: Neuropsychiatric Applications Citation: McLoughlin G, Palmer J, Rijsdijk F and Makeig S (2011). Theta power as an intermediate phenotype of ADHD. Conference Abstract: XI International Conference on Cognitive Neuroscience (ICON XI). doi: 10.3389/conf.fnhum.2011.207.00120 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 17 Nov 2011; Published Online: 28 Nov 2011. * Correspondence: Dr. Gráinne McLoughlin, Institute of Psychiatry, King's College London, London, United Kingdom, grainne.mcloughlin@kcl.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Gráinne McLoughlin Jason Palmer Fruhling Rijsdijk Scott Makeig Google Gráinne McLoughlin Jason Palmer Fruhling Rijsdijk Scott Makeig Google Scholar Gráinne McLoughlin Jason Palmer Fruhling Rijsdijk Scott Makeig PubMed Gráinne McLoughlin Jason Palmer Fruhling Rijsdijk Scott Makeig Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Parallel Outcomes: Comparing Effects of Environmental Contaminant Exposures with ADHD in Children

Vol. 118, No. 12 NewsOpen AccessParallel Outcomes: Comparing Effects of Environmental Contaminant Exposures with ADHD in Children Julia R. BarrettMS, ELS Julia R. Barrett Search for more papers by this author Published:1 December 2010https://doi.org/10.1289/ehp.118-a542aCited by:1AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Attention deficit/hyperactivity disorder (ADHD), the most frequently diagnosed neurobehavioral disorder in children, affects more than 5% of the population worldwide. Although the etiology of ADHD is poorly understood, characteristics similar to those seen in children with ADHD also have been observed in children and animals exposed to lead or polychlorinated biphenyls (PCBs). Two literature reviews in this issue provide an overview of ADHD diagnostic criteria and explore the parallels between behavioral test results from children with ADHD and findings from children and laboratory animals with developmental exposure to lead or PCBs [EHP118(12):1646–1653; Aguiar et al.;EHP118(12):1654–1667; Eubig et al.]. The authors conclude that exposure to these environmental contaminants, and possibly others, may increase the prevalence of ADHD.Deficits in executive function and attention are key characteristics of both ADHD and developmental exposure to lead and PCBs. Executive function encompasses cognitive abilities critical to goal-oriented problem solving, such as working memory, response inhibition, cognitive flexibility (the ability to mentally “switch gears”), and planning. Attention revolves around alertness (the ability to become alert and focus on a task) and vigilance (sustained alertness).ADHD has a strong genetic component but, like other neurodevelopmental disorders, appears to involve interactions between genetic, environmental, and social factors. Neuroimaging studies in children with ADHD have revealed alterations in brain regions that control executive function and attention, such as the prefrontal cortex. Alterations in catecholamine neurotransmitter signaling also are present in children with ADHD. Such signaling is potentially susceptible to damage by environmental toxicants.Developmental exposure to lead has been widely studied and is known to have a negative impact on cognitive function as well as on children’s behavior. Across studies, cognitive flexibility, vigilance, and alertness appear to be the functions most consistently affected by lead, but evidence also exists for negative effects on working memory, response inhibition, and planning. Several studies have reported associations between blood lead levels in children and ADHD.In contrast, researchers are only just beginning to explore the relationship between PCB exposure and ADHD diagnosis. Developmental exposure to PCBs is known to affect cognitive functions including working memory, response inhibition, cognitive flexibility, and alertness, although there appears to be little if any impact on vigilance. Animal studies further show that both lead and PCBs can reduce dopamine (a catecholamine) signaling in the prefrontal cortex of the brain.Although levels of lead and PCBs have declined overall in the environment and in our bodies, they remain public health issues. A better understanding of their roles in ADHD and other neurodevelopmental disorders is needed, and this knowledge could be useful in investigating other environmental agents including brominated flame retardants, bisphenol A, phthalates, organophosphate pesticides, and polyfluoroalkylated chemicals, all of which have been suggested by recent research to possibly be associated with ADHD.FiguresReferencesRelatedDetailsCited by Fordyce T, Leonhard M and Chang E (2017) A critical review of developmental exposure to particulate matter, autism spectrum disorder, and attention deficit hyperactivity disorder, Journal of Environmental Science and Health, Part A, 10.1080/10934529.2017.1383121, 53:2, (174-204), Online publication date: 28-Jan-2018. Vol. 118, No. 12 December 2010Metrics About Article Metrics Publication History Originally published1 December 2010Published in print1 December 2010 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

From the black widow spider to human behavior: Latrophilins, a relatively unknown class of G protein‐coupled receptors, are implicated in psychiatric disorders

The findings of a recent study associate LPHN3, a member of the latrophilin family, with an increased risk of developing attention deficit/hyperactivity disorder (ADHD), the most common psychiatric disorder in childhood and adolescence. Latrophilins comprise a new family of G protein-coupled receptors of unknown native physiological function that mediate the neurotoxic effects of α-latrotoxin, a potent toxin found in black widow spider venom. This receptor-toxin interaction has helped to elucidate the mechanistic aspects of neurotransmitter and hormone release in vertebrates. Such unprecedented discovery points to a new direction in the assessment of ADHD and suggest that further study of this receptor family may provide novel insights into the etiology and treatment of ADHD and other related psychiatric conditions.

Exploring How Symptoms of Attention-Deficit/Hyperactivity Disorder Are Related to Reading and Mathematics Performance

Children with attention-deficit/hyperactivity disorder (ADHD) tend to perform more poorly on tests of reading and mathematical performance than their typical peers. Quantitative genetic analyses allow for a better understanding of the etiology of ADHD and reading and mathematics outcomes, by examining their common and unique genetic and environmental influences. Analyses were conducted on a sample 271 pairs of 10-year-old monozygotic and dizygotic twins drawn from the Western Reserve Reading and Mathematics Project. In general, the results suggested that the associations among ADHD symptoms, reading outcomes, and math outcomes were influenced by both general genetic and general shared-environment factors. The analyses also suggested significant independent genetic effects for ADHD symptoms. The results imply that differing etiological factors underlie the relationships among ADHD and reading and mathematics performance. It appears that both genetic and common family or school environments link ADHD with academic performance.

Attention-deficit/hyperactivity disorder in perspective

Attention-deficit/hyperactivity disorder (ADHD) is not only one of the most frequent child neuropsychiatric disorder [9], but also one of the most investigated conditions in child and adolescent mental health [7]. Interest in the nosology of ADHD is renewed owing to the preliminary ADHD criteria recently presented by the ADHD and Disruptive Behavior Disorder working group for DSM-V of the American Psychiatric Association. Among several aspects considered for review in the criteria [10], two are directly or indirectly addressed by papers in this issue of our journal. DSM-IV criteria exclude ADHD diagnosis in the presence of pervasive development disorders (PDD). A recent body of literature challenges this notion, documenting high comorbidity between the two disorders (see, for instance, [11]). Ghanizadeh [2] performed exploratory and confirmatory factor analyses on DSM-IV ADHD and autistic spectrum disorder (ASD) symptoms from validated scales in a community sample of 1600 school-age children. His findings suggest that the high rate of co-morbidity between ADHD and ASD is probably not due to the overlapping diagnostic criteria of ADHD and ASD. One of the main drives for the revision of the DSM-IV criteria for mental disorders was the promise of a new frame in psychiatric nosology by the incorporation of a more pathophysiological approach resulting in a potential presence of biological markers as part of the diagnostic criteria [3]. Theoretically, ADHD would be a potential candidate to be a ‘‘prime star’’ for this revolution in the classificatory system! The high heritability of the disorder is well established, and large amounts of new data have documented the neurobiological basis of ADHD [5, 13]. However, after more than a decade of intense research on ADHD molecular genetics, neuropsychology and neuroimaging, we are still missing clear biological markers with sufficient sensitivity and specificity to be incorporated in the classificatory system [10]. In addition, the role of environmental risk factors or correlates in the pathophysiology of this heterogenic disorder is not completely understood. Two papers in this issue might help to enlarge our knowledge on potential environmental factors associated with ADHD. Motlagh et al. [8] found that mothers of children with ADHD reported both higher rates of heavy smoking and higher levels of severe psychological stress during pregnancy than mothers of unaffected control children. Documenting the role of comorbidity in the heterogeneity of the disorder, findings were less robust when ADHD was comorbid with Tourette syndrome. However, caution should be exercised when interpreting findings that suggest a role of smoking during pregnancy in the etiology of ADHD, since several other studies found neither an association nor an impact of maternal smoking during pregnancy in attentional control (see for instance, [1, 12]). Li et al. [6] assessed a nationwide population-based cohort sample including all 1,015,912 singletons born in Denmark from 1987 to 2001 to assess the role of prenatal maternal exposure to bereavement in ADHD. They found that boys born to mothers who lost a child or spouse in the 6 months before pregnancy or during pregnancy had significantly increased risk for ADHD. Finally, Jepsen et al. [4] assessed some neuropsychological aspects of executive functioning and attention in two groups of early-onset patients with psychosis and in L. A. Rohde (&) ADHD Outpatient Program, Department of Psychiatry, Hospital de Clinicas de Porto Alegre, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos, 2350, 2nd Floor, Room 2201, Porto Alegre, Brazil e-mail: lrohde@terra.com.br