Etiology Of Attention Deficit Hyperactivity Disorder Research Articles

KCNIP4 as a candidate gene for personality disorders and adult ADHD

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder in children with striking persistence into adulthood and a high co-morbidity with other psychiatric disorders, including personality disorders (PD). The 4p15.31 region was shown to be associated with ADHD in several genome wide association studies (GWAS). In the present study we also report association of the 4p15.31 locus with Cluster B and Cluster C PD as identified by a pooled genome-wide association study in 400 individuals suffering from PD. The gene coding for the Kv channel-interacting protein 4 (KCNIP4) is located in this region. KCNIP4 is an interaction partner of presenilin and plays a role in a negative feedback loop in the Wnt/β-catenin pathway. Thus, we reasoned it to be a promising candidate gene for ADHD as well as for PD. To clarify the role of KCNIP4 in those disorders, we conducted candidate gene based association studies in 594 patients suffering from adult ADHD and 630 PD patients as compared to 974 healthy control individuals. In the adult ADHD sample, six single markers and one haplotype block revealed to be associated with disease (p values from 0.0079 to 0.049). Seven markers within the KCNIP4 gene showed an association with PD (p values from 0.0043 to 0.0437). The results of these studies suggest a role of KCNIP4 in the etiology of ADHD, PD and other co-morbid disorders.

Biochemical and genetic analyses of childhood attention deficit/hyperactivity disorder

Attention deficit/hyperactivity disorder (ADHD) in children is a neurobehavioral disorder characterized by inattention, hyperactivity, and/or impulsivity. The biochemical abnormalities and genetic factors play significant roles in the etiology of ADHD. These symptoms affect the behavior performance and social relationships of children in school and at home. Recently, many studies about biochemical abnormalities in ADHD have been published. Several research groups have also suggested the genetic contribution to ADHD, and attempted to identify susceptibility and candidate genes for this disorder through the genetic linkage and association studies. To date, these studies have reported substantial evidence implicating several genes (dopaminergic: DRD4, DAT1, DRD5, COMT; noradrenergic: DBH, ADRA2A; serotonergic: 5-HTT, HTR1B, HTR2A; cholinergic: CHRNA4, and central nervous system development pathway: SNAP25, BDNF) in the etiology of ADHD. Understanding the biochemistry and genetics of ADHD will allow us to provide a useful addition with other treatment procedures for ADHD.

Diagnosis of ADHD and its Behavioral, Neurologic and Genetic Roots.

Attention-Deficit/Hyperactivity Disorder (ADHD) is a common developmental disorder often associated with other developmental disorders including speech, language, and reading disorders. Here we review the principal features of ADHD and current diagnostic standards for the disorder. We outline the ADHD subtypes, which are based upon the dimensions of inattention and hyperactivity. These serve as the phenotype for ADHD. Current nomenclature implies a deficit in the cognitive construct of attention, and this has taken researchers on an extended inquiry into several potential endophenotypes underlying ADHD, in particular executive function and its subcomponents. We review this literature and then delve into the neurobiology of ADHD. This research has suggested to us that the corticostriatal system is a strong candidate system in the etiology of ADHD, in part because of the dopaminergic system, which is known to play a role in the disorder. We present this system as an important contributor to the comorbidty of ADHD with other developmental disorders, especially language disorder.

Pregnancy-Related Maternal Risk Factors of Attention-Deficit Hyperactivity Disorder: A Case-Control Study

Background. The etiology of attention-deficit hyperactivity disorder (ADHD) is complex.This study was conducted to evaluate the pregnancy-related maternal risk factors of ADHD. Methods. 164 ADHD children attending to Child and Adolescent Psychiatric Clinics compared with 166 normal children selected in a random-cluster method from primary schools. ADHD rating scale and clinical interview based on Schedule for Affective disorders and Schizophrenia for School-Aged Children (K-SADS) were used to diagnose ADHD cases and to select the control group. Results. The mean maternal age at pregnancy, duration of pregnancy, and the mean paternal age were alike in two groups. The ADHD children's mothers compared with those of control group had higher frequencies of somatic diseases, psychiatric disorders, and alcohol and cigarette exposure during the pregnancies (P < 0.01). Also birth by cesarean section was more common among mothers of ADHD children (P < 0.001). These factors plus trauma to the abdomen during pregnancy were significantly predictors of ADHD in children. Conclusions. Some pregnancy-related maternal factors may be considered as environmental risk factors for ADHD. Each of these factors considered in our study as a risk factor needs to be tested and confirmed through next methodologically appropriate researches in this field.

LPHN3 and attention‐deficit/hyperactivity disorder: interaction with maternal stress during pregnancy

Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous behavioral disorder, complex both in etiology and clinical expression. Both genetic and environmental factors have been implicated, and it has been suggested that gene-environment interactions may play a pivotal role in the disorder. Recently, a significant association was reported between ADHD and LPHN3 (which codes for latrophilin 3), and replicated in independent samples. We have examined the association between tag single nucleotide polymorphisms (SNPs) in LPHN3 within the region previously implicated in ADHD. Family based association tests (FBAT) were conducted (n = 380 families) with the categorical diagnosis of ADHD, behavioral and cognitive phenotypes related to ADHD, and response to treatment (given a fixed dose of methylphenidate, 0.5 mg/day). Stratified FBAT analyses, based on maternal smoking and stress during pregnancy, was conducted. Whereas limited association was observed in the total sample, highly significant interaction between four LPHN3 tag SNPs (rs6551665, rs1947274, rs6858066, rs2345039) and maternal stress during pregnancy was noted. Analysis conducted in the sub-group of mothers exposed to minimal stress during pregnancy showed significant associations with ADHD, behavioral and cognitive dimensions related to ADHD, as well as treatment response. Although extensive association was observed with the candidate SNPs, the findings are partially inconsistent with previously published results with the opposite alleles over-transmitted in these studies. These results provide evidence for the interaction between a genetic and environmental factor independently shown to be associated with ADHD. If confirmed in independent large studies, they may present a step forward in unraveling the complex etiology of ADHD.

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.