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Hyperactivity Disorder
Attention-Deficit/Hyperactivity Disorder M Miller, The UC Davis MIND Institute, Sacramento, CA, USA SP Hinshaw, University of California, Berkeley, CA, USA r 2016 Elsevier Inc. All rights reserved.
Glossary
Heritability The proportion of phenotypic variance in a disorder that is attributable to genetic contributions. Prefrontal cortex (PFC) A region of the brain involved in higher-order decision-making and cognitive processes, including executive functioning (e.g., planning, organization, working memory, and response inhibition). Reliability The degree to which an assessment tool produces stable and consistent results. Validity The accuracy of an assessment; the degree to which an assessment tool actually measures what it intends to measure.
Comorbidity The co-occurrence of two (or more) diagnoses. Differential diagnosis The systematic process of determining a diagnosis among multiple plausible diagnoses. False-negative The nonidentification/diagnosis of a disorder when it is actually present. False-positive The identification/diagnosis of a disorder when it is not actually present. Generalization The process by which treatment effects impact nontargeted symptoms and/or behaviors in secondary settings.
Attention-Deficit/Hyperactivity Disorder Attention-deficit/hyperactivity disorder (ADHD) is a common and impairing neurodevelopmental disorder that often persists throughout the lifespan. In this article, we first define the syndrome and its key features and provide a brief historical and sociocultural context. We then describe risk and etiological factors related to ADHD, including both biological and contextual variables, highlight variations in developmental course from the preschool years through adulthood, describe sex differences in the prevalence and clinical presentation of ADHD, and review common comorbidities and associated impairments. Following the description of appropriate assessment and diagnostic procedures, we conclude with a discussion of the (as yet unrealized) potential for future prevention efforts, and provide information on current evidence-based intervention efforts, including medication and behavioral treatments. The goal is for the reader to emerge with a deeper understanding of this syndrome and key avenues for future research on both mechanisms underlying the emergence of ADHD as well as further development of increasingly effective interventions.
Clinical Presentation and Key Features As defined in the most recently released version of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5, 2013), ADHD is characterized by developmentally inappropriate levels of inattentive-disorganized and/or hyperactive-impulsive behavior that are displayed across multiple settings (American Psychiatric Association, 2013). Whereas previous editions of the DSM emphasized distinct subtypes (i.e., Predominantly Inattentive Type; Predominantly Hyperactive-Impulsive type; Combined type), the most recent
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edition has moved away from subtypes per se, instead utilizing specifiers related to symptom presentation based on previous subtype categorizations (American Psychiatric Association, 2013). This shift acknowledges the fact that individuals with ADHD often shift in their symptom presentation over time. To meet diagnostic criteria for the Inattentive presentation, one must display at least six of nine symptoms of inattention (and fewer than six hyperactive-impulsive symptoms); to meet criteria for the Hyperactive-Impulsive presentation, the opposite pattern must be present. Finally, when an individual displays six or more symptoms in each domain, the Combined presentation is specified. Notably, the Hyperactive-Impulsive presentation is rare except in preschoolers, whereas the Combined presentation is most common in referred school-age youth. However, it may be that the Inattentive presentation is the most common in the general population. Based on DSM-5 criteria, one must display at least some of these symptoms to an impairing degree prior to the age of 12 and across multiple settings (e.g., home and school). Notably, fewer total symptoms are required for individuals older than 17, a change from the previous versions of these criteria. This reduction from six to five symptoms per domain is based on increasing knowledge regarding ADHD in adulthood (for more details on developmental trends in ADHD, including ADHD in adulthood, see Section Developmental Course). Prevalence rates indicate that ADHD is quite common, affecting 5–10% of young persons. It is a highly heritable syndrome, with most heritability estimates in the 0.7–0.8 range. Sex differences in rates of diagnosis clearly exist, at least in clinic-referred samples, with boys more frequently affected by ADHD than girls. Current sex ratio estimates are at approximately 3:1, although there is some suggestion that females are more likely to exhibit inattentive rather than hyperactive-impulsive symptoms, with the sex ratio for the Inattentive presentation of ADHD being closer to 2:1. Such a
Encyclopedia of Mental Health, Volume 1
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pattern may result in a later age at diagnosis for girls. Intriguingly, the sex ratio becomes more even by adulthood, even in representative samples, signaling that the Inattentive presentation may be more stable over time.
Historical and Sociocultural Perspectives Initial descriptions of an ADHD-like behavioral phenotype emerged upon the advent of compulsory education (for reviews, see Barkley, 2006; Hinshaw and Scheffler, 2014), once increasing demands to pay attention and sit still were consistently placed on children. Since then, ADHD and its constituent symptoms have been shown to occur in all cultures in which compulsory education is in place (e.g., Nigg, 2006). Thus, it does not appear to be a disorder confined solely to the United States. Historically, ADHD was known by a variety of diagnostic terms including minimal brain dysfunction and hyperkinesis. Upon the publication of DSM-III (American Psychiatric Association, 1980), the terminology became ‘attention deficit disorder’ (with or without hyperactivity), followed by a shift to ADHD (with subtypes) in DSM-IV and DSM-IV-TR (American Psychiatric Association, 1994; 2000). As noted previously, DSM-5 now utilizes presentation specifiers rather than specific subtypes, consistent with data suggesting that individuals with ADHD often shift between presentations across development. Rates of ADHD diagnosis have risen sharply over recent years, an occurrence that has sparked many debates about whether or not ADHD is a legitimate, impairing diagnosis. Part of the issue here is that ADHD is often diagnosed in primary care or pediatric settings after extremely brief and nonevidence-based evaluations, meaning that ‘diagnostic prevalence’ is undoubtedly higher than ‘true prevalence.’ Indeed, results from the National Survey of Children’s Health (NSCH) have highlighted the steep increase in parental reports of a professional diagnosis of their child’s ADHD over the past decade (Visser et al., 2014). Moreover, there is substantial variation in rates of ADHD diagnosis by state and region, with highest rates in the South and Midwest and lower rates in the Western United States (Visser et al., 2010, 2014). Debate also continues about the perceived overuse of medication to treat ADHD: Nearly 70% of children and adolescents with a current diagnosis of ADHD receive medication, a substantial increase from several decades ago (see Hinshaw and Scheffler, 2014 for a more thorough discussion of these topics as well as related policy issues). In light of these multiple controversies, some have concluded that ADHD is not a legitimate diagnosis at all, but instead one created based on our culture’s intolerance of variation from the ‘norm,’ with labeling and treatment serving as an attempt to exert societal control. Although the rising rates of diagnosis and medication of youth are alarming and necessitate concern (see Hinshaw and Scheffler, 2014), results from decades of research are clear: ADHD is a valid and impairing syndrome with both biological and environmental underpinnings, and it typically confers a host of lifelong difficulties across multiple domains. Still, accurate diagnosis is a cornerstone of all assessment and treatmentrelated efforts.
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Risk and Etiological Factors The identification of core mechanisms responsible for the development of ADHD symptomatology has been difficult. Multiple theories implicate deficits in a range of domains spanning problems with sustained attention, inhibitory control, executive functions, reward sensitivity, arousal regulation, and/or motivation. For example, delay aversion models of ADHD have highlighted motivational aspects, suggesting that children with ADHD show a preference for immediate versus delayed rewards (Sonuga-Barke, 1994). Some executive functioning models have highlighted response inhibition as a core deficit in ADHD (see Barkley, 1997), which then cascades to result in impairments across other executive functions. Still other frameworks have sought to combine these individual models in recognition that more than one pathway is likely to be involved in ADHD, highlighting the potential differential impact of executive deficits and delay aversion to inattentive versus hyperactive-impulsive behavior, respectively (e.g., the dual-pathway model of Sonuga-Barke, 2002). In light of these multiple proposed models, it is becoming increasingly clear that the mechanisms underlying the development of ADHD are multifactorial, involving complex transactions across multiple biological and environmental risk variables. In recent years, there have been significant efforts to identify vulnerability genes and to understand the complex potential interactions among genetic, neurobiological, and contextual factors. Recent molecular genetic work has identified multiple susceptibility genes, many of which are involved in dopamine neurotransmission. Such findings are unsurprising, given the role of dopaminergic systems in arousal and reward processing, both of which have been hypothesized to be core deficits in ADHD. Other genetic risk factors include those related to serotonin receptors, and still others are related to noradrenergic pathways. Despite such evidence for vulnerability genes, it is clear that no one genetic risk factor fully accounts for the development of ADHD. Thus, continued research aimed at understanding the exact interactive mechanisms (and epigenetic influences) by which risk genes render one vulnerable to ADHD is crucial. At the neural level, the prefrontal cortex (PFC) has been most strongly implicated in ADHD, including its extensive interconnections with subcortical regions related to attention and regulation. With respect to structural brain findings, small but reliable differences between ADHD and control samples have been found for total brain volume and, more specifically (but somewhat less consistently) for the cerebellar and frontal regions (for a review, see Valera et al., 2007). In terms of brain activity, frontostriatal circuits have been most commonly implicated (for a review, see Bush et al., 2005). Recent examinations have also identified disrupted and/or inefficient structural and functional connectivity patterns in ADHD (for a review, see Konrad and Eickhoff, 2010). A widely-cited prospective longitudinal investigation found that prefrontal cortical development in children with ADHD is delayed by approximately three years compared to such development in non-diagnosed peers (Shaw et al., 2006), highlighting that brain development in ADHD is not characterized so much by static structural brain differences relative to typically developing children as it is by delayed maturation. A similar
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investigation by the same research group focusing on cortical surface area found similar findings, suggesting a more global disturbance in brain development than previously thought (Shaw et al., 2013). Other risk factors have also been identified, including low birth weight and prenatal exposure to alcohol, tobacco, and/or illicit substances (Huizink and Mulder, 2006; Indredavik et al., 2007; Nigg and Breslau, 2007). In terms of prenatal tobacco exposure, the relevant mechanism may be genetic mediation, as noted by Thapar et al. (2009). Exposure to environmental toxins, including pesticides and flame-retardant chemicals, may also increase the risk for ADHD and other neurodevelopmental disorders (de Cock et al., 2012; Kuehn, 2010). Additionally, although there is minimal evidence implicating parenting practices as a direct cause of the development of ADHD, parent–child interactions play an important role in the maintenance of underlying symptomatology. That is, certain parenting styles emerging in response to a child’s temperamental traits related to ADHD (i.e., high activity level and intensity, low effortful control) may well fuel externalizing behavior patterns (see Johnston and Mash, 2001; Johnston et al., 2012). These reciprocal, transactional processes are likely to be important across development. Still another causal pathway has been revealed by studies of early institutional deprivation in Romanian orphanages (Kreppner et al., 2001). Such work has highlighted the role of severe early deprivation in the development of high levels of inattention and hyperactive-impulsive behavior, which appear to persist, often in combination with attachment problems, until at least adolescence (Stevens et al., 2008). Overall, multiple pathways may lead to behavioral presentations consistent with an ADHD diagnosis. The next frontier with respect to identifying causal mechanisms in ADHD will involve more in-depth examination of interactions and transactions among multiple potential risk factors. Illustrative of the importance of elucidating these complex interactions, Retz et al. (2008) identified a significant interaction between the serotonin transporter promoter gene and adverse childhood environment in terms of the presence or absence of ADHD: those with at least one short allele of this risk gene were rendered more sensitive to environmental adversity during childhood than those with two long alleles. Similar findings have resulted from examination of effects of a dopamine transporter gene polymorphism on ADHD symptoms in those children who had experienced early institutional deprivation, a clear risk factor for the development of ADHD (Stevens et al., 2009). Additional studies have focused on interactions between genes related to dopamine function and other risk factors like maternal alcohol use (Brooks et al., 2006). Still other investigations have focused on identifying gene–environment interactions as related to dimensionally measured traits often associated with ADHD rather than ADHD diagnoses or symptoms, per se (e.g., attention and selfregulation; Berry et al., 2014). Although further work is needed to clarify issues related to gene–environment interplay, continued investigation should also focus on dimensional levels of ADHD symptomatology (i.e., inattentive vs. hyperactiveimpulsive), rather than the presence or absence of categorically defined clinical diagnosis, to further our understanding of the heterogeneity inherent in ADHD. Indeed, a continuing
challenge will be linking potential underlying mechanisms and processes to the heterogeneous symptom profiles displayed by individuals with ADHD, particularly over the course of development.
Developmental Course Currently, ADHD is most often diagnosed during the schoolage years, when academic and behavioral problems in the classroom become salient. Although there have been some initial efforts to identify the very earliest manifestations of ADHD, a key issue is that it is quite typical for young children to display high levels of inattention and hyperactive-impulsive behavior. Thus, a critical problem relates to false-positive designations when the aim is to identify how many preschoolaged children at risk for ADHD will actually develop the full syndrome. Preliminary evidence suggests that carefullydiagosed ADHD in preschoolers is relatively stable. Indeed, a recent treatment study found that 89% of preschoolers meeting criteria for ADHD (and who had received medication treatment for their symptoms during the course of the study) maintained the diagnosis over a 6-year period (Riddle et al., 2013). Other studies have found similar rates of persistence of the Combined subtype of ADHD (81%) into the school-age years, but slightly lower rates of persistence for the Inattentive and Hyperactive-Impulsive subtypes (66.7% and 73.9%, respectively), again suggesting that the subtype classification system of DSM-IV may not be reliable in preschoolers (Lahey et al., 2005). Yet these findings do not address the likelihood of false-positive designations with general, population-wide screening efforts for preschoolers. Overall, the stability of ADHD diagnoses in young children and the validity of earlyscreening efforts remain important topics for continued investigation and development. Moreover, it remains quite unclear whether even earlier factors can be identified that predict the onset of ADHD, or at least distinguish those who are at high- versus low-risk for developing the disorder. Several very early behavioral risk signs for ADHD during infancy have been suggested, including variables related to temperament/behavior regulation. Auerbach et al. (2008) found that infants at elevated risk of developing ADHD, by virtue of having a parent with high levels of ADHD symptoms, showed differences from low-risk infants spanning several temperament domains as early as 7 months of age. Continued efforts along these important yet preliminary lines of research aiming to identify the earliest indicators of ADHD will be crucial to our understanding of the developmental unfolding of the syndrome and may allow for the identification of interactions between biological and contextual (e.g., parenting) factors that contribute to the progression of inattentive and hyperactive-impulsive symptoms across development. The ultimate goal will be to understand those factors that account for the transition from risk to disorder. Currently, the earliest age at which ADHD can be accurately and reliably diagnosed remains an open question. However, studies of the developmental course from childhood through adolescence and into young adulthood have shed light on the persistence of ADHD symptoms over time. Several decades
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ago, ADHD was believed to remit with the onset of puberty, but a host of prospective studies reveal that diagnoses of ADHD in childhood often persist until at least young adulthood, although hyperactive-impulsive symptoms tend to decrease more rapidly than inattentive symptoms (Biederman et al., 2000). Because current diagnostic criteria may not accurately capture symptoms of ADHD in adulthood, it is difficult to ascertain accurate prevalence rates of adult ADHD. The difficulties with making diagnoses of ADHD in adulthood may be somewhat improved with the recent changes in DSM-5 (i.e., the reduced number of symptoms required for individuals 17 years of age and older). Regardless, it is clear that ADHD presents risks for lifelong impairments that include poor interpersonal skills and dysfunctional relationships, reduced educational attainment, and rampant employment problems in adulthood. These continuing impairments are extremely costly to society, with ‘indirect’ educational, legal, and employment-related costs for adult manifestations of ADHD totaling US$200 billion to the annual economy of the United States (see review in Hinshaw and Scheffler, 2014).
Sex Differences Like nearly all early-onset neurodevelopmental disorders, ADHD is widely known to be male predominant. Although the sex ratio has been shown to begin to equalize by adulthood (the reasons for which are not yet fully clear), because of the male predominant nature of ADHD in childhood, the literature on ADHD has largely focused on males. When studies do include females, there are often too few girls to conduct reliable comparisons between sexes. Yet understanding the substantial difference in prevalence rates between males and females may provide clues into mechanisms underlying the development of ADHD. Indeed, the investigation of sex differences in psychopathology has been suggested to be an important step in the study of causal processes (Rutter et al., 2003). A growing body of literature has revealed that females with ADHD exhibit substantial impairment across a range of domains, including behavioral, neurocognitive, academic, and interpersonal problems (e.g., Biederman et al., 2010; ChronisTuscano et al., 2010; Hinshaw, 2002; Miller et al., 2012). In some cases, females with ADHD may display a greater degree of impairment than males with ADHD. Recent work focusing on young adult outcomes of females with ADHD has highlighted alarming rates of suicide attempts and self-harm behaviors in this population, particularly those with the Combined presentation (Hinshaw et al., 2012). With respect to sex differences in the clinical presentation of ADHD, a seminal meta-analytic review identified similar impairments between clinic-referred boys and girls across several ADHD symptom domains, along with greater impairment in inattention and IQ for clinic-referred girls relative to clinic-referred boys (Gaub and Carlson, 1997). However, in non-referred samples, girls with ADHD appear to show less impairment than boys with ADHD. A common conclusion is that, because girls are less likely to be clinically referred to begin with, those who are may be the most severely affected (see also Gershon, 2002, who additionally highlighted higher
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levels of internalizing problems in girls vs. boys with ADHD). Thus, although understanding sex differences in ADHD is of great importance both clinically and conceptually, a critical issue for assessment and diagnosis is comparing an individual’s behavior with same sex, typically developing peers (see Koenig and Tsatsanis, 2005).
Comorbidities and Associated Impairments ADHD rarely exists in isolation from other psychiatric conditions, often making differential diagnosis difficult. Anxiety disorders are present in approximately one-third of individuals with ADHD, and approximately half of individuals with ADHD also meet criteria for oppositional defiant disorder or conduct disorder, which substantially increases the risk for delinquency and substance abuse-related problems. Additionally, ADHD often coexists with specific learning disorders (e.g., reading or math disability) or neurological disorders such as Tourette’s syndrome. Aside from co-occurrence with specific diagnostic categories, ADHD is also often associated with a range of other difficulties, including deficits in executive functioning, difficulties with social relationships, higher rates of accidental injury, and concerning driving behavior. With respect to intelligence, on average, children with ADHD have been shown to perform somewhat lower than typically developing children (estimated average of 9 points; Barkley, 2006), although scores still typically fall in the low average to average range. It is also worth noting that ADHD symptoms, whether or not crossing the diagnostic threshold, are quite common across other neurodevelopmental disorders, including autism spectrum disorders (Simonoff et al., 2008) and fragile X syndrome (reviewed in Au and Hagerman, 2013).
Assessment and Diagnosis As described throughout this chapter, evaluation of ADHD requires documentation of the presence of developmentally extreme levels of inattentive and hyperactive-impulsive behaviors, per DSM-5 criteria. Such evaluation necessitates obtaining information from parents and teachers (or, for adults, an outside observer such as a partner or employer) because of the diagnostic criterion requiring cross-situational manifestations. It is also important to obtain caregiver/informant ratings because individuals with ADHD have been shown to under-report their own symptomatology (Manor et al., 2012). Evaluation procedures should involve a combination of informant ratings on standardized instruments, structured or semi-structured interviews of parents/caregivers (and youth, for some symptom domains), a thorough developmental history, review of school and medical records, and clinical observation (American Academy of Pediatrics, 2011). It is critical to evaluate the settings in which symptoms occur, the time periods during which symptoms initially emerged, the duration and intensity of symptoms, and the degree of functional impairment. As increasing numbers of preschool children are being referred for ADHD diagnoses, it is imperative to carefully consider developmental aspects during evaluation.
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Attunement to normative levels of inattentive and hyperactiveimpulsive behavior during a given developmental period is essential. Because concurrent neurocognitive difficulties are present in many (but certainly not all) children with ADHD, standardized tests of neuropsychological functioning – particularly evaluation of various aspects of executive functioning (e.g., working memory, sustained attention, response inhibition) – may provide clinically-relevant information regarding an individual’s strengths and weaknesses. However, such tests are not currently diagnostic in nature. Similarly, whereas evaluations of intelligence (i.e., IQ tests) or academic achievement testing may be relevant, they cannot rule in or out a diagnosis of ADHD (although they are needed for consideration of potentially comorbid diagnoses, including intellectual disability and learning disorders). As part of assessment for differential diagnosis, it is critical to conduct an evaluation for conditions that may resemble or coexist with ADHD (e.g., conduct and oppositional defiant disorders, mood disorders, anxiety disorders, learning disorders, and intellectual disability). A thorough history, a family evaluation, and a medical examination are also required to rule out neurological disease, sensory impairment, and psychosocial influences (e.g., a chaotic home environment and/or maltreatment, the sequelae of which can mimic ADHD). It is critical to gather a range of information when making diagnostic determinations; the common practice of diagnosing ADHD after a brief office visit is not a valid strategy. It is also good clinical practice to review treatment options with families and provide ample opportunity to answer questions, in order to provide accurate information and dispel any myths about the validity of ADHD as a legitimate and impairing diagnosis requiring evidence-based intervention.
Prevention and Intervention Currently, prevention of ADHD is not feasible because known risk and etiological factors either cannot be directly influenced (e.g., genetic risk factors) or are difficult to adequately address (e.g., low birth weight). Still, there is increasing interest in identifying the earliest risk signs of the development ADHD in order to implement interventions as early as possible (see Auerbach et al., 2004, 2005, 2008; Sonuga-Barke and Halperin, 2010; Sonuga-Barke et al., 2011). If successful, such interventions could alter the trajectory of ADHD from the start, thereby preventing the development of the full syndrome and/or later impairments. Although this approach is being used in other neurodevelopmental disorders (e.g., autism spectrum disorder), such methodology has rarely been used in the study of ADHD, largely because, as described in the section Developmental Course, high levels of inattention and hyperactive-impulsive behavior are developmentally typical at younger ages. Thus, treatment for ADHD generally involves the implementation of interventions after the onset of substantial levels of impairment. Currently, only two main classes of treatments are considered empirically supported for ADHD: stimulant medications (and several other medication classes) and behavioral treatment modalities. Although not consistently
found to be effective for children and adolescents with ADHD, cognitive-behavioral approaches have also shown promise for adults with the disorder. Treatments targeting underlying neuropsychological processes (e.g., aspects of executive functioning, such as working memory) or neural processes (e.g., biofeedback) have shown some promise in initial studies but more rigorous research is needed before such interventions can be recommended or considered evidence-based. Key issues with such interventions include generalizability and clinical robustness with respect to symptom improvement and critical areas of functioning (see Rutledge et al., 2012). Stimulant medications exert their effects by enhancing dopaminergic and noradrenergic transmission, thereby positively influencing attentional capacities and inhibitory control. Because such effects are present in both individuals with and without ADHD, a positive response to stimulant medications does not confirm or ‘prove’ a diagnosis of ADHD. Stimulant medications have repeatedly been shown to reduce core symptoms of ADHD as well as some associated impairments, and positive response rates are high (see Paykina and Greenhill, 2007). Still, full normalization of behavior is quite rare, with benefits lasting only as long as medication is active. Side effects are usually transitory and manageable with dose adjustment. Careful monitoring of stimulant treatment appears to markedly increase the likelihood of clinical benefit and decrease the impact of any potential side-effects, the most common of which include appetite suppression and insomnia. Notably, for preschoolaged children diagnosed with ADHD, the American Academy of Pediatrics (2011) recommends behavioral parent training as a first-line treatment rather than medication, an important recommendation since it is not yet clear what effects such medications might have on the developing brains of very young children. Behavioral treatments that feature parent and teacher management training to promote more consistent environmental cues and rewards have also been shown to be effective in addressing ADHD-related symptoms and associated impairments (for a review, see Fabiano et al., 2009). Such interventions, which include direct contingency management, clinical behavior therapy, and social skills training, require substantial effort on the part of parents and teachers to establish consistent, regular incentives for specified target behavioral, academic, and social goals for children and adolescents with ADHD. These approaches also aim to promote the development of increasingly effective parenting strategies, which can often alleviate dysfunctional parent–child interactions that may serve to maintain ADHD symptomatology and behavioral difficulties more broadly. Although such interventions have routinely been shown to be beneficial for individuals with ADHD, there are several barriers to their more consistent and widespread use. For example, the use of these types of interventions is often limited due to socioeconomic resources. Additionally, effects of behavioral interventions, although strong, are often smaller when compared to carefully-monitored medication management. Finally, and critically, the contingencies must remain in place – ideally across settings – for benefits to be maintained. This highlights a key issue in the field: effects of current evidence-based behavioral treatments for ADHD (and many disorders of
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childhood and adolescence) often do not generalize across settings, even when the same contingencies are in place across multiple environments (see Abikoff, 2009). Combination treatment approaches, which involve the administration of both comprehensive behavioral programs and well-delivered medications, may result in the greatest reduction in ADHD-related impairments, even though medication alone is often sufficient for symptom reduction (see Swanson et al., 2001). Unfortunately, in practice, only a minority of children with ADHD receive this type of optimal medication plus behavioral treatment. Additionally, symptoms of comorbidities commonly associated with ADHD may not improve with either stimulant medication or behavioral strategies that directly target ADHD-related behaviors. In such situations, the use of additional behavioral, cognitive, educational, or medication interventions is necessary. For example, comorbid anxiety disorders will often require adjunctive treatment involving exposure-based procedures; comorbid learning disorders will necessitate specific academic interventions and supports. In general, interventions should be individualized and geared toward functional impairments, which, in individuals with ADHD, commonly include social and interpersonal difficulties, academic problems, and organizational skills deficits. Although combined medication and behavioral treatments have been shown to produce optimal benefit, longer-term follow-up of optimally-treated children with ADHD (i.e., the Multimodal Treatment Study of Children with ADHD) has indicated that early symptom severity is more prognostic of later functioning than the type of well-delivered treatment to which participants were initially assigned (Molina et al., 2009). In other words, once the frequency and/or intensity of optimal interventions are phased out, symptoms and impairments return. Thus, whereas medication and behavioral treatments can provide substantial benefits for individuals with ADHD, there is still much room for improvement with respect to developing better and highly effective treatments that produce lasting effects. It is quite apparent that ADHD portends a host of difficulties throughout the lifespan, but not all individuals with ADHD go on to experience such negative outcomes. Thus, crucial topics for both clinical and research efforts are those of resilience and the identification of protective factors that may alter the trajectory of ADHD. That is, what processes might distinguish those who display adaptive developmental patterns and positive outcomes from those who experience negative outcomes? How can such information be leveraged to inform diagnostic and treatment development efforts? Relatedly, what factors distinguish those who will benefit from current evidence-based interventions for ADHD from those who will require the addition of adjunct strategies? Obvious candidates include factors such as higher IQ, lower symptom severity scores in childhood (Molina et al., 2009), lower levels of caregiver depression (Owens et al., 2003), and warm and supportive parent–child interactions (Chronis et al., 2007). Less-explored candidates that may be highly amenable to intervention efforts include self-perceived academic competence (at least in girls, see Mikami and Hinshaw, 2006) and friendship (Cardoos and Hinshaw, 2011).
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Summary and Conclusions ADHD is a valid and impairing psychiatric syndrome marked by developmentally extreme, cross-situationally displayed, and impairing symptoms in the domains of inattention/ disorganization and/or hyperactivity-impulsivity. It is highly heritable and persists throughout development in most cases, although hyperactive-impulsive symptoms appear to decline more rapidly than inattentive symptoms. Because ADHD is more common in males, relatively little research has focused on females or sex differences in ADHD, but it is becoming increasingly apparent that females with ADHD evidence comparable impairment to males with ADHD (and, in some domains, perhaps even greater impairment – e.g., self-injurious behavior/suicide attempts by early adulthood). Comorbidity is common in ADHD, including high rates of anxiety disorders, learning disorders, mood disorders, oppositional defiant disorder, and conduct disorder. Additional impairments include neuropsychological deficits related to executive control and social skills deficits, among others. Underlying etiologic factors are likely to include genes related to dopaminergic, noradrenergic, and serotonergic functions, as well as neural substrates that largely involve the PFC and its projections to other brain regions. Recent work has suggested delayed neural maturation as well as disruption in both structural and functional connectivity patterns in individuals with ADHD. Although biological factors clearly play a key role in the development of ADHD, it is becoming increasingly apparent that environmental/contextual factors are also strongly involved. Understanding complex transactions across these biological and contextual variables will result in more clearly-defined causal models. With respect to diagnostic evaluation for ADHD, careful and thorough assessment is required to evaluate symptoms and to identify comorbid diagnoses that may require separate treatment. Strategies aimed at preventing the development of ADHD-related symptoms and impairments altogether do not currently exist, although there is increasing interest in identifying the earliest manifestations of ADHD in order to move toward earlier intervention. Currently, effective treatment strategies include pharmacologic (mainly stimulant medication) and behavioral interventions. Strategies that involve the combination of these approaches have been shown to result in the greatest reduction of ADHD-related impairments, although initial symptom severity appears to be more predictive of long-term outcomes than the type of treatment received. Generalization of treatment gains across settings and maintenance of gains across time remain elusive goals with respect to effective interventions for ADHD. Finally, efforts to identify protective factors and predictors of resilience or positive outcomes in individuals with ADHD are crucial, with potentially important implications for both diagnostic efforts as well as the development of more targeted interventions.
See also: Adolescence. Child and Adolescent Psychotherapy. Conduct Disorders. Diagnosis and Classification. Disorders of Impulse Control. Psychological Testing
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Hinshaw, S.P., 2002. Preadolescent girls with attention-deficit/hyperactivity disorder: I. Background characteristics, comorbidity, cognitive and social functioning, and parenting practices. Journal of Consulting & Clinical Psychology 70, 1086–1098. Hinshaw, S.P., Owens, E.B., Zalecki, C.Z., et al., 2012. Prospective follow-up of girls with attention-deficit/hyperactivity disorder into early adulthood: Continuing impairment includes risk for suicide attempts and self-injury. Journal of Consulting & Clinical Psychology 80, 1041–1051. Hinshaw, S.P., Scheffler, R.M., 2014. The ADHD Explosion: Myths, Medication, Money, and Today’s Push for Performance. New York, NY: Oxford University Press. Huizink, A.J., Mulder, E.J.H., 2006. Maternal smoking, drinking or cannabis use during pregnancy and neurobehavioral and cognitive functioning in human offspring. Neurosciences & Biobehavioral Reviews 30, 24–41. Indredavik, M.S., Brubakk, A., Romundstad, P., Vik, T., 2007. Prenatal smoking exposure and psychiatric symptoms in adolescence. Acta Paediatrica 96, 377–382. Johnston, C., Mash, E.J., 2001. Families of children with attention-deficit/ hyperactivity disorder: review and recommendations for research. Clinical Child & Family Psychology Review 4, 183–207. Johnston, C., Mash, E.J., Miller, N., Ninowski, J.E., 2012. Parenting in adults with attention-deficit/hyperactivity disorder (ADHD). Clinical Psychology Review 32, 215–228. Kuehn, B.M., 2010. Increased risk of ADHD associated with early exposure to pesticides, PCBs. Journal of the American Medical Association 304, 27–28. Koenig, K., Tsatsanis, K., 2005. Pervasive developmental disorders in girls. In: BellDolan, D., Foster, S.L., Mash, E.J. (Eds.), Behavioral and Emotional Problems in Girls. New York, NY: Kluwer Academic/Plenum Press, pp. 211–238. Konrad, K., Eickhoff, S.B., 2010. Is the ADHD brain wired differently? A review on structural and functional connectivity in attention deficit hyperactivity disorder. Human Brain Mapping 31, 904–916. Kreppner, J.M., O’Connor, T.G., Rutter, M., English & Romanian Adoptees Study Team, 2001. Can inattention/overactivity be an institutional deprivation syndrome? Journal of Abnormal Child Psychology 29, 513–528. Lahey, B.B., Pelham, W.E., Loney, J., Lee, S.S., Willcutt, E., 2005. Instability of the DSM-IV subtypes of ADHD from preschool through elementary school. Archives of General Psychiatry 62, 896–902. Manor, I., Vurembrandt, N., Rozen, S., et al., 2012. Low self-awareness of ADHD in adults using a self-report screening questionnaire. European Psychiatry 27, 314–320. Mikami, A.Y., Hinshaw, S.P., 2006. Resilient adolescent adjustment among girls: Buffers of childhood peer rejection and attention-deficit/hyperactivity disorder. Journal of Abnormal Child Psychology 34, 825–839. Miller, M., Ho, J., Hinshaw, S.P., 2012. Executive functions in girls with ADHD followed prospectively into young adulthood. Neuropsychology 26, 278–287. Molina, B.S.G., Hinshaw, S.P., Swanson, J.M., et al., 2009. The MTA at 8 years: Prospective follow-up of children treated for combined-type ADHD in a multisite study. Journal of the American Academy of Child & Adolescent Psychiatry 48, 484–500. Nigg, J.T., 2006. What Causes ADHD? Understanding What Goes Wrong and Why. New York, NY: Guilford Press. Nigg, J.T., Breslau, N., 2007. Prenatal smoking exposure, low birth weight, and disruptive behavior disorders. Journal of the American Academy of Child & Adolescent Psychiatry 46, 362–369. Owens, E.B., Hinshaw, S.P., Kraemer, H.C., et al., 2003. Which treatment for whom for ADHD? Moderators of treatment response in the MTA. Journal of Consulting and Clinical Psychology 71, 540–552. Paykina, N., Greenhill, L.L., 2007. Pharmacological treatments for attention-deficit/ hyperactivity disorder. In: Nathan, P.E., Gorman, J.M. (Eds.), A Guide to Treatments That Work, third ed. New York, NY: Oxford University Press, pp. 29–70. Retz, W., Freitag, C.M., Retz-Junginer, P., et al., 2008. A functional serotonin transporter promoter gene polymorphism increases ADHD symptoms in delinquents: Interaction with adverse childhood environment. Psychiatry Research 158, 123–131. Riddle, M.A., Yershova, K., Lazzaretto, D., et al., 2013. The preschool attentiondeficit/hyperactivity disorder treatment study (PATS) 6-year follow-up. Journal of the American Academy of Child & Adolescent Psychiatry 52, 264–278. Rutledge, K.J., van den Bos, W., McClure, S.M., Schweitzer, J.B., 2012. Training cognition in ADHD: Current findings, borrowed concepts, and future directions. Neurotherapeutics 9, 542–558. Rutter, M., Caspi, A., Moffitt, T.E., 2003. Using sex differences in psychopathology to study causal mechanisms: Unifying issues and research strategies. Journal of Child Psychology & Psychiatry 44, 1092–1115.
Attention-Deficit/Hyperactivity Disorder Shaw, P., Lerch, J., Greenstein, D., et al., 2006. Longitudinal mapping of cortical thickness and clinical outcomes in children and adolescents with attentiondeficit/hyperactivity disorder. Archives of General Psychiatry 63, 540–549. Shaw, P., Malek, M., Watson, B., et al., 2013. Development of cortical surface area and gyrification in attention-deficit/hyperactivity disorder. Biological Psychiatry 72, 191–197. Simonoff, E., Pickles, A., Charman, T., et al., 2008. Psychiatric disorders in children with autism spectrum disorders: Prevalence, comorbidity, and associated factors in a population-derived sample. Journal of the American Academy of Child & Adolescent Psychiatry 47, 921–929. Sonuga-Barke, E.J.S., 1994. On dysfunction and function in psychological accounts of childhood disorder. Journal of Child Psychology & Psychiatry 35, 801–815. Sonuga-Barke, E.J.S., 2002. Psychological heterogeneity in AD/HD − A dual pathway model of behaviour and cognition. Behavioral Brain Research 130, 29–36. Sonuga-Barke, E.J.S., Halperin, J.M., 2010. Developmental phenotypes and causal pathways in attention deficit/hyperactivity disorder: Potential targets for early intervention? Journal of Child Psychology and Psychiatry 51, 368–389. Sonuga-Barke, E.J.S., Koerting, J., Smith, E., McCann, D.C., Thompson, M., 2011. Early detection and intervention for attention-deficit/hyperactivity disorder. Expert Reviews of Neurotherapeutics 11, 557–563. Stevens, S.E., Kumsta, R., Kreppner, J.M., et al., 2009. Dopamine transporter gene polymorphism moderates the effects of severe deprivation on ADHD
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symptoms: Developmental continuities in gene-environment interplay. American Journal of Medical Genetics Part B 150B, 753–761. Stevens, S.E., Sonuga-Barke, E.J.S., Kreppner, J.M., et al., 2008. Inattention/ overactivity following early severe institutional deprivation: Presentation and associations in early adolescence. Journal of Abnormal Child Psychology 36, 385–398. Swanson, J.M., Kraemer, H.C., Hinshaw, S.P., et al., 2001. Clinical relevance of the primary findings of the MTA: Success rates based on severity of ADHD symptoms at the end of treatment. Journal of the American Academy of Child & Adolescent Psychiatry 40, 168–179. Thapar, A., Rice, F., Hay, D., et al., 2009. Prenatal smoking might not cause attention-deficit/hyperactivity disorder: Evidence from a novel design. Biological Psychiatry 66, 722–727. Valera, E.M., Faraone, S.V., Murray, K.E., Seidman, L., 2007. Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder. Biological Psychiatry 61, 1361–1369. Visser, S.M., Danielson, R., Bitsko, J., et al., 2014. Trends in the prevalence of parent-reported ADHD diagnosis and medication treatment by a health care professional: United States, 2003−2011. Journal of the American Academy of Child and Adolescent Psychiatry 53, 34–46. Visser, S.N., Bitsko, R.H., Danielson, M.L., Perou, R., 2010. Increasing prevalence of parent-reported attention-deficit/hyperactivity disorder among children − United States, 2003 and 2007. Morbidity and Mortality Weekly Report 59, 1439–1443.
Glossary
Heritability The proportion of phenotypic variance in a disorder that is attributable to genetic contributions. Prefrontal cortex (PFC) A region of the brain involved in higher-order decision-making and cognitive processes, including executive functioning (e.g., planning, organization, working memory, and response inhibition). Reliability The degree to which an assessment tool produces stable and consistent results. Validity The accuracy of an assessment; the degree to which an assessment tool actually measures what it intends to measure.
Comorbidity The co-occurrence of two (or more) diagnoses. Differential diagnosis The systematic process of determining a diagnosis among multiple plausible diagnoses. False-negative The nonidentification/diagnosis of a disorder when it is actually present. False-positive The identification/diagnosis of a disorder when it is not actually present. Generalization The process by which treatment effects impact nontargeted symptoms and/or behaviors in secondary settings.
Attention-Deficit/Hyperactivity Disorder Attention-deficit/hyperactivity disorder (ADHD) is a common and impairing neurodevelopmental disorder that often persists throughout the lifespan. In this article, we first define the syndrome and its key features and provide a brief historical and sociocultural context. We then describe risk and etiological factors related to ADHD, including both biological and contextual variables, highlight variations in developmental course from the preschool years through adulthood, describe sex differences in the prevalence and clinical presentation of ADHD, and review common comorbidities and associated impairments. Following the description of appropriate assessment and diagnostic procedures, we conclude with a discussion of the (as yet unrealized) potential for future prevention efforts, and provide information on current evidence-based intervention efforts, including medication and behavioral treatments. The goal is for the reader to emerge with a deeper understanding of this syndrome and key avenues for future research on both mechanisms underlying the emergence of ADHD as well as further development of increasingly effective interventions.
Clinical Presentation and Key Features As defined in the most recently released version of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5, 2013), ADHD is characterized by developmentally inappropriate levels of inattentive-disorganized and/or hyperactive-impulsive behavior that are displayed across multiple settings (American Psychiatric Association, 2013). Whereas previous editions of the DSM emphasized distinct subtypes (i.e., Predominantly Inattentive Type; Predominantly Hyperactive-Impulsive type; Combined type), the most recent
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edition has moved away from subtypes per se, instead utilizing specifiers related to symptom presentation based on previous subtype categorizations (American Psychiatric Association, 2013). This shift acknowledges the fact that individuals with ADHD often shift in their symptom presentation over time. To meet diagnostic criteria for the Inattentive presentation, one must display at least six of nine symptoms of inattention (and fewer than six hyperactive-impulsive symptoms); to meet criteria for the Hyperactive-Impulsive presentation, the opposite pattern must be present. Finally, when an individual displays six or more symptoms in each domain, the Combined presentation is specified. Notably, the Hyperactive-Impulsive presentation is rare except in preschoolers, whereas the Combined presentation is most common in referred school-age youth. However, it may be that the Inattentive presentation is the most common in the general population. Based on DSM-5 criteria, one must display at least some of these symptoms to an impairing degree prior to the age of 12 and across multiple settings (e.g., home and school). Notably, fewer total symptoms are required for individuals older than 17, a change from the previous versions of these criteria. This reduction from six to five symptoms per domain is based on increasing knowledge regarding ADHD in adulthood (for more details on developmental trends in ADHD, including ADHD in adulthood, see Section Developmental Course). Prevalence rates indicate that ADHD is quite common, affecting 5–10% of young persons. It is a highly heritable syndrome, with most heritability estimates in the 0.7–0.8 range. Sex differences in rates of diagnosis clearly exist, at least in clinic-referred samples, with boys more frequently affected by ADHD than girls. Current sex ratio estimates are at approximately 3:1, although there is some suggestion that females are more likely to exhibit inattentive rather than hyperactive-impulsive symptoms, with the sex ratio for the Inattentive presentation of ADHD being closer to 2:1. Such a
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pattern may result in a later age at diagnosis for girls. Intriguingly, the sex ratio becomes more even by adulthood, even in representative samples, signaling that the Inattentive presentation may be more stable over time.
Historical and Sociocultural Perspectives Initial descriptions of an ADHD-like behavioral phenotype emerged upon the advent of compulsory education (for reviews, see Barkley, 2006; Hinshaw and Scheffler, 2014), once increasing demands to pay attention and sit still were consistently placed on children. Since then, ADHD and its constituent symptoms have been shown to occur in all cultures in which compulsory education is in place (e.g., Nigg, 2006). Thus, it does not appear to be a disorder confined solely to the United States. Historically, ADHD was known by a variety of diagnostic terms including minimal brain dysfunction and hyperkinesis. Upon the publication of DSM-III (American Psychiatric Association, 1980), the terminology became ‘attention deficit disorder’ (with or without hyperactivity), followed by a shift to ADHD (with subtypes) in DSM-IV and DSM-IV-TR (American Psychiatric Association, 1994; 2000). As noted previously, DSM-5 now utilizes presentation specifiers rather than specific subtypes, consistent with data suggesting that individuals with ADHD often shift between presentations across development. Rates of ADHD diagnosis have risen sharply over recent years, an occurrence that has sparked many debates about whether or not ADHD is a legitimate, impairing diagnosis. Part of the issue here is that ADHD is often diagnosed in primary care or pediatric settings after extremely brief and nonevidence-based evaluations, meaning that ‘diagnostic prevalence’ is undoubtedly higher than ‘true prevalence.’ Indeed, results from the National Survey of Children’s Health (NSCH) have highlighted the steep increase in parental reports of a professional diagnosis of their child’s ADHD over the past decade (Visser et al., 2014). Moreover, there is substantial variation in rates of ADHD diagnosis by state and region, with highest rates in the South and Midwest and lower rates in the Western United States (Visser et al., 2010, 2014). Debate also continues about the perceived overuse of medication to treat ADHD: Nearly 70% of children and adolescents with a current diagnosis of ADHD receive medication, a substantial increase from several decades ago (see Hinshaw and Scheffler, 2014 for a more thorough discussion of these topics as well as related policy issues). In light of these multiple controversies, some have concluded that ADHD is not a legitimate diagnosis at all, but instead one created based on our culture’s intolerance of variation from the ‘norm,’ with labeling and treatment serving as an attempt to exert societal control. Although the rising rates of diagnosis and medication of youth are alarming and necessitate concern (see Hinshaw and Scheffler, 2014), results from decades of research are clear: ADHD is a valid and impairing syndrome with both biological and environmental underpinnings, and it typically confers a host of lifelong difficulties across multiple domains. Still, accurate diagnosis is a cornerstone of all assessment and treatmentrelated efforts.
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Risk and Etiological Factors The identification of core mechanisms responsible for the development of ADHD symptomatology has been difficult. Multiple theories implicate deficits in a range of domains spanning problems with sustained attention, inhibitory control, executive functions, reward sensitivity, arousal regulation, and/or motivation. For example, delay aversion models of ADHD have highlighted motivational aspects, suggesting that children with ADHD show a preference for immediate versus delayed rewards (Sonuga-Barke, 1994). Some executive functioning models have highlighted response inhibition as a core deficit in ADHD (see Barkley, 1997), which then cascades to result in impairments across other executive functions. Still other frameworks have sought to combine these individual models in recognition that more than one pathway is likely to be involved in ADHD, highlighting the potential differential impact of executive deficits and delay aversion to inattentive versus hyperactive-impulsive behavior, respectively (e.g., the dual-pathway model of Sonuga-Barke, 2002). In light of these multiple proposed models, it is becoming increasingly clear that the mechanisms underlying the development of ADHD are multifactorial, involving complex transactions across multiple biological and environmental risk variables. In recent years, there have been significant efforts to identify vulnerability genes and to understand the complex potential interactions among genetic, neurobiological, and contextual factors. Recent molecular genetic work has identified multiple susceptibility genes, many of which are involved in dopamine neurotransmission. Such findings are unsurprising, given the role of dopaminergic systems in arousal and reward processing, both of which have been hypothesized to be core deficits in ADHD. Other genetic risk factors include those related to serotonin receptors, and still others are related to noradrenergic pathways. Despite such evidence for vulnerability genes, it is clear that no one genetic risk factor fully accounts for the development of ADHD. Thus, continued research aimed at understanding the exact interactive mechanisms (and epigenetic influences) by which risk genes render one vulnerable to ADHD is crucial. At the neural level, the prefrontal cortex (PFC) has been most strongly implicated in ADHD, including its extensive interconnections with subcortical regions related to attention and regulation. With respect to structural brain findings, small but reliable differences between ADHD and control samples have been found for total brain volume and, more specifically (but somewhat less consistently) for the cerebellar and frontal regions (for a review, see Valera et al., 2007). In terms of brain activity, frontostriatal circuits have been most commonly implicated (for a review, see Bush et al., 2005). Recent examinations have also identified disrupted and/or inefficient structural and functional connectivity patterns in ADHD (for a review, see Konrad and Eickhoff, 2010). A widely-cited prospective longitudinal investigation found that prefrontal cortical development in children with ADHD is delayed by approximately three years compared to such development in non-diagnosed peers (Shaw et al., 2006), highlighting that brain development in ADHD is not characterized so much by static structural brain differences relative to typically developing children as it is by delayed maturation. A similar
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investigation by the same research group focusing on cortical surface area found similar findings, suggesting a more global disturbance in brain development than previously thought (Shaw et al., 2013). Other risk factors have also been identified, including low birth weight and prenatal exposure to alcohol, tobacco, and/or illicit substances (Huizink and Mulder, 2006; Indredavik et al., 2007; Nigg and Breslau, 2007). In terms of prenatal tobacco exposure, the relevant mechanism may be genetic mediation, as noted by Thapar et al. (2009). Exposure to environmental toxins, including pesticides and flame-retardant chemicals, may also increase the risk for ADHD and other neurodevelopmental disorders (de Cock et al., 2012; Kuehn, 2010). Additionally, although there is minimal evidence implicating parenting practices as a direct cause of the development of ADHD, parent–child interactions play an important role in the maintenance of underlying symptomatology. That is, certain parenting styles emerging in response to a child’s temperamental traits related to ADHD (i.e., high activity level and intensity, low effortful control) may well fuel externalizing behavior patterns (see Johnston and Mash, 2001; Johnston et al., 2012). These reciprocal, transactional processes are likely to be important across development. Still another causal pathway has been revealed by studies of early institutional deprivation in Romanian orphanages (Kreppner et al., 2001). Such work has highlighted the role of severe early deprivation in the development of high levels of inattention and hyperactive-impulsive behavior, which appear to persist, often in combination with attachment problems, until at least adolescence (Stevens et al., 2008). Overall, multiple pathways may lead to behavioral presentations consistent with an ADHD diagnosis. The next frontier with respect to identifying causal mechanisms in ADHD will involve more in-depth examination of interactions and transactions among multiple potential risk factors. Illustrative of the importance of elucidating these complex interactions, Retz et al. (2008) identified a significant interaction between the serotonin transporter promoter gene and adverse childhood environment in terms of the presence or absence of ADHD: those with at least one short allele of this risk gene were rendered more sensitive to environmental adversity during childhood than those with two long alleles. Similar findings have resulted from examination of effects of a dopamine transporter gene polymorphism on ADHD symptoms in those children who had experienced early institutional deprivation, a clear risk factor for the development of ADHD (Stevens et al., 2009). Additional studies have focused on interactions between genes related to dopamine function and other risk factors like maternal alcohol use (Brooks et al., 2006). Still other investigations have focused on identifying gene–environment interactions as related to dimensionally measured traits often associated with ADHD rather than ADHD diagnoses or symptoms, per se (e.g., attention and selfregulation; Berry et al., 2014). Although further work is needed to clarify issues related to gene–environment interplay, continued investigation should also focus on dimensional levels of ADHD symptomatology (i.e., inattentive vs. hyperactiveimpulsive), rather than the presence or absence of categorically defined clinical diagnosis, to further our understanding of the heterogeneity inherent in ADHD. Indeed, a continuing
challenge will be linking potential underlying mechanisms and processes to the heterogeneous symptom profiles displayed by individuals with ADHD, particularly over the course of development.
Developmental Course Currently, ADHD is most often diagnosed during the schoolage years, when academic and behavioral problems in the classroom become salient. Although there have been some initial efforts to identify the very earliest manifestations of ADHD, a key issue is that it is quite typical for young children to display high levels of inattention and hyperactive-impulsive behavior. Thus, a critical problem relates to false-positive designations when the aim is to identify how many preschoolaged children at risk for ADHD will actually develop the full syndrome. Preliminary evidence suggests that carefullydiagosed ADHD in preschoolers is relatively stable. Indeed, a recent treatment study found that 89% of preschoolers meeting criteria for ADHD (and who had received medication treatment for their symptoms during the course of the study) maintained the diagnosis over a 6-year period (Riddle et al., 2013). Other studies have found similar rates of persistence of the Combined subtype of ADHD (81%) into the school-age years, but slightly lower rates of persistence for the Inattentive and Hyperactive-Impulsive subtypes (66.7% and 73.9%, respectively), again suggesting that the subtype classification system of DSM-IV may not be reliable in preschoolers (Lahey et al., 2005). Yet these findings do not address the likelihood of false-positive designations with general, population-wide screening efforts for preschoolers. Overall, the stability of ADHD diagnoses in young children and the validity of earlyscreening efforts remain important topics for continued investigation and development. Moreover, it remains quite unclear whether even earlier factors can be identified that predict the onset of ADHD, or at least distinguish those who are at high- versus low-risk for developing the disorder. Several very early behavioral risk signs for ADHD during infancy have been suggested, including variables related to temperament/behavior regulation. Auerbach et al. (2008) found that infants at elevated risk of developing ADHD, by virtue of having a parent with high levels of ADHD symptoms, showed differences from low-risk infants spanning several temperament domains as early as 7 months of age. Continued efforts along these important yet preliminary lines of research aiming to identify the earliest indicators of ADHD will be crucial to our understanding of the developmental unfolding of the syndrome and may allow for the identification of interactions between biological and contextual (e.g., parenting) factors that contribute to the progression of inattentive and hyperactive-impulsive symptoms across development. The ultimate goal will be to understand those factors that account for the transition from risk to disorder. Currently, the earliest age at which ADHD can be accurately and reliably diagnosed remains an open question. However, studies of the developmental course from childhood through adolescence and into young adulthood have shed light on the persistence of ADHD symptoms over time. Several decades
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ago, ADHD was believed to remit with the onset of puberty, but a host of prospective studies reveal that diagnoses of ADHD in childhood often persist until at least young adulthood, although hyperactive-impulsive symptoms tend to decrease more rapidly than inattentive symptoms (Biederman et al., 2000). Because current diagnostic criteria may not accurately capture symptoms of ADHD in adulthood, it is difficult to ascertain accurate prevalence rates of adult ADHD. The difficulties with making diagnoses of ADHD in adulthood may be somewhat improved with the recent changes in DSM-5 (i.e., the reduced number of symptoms required for individuals 17 years of age and older). Regardless, it is clear that ADHD presents risks for lifelong impairments that include poor interpersonal skills and dysfunctional relationships, reduced educational attainment, and rampant employment problems in adulthood. These continuing impairments are extremely costly to society, with ‘indirect’ educational, legal, and employment-related costs for adult manifestations of ADHD totaling US$200 billion to the annual economy of the United States (see review in Hinshaw and Scheffler, 2014).
Sex Differences Like nearly all early-onset neurodevelopmental disorders, ADHD is widely known to be male predominant. Although the sex ratio has been shown to begin to equalize by adulthood (the reasons for which are not yet fully clear), because of the male predominant nature of ADHD in childhood, the literature on ADHD has largely focused on males. When studies do include females, there are often too few girls to conduct reliable comparisons between sexes. Yet understanding the substantial difference in prevalence rates between males and females may provide clues into mechanisms underlying the development of ADHD. Indeed, the investigation of sex differences in psychopathology has been suggested to be an important step in the study of causal processes (Rutter et al., 2003). A growing body of literature has revealed that females with ADHD exhibit substantial impairment across a range of domains, including behavioral, neurocognitive, academic, and interpersonal problems (e.g., Biederman et al., 2010; ChronisTuscano et al., 2010; Hinshaw, 2002; Miller et al., 2012). In some cases, females with ADHD may display a greater degree of impairment than males with ADHD. Recent work focusing on young adult outcomes of females with ADHD has highlighted alarming rates of suicide attempts and self-harm behaviors in this population, particularly those with the Combined presentation (Hinshaw et al., 2012). With respect to sex differences in the clinical presentation of ADHD, a seminal meta-analytic review identified similar impairments between clinic-referred boys and girls across several ADHD symptom domains, along with greater impairment in inattention and IQ for clinic-referred girls relative to clinic-referred boys (Gaub and Carlson, 1997). However, in non-referred samples, girls with ADHD appear to show less impairment than boys with ADHD. A common conclusion is that, because girls are less likely to be clinically referred to begin with, those who are may be the most severely affected (see also Gershon, 2002, who additionally highlighted higher
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levels of internalizing problems in girls vs. boys with ADHD). Thus, although understanding sex differences in ADHD is of great importance both clinically and conceptually, a critical issue for assessment and diagnosis is comparing an individual’s behavior with same sex, typically developing peers (see Koenig and Tsatsanis, 2005).
Comorbidities and Associated Impairments ADHD rarely exists in isolation from other psychiatric conditions, often making differential diagnosis difficult. Anxiety disorders are present in approximately one-third of individuals with ADHD, and approximately half of individuals with ADHD also meet criteria for oppositional defiant disorder or conduct disorder, which substantially increases the risk for delinquency and substance abuse-related problems. Additionally, ADHD often coexists with specific learning disorders (e.g., reading or math disability) or neurological disorders such as Tourette’s syndrome. Aside from co-occurrence with specific diagnostic categories, ADHD is also often associated with a range of other difficulties, including deficits in executive functioning, difficulties with social relationships, higher rates of accidental injury, and concerning driving behavior. With respect to intelligence, on average, children with ADHD have been shown to perform somewhat lower than typically developing children (estimated average of 9 points; Barkley, 2006), although scores still typically fall in the low average to average range. It is also worth noting that ADHD symptoms, whether or not crossing the diagnostic threshold, are quite common across other neurodevelopmental disorders, including autism spectrum disorders (Simonoff et al., 2008) and fragile X syndrome (reviewed in Au and Hagerman, 2013).
Assessment and Diagnosis As described throughout this chapter, evaluation of ADHD requires documentation of the presence of developmentally extreme levels of inattentive and hyperactive-impulsive behaviors, per DSM-5 criteria. Such evaluation necessitates obtaining information from parents and teachers (or, for adults, an outside observer such as a partner or employer) because of the diagnostic criterion requiring cross-situational manifestations. It is also important to obtain caregiver/informant ratings because individuals with ADHD have been shown to under-report their own symptomatology (Manor et al., 2012). Evaluation procedures should involve a combination of informant ratings on standardized instruments, structured or semi-structured interviews of parents/caregivers (and youth, for some symptom domains), a thorough developmental history, review of school and medical records, and clinical observation (American Academy of Pediatrics, 2011). It is critical to evaluate the settings in which symptoms occur, the time periods during which symptoms initially emerged, the duration and intensity of symptoms, and the degree of functional impairment. As increasing numbers of preschool children are being referred for ADHD diagnoses, it is imperative to carefully consider developmental aspects during evaluation.
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Attunement to normative levels of inattentive and hyperactiveimpulsive behavior during a given developmental period is essential. Because concurrent neurocognitive difficulties are present in many (but certainly not all) children with ADHD, standardized tests of neuropsychological functioning – particularly evaluation of various aspects of executive functioning (e.g., working memory, sustained attention, response inhibition) – may provide clinically-relevant information regarding an individual’s strengths and weaknesses. However, such tests are not currently diagnostic in nature. Similarly, whereas evaluations of intelligence (i.e., IQ tests) or academic achievement testing may be relevant, they cannot rule in or out a diagnosis of ADHD (although they are needed for consideration of potentially comorbid diagnoses, including intellectual disability and learning disorders). As part of assessment for differential diagnosis, it is critical to conduct an evaluation for conditions that may resemble or coexist with ADHD (e.g., conduct and oppositional defiant disorders, mood disorders, anxiety disorders, learning disorders, and intellectual disability). A thorough history, a family evaluation, and a medical examination are also required to rule out neurological disease, sensory impairment, and psychosocial influences (e.g., a chaotic home environment and/or maltreatment, the sequelae of which can mimic ADHD). It is critical to gather a range of information when making diagnostic determinations; the common practice of diagnosing ADHD after a brief office visit is not a valid strategy. It is also good clinical practice to review treatment options with families and provide ample opportunity to answer questions, in order to provide accurate information and dispel any myths about the validity of ADHD as a legitimate and impairing diagnosis requiring evidence-based intervention.
Prevention and Intervention Currently, prevention of ADHD is not feasible because known risk and etiological factors either cannot be directly influenced (e.g., genetic risk factors) or are difficult to adequately address (e.g., low birth weight). Still, there is increasing interest in identifying the earliest risk signs of the development ADHD in order to implement interventions as early as possible (see Auerbach et al., 2004, 2005, 2008; Sonuga-Barke and Halperin, 2010; Sonuga-Barke et al., 2011). If successful, such interventions could alter the trajectory of ADHD from the start, thereby preventing the development of the full syndrome and/or later impairments. Although this approach is being used in other neurodevelopmental disorders (e.g., autism spectrum disorder), such methodology has rarely been used in the study of ADHD, largely because, as described in the section Developmental Course, high levels of inattention and hyperactive-impulsive behavior are developmentally typical at younger ages. Thus, treatment for ADHD generally involves the implementation of interventions after the onset of substantial levels of impairment. Currently, only two main classes of treatments are considered empirically supported for ADHD: stimulant medications (and several other medication classes) and behavioral treatment modalities. Although not consistently
found to be effective for children and adolescents with ADHD, cognitive-behavioral approaches have also shown promise for adults with the disorder. Treatments targeting underlying neuropsychological processes (e.g., aspects of executive functioning, such as working memory) or neural processes (e.g., biofeedback) have shown some promise in initial studies but more rigorous research is needed before such interventions can be recommended or considered evidence-based. Key issues with such interventions include generalizability and clinical robustness with respect to symptom improvement and critical areas of functioning (see Rutledge et al., 2012). Stimulant medications exert their effects by enhancing dopaminergic and noradrenergic transmission, thereby positively influencing attentional capacities and inhibitory control. Because such effects are present in both individuals with and without ADHD, a positive response to stimulant medications does not confirm or ‘prove’ a diagnosis of ADHD. Stimulant medications have repeatedly been shown to reduce core symptoms of ADHD as well as some associated impairments, and positive response rates are high (see Paykina and Greenhill, 2007). Still, full normalization of behavior is quite rare, with benefits lasting only as long as medication is active. Side effects are usually transitory and manageable with dose adjustment. Careful monitoring of stimulant treatment appears to markedly increase the likelihood of clinical benefit and decrease the impact of any potential side-effects, the most common of which include appetite suppression and insomnia. Notably, for preschoolaged children diagnosed with ADHD, the American Academy of Pediatrics (2011) recommends behavioral parent training as a first-line treatment rather than medication, an important recommendation since it is not yet clear what effects such medications might have on the developing brains of very young children. Behavioral treatments that feature parent and teacher management training to promote more consistent environmental cues and rewards have also been shown to be effective in addressing ADHD-related symptoms and associated impairments (for a review, see Fabiano et al., 2009). Such interventions, which include direct contingency management, clinical behavior therapy, and social skills training, require substantial effort on the part of parents and teachers to establish consistent, regular incentives for specified target behavioral, academic, and social goals for children and adolescents with ADHD. These approaches also aim to promote the development of increasingly effective parenting strategies, which can often alleviate dysfunctional parent–child interactions that may serve to maintain ADHD symptomatology and behavioral difficulties more broadly. Although such interventions have routinely been shown to be beneficial for individuals with ADHD, there are several barriers to their more consistent and widespread use. For example, the use of these types of interventions is often limited due to socioeconomic resources. Additionally, effects of behavioral interventions, although strong, are often smaller when compared to carefully-monitored medication management. Finally, and critically, the contingencies must remain in place – ideally across settings – for benefits to be maintained. This highlights a key issue in the field: effects of current evidence-based behavioral treatments for ADHD (and many disorders of
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childhood and adolescence) often do not generalize across settings, even when the same contingencies are in place across multiple environments (see Abikoff, 2009). Combination treatment approaches, which involve the administration of both comprehensive behavioral programs and well-delivered medications, may result in the greatest reduction in ADHD-related impairments, even though medication alone is often sufficient for symptom reduction (see Swanson et al., 2001). Unfortunately, in practice, only a minority of children with ADHD receive this type of optimal medication plus behavioral treatment. Additionally, symptoms of comorbidities commonly associated with ADHD may not improve with either stimulant medication or behavioral strategies that directly target ADHD-related behaviors. In such situations, the use of additional behavioral, cognitive, educational, or medication interventions is necessary. For example, comorbid anxiety disorders will often require adjunctive treatment involving exposure-based procedures; comorbid learning disorders will necessitate specific academic interventions and supports. In general, interventions should be individualized and geared toward functional impairments, which, in individuals with ADHD, commonly include social and interpersonal difficulties, academic problems, and organizational skills deficits. Although combined medication and behavioral treatments have been shown to produce optimal benefit, longer-term follow-up of optimally-treated children with ADHD (i.e., the Multimodal Treatment Study of Children with ADHD) has indicated that early symptom severity is more prognostic of later functioning than the type of well-delivered treatment to which participants were initially assigned (Molina et al., 2009). In other words, once the frequency and/or intensity of optimal interventions are phased out, symptoms and impairments return. Thus, whereas medication and behavioral treatments can provide substantial benefits for individuals with ADHD, there is still much room for improvement with respect to developing better and highly effective treatments that produce lasting effects. It is quite apparent that ADHD portends a host of difficulties throughout the lifespan, but not all individuals with ADHD go on to experience such negative outcomes. Thus, crucial topics for both clinical and research efforts are those of resilience and the identification of protective factors that may alter the trajectory of ADHD. That is, what processes might distinguish those who display adaptive developmental patterns and positive outcomes from those who experience negative outcomes? How can such information be leveraged to inform diagnostic and treatment development efforts? Relatedly, what factors distinguish those who will benefit from current evidence-based interventions for ADHD from those who will require the addition of adjunct strategies? Obvious candidates include factors such as higher IQ, lower symptom severity scores in childhood (Molina et al., 2009), lower levels of caregiver depression (Owens et al., 2003), and warm and supportive parent–child interactions (Chronis et al., 2007). Less-explored candidates that may be highly amenable to intervention efforts include self-perceived academic competence (at least in girls, see Mikami and Hinshaw, 2006) and friendship (Cardoos and Hinshaw, 2011).
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Summary and Conclusions ADHD is a valid and impairing psychiatric syndrome marked by developmentally extreme, cross-situationally displayed, and impairing symptoms in the domains of inattention/ disorganization and/or hyperactivity-impulsivity. It is highly heritable and persists throughout development in most cases, although hyperactive-impulsive symptoms appear to decline more rapidly than inattentive symptoms. Because ADHD is more common in males, relatively little research has focused on females or sex differences in ADHD, but it is becoming increasingly apparent that females with ADHD evidence comparable impairment to males with ADHD (and, in some domains, perhaps even greater impairment – e.g., self-injurious behavior/suicide attempts by early adulthood). Comorbidity is common in ADHD, including high rates of anxiety disorders, learning disorders, mood disorders, oppositional defiant disorder, and conduct disorder. Additional impairments include neuropsychological deficits related to executive control and social skills deficits, among others. Underlying etiologic factors are likely to include genes related to dopaminergic, noradrenergic, and serotonergic functions, as well as neural substrates that largely involve the PFC and its projections to other brain regions. Recent work has suggested delayed neural maturation as well as disruption in both structural and functional connectivity patterns in individuals with ADHD. Although biological factors clearly play a key role in the development of ADHD, it is becoming increasingly apparent that environmental/contextual factors are also strongly involved. Understanding complex transactions across these biological and contextual variables will result in more clearly-defined causal models. With respect to diagnostic evaluation for ADHD, careful and thorough assessment is required to evaluate symptoms and to identify comorbid diagnoses that may require separate treatment. Strategies aimed at preventing the development of ADHD-related symptoms and impairments altogether do not currently exist, although there is increasing interest in identifying the earliest manifestations of ADHD in order to move toward earlier intervention. Currently, effective treatment strategies include pharmacologic (mainly stimulant medication) and behavioral interventions. Strategies that involve the combination of these approaches have been shown to result in the greatest reduction of ADHD-related impairments, although initial symptom severity appears to be more predictive of long-term outcomes than the type of treatment received. Generalization of treatment gains across settings and maintenance of gains across time remain elusive goals with respect to effective interventions for ADHD. Finally, efforts to identify protective factors and predictors of resilience or positive outcomes in individuals with ADHD are crucial, with potentially important implications for both diagnostic efforts as well as the development of more targeted interventions.
See also: Adolescence. Child and Adolescent Psychotherapy. Conduct Disorders. Diagnosis and Classification. Disorders of Impulse Control. Psychological Testing
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