Aggression in children with attention-deficit/hyperactivity disorder

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Review

www.expert-reviews.com ISSN 1473-7175© 2010 Expert Reviews Ltd 10.1586/ERN.10.146

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common and most studied neurodevelopmental disorders of childhood [1–3], affecting between 3 and 10% of the general childhood population [4–6]. The Diagnostic and Statistical Manual of Mental Disorders IV characterizes ADHD as a unitary construct that can be further divided into three subtypes [7]: predominately inattentive (ADHD-I); predomi-nately hyperactive/impulsive (ADHD-HI); and combined type (ADHD-C) [7,8]. To meet diag-nostic criteria for the disorder, individuals are required to exhibit developmentally inappropri-ate levels of inattention, hyperactivity and/or impulsivity prior to age of 7 years, and symptoms must be present for at least 6 months prior to the diagnosis. Symptoms should be present in more than one context (e.g., home and school), must be associated with significant impairment and should not be better accounted for by another disorder [7].

Aside from the inattentive, hyperactive and impulsive symptoms most commonly associated with ADHD, a key question for researchers and clinicians in the area is whether or not children with ADHD exhibit higher levels of aggressive behavior than typically developing children. This question is important because it can have

implications for characterizing the disorder and for treatment development. Furthermore, research generally suggests that aggressive behav-ior in children with ADHD is not a spurious occurrence; rather, that children with ADHD tend to engage in high levels of aggression [4,9,10]. In fact, it is often aggressive behavior that drives treatment referrals to health and mental health practitioners and determines the type of treat-ment administered, especially when parents no longer feel able to manage their child’s aggressive behavior [11,12]. Based on these findings, it has been suggested that problems with aggression may be specific to ADHD itself and not simply a result of comorbid conduct problems (CPs), such as oppositional defiant disorder (ODD) and con-duct disorder (CD) [13]. In sum, it is apparent that aggression is often an important consider-ation when assessing and treating children with ADHD. In fact, several leading researchers and clinicians have concluded that aggression, par-ticularly impulsive aggression, is a serious public health concern and that it should be a key target when treating children with ADHD [12,14].

The purpose of this article is to selectively review studies of aggression in children with ADHD. We first discuss how aggression is defined and conceptualized. Next, we discuss

Sara King†1,2 and Daniel A Waschbusch3

1Wood Street Centre, Nova Scotia, Canada 2Dalhousie University, Nova Scotia, Canada 3Florida International University, FL, USA †Author for correspondence: Wood Street Centre, 225 Wood Street, Truro, Nova Scotia, B2N 7H8, Canada

Tel.: +1 902 896 7040 [email protected]

Research shows that aggression is an important associated feature of attention-deficit/hyperactivity disorder (ADHD) and is important in understanding the impact of the disorder and its treatment. The occurrence of aggressive behavior in combination with ADHD does not appear to be spurious and the severity and/or presence of aggression and ADHD may significantly impact long-term prognosis. This article defines subtypes of aggression in relation to ADHD, identifies individual differences contributing to aggressive behavior in children with ADHD and discusses selected possible underlying mechanisms of aggression in ADHD, as well as current and emerging treatment approaches. Although aggressive behavior in children with ADHD is common, the reasons for this are not yet well understood. Multidisciplinary research should focus on investigating underlying mechanisms related to aggression in ADHD, as well as the utility of various treatment modalities.

Keywords: ADHD • aggression • children • comorbidity • disruptive behavior

Aggression in children with attention-deficit/hyperactivity disorderExpert Rev. Neurother. 10(10), 1581–1594 (2010)

THeMed ArTICLe y ADHD

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Expert Rev. Neurother. 10(10), (2010)1582

Review King & Waschbusch

aggression in the context of ADHD, individual differences in aggression use in children with ADHD, proposed underlying mechanisms of aggression in this population and the treatment of aggressive behavior in children with ADHD. It is important to note that our intention is not a comprehensive review, but rather a selective one to provide an overview of the topic. Where appropriate, we have included references for more comprehensive reviews of specific topics in this area.

Definition & conceptualization of aggressionHuman aggression can be defined as behavior with the proximate (i.e., immediate) intent of causing harm to another person [15,16]. Furthermore, the target must be motivated to avoid the aggressive behavior [15]. Although there are situations in which aggressive behavior can serve an adaptive function (i.e., all humans display aggression, ranging from mild irritation to verbal or physical aggression, at some point) [12], maladaptive aggression can have a serious impact on the individual and others in their environ-ment (e.g., family members and peers). Maladaptive aggression in children has been shown to have a significant impact on social development and is associated with negative outcomes, such as school difficulties [17,18], cognitive deficits [12], peer victimization and rejection [12], and antisocial behavior [19–21].

Several taxonomies have been used to define subtypes of aggres-sion, including: reactive/proactive, in which reactive aggression can be defined as impulsive, angry, ‘hot’ aggression used in response to a perceived threat and proactive aggression can be defined as nonangry, goal-oriented, ‘cold’ aggression [22–24]; hos-tile/instrumental, in which hostile aggression can be defined as aggression with the intention of inflicting pain or injury (with no benefit to the aggressor) and instrumental aggression can be defined as aggression that provides some advantage to the aggres-sor [15,16,25,26]; and overt/covert, in which overt aggression can be defined as visible aggression (e.g., physical assault or temper tantrums), whereas covert aggression can be defined as hidden aggression (e.g., cheating, lying or vandalism) [27]. Each of these taxonomic systems has proven to be useful in the study of aggres-sion; however, much research is needed to determine how these classification systems fit together.

Aggressive behavior in children with ADHDDespite some debate concerning the best way to conceptualize human aggression in general [16] and in the context of ADHD, there is near universal agreement that it is essential to consider aggressive behavior when working with children with ADHD, both in research and clinical practice. This is because children with ADHD appear to be at risk for engaging in high levels of aggressive behavior, even when comorbid CPs, such as ODD and CD, are taken into account [4,9,10]. Furthermore, aggressive behavior that co-occurs with ADHD appears to be more debilitating compared with aggressive behavior that occurs without ADHD [28,29].

Whereas inattentive–hyperactive–impulsive symptoms are con-sidered to be the primary symptoms of ADHD, research sug-gests that the severity and/or presence of aggression also seriously impacts long-term development. Aggression and ADHD have

historically been conceptualized as distinct but correlated dimen-sions of externalizing behavior, as reviewed by Hinshaw [28]. Other research, however, serves to further clarify the relation between the two dimensions by suggesting that emotional dys-regulation in children with ADHD is at least partially responsible for the aggressive behavior observed in this population [5,30–32]. Specifically, Barkley asserts that emotional dysregulation in chil-dren with ADHD is a manifestation of impulsivity extended to another domain (i.e., emotions); just as children with ADHD are behaviorally and cognitively impulsive, so too are they emotion-ally impulsive [32]. Emotional impulsivity or emotional dysregu-lation is often expressed through maladaptive behaviors, such as frequent and intense temper tantrums and being quick to anger, which are in turn risk factors for aggression. Thus, there is clear evidence that ADHD and aggression are distinct constructs, but there is also evidence that the primary features of ADHD put children at high risk for problems with aggression.

Further support for the hypothesis that at least some of the aggressive behavior observed in children with ADHD is related to impulsivity comes from studies of the dichotomies described above. Specifically, reactive aggression appears to be more strongly associated with ADHD than other types of aggression, suggesting that the impulsivity and dysregulation associated with the disor-der are partly responsible for aggression in this population. For example, a study conducted by Dodge and colleagues found that children who exhibit higher levels of reactive aggression also tend to exhibit more inattention and impulsivity problems than proac-tively aggressive children or nonaggressive children [33]. Likewise, another study examining the relationship between reactive aggres-sion and ADHD, ODD and CD [24] found that 66–72% of reac-tively aggressive children met diagnostic criteria for ADHD plus ODD/CD, whereas 13% met criteria for ODD/CD only and 6% met criteria for ADHD only. Interestingly, those children who met the criteria for ADHD plus ODD/CD and reactive aggression were shown to be more impaired overall (e.g., poorer peer relationships and classroom behavior) than ADHD plus ODD/CD children who did not engage in reactive aggression. However, attention and impulse control difficulties do not fully account for differences between reactively aggressive children and other children on measures of psychosocial adjustment, social cognition or developmental history, lending further credence to the suggestion that reactive aggression and ADHD are related but separate constructs [4].

Laboratory studies have also highlighted individual differences in the use of aggression subtypes in children with ADHD. Results of a study examining aggression in children with ADHD only, ADHD plus ODD/CD and typically developing controls [34] indicated that all children, regardless of diagnostic group, used reactive aggression in response to high levels of provocation, but only boys with comorbid ADHD plus ODD/CD engaged in reac-tive aggression in response to low levels of provocation. Boys with the comorbid condition were also more likely to hold a grudge (i.e., they behave aggressively for a longer period of time) follow-ing provocation. Research using the hostile/instrumental aggres-sion dichotomy has also demonstrated that aggressive boys with

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www.expert-reviews.com 1583

ReviewAggression & ADHD

and without ADHD can be reliably distinguished from typically developing children [26]. Specifically, aggressive boys with and without ADHD have been shown to engage in higher levels of instrumental aggression compared with typically developing con-trol children; however, only those children with ADHD showed higher rates of hostile aggression. These findings suggest that children with ADHD plus ODD/CD may be more prone to using reactive aggression in response to provocation, and that this characteristic may be important in distinguishing this group from children who meet criteria for ADHD only or ODD/CD only. Additionally, results such as these suggest that the focus of treatment may need to be specifically tailored to the type of aggression children exhibit.

Psychostimulant treatment was examined as part of a labora-tory study conducted by King and colleagues [35]. Specifically, the reactive/proactive and instrumental/hostile dichotomies were examined in a single study using a computerized analogue aggres-sion task similar to that used by previous researchers [9,26,36,37]. Results indicated that children with ADHD on placebo exhibited increased reactive aggression following high levels of provocation compared with control children, but children with ADHD on medication (methylphenidate [MPH]; Ritalin®) did not. Over the last several trials of the task, only instrumental aggression dis-sipated in controls, whereas only hostile aggression dissipated in children in the placebo group. Both types of aggression dissipated for children in the medication group. Although preliminary, these results highlight the complex nature of aggression use in children with ADHD and make it clear that aggression use in this group depends on a large constellation of factors, a selection of which are described below.

Factors contributing to development & maintenance of aggressive behavior in ADHDComorbid conduct problems Research suggests that the co-occurrence of comorbid ADHD and CPs is high, with findings indicating that the comorbid-ity between ADHD and CPs is more common than not [38]. Estimates suggest that the prevalence of comorbid ADHD plus ODD is approximately 60% in clinically referred children [39], and the prevalence of comorbid ADHD plus CD is approxi-mately 20% [39]; this co-occurrence is much higher than would be expected by chance [4]. Research consistently shows that the presence of comorbid CPs (e.g., ODD and CD) greatly increases the risk that children with ADHD will show frequent and severe aggression [4]. Research is less clear about whether aggression and other antisocial outcomes are a risk for children with ADHD after CPs are taken into account. However, at least some studies indicate that ADHD predicts aggression and antisocial outcomes even after controlling for co-occurring CPs [40–44], although not all studies are consistent [45–48]. Interestingly, the type of aggres-sion seems to be differentially associated with different types of CPs in youths with ADHD. That is, some research has found that adolescents diagnosed with ADHD plus CD tend to engage in more overt physical aggression compared with typical adolescents, whereas adolescents diagnosed with ADHD plus ODD are more

likely to engage in verbal aggression compared with typical ado-lescents [49]. Therefore, the presence of comorbid CPs is a salient factor in understanding and predicting aggression use in children and adolescents with ADHD [49].

Along the same lines, studies have shown that children with ADHD plus CPs tend to use aggression differently than children who do not have comorbid diagnoses [34]. Boys with ADHD plus CPs have been found to be more prone to engage in reac-tive aggression and show greater behavioral and physiological reactivity (i.e., increased heart rate) to low levels of provocation compared with boys with ADHD only, ODD/CD only or no diagnosis [34]. Other research shows that ADHD moderates the relationship between reactive aggression and CPs, but does not moderate the relationship between CPs and proactive aggres-sion [50]. These findings echo earlier results demonstrating that reactive antisocial behavior is more closely related to ADHD than proactive antisocial behavior in children aged 8–15 years [51]. This pattern is also evident in adulthood, as strong associations between violent reactive aggression and ADHD have been found in adult offenders who meet criteria for ADHD, whereas proac-tive aggression was found largely in offenders who did not have ADHD [52].

Sex differences in aggressive behavior Epidemiological research suggests that ADHD is more prevalent in boys than in girls [6], with boys outnumbering girls by a ratio of approximately 9:1 in clinically referred samples and by a ratio of approximately 3:1 in nonreferred samples [5,53–55]. Additionally, when girls are diagnosed with the disorder, they are more often diagnosed with the inattentive subtype rather than the hyper-active/impulsive or combined subtypes [56], suggesting that there may be sex differences in aggression use in ADHD, as aggression is commonly associated with hyperactivity and impulsivity.

Girls with ADHD have been shown to exhibit higher rates of overt and relational aggression (i.e., aggression intended to harm others by targeting their social relationships) than comparison girls, with girls with the combined type of ADHD engaging in more aggressive behavior than girls with the inattentive type [55]. As with boys, the presence of comorbid CPs also influences aggression use in girls with ADHD, as girls with comorbid CPs tend to be more aggressive than controls and more aggressive than girls with ADHD only. One recent study found that girls with ADHD only and with ADHD plus ODD were less socially adept than typically developing girls, but only girls with the ADHD plus ODD exhibited more overt aggression and more relational aggression than controls [57]. Another recent study examining social information processing biases and aggressive behavior in girls with ADHD reported that correlations between aggression (both overt and relational aggression) and social information processing biases were stronger in the comparison sample than in the ADHD sample [58]. The authors suggest that, since base-line aggressive behaviors and difficulties with peer relationships are much more prevalent in ADHD samples than in typically developing samples, it is possible that the stronger associations in the comparison group are a result of a unique set of cognitive

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biases rather than the wide range of difficulties as seen in girls with ADHD [58]. Results such as these indicate that, as with boys who have ADHD, girls with ADHD are also prone to increased aggression use compared with their typically developing peers; it will be important for future research to continue investigating relational aggression use if a complete understanding of aggression use in girls with ADHD is to be attained.

Family factors Some studies using parent reports of family functioning indicate that families of children with ADHD tend to experience more stressful family environments [59], poorer parenting practices and less author-itative parenting compared with control families [59]. However, find-ings are inconsistent and other studies have failed to find an asso-ciation with impaired family functioning and ADHD [59]. Mixed results have also been reported with respect to the impact of family factors on aggressive behavior in children with ADHD, but some findings suggest that family factors, such as socioeconomic status and parenting style, are associated more strongly with aggressive and defiant behavior than with ADHD/hyperactivity in clinic-referred children [60,61]. Clearly, it is important to consider cause and effect when investigating family factors and aggression; how-ever, available research seems to show that ODD (or the interaction between ODD and ADHD), rather than ADHD, is a stronger predictor of parent–child relationship difficulties in children with ADHD [59]. However, it should be emphasized that this finding should be interpreted in light of the fact that most children with ODD also meet criteria for ADHD [6,62], suggesting that it is the combination of ADHD and ODD, rather than ODD alone, that accounts for the greatest parent–child relationship strain. While it is important to consider the abovementioned factors in the devel-opment of aggression in the context of ADHD, it is likely that research investigating the underlying mechanisms of aggression will be crucial to developing prevention and treatment plans for aggressive children with ADHD.

Underlying mechanisms of aggression in children with ADHDThe heterogeneity of ADHD suggests that several pathways underlie the behaviors exhibited by children with the disorder [59]. For decades, researchers have attempted to explain the origins and maintenance of aggression, with theories such as the frustra-tion–aggression model [63,64] and social learning theory [65] being proposed. Detailed discussion of all potential mechanisms of aggression and how they relate to ADHD would likely fill volumes of books. Here we are limited to a brief presentation of the three mechanisms that are currently prominent: social information pro-cessing abilities [66,67]; the role of parenting and peers as articulated by Patterson’s Coercive Model [68–70]; and research investigating the neurobiological/genetic underpinnings of aggression.

Social cognitive mechanisms Social cognitive frameworks have long been useful in identifying specific processing deficits involved in aggressive behavior in chil-dren [71,72]. One such framework is the social information processing

(SIP) model proposed by Crick and Dodge [67]. Aggressive children have been shown to exhibit two specific social information process-ing deficits when interacting with peers. First, aggressive children have been shown to exhibit a hostile attribution bias in ambiguous social situations [73–76]; that is, aggressive children tend to attri-bute hostility to the actions of others and will react accordingly to this. Second, aggressive children exhibit a response decision bias in ambiguous social situations [73,77]; that is, aggressive children generate more aggressive responses to ambiguous social situations than typical children.

Although many studies have examined the SIP abilities of aggres-sive children, relatively little is known about the SIP abilities of ADHD [78,79] – a shortcoming in the literature, as children with ADHD show high rates of aggression. It follows, then, that SIP deficits may underlie the aggressive behaviors observed in children with ADHD. However, the few studies that have examined SIP in aggressive children with ADHD suggest difficulties in this area. For example, children with both ADHD and aggression have been found to show deviant responding compared with children with ADHD only and aggression only, in terms of response decisions and cue utilization [77], to have more difficulty than other children when anticipating the consequences of their actions [80], and to generate more aggressive solutions to problems [80]. Finally, it has been shown that children with ADHD-only differ from controls in terms of their ability to encode cues in social situations, but children with ADHD/ODD/CD or ODD/CD only are more likely to be confident in their ability to enact an aggressive response and to select an aggressive response in a social situation when given the choice [81].

A more recent study examined whether SIP in children with ADHD may differ depending on the valence of the social situ-ation – that is, whether children are considering a social event with a positive, negative or ambiguous outcome [82]. Control chil-dren in this study detected more positive, negative and neutral cues, attributed less negative and positive intent to peers, focused more on situational outcomes of vignettes, and generated more positive responses compared with the ADHD group regardless of the valence. These results indicate that children with ADHD are robustly different from typically developing children in how they interpret social experiences; that is, children with ADHD exhibit more SIP errors regardless of whether they are considering social situations with positive, negative or ambiguous outcomes. Other analyses with the same sample demonstrated that SIP abilities were significantly associated with proactive but not reactive aggression, in that children who generated the most aggressive responses were rated by teachers as displaying more proactively aggressive behavior. Collectively, this research suggests that that children who exhibit symptoms of ADHD and aggression may differ from nonaggressive children in terms of both how and what they think when faced with social dilemmas and that the SIP errors exhibited by children with ADHD are related to proactive aggressive behavior.

Coercive model of antisocial behavior Patterson’s [68–70] coercive family theory of aggressive/anti-social behavior has its origins in naturalistic observations of parents and children and is based on the premise that children

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and parents ‘train’ each other through positive and negative reinforcement to behave in a manner that results in increased child aggressive behavior and decreased parental control over the child’s behavior [70]. Essentially, parents and children each use increasingly aversive techniques to try to get what they want from the other; these techniques are intermittently successful, which serves to intermittently reinforce the parent and child to use the more aversive technique in the future. At the same time, when the parent accedes to the child’s demands, the parent is negatively reinforced for ‘giving in’ to the child by the removal of the child’s aversive behavior. Consider, for instance, a child who throws a temper tantrum because (s)he wants candy, and a parent who accedes to the demand. Coercion theory posits that in this interaction, the parent has been negatively reinforced by the removal of the child’s aversive behavior (the end of the temper tantrum) and, therefore, learned to accede to the child’s demands. On the other hand, the child has been positively rein-forced by earning what (s)he wanted (candy) and, therefore, learns that aversive behavior (a temper tantrum) is a viable means of achieving a desired outcome. Over time, these patterns esca-late into increasingly aversive behaviors and greater withdrawal by the parent.

Studies of children with ADHD with and without aggression and their parents have supported the notion that a negative reinforcement and escalation process is responsible for many of the negative interactions between parents and children with the disorder [83]. In general, parents of children with ADHD find interacting with their children highly aversive, a key component of the coercion model outlined above. In their comprehensive review of families of children with ADHD, Johnston and Mash note that mothers of children with ADHD are typically more negative and less socially interactive [59], with their children exhibiting negative, noncompliant behavior. Johnston and Mash also point out that this type of interaction pattern has been observed in both boys and girls with ADHD and with moth-ers and fathers of these children. Additional research investi-gating parent–child interactions in the context of disruptive behavior disorders, such as ADHD, ODD and CD, indicates that defiant behavior on the part of the child can often lead to more serious consequences in these families. Specifically, a series of experimental laboratory analogue studies carried out in the 1980s and 1990s indicate that parents of typical children and mothers of children with ADHD tend to increase alcohol consumption following an interaction with a child exhibiting deviant behavior [84–87]. This relation is especially strong for mothers of children with ADHD who also have a family his-tory and high family density of alcoholism [87,88]. Coping with disruptive and aversive child behavior using alcohol has also been found to negatively influence parenting behaviors, such as lax monitoring of behavior that mediates the development of CPs as per Patterson’s model [89]. Studies such as these suggest that challenging child behaviors (such as those associated with ADHD) lead to maladaptive parenting techniques and coping skills, which then lead to increased disruptive and aggressive behaviors in the child.

Genetic mechanisms It is well established that genetic factors play an important role in the disruptive behavior disorders [90]. Boys with comorbid ADHD plus CD and ADHD plus ODD have been found to be more likely than boys with ADHD only to have fathers with antisocial personality disorder [91]. Similarly, Pfiffner and col-leagues reported that children of fathers who had left the fam-ily home were more at-risk of developing symptoms of CD and of lower socioeconomic status compared with children in intact families [92]. These authors suggest that perhaps fathers who leave the home are more likely to have antisocial personality disorder and, therefore, their children are placed at a higher risk for CD by way of genetic transmission.

In an excellent review of genetic and epidemiological studies of ADHD and aggressive behavior, Retz and Rösler note that ADHD and aggression are not inevitably linked; rather, the co-occurrence of the two depends on a specific constellation of genetic and environmental factors [52]. To illustrate this point, Retz and Rösler note that carriers of the 5-HTTLRSS/SL genotype have been found to be at low risk for co-occurring ADHD and violent behavior in the absence of psychosocial adversity, but the risk of this group developing ADHD accompanied by violent behavior is significantly increased in the presence of psychosocial adver-sity [52]. However, it is important to note that genes do not affect behavior in a linear fashion and the heterogeneity of phenotypes of disruptive behavior disorders, such as ADHD, ODD and CD, suggests that there is a great deal of heterogeneity in genotypes.

Treatment of aggressive behavior in children with ADHDThe pervasive behavioral and social difficulties commonly asso-ciated with ADHD have prompted researchers and clinicians to investigate the most effective methods of treating the disor-der; when a child with ADHD also exhibits aggressive behav-ior, treatment considerations become even more important. Currently, the most effective treatment for ADHD with and without aggression is a combination of behavior therapy (i.e., social skills training and parent management training focused on teaching parents to administer rewards and consequences for behavior) and psycho stimulant medications [93–96,Waschbusch DA

et al. Unpublished Data]. This course of treatment has been exten-sively studied in randomized control studies and, therefore, has the greatest amount of empirical support at this time. However, in cases where the child does not respond to this type of treat-ment (e.g., symptoms of ADHD are reduced, but symptoms of aggression are not), it may be necessary to consider addi-tional pharmacological treatment. Each of these treatments are reviewed briefly in the following section.

Psychostimulants Attention-deficit/hyperactivity disorder is most commonly treated with psychostimulant medications, such as MPH (Ritalin, Concerta®), dextroamphetamine (Dexedrine) and Adderall® [97–99]. Estimates indicate that approximately 80–90% of children with ADHD are treated with psychostimulant

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medications at some point in their life [27,98,99]. Treatment with psychostimulant medication typically results in cross-situational (e.g., home and school) improvement in the behavioral symptoms of ADHD when the medication is active [100,101], but there is cur-rently no evidence that these short-term improvements translate into long-term improvement [94].

Compared with studies examining stimulant effects on gen-eral behavior in children with ADHD, few studies have spe-cifically examined medication effects on reducing aggressive behavior. Early studies examining the treatment of aggression in children with ADHD suggested that psychostimulant treatment was probably only useful in treating the underlying biological symptoms of the disorder (i.e., inattention, hyperactivity and impulsivity), and that family-oriented psychosocial treatments were probably best for targeting aggressive behaviors associated with ADHD [102]. It was also speculated that medication may have an iatrogenic effect on some types of antisocial behaviors in some children with ADHD, in that it may reduce impul-sive (reactive) aggression while simultaneously increasing non-impulsive (proactive) aggression [103]. However, more recent research has shown that MPH is effective at reducing more seri-ous aggressive behavior in children with ADHD, at least in the short-term [27]. Specifically, a meta-ana lysis of stimulant effects on aggression in children with ADHD found that medication reduced both overt aggression (i.e., physical violence, noncom-pliance, teasing and hostility) and covert aggression (i.e., lying, stealing and vandalizing) in children with ADHD indepen-dently of the effects on ADHD symptoms [27]. It is important to note that stimulant medications may have differential effects based on the subtype of aggression being targeted and the pres-ence of comorbid CPs. A study conducted by Biederman and colleagues suggested that there may be a subtype of comorbid ADHD plus CD with overt aggressive features that may be especially resistant to treatment [104].

A recent series of laboratory studies examining the effects of pla-cebo and a low dose of MPH (i.e., 0.3 mg/kg) on SIP and aggres-sion use suggests that the drug may allow children with ADHD to use aggression selectively rather than indiscriminately [35,79]. Specifically, children in the placebo group engaged in higher levels of reactive aggression on a computerized aggression task; however, children in the treatment group tended to generate more aggressive responses to hypothetical social situations in an SIP task. These findings are consistent with previous findings [37] and they suggest prudence when prescribing MPH to children with ADHD, especially those who exhibit aggressive behaviors, as it may negatively influence social cognition and, subsequently, aggression. The effects of MPH on the underlying social cognitive mechanisms of aggression are not well understood, as drug-related decreases in aggressive behavior do not typically correspond to improvements in SIP, despite the fact that SIP and aggression are thought to be related [23,71,105]. Due to the dearth of research in this area, further investigation of the effects of MPH on SIP and aggression is needed to clarify the effects of MPH on SIP, optimal doses for reducing aggression and the types of aggression best targeted by MPH treatment.

Social skills treatmentSome research has shown that social skills and problem solving training may be effective in reducing antisocial and aggressive behavior and increasing prosocial behavior in ‘hard to manage’ children [106–108]. In an excellent review of current directions in the treatment of aggressive behavior, Nangle and colleagues note that the concept of social skills training as a treatment for aggression emerged as a result of dissatisfaction with the purely behavioral approach to treatment [106]. The social skills train-ing model of treatment is based on the principle that aggressive behavior is the result of a lack of skills needed to interact in a competent manner with peers. Four fundamental processes or training variables underlie all social skills interventions: instruc-tion, rehearsal, reinforcement/feedback and reductive processes; these variables are essential if an intervention is to be effective and if social behavior change is to be observed [109].

Two extensive reviews of social skills interventions point to several issues with this method of treatment and the reader is directed to them for a more detailed discussion [109,110]. Elliott et al. note that social skill interventions are generally most effec-tive for withdrawn children and least effective for aggressive children, with the most positive results shown in studies that effectively match social skill deficits with intervention strate-gies [109]. Furthermore, increased benefits are generally observed with extensive use of operant methods to reinforce existing social skills; that is, reinforcement of socially appropriate behavior and ignoring (rather than punishment of ) socially inappropriate behavior. Despite some promising findings from studies of social skill interventions, DuPaul and Eckert highlight that there is a lack of evidence for generalization of skills across settings, as well as very little evidence of maintenance of social skill gains over time [110]. Indeed, these authors note that, in many social skills programs, generalization and maintenance are often viewed as ‘afterthoughts’ and are not adequately assessed as part of program evaluations. Failing to consider generalization of skills tends to lead to minimal effects on behavior in naturalistic settings, especially for aggressive boys.

In terms of social skills treatment for combined ADHD/aggression, research has found that young children with clinically significant symptoms of ADHD and conduct disorder are less prosocial than other children, but the relation between aggressive conduct symptoms and prosocial behavior is no longer significant once symptoms of ADHD are taken into account [111]. This suggests that it may be prudent to focus on ADHD symp-tomatology when offering social skill interventions to aggressive children who have ADHD. Unfortunately, examinations of the utility of social skills training interventions in children with ADHD have produced mixed findings, with the majority of studies failing to find lasting social behavior change as a result of social skills training in this group of children [112,113]. In an early study of behavioral interventions for social skill deficits in children with ADHD, Pelham and Bender reported that social skills training was successful only when delivered concurrently with a token economy reinforcement system [114]. Additionally, these authors note that although some social skill interventions

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reach statistical significance, they often do not reach clinical significance, as social skills in children with ADHD are not normalized. More recent research has also cast doubt on the efficacy of social skill interventions for children with ADHD. For example, Antshel and Remer found that an 8-week social skills training program for children with ADHD resulted in greater child- and parent-perceived assertion skills, but did not result in improvements in any other domains of social compe-tence [112]. Much of the difficulty in using social skills train-ing with children with ADHD stems from the fact that skills taught in clinic/laboratory settings do not generalize to other settings [113]; this is an area in which drastic improvements need to be made if progress is to be seen with respect to social skills training in this group.

Parent management treatmentAs noted previously, the behaviors associated with ADHD (including aggression) can significantly impact parent–child relationships; therefore, it is important to consider par-ent management training in the treatment of ADHD and aggression. The reader is directed to two recent reviews of nonpharmacological/psychosocial treatments for ADHD for a comprehensive overview of parent management training for ADHD/aggression [115,116]. Parent management training is one of the oldest, most studied and most substantiated treatments for child mental health difficulties, especially for children with aggression/CPs [115,117]. Parent management training for ADHD is based on social learning principles that teach the child socially acceptable behaviors by teaching parents how to effectively man-age and model such behaviors [118]. Parents learn to identify and manipulate antecedents to disruptive behavior and to engage in positive parenting practices, such as positive reinforcement, praise and the use of tangible rewards for appropriate behavior. Additionally, parents are taught to reduce any nonintentional reinforcement of disruptive behavior while providing differential reinforcement of positive behaviors [115]. Parent training has been shown to be effective in reducing problem behaviors in children with ADHD, as well as children with comorbid ADHD/CD and antisocial behaviors [117,119], suggesting that this form of treatment is appropriate for children with ADHD who also exhibit aggressive behaviors. Parent management training has been found to be more effective for parents of younger children who have difficulties with defiance, compliance, rule-following and aggression [116].

Other psychopharmacological treatmentsAs previously noted, in cases where stimulants and/or behav-ior therapy – both of which are empirically supported treat-ments for children with ADHD – are not effective in reduc-ing aggression, other treatments may be needed. These could include other psychosocial treatments or other pharmacological treatments. Recent clinical research has focused on developing new treatment courses for children who are unresponsive to the typical front-line treatments for ADHD and aggression offered by psychologists and physicians [120]. The reader is referred to

a comprehensive review of pharmacotherapy of aggression in children and adolescents for a more complete description of treatments [121]; however, a brief description of promising new pharmacotherapies is offered here.

Atypical antipsychotic drugs, such as risperidone (Risperdal®), olanzapine (Zyprexa®) and quetiapine (Seroquel®) are typically used as front-line treatments for schizophrenia and bipolar dis-order [121], but have been shown to be promising in the treat-ment of aggressive behavior. Risperidone has been shown to be especially affective in targeting aggression, CD and ADHD in youth [122–124], reducing aggressive and defiant behaviors, while causing mild-to-moderate side effects (e.g., extra pyramidal symptoms, weight gain, somnolence). Studies of other atypi-cal antipsychotics in the treatment of aggressive behavior are rare; however, it has been suggested that more studies should be conducted, given trends towards prescribing these agents for aggressive children and adolescents. Given the side effect profile (e.g., extrapyramidal symptoms, tardive dyskinesia) associated with typical antipsychotics, such as haloperidol (Haldol®) and thioridazine (Mellaril®), these agents are less commonly pre-scribed to treat aggressive behavior in children and adolescents. Additionally, research suggests that these agents offer minimal behavioral benefits and are often less effective than MPH at reducing problem behavior.

One promising class of drug in the treatment of aggressive behavior in children with ADHD is mood stabilizers, such as lithium and divalproex (Depakote®). Indeed, it has been sug-gested that divalproex may be a useful adjunctive therapy in response to refractory monotherapy with a stimulant medication in children with ADHD [125,126]. This is an important finding, as many aggressive children with ADHD experience a reduc-tion in many of the aggressive behaviors associated with the disorder, but effect sizes in existing studies are extremely varied, making it difficult to provide treatment recommendations for those children whose aggression does not decrease [126]. In a recent study to investigate the efficacy of divalproex in aggres-sive children with ADHD, Blader and colleagues found that a significantly higher proportion of children receiving divalproex as an adjunct stimulant medication met remission criteria com-pared with those assigned to the placebo condition (58 vs 15%) [125]. This finding is interesting and suggests the need for fur-ther research. However, it should be emphasized that stimulant medication is the only approved pharmacoptherapy for children with ADHD. Other medications, although seemingly promis-ing – especially for the treatment of aggression – are still in the experimental stage with respect to treating children with ADHD, and many have unknown long-term side effects. Furthermore, a key question that must be answered before considering adding non stimulant medications when treating aggressive behavior in children with ADHD is whether other approaches may better serve the child. Specifically, adding behavior therapy to stimu-lant medication has been shown to dramatically increase the effectiveness of treatment and – unlike nonstimulant treatments – the side effects are minimal and it is a well-established treat-ment for both aggression and ADHD [127]. Clinicians need to

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carefully consider the decision to add nonsupported treatments when supported treatments are available, and research addressing this topic is sorely needed.

When choosing an appropriate treatment to target both ADHD and aggression in children, it is important to consider both child and family factors; however, it is likely that the most appropriate treatment course for aggressive children with ADHD is a com-bination of pharmacological treatment (usually using a psycho-stimulant medication), along with an evidence-based psychosocial treatment, such as social skills training and parent management training. Recent research suggests that it may be appropriate to add an adjunct pharmaco logical agent, such as divalproex, when treating children with refractory aggression following stimulant monotherapy. The treating clinician should take these factors into account when deciding the best treatment course for children and adolescents with ADHD and aggressive behavior – treatment plans may vary significantly for this group, given the heterogeneity of the disorder across patients.

Expert commentaryIt is not entirely clear why some children with ADHD exhibit higher levels of aggressive behaviors than others; it is likely that this clinical presentation is a complex mix of genetic/neuro biological and environmental/family factors. However, it is clear that aggres-sion is a concerning associated feature of ADHD, resulting in sig-nificant consequences for children and families challenged by the disorder. The presence of aggressive behavior along with ADHD has wide-ranging consequences that continue to impact the indi-vidual into adulthood, resulting in outcomes such as increased pro-pensity for violent behavior, lower employment status and greater family dysfunction. Studies have shown that children with ADHD are at risk for aggressive behavior, even after controlling for CPs, such as ODD and CD, and the presence of ADHD symptomatol-ogy tends to exacerbate CPs such that children with ADHD plus CPs are more aggressive than children with CPs only. Given these findings, it is essential to carefully evaluate aggression when assess-ing and treating children with ADHD. Understanding subtypes of aggressive behavior may be helpful to both researchers and clini-cians when evaluating children with ADHD, as this may not only provide insight into the most commonly used types of aggression among this group, but may also guide treatment.

Given that comorbid CPs probably have an impact on the types of aggressive behavior exhibited by children with ADHD, it is also likely that this group of children will require more intensive, pervasive and persistent interventions compared with children with only one disorder. It is also important to consider that dif-ferent underlying mechanisms may be responsible for aggression in children with ADHD only, CPs only and ADHD plus CPs. For example, different aspects of the social information process-ing cycle described above may be related to aggressive behavior in each of these groups of children. Again, much research in the area of social information processing has been conducted with children selected based on aggressive behavior; it is only recently that research has begun to consider the effects of ADHD on social information processing.

Aggression use in children with ADHD depends on many factors, both psychological and environmental, but research in this area suggests that using psychostimulants, such as MPH, may be an important part of treatment. In addition to improving the behavioral symptoms of ADHD (i.e., inat-tention, hyperactivity and impulsivity) in the home and class-room settings, psychostimulants may also reduce some types of aggressive behavior and anger in children with ADHD. Further research in this area is needed to determine how children with ADHD engage in aggressive behavior both on and off medi-cation, particularly studies that use within-subjects designs to examine the effects of medication on the hypothesized mecha-nisms underlying aggression in children with ADHD (e.g., social processing, parent–child relationships) and studies that look at the long-term risks and benefits of stimulant medication treatment for aggression. In addition to pharmacological treat-ments, it has been suggested that social skills training may be an important component of treatment for aggressive behavior; however, given the limited success of these programs with both aggressive children and children with ADHD, it remains to be seen whether this type of intervention provides benefits above and beyond pharmacological or behavioral treatments. If social skills training programs are to be successful, greater emphasis should be placed on ensuring that skills generalize to multiple settings, rather than simply improving aggressive behavior in laboratory or clinic settings.

Five-year viewAttention-deficit/hyperactivity disorder is extremely complex, given the range of symptoms associated with the disorder, as well as the comorbid CPs and aggressive behavior observed in children with the disorder. Research has elucidated many of the factors that predict and maintain aggressive behavior in this group; however, this is an area with exciting potential for future research. Some of the most promising avenues for research over the next several years will now be discussed briefly. First, as previ-ously noted, the role of social information processing deficits in aggressive behavior is generally well understood, but the exact role of ADHD in SIP is not well understood – in fact, it has yet to be determined conclusively whether SIP is affected by symptoms of ADHD. Related to SIP, a more general concern is peer rejection in children with ADHD; that is, future research is needed to clarify the role of inattentive versus hyperactive versus aggressive symptoms with respect to social behavior and peer rejection in children with the disorder. Conversely, the role of SIP in ADHD is also not well understood. Specifically, it is not clear which underlying mechanisms lead to or account for aggression in children with ADHD. It remains to be determined whether the same mechanisms are at play in children with ADHD only versus CPs only versus ADHD plus CPs, and whether or not these mechanisms can account for ADHD symptoms as they do for aggressive behavior.

With respect to long-term issues in treatment for ADHD/aggression, several points deserve attention. First, it will be important to determine how treatments for ADHD and

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treatments for aggression can be synthesized to produce the most positive outcomes for children with both types of symptoms. There are currently well-supported treatments available for both ADHD (e.g., behavioral treatments, psychostimulant medica-tions) and aggression (e.g., parent management training), but it is not yet clear which components of each treatment method work best for children with ADHD who are also aggressive. One treat-ment that may be promising is the ‘Coping Power’ program devel-oped by Lochman and Wells [128–130], which is a multicomponent preventative intervention that uses a contextual social–cognitive model as a framework for the intervention. One strength of this particular model is that it has been shown to reduce aggression and antisocial behavior in the long term [128]. Future research should examine whether this model of treatment is more useful for aggressive children with ADHD and children with ADHD plus CPs to determine the most appropriate treatment modality for these children.

Another important issue with respect to treatment of ADHD plus aggression is teasing apart the reasons for treatment success with various treatment modalities. Specifically, it is clear, based on several well-designed studies, that psychostimulant treat-ment decreases aggressive behavior in children with ADHD, but it is not clear why this is the case. Research must deter-mine whether psychostimulants act by reducing symptoms of ADHD, which, in turn, results in decreased aggressive behav-ior, or whether they act on a completely separate mechanism to reduce aggression. Similarly, it will be important to ask the same questions of behavioral treatments for ADHD. Research providing a greater understanding of the mechanisms through which empirically supported treatment work may lead to more streamlined and effective treatments for aggression in children with ADHD is needed.

Finally, several other research priorities are worth mention-ing. It will be important to conduct longitudinal studies to examine outcomes in treated versus untreated children, as well as to examine the long-term effects of various treatment modalities (i.e., psychostimulants vs social skills training vs multicomponent treatments). Studies of the subtle etiological

factors leading to combined ADHD and aggression would help in elucidating differences between children with ADHD who exhibit aggression/CPs and those who do not. Previous research has suggested that there are several etiological fac-tors that could account for these different trajectories [28], but more investigations of etiology will serve to clarify the most salient risk factors for comorbid ADHD plus CPs/aggression. Using rigorous and novel experimental designs to examine the issues described above would increase confidence in conclu-sions regarding the origins and expected outcomes for aggres-sive behavior and ADHD. Embracing new technologies, such as incorporating mobile devices to gain moment-to-moment data [131–133] or virtual reality software to provide more real-istic hypothetical scenarios, may help answer these questions. Finally, given that the current state of research in ADHD sug-gests that biological, psychological and social factors must be considered when studying and treating this disorder, it will be important for researchers and clinicians in the field to conduct high-quality multidisciplinary research – it is likely that this is the most promising avenue for developing unified theories of aggression in this population.

Financial & competing interests disclosureSara King is a CIHR Training Fellow in the Canadian Child Health Clinician Scientist Program (CCHCSP) in partnership with SickKids Foundation (Toronto, Ontario), Child and Family Research Institute (Vancouver, British Columbia), Women and Children’s Health Research Institute (Edmonton, Alberta) and Manitoba Institute of Child Health (Winnipeg, Manitoba). During the preparation of this manuscript, Daniel Waschbusch was partially supported on US grants from the NIMH (1R34MH085796-01A2, R0MH069614, R34MH080791),IES (R324B06045, R305A080337), DHHS (97YR0017) and NICHD. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Aggressive behavior in children has been shown to have a significant impact on social development and is associated with negative long-term outcomes.

• Aggression is acknowledged as an important associated feature of attention-deficit/hyperactivity disorder (ADHD) – children with ADHD are at risk for engaging in high levels of aggression, even after controlling for comorbid conduct problems.

• Aggressive behavior that co-occurs with ADHD appears to be more debilitating than aggressive behavior that occurs without ADHD.

• Boys with comorbid ADHD plus conduct problems are more prone to engage in reactive aggression and show greater behavioral and physiological reactivity to low levels of provocation compared with boys with ADHD only or conduct problems only.

• Girls with ADHD engage in higher rates of overt and relational aggression than comparison girls. Girls with the combined subtype of ADHD engage in more aggression than girls with the inattentive subtype.

• There are several possible mechanisms that may explain the emergence of aggression in children with ADHD, including impaired social cognition, parent–child relationship problems and genetic/neurological factors.

• Placebo-controlled randomized trials have shown that psychostimulant medication, behavior therapy and their combination are effective in treating ADHD, including aggressive behavior in children with ADHD.

• Numerous questions about aggression in children with ADHD remain for future research, such as further examination of the role of specific social information processing and evaluation of multicomponent treatments for aggressive behavior in children with ADHD.

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Aggression in children with attention-deficit/hyperactivity disorder