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Title: Finding a Needed Diagnostic Home for Children with Impulsive Aggression

Ekaterina Stepanova, MD, PhD, Joshua A. Langfus, MA, Eric A. Youngstrom, PhD, Spencer C. Evans, PhD, Joel Stoddard, MD, MAS, Andrea S. Young, PhD, Kathryn Van Eck, PhD, Robert L. Findling, MD, MBA

  • Ekaterina Stepanova, MD, PhD (Q91540088)
    • Affiliation: Virginia Commonwealth University, Department of Psychiatry
    • ORCID: https://orcid.org/0000-0003-4033-2280
    • Email: ekaterina.stepanova@vcuhealth.org
    • Conflict of Interest Declaration: In the past 24 months, Dr. Stepanova receives or has received research support from Psychnostics, LLC and NIMH
  • Joshua A. Langfus, MA (Corresponding Author; Q103815757)
    • Affiliation: University of North Carolina at Chapel Hill, Department of Psychology & Neuroscience
    • ORCID: https://orcid.org/0000-0003-1096-966X
    • Email: langfus@unc.edu
    • Conflict of Interest Declaration: Mr. Langfus reports no real or potential conflict of interest
  • Eric A Youngstrom, PhD (Q27734333)
    • Affiliation: University of North Carolina at Chapel Hill, Department of Psychiatry & Neuroscience
    • ORCID: https://orcid.org/0000-0003-2251-6860
    • Email: eay@unc.edu
    • Conflict of Interest Declaration: In the past 24 months, Dr. Youngstrom receives or has received research support, acted as a consultant and/or has received honoraria from Pearson, Janssen, Joe Startup Technologies, Western Psychological Services, American Psychological Association, Guilford Press
  • Spencer C. Evans, PhD (Q56332127)
    • Affiliation: University of Miami, Department of Psychology
    • Email: sevans@miami.edu
    • Conflict of Interest Declaration: Dr. Evans reports no real or potential conflict of interest
  • Joel Stoddard, MD, MAS (Q64611623)
    • Affiliation: University of Colorado Anschutz Medical Campus, Aurora
    • Email: Joel.Stoddard@cuanschutz.edu
    • Conflict of Interest Declaration: Dr. Stoddard receives or has received grant or research support from the National Institute of Mental Health and Brain and Behavior Research Foundation. He has served as a DSMB committee member: Threat Interpretation Bias as Cognitive Marker and Treatment Target in Pediatric Anxiety (R61 Phase).
  • Andrea S. Young, PhD (Q38547062)
    • Affiliation: Johns Hopkins University, Department of Psychiatry and Behavioral Sciences
    • ORCID: https://orcid.org/0000-0002-8486-0643
    • Email: ayoung90@jhmi.edu
    • Conflict of Interest Declaration: In the past 24 months, Dr. Young receives or has received research funding from NIDA, the Brain and Behavior Research Foundation, Psychnostics, LLC, and Supernus Pharmaceuticals, has served as a consultant/grant reviewer for PCORI, NIH and Montana State University, serves on editorial boards for American Psychological Association journals, and on the advisory board for Helping Give Away Psychological Science (501c3).
  • Kathryn Van Eck, PhD (Q87955302)
    • Affiliation: Johns Hopkins University and Kennedy Krieger Institute
    • Email: vaneckk@kennedykrieger.org
    • Conflict of Interest Declaration: In the past 24 months, Dr. Van Eck receives or has received research support from Supernus Pharmaceuticals, Center for Disease Control, Health Resources and Services Administration, the National Institute of Child Health and Human Development.
  • Robert L. Findling, MD, MBA (Q90314248)
    • Affiliation: Virginia Commonwealth University, Department of Psychiatry
    • Email: Robert.Findling@vcuhealth.org
    • Conflict of Interest Declaration: In the past 24 months, Dr. Findling receives or has received research support, acted as a consultant and/or has received honoraria from Acadia, Adamas, Afecta, Akili, Alkermes, Allergan, American Academy of Child & Adolescent Psychiatry, American Psychiatric Press, Arbor, Axsome, Emelex, Gedeon Richter, Genentech, Idorsia, Intra-Cellular Therapies, Luminopia, Lundbeck, MedAvante-ProPhase, NIH, Neurim, Otsuka, PaxMedica, Pfizer, Q BioMed, Receptor Life Sciences, Roche, Sage, Signant Health, Sunovion, Supernus Pharmaceuticals, Syneos, Syneurx, Takeda, Teva, and Tris.

Abstract

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Aggressive behavior is one of the most common reasons for referrals of youth to mental health treatment. While there are multiple publications describing different types of aggression in children, it is still challenging for clinicians to diagnose and treat aggressive youth, especially those with impulsively aggressive behaviors. The reason for this dilemma is that currently several psychiatric diagnoses include only some symptoms of aggression into the criteria. However, no diagnosis adequately captures youth with impulsive aggression (IA). Here we review the current diagnostic categories, including behavior and mood disorders, and show that they do not provide an adequate description of youth with IA. We also specifically focus on the construct of IA as a distinct entity from other diagnoses and propose an evidence-based set of diagnostic criteria that describes youth with IA to use for future evaluation in clinical practice.

Keywords: Developmental Psychology, Toddler, Medical Diagnosis, ICD criteria

Introduction

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Aggressive behavior in young children is often considered to be a typical part of early development. Parents of toddlers are generally prepared to deal with the “terrible twos” expecting that aggressive behaviors will subside as the child grows older. In a vast majority of children, aggression begins to subside after their 3rd birthday.[1] However, when aggression becomes impairing to the point of interfering with the child’s and family’s functioning, parents may seek help from a mental health provider. The job of the mental health provider during an evaluation becomes to accurately diagnose the child that presents with aggressive behaviors in order to recommend appropriate treatment. Unfortunately, no diagnosis in the DSM5 or ICD11 adequately captures aggression in children. The purpose of this review is to examine the limitations of the current nosology in describing children with aggression, specifically focusing on impulsive aggression (IA).

Aggression is one of the most common reasons for referrals to pediatric mental health clinics, emergency room visits and admissions to inpatient units.[2] Historically, aggression has been divided into proactive (premeditated, instrumental goal-directed behavior that occurs with little or no provocation) and reactive (in response to a stimulus, such as a frustrating event or a perceived threat) types[3][4][5][6] with many individuals exhibiting elements of both.[7][8] Reactive aggression is often described as “angry”, “hostile” or “hot,” while proactive aggression is commonly referred to as “cold” or “premeditated”.[2][9] These two types of aggression have different biological and developmental correlates, as well as longitudinal course, and are likely distinct phenomena.[10][11] Studies showed a correlation between proactive aggression and the development of delinquency and psychopathy later in life,[12][13][14] while reactive aggression was associated with internalizing problems (including depression and anxiety symptoms), negative affect, ADHD, and peer problems.[7][13][14][15] However, other studies report that reactive aggression may precede proactive aggression during the course of child’s development,[11] suggesting a more complex interaction and co-occurrence between the two forms of aggression. This overlap is likely due to a shared neural basis, that is both types of aggression involve regions that mediate evaluating the subjective value of actions in any situation, social threat, and affective regulation.[16][17]

For the purpose of this review, we take it that reactive aggression and IA describe similar, if not identical behaviors; however, we use the term IA because of recent work linking impulsivity and aggressive behavior in the context of ADHD,[18][19] as we will elaborate further below.[18][19] Here we primarily focus on children with impairing IA that’s inconsistent with their developmental level. In our experience, youth with debilitating symptoms of IA are often challenging to correctly diagnose and effectively treat. Families often describe aggressive behaviors as “outbursts”, “tantrums”, or “rages”. These children can have aggressive episodes several times a week, often daily, that include verbal and even substantial physical aggression. The severity and duration of these episodes vary greatly and do not seem to be predictable. These children may snap at a peer’s comment or destroy their room in a fit of rage. Their aggressive behavior is impulsive in nature and is triggered by events that are perceived as minor or insignificant by others. In the absence of triggers, however, these youths are generally calm. Nevertheless, the aggression can be so impairing that it leads to expulsion from daycare or school, causes difficulty functioning at home, negatively affects peer relationships, contributes substantially to caregiver burden, and even increases the rates of suicidal behaviors and ideation,[20] all of which lead to seeking mental health treatment.

Although mental health providers frequently encounter and assess youth with impairing IA, there is no clear diagnostic framework to capture such behaviors. These children are therefore described as “diagnostically homeless”,[21] despite symptoms of IA cutting across several extant diagnostic categories (DSM-5 and ICD-11).[22][23] In particular, symptoms of impulsivity and aggression appear in the criteria for conduct disorder (CD), intermittent explosive disorder (IED), and disruptive mood dysregulation disorder (DMDD) , and are often associated with attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD) and other mood disorder diagnoses. Below, we suggest that these categories, as they are currently defined, do not sufficiently capture the phenomenology of IA. For that reason, our group evaluated the construct of IA and determined that it is distinct from attention, mood and rule-breaking problems.[24] Here we propose to address the lack of an adequate diagnosis for children with IA by suggesting a set of diagnostic criteria to capture IA construct.

Disruptive Behavior Disorders

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Conduct Disorder

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Early research on childhood onset CD focused on identifying and treating youth with “severe aggressiveness, explosiveness, and disruptiveness unresponsive to various outpatient treatments”.[25] Other studies have focused on a group of youngsters with early onset CD and ADHD that fit the same criteria.[26] This description temporarily created a diagnostic home for those impulsively aggressive youth who frequently present for treatment. With the transition from DSM-III[27] to DSM-III-R,[28] however, more symptoms of proactive aggression and other behaviors (such as truancy, running away, using a weapon) were included, gradually shifting the diagnostic criteria away from a focus on impulsive aggressive symptoms. Over the transition from DSM-III to DSM-IV,[29] the antisocial behavior presentations that were then captured by different subtypes of CD came to be codified in a single CD category defined by a heterogeneous array of problem behaviors. These criteria (in DSM-5 there are 15, of which only 3 are needed for diagnosis) are classified not only as aggression—which is our focus here—but also include acts of deceitfulness/theft and serious rule violations. As this modern conceptualization of CD crystalized in DSM-IV and beyond, so too did it become clear that CD and ODD (discussed below) were both clearly distinct and closely related, with CD being the more severe of the two.[7][30][31] Perhaps due to this evolution, including the increasing prominence of rule-breaking behaviors in CD criteria, the diagnosis became more stigmatizing.[32] The focus on rule-breaking behavior also confounded legal with mental health issues. These behaviors were considered to be difficult to treat, which led to most insurances not covering treatment of CD, leaving providers to search for another billable diagnosis for youngsters with IA. Nevertheless, many if not most youngsters with IA likely also meet current criteria for CD. Despite this, CD no longer provides an accurate description of youth with IA.

Understandably, research on CD followed the diagnostic criteria and lumped together youth with IA and rule-breaking behaviors. However, it is possible that childhood onset CD encompasses a different set of behaviors compared to the adolescent onset form of the disorder. Although CD can be diagnosed in children as young as 4-5 years of age,[33][34] the age of onset of aggressive behavior problems generally ranges from 4 to 10 years with a sharp decline of aggression after age 10.[35][36] Additionally, some studies show that symptoms of CD in younger children may not be stable over time, and most children will no longer meet the full criteria for CD after 2-5 years.[33] Thus, these studies suggest that a childhood-limited course of CD could be a hallmark of a diagnosis separate from the persistent course of CD. Additionally, there is evidence that many individuals with CD have family history of antisocial personality disorder, and often have comorbid anxiety and ADHD.[35][37] However, the family and comorbidity studies did not separate proactive aggression from IA and it is unclear if youth with IA and proactive aggression share the same characteristics. Given that prior studies of childhood-onset CD provided inconsistent results in examining the of age of onset, presence of impulsivity alongside proactive aggression, and family history of ADHD or mood disorders, it remains an open question whether the current criteria for CD could represent a diagnostic home for youth with IA or if a separate category is needed.

Oppositional Defiant Disorder

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As noted above, CD and ODD are distinct but related. Rates of comorbidity between the two disorders are high, and ODD frequently co-occurs with various other mental disorders.[38][39] Further, ODD and CD share developmental pathways such that many youths with CD previously had ODD as a developmental precursor.[26][40] Accordingly, clinicians and researchers typically do not focus solely on CD or ODD without any consideration of the other. Yet our attention to ODD here is not merely obligatory. Whereas CD includes many symptoms of proactive aggression (see above), ODD is characterized by reactive disruptive behaviors, akin to reactive aggression or IA. Specifically, ODD is defined by 8 symptoms (of which 4 must be present for the diagnosis), organized around at least two symptom dimensions: an angry/irritable dimension (temper; touchy; angry) and a defiant/headstrong dimension (argues; defies; annoys; blames; spiteful/vindictive.[41][42][43]

Although the diagnostic criteria for ODD do not explicitly include aggressive behaviors, ODD symptoms are very highly correlated with aggression, especially with reactive aggression.[44] Indeed, many empirical models of youth psychopathology consider oppositional and aggressive behaviors as being closely related to one another, both falling along the overt (rather than covert) dimension of disruptive behavior problems.[45][46][47][48] However, clinical decision-making is categorical rather than dimensional. Thus, from a person-centered perspective, latent class/profile analyses support differential prediction of aggressive behavior as an outcome of different dimensions of ODD (irritable vs defiant).[49][50] At the same time, the distinction between ODD dimensions should not be overstated, and linkages to aggression require further investigation. In sum, ODD is a disorder with high comorbidity, great heterogeneity in presentation and outcome, characterized by emotional and behavioral dysregulation. For many youths with ODD, IA can be an important part of the clinical presentation. However, ODD, as currently defined in DSM-5 and ICD-11, does not identify IA as such; nor does it capture youths with IA in need of clinical care.

Attention-Deficit Hyperactivity Disorder

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At this time, aggression is not conceptualized to be a core symptom of ADHD in the current nosology.[22][23] However, impulsivity is a core feature of ADHD, therefore it may not be surprising that children with this disorder are at a higher risk of exhibiting IA.[18] About 54% of youth with ADHD showed clinically significant levels of aggression in the Multimodal Treatment Study of Children with ADHD.[51] In fact, aggression is considered to be an associated feature of ADHD.[52] Specifically, reactive aggression (or IA) showed a much stronger correlation with ADHD, compared to proactive aggression.[53] The severity and frequency of aggressive behaviors further increase when ADHD is comorbid with other behavior disorders, such as ODD and CD.[18] There is evidence that IA and ADHD are distinct constructs, however, the relationship between the two is not entirely clear and may involve emotional impulsivity leading to anger outbursts.[52]

Despite the paucity of studies evaluating the nosology of ADHD and IA, a lot of aggressive children with ADHD are impaired and require treatment. For example, 26% of youth with ADHD and IA continued to have impairing symptoms of IA despite adequate treatment of ADHD.[51] To address the dearth of data in clinical interventions for aggressive children with ADHD, several trials were designed and targeted aggressive behaviors in addition to the primary diagnosis. In a large NIH-sponsored trial Treatment of Severe Childhood Aggression (TOSCA) participants were included if they had a primary diagnosis of ADHD with comorbid ODD or CD, as well as high baseline levels of aggression.[54][55][56][57] Some studies utilized similar methodology,[58][59][60] while others targeted aggressive behaviors in youth with primary diagnosis of CD[25][61][62][63][64][65] with or without comorbid ADHD[66] or a combination of disruptive behavior disorders (DBD), including CD, ODD or DBD, not otherwise specified.[67] Mood disorders, such as Major Depressive Disorder (MDD) or Bipolar Disorder (BD), were excluded in most of these trials. While the methodology of these studies was drastically different, all of them attempted to select a population of highly aggressive and impaired children with disruptive behavior disorders that do not have significant mood problems. Unfortunately, none of these trials separated aggression into proactive or reactive subtypes and it is unclear if only youth with IA were selected for these studies. However, the trials not only highlight efficacy (or lack of efficacy) of different psychopharmacological agents for management of aggressive behaviors, but also bring attention to this unique population of aggressive children without comorbid mood symptoms that do not yet have a diagnostic home.

IED

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Another possible home for youth with IA is IED. As the definition implies, IED manifests as a failure to control aggressive impulses. Changes made to the IED criteria in the DSM-5 allow for more frequent verbal and physical aggression (up to 3 times a week) than did earlier iterations of the DSM. However, most prior research on IED used the DSM-IV criteria (3 major aggressive episodes in the past 12 months), which likely captures a different phenotype from aggression that occurs on an almost daily basis. Unlike the group of children with early onset CD and ADHD, described above, IED is frequently comorbid with mood, anxiety and substance use disorders.[68][69][70][71] Some studies report additional comorbidity of IED with ADHD and ODD.[72][73] Family history of individuals with IED also differs from that of CD. First degree relatives generally have mood disorders, substance abuse and other impulse control disorders.[73] In addition, available data suggest the age of onset of IED ranges from around adolescence to early adulthood rather than early childhood69,[73][74][75] setting IED apart from ADHD and CD. To our knowledge, there have not been prospective studies examining the prevalence and persistence of IED in preschool or elementary school children. Although IED and IA appear to have a similar behavioral profile, the combination of other attributes substantially differ between IED and IA. Those include adolescent age of onset of IED, family history of mood disorders and comorbidity with mood and other impulse-control disorders, all of which make IED an unlikely nosological entity for kids with IA.

Mood Disorders

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Aggression and irritability can also occur in the context of mood disorders. Severe outbursts were once hypothesized to be a hallmark of the pediatric BD,[76] drastically increasing its rate of diagnosis in youth. Subsequently, it was shown that most irritable and aggressive children do not develop BD later in life, in contrast to those with more episodic presentations.[77] To find an alternate “home” for youth with irritability, DSM-5 introduced a diagnosis of Disruptive Mood Dysregulation Disorder (DMDD), which specifically focuses on chronic irritability and frequent temper tantrums. However, in BD and DMDD (both of which DSM considers mood disorders), aggression tends to occur specifically in the context of changes in mood.[21] In contrast, many children with IA appear angry during relatively brief episodes but are otherwise generally euthymic.

DMDD was revised from its research precursor, Severe Mood Dysregulation, largely by removing criteria for hyperactivity/arousal. The revision left DMDD to solely focus on a single, core construct, irritability, which is defined by two indicators: temper outburst and “irritable”/angry mood in between outbursts. Despite emerging from investigations on mood disorders, the revision brought DMDD close to chronic irritability as it is defined in the aggression literature.[78] In current investigations, the degree to which these two indicators of irritability co-occur in clinical populations is being tested. Recent evidence suggesting they each may be individually present at a clinical significant level, i.e. they are separable.[79][80] IA is promising in that it may be diagnosed when there is no evidence of chronic, between outburst negative mood. However, clinicians will need to take care in assessment, considering known issues by developmental stage and informant[81] that obscure the detection of between outburst negative affect.

Aggression as a Construct

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While symptoms of IA cut across several psychiatric diagnoses, none of the aforementioned diagnostic categories accurately capture phenomenology of IA. Aggression can, at times, be adaptive or maladaptive; it can present with a variety of psychiatric diagnoses or in the absence of psychopathology.[82] There is not yet a consensus on whether maladaptive aggression should be a criterion of several diagnoses, an associated feature, a separate disorder, or all of the above. Connor et al[83] began to answer that question by examining aggression in a group of psychiatrically referred children compared to healthy controls.[83] They found that aggression scores were much higher in referred children with a variety of diagnoses, including disruptive behavior, anxiety and mood disorders, when compared to controls. In this study different types of aggression, including reactive and proactive, were highly correlated with each other, which supported the authors’ suggestion that there is a single distinct underlying aggressive construct that is transdiagnostic.

One recent effort to specifically focus on evaluating IA as a clinical construct occurred in a consensus conference with multiple experts, where the participants evaluated the research evidence available at that time.[51] They concluded that there was indeed sufficient scientific evidence for the construct of IA, which can be measured and reliably recognized by experts. However, this construct is not specific to any particular diagnosis and can be present in youth with BD, depression, and ADHD. One possibility is that it constitutes a marker of severity. The authors of the report compared IA to non-specific symptoms such as pain or fever. The consensus conference helped advance the field’s understanding of IA and its boundaries in relation to other disorders.

Several years ago, our group began to work on validating the IA construct on a much larger scale using three data sets,[24] as well as further clarifying the boundaries of IA as it relates to psychiatric diagnoses. Results from our work, which combined rational and empirical approaches, indicated that IA or Aggression with Impulsivity and Reactivity (AIR) is distinct from other mental health problems (such as mood problems, hyperactivity and rule-breaking behavior).[34]

Forthcoming work from our group examined the conceptual boundaries of the AIR construct in the context of other mood and behavior symptoms. Drawing from the same three, heterogeneous samples as Young et al.,[24] provided access to a diverse group of participants from community and academic settings with different demographic characteristics (table 2). The latent profile analysis (LPA) identified groups of children with similar patterns of symptom elevation across five domains: AIR, depression, mania, rule-breaking and self-harm. Seven distinct symptom profiles replicated across the three samples. Of these, one had AIR as the predominantly elevated domain. Rates of ADHD diagnoses were higher in this group compared to sample averages, as were rates of ODD and CD. Children in this group were slightly younger than average, and they did not have elevated mood or anxiety concerns. Of the other profiles that emerged, several showed high levels of AIR co-occurring with mood and self-harm symptoms, and others showed mood symptoms without the presence of AIR.

Overall, this work supports three implications important for defining the AIR construct: first, a profile exists where AIR is the primary concern, establishing that AIR is not solely an associated feature of mood or disruptive behavior disorder; second, profiles exist where AIR does co-occur with mood and disruptive behavior diagnoses; third, AIR is not a necessary symptom for these diagnoses, since groups of children exist with these disorders and no elevation in AIR. Taken together, these results support a definition of AIR as both a distinct construct, and a transdiagnostic feature that co-occurs with other psychiatric conditions. These observations are therefore an important step toward identifying a diagnostic home for youngsters with IA, as well as an optimal setting for evaluating appropriate treatment.

To further the aim of creating a diagnostic home for youth with IA, we propose to develop data-driven research diagnostic criteria (RDC), and subsequently evaluate them in a clinical setting. At this time, our findings do not constitute a final set of clinical diagnostic criteria, but rather a starting point to move towards a potential new diagnosis. Establishing the RDC provides an opportunity for further evaluation of its applicability in clinical practice, as well as fine-tuning the criteria to accurately reflect the population of children with AIR. In addition, developing the RDC for youth with IA provides a framework for designing improved rating scales and other assessment tools for accurate identification of children with IA.

In order to establish preliminary RDC of AIR, we selected items included in the empirically-developed AIR construct, such as “assaults people physically”, “makes threats to others”, “fights frequently with others”, “acts impulsively or rash”. Unfortunately, many of the aggression items on the assessments are not specific to IA and do not provide context. We, therefore, supplemented the available AIR items from the assessments with other criteria that in our opinion describes IA. For that purpose, we added a more thorough description of verbal aggression (“screams, yells” and “insults adults”) and physical aggression (“kicks, hits, bites”, “scratches”). We also added the description of aggressive behaviors being impulsive, rather than planned. These additional criteria, including frequency and duration of the behaviors, as well as the number of criteria used to make the diagnosis of AIR were added on the basis of extensive clinical experience and consensus among several experts. The provisional age of onset was informed by early research on CD.[35][37]

Proposed: AIR Criteria

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  1. Recurrent failure to control aggressive impulses resulting in frequent outbursts (verbal and/or physical) often in response to minimal triggers (such as being given directions, non-preferred tasks or comments that are perceived as critical). The outbursts are grossly out of proportion in intensity or duration to the situation. The outbursts include at least 3 symptoms out of 7 from the following categories, and not limited to interaction with one person, such as parent or guardian
    1. Verbal aggression
    2. Screams, yells; extraordinarily loud
      1. Insults adults
      2. Threatens others
    3. Physical aggression
      1. Hits, kicks, bites, pushes other people or animals
      2. Hits, bites, scratches him/herself
    4. Destruction of property
      1. Punches walls, kicks or hits furniture resulting in property damage
      2. Slams doors, throws small items or furniture
  2. Aggressive outbursts are inconsistent with developmental level
  3. Most aggressive behaviors occur at least 5 days out of a week
  4. Duration – at least 6 months
  5. Behavior occurs in at least two settings (ex. home and school) and is not restricted to the individual’s relationship with his/her parents or guardians
  6. Age of onset – prior to age 10
  7. Behaviors are not better explained by an episode of a mood disorder (depression or mania), anxiety disorder, psychotic disorder or ASD
  8. Symptoms are not attributable to the physiological effects of a substance or another medical/neurological condition
  9. The majority of recurrent aggressive outbursts are not premeditated
  10. The behavior causes clinically significant impairment in social, academic, or occupational functioning


The preliminary RDC of AIR listed above are a constellation of data-driven AIR-specific items, earlier research on childhood aggression (CD) and clinical experience of several experts (Fig. 1). While these RDC have face validity, we wanted to ascertain the clinical utility of AIR criteria. For this purpose, we applied the criteria to a small sample of patients presenting with a chief complaint of “aggression” at a community mental health clinic. Out of 15 patients with aggression, 7 met full criteria for AIR, while others were excluded due to IA occurring only in the context of a mood episode. We recognize the limitations of using such a small sample, however, this is the first step towards applying the criteria in a clinical setting.

It is apparent that these RDC of AIR resemble criteria for IED, which is a well-established diagnosis in the DSM-5 (Table 1). Naturally, we wondered if AIR is an early onset of IED in children. Unfortunately, there are no data available to date to answer that question. The symptom frequency criterion for IED changed significantly from the DSMIII to the DSM-5, with DSM-5 resembling AIR the most. However, to our knowledge, no prospective clinical trials evaluated the onset of the IED criteria in pediatric population and long-term outcomes in adulthood. Whether children with AIR grow up to be adults with IED is an empirical question that will need to be addressed in future studies.

In this proposal, IA in AIR is distinguished from temper outbursts in DMDD by requiring more frequent outbursts and defining the behavior as aggressive. Patient characteristics described in AIR such as explosiveness, sensitivity to provocation, having impairment in two domains (e.g. with family, school, or peers), and having affective dysregulation are similar to those in DMDD. Thus, the focus on aggression is important here as a potential for discriminant validity aside from lack of predominantly negative between-outburst mood. Aggression has most prominently been defined as a behavior intended to cause another person harm.[84][85] Temper outbursts are intense, transient, negative affective expressions that often involve emotional, unplanned aggression and other affective displays. They have developmentally specific presentations, time course, and indicators for pathology.[86] In the general population, trait aggression diverges from trait irritability[87][88] and in pediatric clinical populations.[7][89][90] More specifically, aggression is not necessarily observed during outbursts in clinical populations, where for example, property destruction, self harm, and negative self-talk are also reported by caregivers[79]. In sum, AIR differs from DMDD in highlighting the importance of aggression during extreme affective reactions to provocation. This distinction has promise in that aggression is readily observable, especially when directed towards peers,[91] and has predictive value for psychopathology.

Conclusion

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Future research should examine the RDC of AIR in prospective field trials in a variety of clinical settings. These trials will provide additional data on the number of specific criteria needed to identify youth with AIR, as well as duration of illness, frequency of outbursts and age of onset, as these were selected via expert opinion and informed by criteria of other disruptive behavior problems rather than empirically defined. It is important to test these criteria in the general population of young children as well, since tantrums can occur as a part of normal early development. As comorbidity is usually the rule, rather than the exception, we recommend that future studies explore increases in impairment resulting from additive effects between AIR and other diagnoses. It is important to understand the longitudinal course and prognosis of AIR, including whether AIR in childhood leads to the development of IED later in adolescence or adulthood. Perhaps the most crucial question that needs to be answered is how to best help children with AIR and their families.

TABLE 1
Diagnosis Similarities Differences
IED Failure to control aggressive impulses Increased frequency of aggressive outbursts in AIR
Presence of both verbal and physical aggression Low frequency of physical aggression in IED (3 times a year)
Aggressive outbursts are not premeditated Specific details in description of aggressive outbursts in AIR
Age of onset is under 10 years (starting age 6 in IED) Presence of symptoms in 2 settings in AIR
Exclusion of mood disorders and psychotic disorders
CD Presence of both verbal and physical aggression Focus on premeditated aggression, deliberate behavior to cause harm and violation of rules in CD
Age of onset prior to 10 years Inclusion other symptoms, such as of cruelty, stealing, lying, deliberate fire setting in CD
Exclusion of mood, anxiety and psychotic diagnoses in AIR
Presence of symptoms in 2 settings in AIR
CD diagnosis does not exclude mood disorders
DMDD Outbursts may include verbal and physical aggression Mood state between temper outbursts is euthymic in AIR and irritable in DMDD
Presence of symptoms in 2 settings Frequency of outbursts 3 or more times a week in DMDD and 5 times a week in AIR
Exclusion of other mood disorders, including BD Diagnosis of DMDD cannot be made prior to age 6 years
TABLE 1. Comparison between proposed AIR criteria to existing DSM-5 diagnoses of IED, CD, and DMDD
Note: IED = Intermittent Explosive Disorder, CD = Conduct Disorder, DMDD = Disruptive Mood Dysregulation Disorder, AIR = Aggression with Impulsivity and Reactivity
TABLE 2
Youth Demographics Stanley (N=392) ABACAB (N=636) LAMS (N=636)
Race

Native American/Alaskan

Asian

Black/African American

Pacific Islander

White

0

1

46

1

326

0

2

435

2

157

20

6

210

2

437

Ethnicity

Hispanic/Latino

Not Hispanic/Latino

5 11 32
Age 11.4 (3.3) 11.1 (3.3) 9.4 (1.9)
Family Income $36,700 $18,400
Gender (M) 240 387 477
TABLE 2. Demographic characteristics of Stanley, ABACAB and LAMS samples
Diagram of how symptoms of Aggression that is Impulsive/Reactive (AIR) differ from other common diagnoses
FIGURE 1. Overlap between symptoms of AIR and other diagnoses in the DSM 5
Note. Each box in the middle represents one of the diagnostic criteria of AIR. Boxes and arrows on the left show overlap of symptoms between related diagnostic constructs and AIR. Dotted line represents the difference between specific behaviors in the diagnosis of CD and AIR.
IED = Intermittent Explosive Disorder, CD = Conduct Disorder, DMDD = Disruptive Mood Dysregulation Disorder, AIR = Aggression with Impulsivity and Reactivity

Discussion

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References

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  1. ↑ Tremblay, Richard E.; Nagin, Daniel S.; Séguin, Jean R.; Zoccolillo, Mark; Zelazo, Philip D.; Boivin, Michel; Pérusse, Daniel; Japel, Christa (2005-2). "Physical Aggression During Early Childhood: Trajectories and Predictors". The Canadian child and adolescent psychiatry review 14 (1): 3–9. ISSN 1716-9119. PMID 19030494. PMC 2538721. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2538721/. 
  2. ↑ 2.0 2.1 Connor, Daniel F. (2002). Aggression and antisocial behavior in children and adolescents : research and treatment. New York: Guilford Press. ISBN 1-57230-738-2. OCLC 49305842. https://www.worldcat.org/oclc/49305842. 
  3. ↑ "Subtyping aggression in children and adolescents". The Journal of Neuropsychiatry and Clinical Neurosciences 2 (2): 189–192. 1990-05. doi:10.1176/jnp.2.2.189. ISSN 0895-0172. http://psychiatryonline.org/doi/abs/10.1176/jnp.2.2.189. 
  4. ↑ Smeets, K. C.; Oostermeijer, S.; Lappenschaar, M.; Cohn, M.; van der Meer, J. M. J.; Popma, A.; Jansen, L. M. C.; Rommelse, N. N. J. et al. (2017-01). "Are Proactive and Reactive Aggression Meaningful Distinctions in Adolescents? A Variable- and Person-Based Approach". Journal of Abnormal Child Psychology 45 (1): 1–14. doi:10.1007/s10802-016-0149-5. ISSN 0091-0627. PMID 27113216. PMC PMC5219021. http://link.springer.com/10.1007/s10802-016-0149-5. 
  5. ↑ Poulin, François; Boivin, Michel (2000-06). "Reactive and proactive aggression: Evidence of a two-factor model.". Psychological Assessment 12 (2): 115–122. doi:10.1037/1040-3590.12.2.115. ISSN 1939-134X. http://doi.apa.org/getdoi.cfm?doi=10.1037/1040-3590.12.2.115. 
  6. ↑ Connor, Daniel F.; Steingard, Ronald J.; Cunningham, Julie A.; Anderson, Jennifer J.; Melloni, Richard H. (2004-04). "Proactive and Reactive Aggression in Referred Children and Adolescents.". American Journal of Orthopsychiatry 74 (2): 129–136. doi:10.1037/0002-9432.74.2.129. ISSN 1939-0025. http://doi.apa.org/getdoi.cfm?doi=10.1037/0002-9432.74.2.129. 
  7. ↑ 7.0 7.1 7.2 7.3 Evans, Spencer C.; Roberts, Michael C.; Keeley, Jared W.; Rebello, Tahilia J.; Peña, Francisco; Lochman, John E.; Burke, Jeffrey D.; Fite, Paula J. et al. (2021-03). "Diagnostic classification of irritability and oppositionality in youth: a global field study comparing ICD‐11 with ICD‐10 and DSM‐5". Journal of Child Psychology and Psychiatry 62 (3): 303–312. doi:10.1111/jcpp.13244. ISSN 0021-9630. PMID 32396664. PMC PMC7657976. https://onlinelibrary.wiley.com/doi/10.1111/jcpp.13244. 
  8. ↑ Barker, Edward D.; Tremblay, Richard E.; Nagin, Daniel S.; Vitaro, Frank; Lacourse, Eric (2006-01-30). "Development of male proactive and reactive physical aggression during adolescence: Proactive and reactive aggression". Journal of Child Psychology and Psychiatry 47 (8): 783–790. doi:10.1111/j.1469-7610.2005.01585.x. https://onlinelibrary.wiley.com/doi/10.1111/j.1469-7610.2005.01585.x. 
  9. ↑ Connor, Daniel F.; Newcorn, Jeffrey H.; Saylor, Keith E.; Amann, Birgit H.; Scahill, Lawrence; Robb, Adelaide S.; Jensen, Peter S.; Vitiello, Benedetto et al. (2019-10-01). "Maladaptive Aggression: With a Focus on Impulsive Aggression in Children and Adolescents". Journal of Child and Adolescent Psychopharmacology 29 (8): 576–591. doi:10.1089/cap.2019.0039. ISSN 1044-5463. PMID 31453715. PMC PMC6786344. https://www.liebertpub.com/doi/10.1089/cap.2019.0039. 
  10. ↑ Kempes, Maaike; Matthys, Walter; de Vries, Han; van Engeland, Herman (2005-02). "Reactive and proactive aggression in children A review of theory, findings and the relevance for child and adolescent psychiatry". European Child & Adolescent Psychiatry 14 (1): 11–19. doi:10.1007/s00787-005-0432-4. ISSN 1018-8827. http://link.springer.com/10.1007/s00787-005-0432-4. 
  11. ↑ 11.0 11.1 Vitaro, Frank; Brendgen, Mara; Barker, Edward D. (2006-01). "Subtypes of aggressive behaviors: A developmental perspective". International Journal of Behavioral Development 30 (1): 12–19. doi:10.1177/0165025406059968. ISSN 0165-0254. http://journals.sagepub.com/doi/10.1177/0165025406059968. 
  12. ↑ Hubbard, Julie A.; McAuliffe, Meghan D.; Morrow, Michael T.; Romano, Lydia J. (2010-02). "Reactive and Proactive Aggression in Childhood and Adolescence: Precursors, Outcomes, Processes, Experiences, and Measurement". Journal of Personality 78 (1): 95–118. doi:10.1111/j.1467-6494.2009.00610.x. https://onlinelibrary.wiley.com/doi/10.1111/j.1467-6494.2009.00610.x. 
  13. ↑ 13.0 13.1 Card, Noel A.; Little, Todd D. (2006-09). "Proactive and reactive aggression in childhood and adolescence: A meta-analysis of differential relations with psychosocial adjustment". International Journal of Behavioral Development 30 (5): 466–480. doi:10.1177/0165025406071904. ISSN 0165-0254. http://journals.sagepub.com/doi/10.1177/0165025406071904. 
  14. ↑ 14.0 14.1 Fite, Paula J.; Stoppelbein, Laura; Greening, Leilani (2009-03-17). "Proactive and Reactive Aggression in a Child Psychiatric Inpatient Population". Journal of Clinical Child & Adolescent Psychology 38 (2): 199–205. doi:10.1080/15374410802698461. ISSN 1537-4416. PMID 19283598. PMC PMC2664256. https://www.tandfonline.com/doi/full/10.1080/15374410802698461. 
  15. ↑ Fite, Paula J.; Raine, Adrian; Stouthamer-Loeber, Magda; Loeber, Rolf; Pardini, Dustin A. (2010-02). "Reactive and Proactive Aggression in Adolescent Males: Examining Differential Outcomes 10 Years Later in Early Adulthood". Criminal Justice and Behavior 37 (2): 141–157. doi:10.1177/0093854809353051. ISSN 0093-8548. PMID 20589225. PMC PMC2892867. http://journals.sagepub.com/doi/10.1177/0093854809353051. 
  16. ↑ Blair, R. J. R. (2010-08-01). "Psychopathy, frustration, and reactive aggression: The role of ventromedial prefrontal cortex". British Journal of Psychology 101 (3): 383–399. doi:10.1348/000712609X418480. http://doi.wiley.com/10.1348/000712609X418480. 
  17. ↑ Harenski, Carla L.; Harenski, Keith A.; Kiehl, Kent A. (2014-10). "Neural processing of moral violations among incarcerated adolescents with psychopathic traits". Developmental Cognitive Neuroscience 10: 181–189. doi:10.1016/j.dcn.2014.09.002. PMID 25279855. PMC PMC4252617. https://linkinghub.elsevier.com/retrieve/pii/S1878929314000656. 
  18. ↑ 18.0 18.1 18.2 18.3 Waschbusch, Daniel A. (2002). "A meta-analytic examination of comorbid hyperactive-impulsive-attention problems and conduct problems.". Psychological Bulletin 128 (1): 118–150. doi:10.1037/0033-2909.128.1.118. ISSN 1939-1455. http://doi.apa.org/getdoi.cfm?doi=10.1037/0033-2909.128.1.118. 
  19. ↑ 19.0 19.1 Nigg, Joel T.; Karalunas, Sarah L.; Gustafsson, Hanna C.; Bhatt, Priya; Ryabinin, Peter; Mooney, Michael A.; Faraone, Stephen V.; Fair, Damien A. et al. (2020-02). "Evaluating chronic emotional dysregulation and irritability in relation to ADHD and depression genetic risk in children with ADHD". Journal of Child Psychology and Psychiatry 61 (2): 205–214. doi:10.1111/jcpp.13132. ISSN 0021-9630. PMID 31605387. PMC PMC6980250. https://onlinelibrary.wiley.com/doi/10.1111/jcpp.13132. 
  20. ↑ Hartley, Chelsey M.; Pettit, Jeremy W.; Castellanos, Daniel (2018-02). "Reactive Aggression and Suicide‐Related Behaviors in Children and Adolescents: A Review and Preliminary Meta‐Analysis". Suicide and Life-Threatening Behavior 48 (1): 38–51. doi:10.1111/sltb.12325. ISSN 0363-0234. PMID 28044358. PMC PMC7894982. https://onlinelibrary.wiley.com/doi/10.1111/sltb.12325. 
  21. ↑ 21.0 21.1 Carlson, Gabrielle A. (2009-12). "Are Children With Severe Outbursts Diagnostically Homeless?". Child and Adolescent Psychopharmacology News 14 (6): 1–7. doi:10.1521/capn.2009.14.6.1. ISSN 1085-0295. http://guilfordjournals.com/doi/10.1521/capn.2009.14.6.1. 
  22. ↑ 22.0 22.1 American Psychiatric Association (2013-05-22). Diagnostic and Statistical Manual of Mental Disorders (in en) (Fifth Edition ed.). American Psychiatric Association. doi:10.1176/appi.books.9780890425596. ISBN 978-0-89042-555-8. https://psychiatryonline.org/doi/book/10.1176/appi.books.9780890425596. 
  23. ↑ 23.0 23.1 World Health Organization. International Classification of Diseases for Mortality and Morbidity Statistics. 11th ed.; 2020. https://icd.who.int/browse11/l-m/en
  24. ↑ 24.0 24.1 24.2 Young, Andrea S.; Youngstrom, Eric A.; Findling, Robert L.; Van Eck, Kathryn; Kaplin, Dana; Youngstrom, Jennifer K.; Calabrese, Joseph; Stepanova, Ekaterina et al. (2020-11-01). "Developing and Validating a Definition of Impulsive/Reactive Aggression in Youth". Journal of Clinical Child & Adolescent Psychology 49 (6): 787–803. doi:10.1080/15374416.2019.1622121. ISSN 1537-4416. PMID 31343896. PMC PMC6980978. https://www.tandfonline.com/doi/full/10.1080/15374416.2019.1622121. 
  25. ↑ 25.0 25.1 Campbell, Magda (1984-07-01). "Behavioral Efficacy of Haloperidol and Lithium Carbonate: A Comparison in Hospitalized Aggressive Children With Conduct Disorder". Archives of General Psychiatry 41 (7): 650. doi:10.1001/archpsyc.1984.01790180020002. ISSN 0003-990X. http://archpsyc.jamanetwork.com/article.aspx?doi=10.1001/archpsyc.1984.01790180020002. 
  26. ↑ 26.0 26.1 Loeber, Rolf; Burke, Jeffrey D.; Lahey, Benjamin B.; Winters, Alaina; Zera, Marcie (2000-12). "Oppositional Defiant and Conduct Disorder: A Review of the Past 10 Years, Part I". Journal of the American Academy of Child & Adolescent Psychiatry 39 (12): 1468–1484. doi:10.1097/00004583-200012000-00007. https://linkinghub.elsevier.com/retrieve/pii/S0890856709604123. 
  27. ↑ Diagnostic and statistical manual of mental disorders.. American Psychiatric Association. Task Force on Nomenclature and Statistics, American Psychiatric Association. Committee on Nomenclature and Statistics (3d ed ed.). Washington, D.C.. 1980. ISBN 9780521315289. OCLC 643701118. https://www.worldcat.org/oclc/643701118. 
  28. ↑ Diagnostic and statistical manual of mental disorders : DSM-III-R.. American Psychiatric Association, American Psychiatric Association. Work Group to Revise DSM-III (Third edition, revised ed.). Washington, DC. 1987. ISBN 0-89042-018-1. OCLC 16395933. https://www.worldcat.org/oclc/16395933. 
  29. ↑ Diagnostic and statistical manual of mental disorders : DSM-IV.. American Psychiatric Association, American Psychiatric Association. Task Force on DSM-IV (4th ed ed.). Washington, DC: American Psychiatric Association. 1994. ISBN 0-89042-061-0. OCLC 29953039. https://www.worldcat.org/oclc/29953039. 
  30. ↑ Lahey, Benjamin B.; Loeber, Rolf; Quay, Herbert C.; Frick, Paul J.; Grimm, James (1992-05). "Oppositional Defiant and Conduct Disorders: Issues to be Resolved for DSM-IV". Journal of the American Academy of Child & Adolescent Psychiatry 31 (3): 539–546. doi:10.1097/00004583-199205000-00023. https://linkinghub.elsevier.com/retrieve/pii/S0890856709640351. 
  31. ↑ Frick, Paul J.; Nigg, Joel T. (2012-04-27). "Current Issues in the Diagnosis of Attention Deficit Hyperactivity Disorder, Oppositional Defiant Disorder, and Conduct Disorder". Annual Review of Clinical Psychology 8 (1): 77–107. doi:10.1146/annurev-clinpsy-032511-143150. ISSN 1548-5943. PMID 22035245. PMC PMC4318653. https://www.annualreviews.org/doi/10.1146/annurev-clinpsy-032511-143150. 
  32. ↑ Murrie, Daniel C.; Cornell, Dewey G.; McCoy, Wendy K. (2005). "Psychopathy, Conduct Disorder, and Stigma: Does Diagnostic Labeling Influence Juvenile Probation Officer Recommendations?". Law and Human Behavior 29 (3): 323–342. doi:10.1007/s10979-005-2415-x. ISSN 1573-661X. http://doi.apa.org/getdoi.cfm?doi=10.1007/s10979-005-2415-x. 
  33. ↑ 33.0 33.1 Kim-Cohen, Julia; Arseneault, Louise; Newcombe, Rhiannon; Adams, Felicity; Bolton, Heather; Cant, Lisa; Delgado, Kira; Freeman, Jo et al. (2009-05). "Five-year predictive validity of DSM-IV conduct disorder research diagnosis in 4½–5-year-old children". European Child & Adolescent Psychiatry 18 (5): 284–291. doi:10.1007/s00787-008-0729-1. ISSN 1018-8827. PMID 19165535. PMC PMC4212821. http://link.springer.com/10.1007/s00787-008-0729-1. 
  34. ↑ 34.0 34.1 Moffitt, Terrie E.; and in alphabetical order; Arseneault, Louise; Jaffee, Sara R.; Kim-Cohen, Julia; Koenen, Karestan C.; Odgers, Candice L.; Slutske, Wendy S. et al. (2008-01). "Research Review: DSM-V conduct disorder: research needs for an evidence base". Journal of Child Psychology and Psychiatry 49 (1): 3–33. doi:10.1111/j.1469-7610.2007.01823.x. PMID 18181878. PMC PMC2822647. https://onlinelibrary.wiley.com/doi/10.1111/j.1469-7610.2007.01823.x. 
  35. ↑ 35.0 35.1 35.2 Lahey, Benjamin B.; Loeber, Rolf; Quay, Herbert C.; Applegate, Brooks; Shaffer, David; Waldman, Irwin; Hart, Elizabeth L.; Mcburnett, Keith et al. (1998-04). "Validity of DSM‐IV Subtypes of Conduct Disorder Based on Age of Onset". Journal of the American Academy of Child & Adolescent Psychiatry 37 (4): 435–442. doi:10.1097/00004583-199804000-00022. https://linkinghub.elsevier.com/retrieve/pii/S0890856709630525. 
  36. ↑ Shaw, Daniel S.; Lacourse, Eric; Nagin, Daniel S. (2005-09). "Developmental trajectories of conduct problems and hyperactivity from ages 2 to 10". Journal of Child Psychology and Psychiatry 46 (9): 931–942. doi:10.1111/j.1469-7610.2004.00390.x. ISSN 0021-9630. https://onlinelibrary.wiley.com/doi/10.1111/j.1469-7610.2004.00390.x. 
  37. ↑ 37.0 37.1 Stewart, Mark A. (1985). "Aggressive conduct disorder: A brief review". Aggressive Behavior 11 (4): 323–331. doi:10.1002/1098-2337(1985)11:4<323::AID-AB2480110407>3.0.CO;2-W. ISSN 1098-2337. https://onlinelibrary.wiley.com/doi/abs/10.1002/1098-2337%281985%2911%3A4%3C323%3A%3AAID-AB2480110407%3E3.0.CO%3B2-W. 
  38. ↑ Costello, E. Jane; Mustillo, Sarah; Erkanli, Alaattin; Keeler, Gordon; Angold, Adrian (2003-08-01). "Prevalence and Development of Psychiatric Disorders in Childhood and Adolescence". Archives of General Psychiatry 60 (8): 837. doi:10.1001/archpsyc.60.8.837. ISSN 0003-990X. http://archpsyc.jamanetwork.com/article.aspx?doi=10.1001/archpsyc.60.8.837. 
  39. ↑ Nock, Matthew K.; Kazdin, Alan E.; Hiripi, Eva; Kessler, Ronald C. (2007-07). "Lifetime prevalence, correlates, and persistence of oppositional defiant disorder: results from the National Comorbidity Survey Replication". Journal of Child Psychology and Psychiatry 48 (7): 703–713. doi:10.1111/j.1469-7610.2007.01733.x. ISSN 0021-9630. https://onlinelibrary.wiley.com/doi/10.1111/j.1469-7610.2007.01733.x. 
  40. ↑ Burke, Jeffrey D.; Loeber, Rolf; Birmaher, Boris (2002-11). "Oppositional Defiant Disorder and Conduct Disorder: A Review of the Past 10 Years, Part II". Journal of the American Academy of Child & Adolescent Psychiatry 41 (11): 1275–1293. doi:10.1097/00004583-200211000-00009. https://linkinghub.elsevier.com/retrieve/pii/S089085670960633X. 
  41. ↑ Burke, Jeffrey D.; Boylan, Khrista; Rowe, Richard; Duku, Eric; Stepp, Stephanie D.; Hipwell, Alison E.; Waldman, Irwin D. (2014-11). "Identifying the irritability dimension of ODD: Application of a modified bifactor model across five large community samples of children.". Journal of Abnormal Psychology 123 (4): 841–851. doi:10.1037/a0037898. ISSN 1939-1846. PMID 25314267. PMC PMC4227955. http://doi.apa.org/getdoi.cfm?doi=10.1037/a0037898. 
  42. ↑ Evans, Spencer C.; Burke, Jeffrey D.; Roberts, Michael C.; Fite, Paula J.; Lochman, John E.; de la Peña, Francisco R.; Reed, Geoffrey M. (2017-04). "Irritability in child and adolescent psychopathology: An integrative review for ICD-11". Clinical Psychology Review 53: 29–45. doi:10.1016/j.cpr.2017.01.004. https://linkinghub.elsevier.com/retrieve/pii/S0272735816301659. 
  43. ↑ Stringaris, Argyris; Goodman, Robert (2009-04). "Longitudinal Outcome of Youth Oppositionality: Irritable, Headstrong, and Hurtful Behaviors Have Distinctive Predictions". Journal of the American Academy of Child & Adolescent Psychiatry 48 (4): 404–412. doi:10.1097/CHI.0b013e3181984f30. https://linkinghub.elsevier.com/retrieve/pii/S0890856709600484. 
  44. ↑ Evans, Spencer C.; Pederson, Casey A.; Fite, Paula J.; Blossom, Jennifer B.; Cooley, John L. (2016-06). "Teacher-Reported Irritable and Defiant Dimensions of Oppositional Defiant Disorder: Social, Behavioral, and Academic Correlates". School Mental Health 8 (2): 292–304. doi:10.1007/s12310-015-9163-y. ISSN 1866-2625. http://link.springer.com/10.1007/s12310-015-9163-y. 
  45. ↑ Achenbach, Thomas M. (2001). Manual for the ASEBA school-age forms & profiles : an integrated system of multi-informant assessment. Leslie Rescorla. Burlington, VT. ISBN 0-938565-73-7. OCLC 53902766. https://www.worldcat.org/oclc/53902766. 
  46. ↑ Conners 3rd, K. C. (2008). Conners 3rd edition manual. New York: Multi-Health Systems.
  47. ↑ Frick, Paul J.; Lahey, Benjamin B.; Loeber, Rolf; Tannenbaum, Lynne; Van Horn, Yolanda; Christ, Mary Anne G.; Hart, Elizabeth A.; Hanson, Kelly (1993-01). "Oppositional defiant disorder and conduct disorder: A meta-analytic review of factor analyses and cross-validation in a clinic sample". Clinical Psychology Review 13 (4): 319–340. doi:10.1016/0272-7358(93)90016-F. https://linkinghub.elsevier.com/retrieve/pii/027273589390016F. 
  48. ↑ Lahey, Benjamin B.; Rathouz, Paul J.; Van Hulle, Carol; Urbano, Richard C.; Krueger, Robert F.; Applegate, Brooks; Garriock, Holly A.; Chapman, Derek A. et al. (2008-02). "Testing Structural Models of DSM-IV Symptoms of Common Forms of Child and Adolescent Psychopathology". Journal of Abnormal Child Psychology 36 (2): 187–206. doi:10.1007/s10802-007-9169-5. ISSN 0091-0627. http://link.springer.com/10.1007/s10802-007-9169-5. 
  49. ↑ Althoff, Robert R.; Kuny-Slock, Ana V.; Verhulst, Frank C.; Hudziak, James J.; van der Ende, Jan (2014-10). "Classes of oppositional-defiant behavior: concurrent and predictive validity". Journal of Child Psychology and Psychiatry 55 (10): 1162–1171. doi:10.1111/jcpp.12233. PMID 24673629. PMC PMC4159429. https://onlinelibrary.wiley.com/doi/10.1111/jcpp.12233. 
  50. ↑ Aebi, Marcel; Barra, Steffen; Bessler, Cornelia; Steinhausen, Hans‐Christoph; Walitza, Susanne; Plattner, Belinda (2016-06). "Oppositional defiant disorder dimensions and subtypes among detained male adolescent offenders". Journal of Child Psychology and Psychiatry 57 (6): 729–736. doi:10.1111/jcpp.12473. ISSN 0021-9630. https://onlinelibrary.wiley.com/doi/10.1111/jcpp.12473. 
  51. ↑ 51.0 51.1 51.2 Schmoldt, A.; Benthe, H. F.; Haberland, G. (1975-09-01). "Digitoxin metabolism by rat liver microsomes". Biochemical Pharmacology 24 (17): 1639–1641. ISSN 1873-2968. PMID 10. https://pubmed.ncbi.nlm.nih.gov/10. 
  52. ↑ 52.0 52.1 King, Sara; Waschbusch, Daniel A (2010-10). "Aggression in children with attention-deficit/hyperactivity disorder". Expert Review of Neurotherapeutics 10 (10): 1581–1594. doi:10.1586/ern.10.146. ISSN 1473-7175. http://www.tandfonline.com/doi/full/10.1586/ern.10.146. 
  53. ↑ Murray, Aja Louise; Obsuth, Ingrid; Zirk-Sadowski, Jan; Ribeaud, Denis; Eisner, Manuel (2020-10). "Developmental Relations Between ADHD Symptoms and Reactive Versus Proactive Aggression Across Childhood and Adolescence". Journal of Attention Disorders 24 (12): 1701–1710. doi:10.1177/1087054716666323. ISSN 1087-0547. http://journals.sagepub.com/doi/10.1177/1087054716666323. 
  54. ↑ Gadow, Kenneth D.; Arnold, L. Eugene; Molina, Brooke S.G.; Findling, Robert L.; Bukstein, Oscar G.; Brown, Nicole V.; McNamara, Nora K.; Rundberg-Rivera, E. Victoria et al. (2014-09). "Risperidone Added to Parent Training and Stimulant Medication: Effects on Attention-Deficit/Hyperactivity Disorder, Oppositional Defiant Disorder, Conduct Disorder, and Peer Aggression". Journal of the American Academy of Child & Adolescent Psychiatry 53 (9): 948–959.e1. doi:10.1016/j.jaac.2014.05.008. PMID 25151418. PMC PMC4145805. https://linkinghub.elsevier.com/retrieve/pii/S0890856714003694. 
  55. ↑ Gadow, Kenneth D.; Brown, Nicole V.; Arnold, L. Eugene; Buchan-Page, Kristin A.; Bukstein, Oscar G.; Butter, Eric; Farmer, Cristan A.; Findling, Robert L. et al. (2016-06). "Severely Aggressive Children Receiving Stimulant Medication Versus Stimulant and Risperidone: 12-Month Follow-Up of the TOSCA Trial". Journal of the American Academy of Child & Adolescent Psychiatry 55 (6): 469–478. doi:10.1016/j.jaac.2016.03.014. PMID 27238065. PMC PMC4886346. https://linkinghub.elsevier.com/retrieve/pii/S089085671630106X. 
  56. ↑ Farmer, Cristan A.; Brown, Nicole V.; Gadow, Kenneth D.; Arnold, L. Eugene; Kolko, David G.; Findling, Robert L.; Molina, Brooke S.G.; Buchan-Page, Kristin A. et al. (2015-04). "Comorbid Symptomatology Moderates Response to Risperidone, Stimulant, and Parent Training in Children with Severe Aggression, Disruptive Behavior Disorder, and Attention-Deficit/Hyperactivity Disorder". Journal of Child and Adolescent Psychopharmacology 25 (3): 213–224. doi:10.1089/cap.2014.0109. ISSN 1044-5463. PMID 25885011. PMC PMC4403232. http://www.liebertpub.com/doi/10.1089/cap.2014.0109. 
  57. ↑ Findling, Robert L.; Townsend, Lisa; Brown, Nicole V.; Arnold, L. Eugene; Gadow, Kenneth D.; Kolko, David J.; McNamara, Nora K.; Gary, Devin S. et al. (2017-02). "The Treatment of Severe Childhood Aggression Study: 12 Weeks of Extended, Blinded Treatment in Clinical Responders". Journal of Child and Adolescent Psychopharmacology 27 (1): 52–65. doi:10.1089/cap.2016.0081. ISSN 1044-5463. PMID 28212067. PMC PMC5327034. http://www.liebertpub.com/doi/10.1089/cap.2016.0081. 
  58. ↑ Blader, Joseph C.; Schooler, Nina R.; Jensen, Peter S.; Pliszka, Steven R.; Kafantaris, Vivian (2009-12). "Adjunctive Divalproex Versus Placebo for Children With ADHD and Aggression Refractory to Stimulant Monotherapy". American Journal of Psychiatry 166 (12): 1392–1401. doi:10.1176/appi.ajp.2009.09020233. ISSN 0002-953X. PMID 19884222. PMC PMC2940237. http://psychiatryonline.org/doi/abs/10.1176/appi.ajp.2009.09020233. 
  59. ↑ Blader, J. C.; Pliszka, S. R.; Jensen, P. S.; Schooler, N. R.; Kafantaris, V. (2010-10-01). "Stimulant-Responsive and Stimulant-Refractory Aggressive Behavior Among Children With ADHD". PEDIATRICS 126 (4): e796–e806. doi:10.1542/peds.2010-0086. ISSN 0031-4005. PMID 20837589. PMC PMC2956067. https://publications.aap.org/pediatrics/article/126/4/e796-e806/65626. 
  60. ↑ Stocks, Jennifer Dugan; K. Taneja, Baldeo; Baroldi, Paolo; L. Findling, Robert (2012-04). "A Phase 2a Randomized, Parallel Group, Dose-Ranging Study of Molindone in Children with Attention-Deficit/Hyperactivity Disorder and Persistent, Serious Conduct Problems". Journal of Child and Adolescent Psychopharmacology 22 (2): 2. doi:10.1089/cap.2011.0087. ISSN 1044-5463. http://www.liebertpub.com/doi/10.1089/cap.2011.0087. 
  61. ↑ Malone, Richard P.; Luebbert, James F.; Delaney, Mary Anne; Biesecker, Krista A.; Blaney, Bridget L.; Rowan, Amy B.; Campbell, Magda (1997-02). "Nonpharmacological Response in Hospitalized Children With Conduct Disorder". Journal of the American Academy of Child & Adolescent Psychiatry 36 (2): 242–247. doi:10.1097/00004583-199702000-00015. https://linkinghub.elsevier.com/retrieve/pii/S0890856709628057. 
  62. ↑ Cueva, Jeanette E.; Overall, John E.; Small, Arthur M.; Armenteros, Jorge L.; Perry, Richard; Campbell, Magda (1996-04). "Carbamazepine in Aggressive Children with Conduct Disorder: A Double-Blind and Placebo-Controlled Study". Journal of the American Academy of Child & Adolescent Psychiatry 35 (4): 480–490. doi:10.1097/00004583-199604000-00014. https://linkinghub.elsevier.com/retrieve/pii/S0890856709635188. 
  63. ↑ Platt, Jane E.; Campbell, Magda; Green, Wayne H.; Perry, Richard; Cohen, Ira L. (1981-01). "Effects of Lithium Carbonate and Haloperidol on Cognition in Aggressive Hospitalized School-age Children*:". Journal of Clinical Psychopharmacology 1 (1): 8–13. doi:10.1097/00004714-198101000-00003. ISSN 0271-0749. http://journals.lww.com/00004714-198101000-00003. 
  64. ↑ Malone, Richard P.; Delaney, Mary Anne; Luebbert, James F.; Cater, Jacqueline; Campbell, Magda (2000-07-01). "A Double-Blind Placebo-Controlled Study of Lithium in Hospitalized Aggressive Children and Adolescents With Conduct Disorder". Archives of General Psychiatry 57 (7): 649. doi:10.1001/archpsyc.57.7.649. ISSN 0003-990X. http://archpsyc.jamanetwork.com/article.aspx?doi=10.1001/archpsyc.57.7.649. 
  65. ↑ Findling, Robert L.; Reed, Michael D.; O'Riordan, Mary Ann; Demeter, Christine A.; Stansbrey, Robert J.; Mcnamara, Nora K. (2006-07). "Effectiveness, Safety, and Pharmacokinetics of Quetiapine in Aggressive Children With Conduct Disorder". Journal of the American Academy of Child & Adolescent Psychiatry 45 (7): 792–800. doi:10.1097/01.chi.0000219832.23849.31. https://linkinghub.elsevier.com/retrieve/pii/S0890856709615252. 
  66. ↑ Klein, Rachel G. (1997-12-01). "Clinical Efficacy of Methylphenidate in Conduct Disorder With and Without Attention Deficit Hyperactivity Disorder". Archives of General Psychiatry 54 (12): 1073. doi:10.1001/archpsyc.1997.01830240023003. ISSN 0003-990X. http://archpsyc.jamanetwork.com/article.aspx?doi=10.1001/archpsyc.1997.01830240023003. 
  67. ↑ Reyes, Magali; Buitelaar, Jan; Toren, Paz; Augustyns, Ilse; Eerdekens, Marielle (2006-03). "A Randomized, Double-Blind, Placebo-Controlled Study of Risperidone Maintenance Treatment in Children and Adolescents With Disruptive Behavior Disorders". American Journal of Psychiatry 163 (3): 402–410. doi:10.1176/appi.ajp.163.3.402. ISSN 0002-953X. http://psychiatryonline.org/doi/abs/10.1176/appi.ajp.163.3.402. 
  68. ↑ Kessler, Ronald C.; Coccaro, Emil F.; Fava, Maurizio; Jaeger, Savina; Jin, Robert; Walters, Ellen (2006-06-01). "The Prevalence and Correlates of DSM-IV Intermittent Explosive Disorder in the National Comorbidity Survey Replication". Archives of General Psychiatry 63 (6): 669. doi:10.1001/archpsyc.63.6.669. ISSN 0003-990X. PMID 16754840. PMC PMC1924721. http://archpsyc.jamanetwork.com/article.aspx?doi=10.1001/archpsyc.63.6.669. 
  69. ↑ McLaughlin, Katie A.; Green, Jennifer Greif; Hwang, Irving; Sampson, Nancy A.; Zaslavsky, Alan M.; Kessler, Ronald C. (2012-11-01). "Intermittent Explosive Disorder in the National Comorbidity Survey Replication Adolescent Supplement". Archives of General Psychiatry 69 (11). doi:10.1001/archgenpsychiatry.2012.592. ISSN 0003-990X. PMID 22752056. PMC PMC3637919. http://archpsyc.jamanetwork.com/article.aspx?doi=10.1001/archgenpsychiatry.2012.592. 
  70. ↑ Oliver, Diane Graves; Caldwell, Cleopatra H.; Faison, Nakesha; Sweetman, Julie A.; Abelson, Jamie M.; Jackson, James S. (2016). "Prevalence of DSM-IV intermittent explosive disorder in Black adolescents: Findings from the National Survey of American Life, Adolescent Supplement.". American Journal of Orthopsychiatry 86 (5): 552–563. doi:10.1037/ort0000170. ISSN 1939-0025. PMID 27078052. PMC PMC5021557. http://doi.apa.org/getdoi.cfm?doi=10.1037/ort0000170. 
  71. ↑ Coccaro, Emil F. (2019-11). "Psychiatric comorbidity in Intermittent Explosive Disorder". Journal of Psychiatric Research 118: 38–43. doi:10.1016/j.jpsychires.2019.08.012. https://linkinghub.elsevier.com/retrieve/pii/S002239561930634X. 
  72. ↑ Olvera, Rene L; Pliszka, Steven R; Konyecsni, William M; Hernandez, Yadira; Farnum, Stacy; Tripp, Roger F (2001-04). "Validation of the Interview Module for Intermittent Explosive Disorder (M-IED) in children and adolescents: a pilot study". Psychiatry Research 101 (3): 259–267. doi:10.1016/S0165-1781(01)00224-4. https://linkinghub.elsevier.com/retrieve/pii/S0165178101002244. 
  73. ↑ 73.0 73.1 73.2 McElroy, Susan L.; Soutullo, Cesar A.; Beckman, DeAnna A.; Taylor, Purcell; Keck, Paul E. (1998-04-15). "DSM-IV Intermittent Explosive Disorder: A Report of 27 Cases". The Journal of Clinical Psychiatry 59 (4): 203–210. doi:10.4088/JCP.v59n0411. ISSN 0160-6689. http://article.psychiatrist.com/?ContentType=START&ID=10006061. 
  74. ↑ Coccaro, Emil F.; Posternak, Michael A.; Zimmerman, Mark (2005-10-15). "Prevalence and Features of Intermittent Explosive Disorder in a Clinical Setting". The Journal of Clinical Psychiatry 66 (10): 1221–1227. doi:10.4088/JCP.v66n1003. ISSN 0160-6689. http://article.psychiatrist.com/?ContentType=START&ID=10001473. 
  75. ↑ Galbraith, Todd; Carliner, Hannah; Keyes, Katherine M.; McLaughlin, Katie A.; McCloskey, Michael S.; Heimberg, Richard G. (2018-11). "The co-occurrence and correlates of anxiety disorders among adolescents with intermittent explosive disorder". Aggressive Behavior 44 (6): 581–590. doi:10.1002/ab.21783. PMID 30040122. PMC PMC6249027. https://onlinelibrary.wiley.com/doi/10.1002/ab.21783. 
  76. ↑ Wozniak, Janet; Biederman, Joseph; Kiely, Kathleen; Ablon, J. Stuart; Faraone, Stephen V.; Mundy, Elizabeth; Mennin, Douglas (1995-07). "Mania-Like Symptoms Suggestive of Childhood-Onset Bipolar Disorder in Clinically Referred Children". Journal of the American Academy of Child & Adolescent Psychiatry 34 (7): 867–876. doi:10.1097/00004583-199507000-00010. https://linkinghub.elsevier.com/retrieve/pii/S0890856709635978. 
  77. ↑ Stringaris, Argyris; Baroni, Argelinda; Haimm, Caroline; Brotman, Melissa; Lowe, Catherine H.; Myers, Frances; Rustgi, Eileen; Wheeler, Wanda et al. (2010-04). "Pediatric bipolar disorder versus severe mood dysregulation: risk for manic episodes on follow-up". Journal of the American Academy of Child and Adolescent Psychiatry 49 (4): 397–405. ISSN 1527-5418. PMID 20410732. PMC 3000433. https://pubmed.ncbi.nlm.nih.gov/20410732. 
  78. ↑ Leibenluft, Ellen; Stoddard, Joel (2013-11). "The developmental psychopathology of irritability". Development and Psychopathology 25 (4pt2): 1473–1487. doi:10.1017/S0954579413000722. ISSN 0954-5794. PMID 24342851. PMC PMC4476313. https://www.cambridge.org/core/product/identifier/S0954579413000722/type/journal_article. 
  79. ↑ 79.0 79.1 Laporte, Paola Paganella; Matijasevich, Alicia; Munhoz, Tiago N.; Santos, Iná S.; Barros, Aluísio J.D.; Pine, Daniel Samuel; Rohde, Luis Augusto; Leibenluft, Ellen et al. (2021-02). "Disruptive Mood Dysregulation Disorder: Symptomatic and Syndromic Thresholds and Diagnostic Operationalization". Journal of the American Academy of Child & Adolescent Psychiatry 60 (2): 286–295. doi:10.1016/j.jaac.2019.12.008. https://linkinghub.elsevier.com/retrieve/pii/S0890856720300630. 
  80. ↑ Cardinale, Elise M.; Freitag, Gabrielle F.; Brotman, Melissa A.; Pine, Daniel S.; Leibenluft, Ellen; Kircanski, Katharina (2021-01). "Phasic Versus Tonic Irritability: Differential Associations With Attention-Deficit/Hyperactivity Disorder Symptoms". Journal of the American Academy of Child & Adolescent Psychiatry: S0890856721000022. doi:10.1016/j.jaac.2020.11.022. https://linkinghub.elsevier.com/retrieve/pii/S0890856721000022. 
  81. ↑ Schmoldt, A.; Benthe, H. F.; Haberland, G. (1975-09-01). "Digitoxin metabolism by rat liver microsomes". Biochemical Pharmacology 24 (17): 1639–1641. ISSN 1873-2968. PMID 10. https://pubmed.ncbi.nlm.nih.gov/10. 
  82. ↑ Connor, Daniel F.; Newcorn, Jeffrey H.; Saylor, Keith E.; Amann, Birgit H.; Scahill, Lawrence; Robb, Adelaide S.; Jensen, Peter S.; Vitiello, Benedetto et al. (2019-10-01). "Maladaptive Aggression: With a Focus on Impulsive Aggression in Children and Adolescents". Journal of Child and Adolescent Psychopharmacology 29 (8): 576–591. doi:10.1089/cap.2019.0039. ISSN 1044-5463. PMID 31453715. PMC PMC6786344. https://www.liebertpub.com/doi/10.1089/cap.2019.0039. 
  83. ↑ 83.0 83.1 Connor, Daniel F.; McLaughlin, Thomas J. (2006-09). "Aggression and Diagnosis in Psychiatrically Referred children". Child Psychiatry and Human Development 37 (1): 1–14. doi:10.1007/s10578-006-0015-8. ISSN 0009-398X. http://link.springer.com/10.1007/s10578-006-0015-8. 
  84. ↑ Olweus, Dan (1979). "Stability of aggressive reaction patterns in males: A review.". Psychological Bulletin 86 (4): 852–875. doi:10.1037/0033-2909.86.4.852. ISSN 1939-1455. http://doi.apa.org/getdoi.cfm?doi=10.1037/0033-2909.86.4.852. 
  85. ↑ Berkowitz, Leonard (2012-07). "A Different View of Anger: The Cognitive-Neoassociation Conception of the Relation of Anger to Aggression: A Different View of Anger". Aggressive Behavior 38 (4): 322–333. doi:10.1002/ab.21432. https://onlinelibrary.wiley.com/doi/10.1002/ab.21432. 
  86. ↑ Potegal, Michael (2019-04). Roy, Amy Krain. ed. On Being Mad, Sad, and Very Young (in en). Oxford University Press. pp. 105–146. doi:10.1093/med-psych/9780190846800.003.0007. ISBN 978-0-19-084680-0. http://www.oxfordclinicalpsych.com/view/10.1093/med-psych/9780190846800.001.0001/med-9780190846800-chapter-7. 
  87. ↑ Bettencourt, B. Ann; Talley, Amelia; Benjamin, Arlin James; Valentine, Jeffrey (2006-09). "Personality and aggressive behavior under provoking and neutral conditions: A meta-analytic review.". Psychological Bulletin 132 (5): 751–777. doi:10.1037/0033-2909.132.5.751. ISSN 1939-1455. http://doi.apa.org/getdoi.cfm?doi=10.1037/0033-2909.132.5.751. 
  88. ↑ Bolhuis, Koen; Lubke, Gitta H.; van der Ende, Jan; Bartels, Meike; van Beijsterveldt, Catharina E.M.; Lichtenstein, Paul; Larsson, Henrik; Jaddoe, Vincent W.V. et al. (2017-08). "Disentangling Heterogeneity of Childhood Disruptive Behavior Problems Into Dimensions and Subgroups". Journal of the American Academy of Child & Adolescent Psychiatry 56 (8): 678–686. doi:10.1016/j.jaac.2017.05.019. https://linkinghub.elsevier.com/retrieve/pii/S0890856717302472. 
  89. ↑ Van Meter, Anna R.; Burke, Coty; Youngstrom, Eric A.; Faedda, Gianni L.; Correll, Christoph U. (2016-07). "The Bipolar Prodrome: Meta-Analysis of Symptom Prevalence Prior to Initial or Recurrent Mood Episodes". Journal of the American Academy of Child & Adolescent Psychiatry 55 (7): 543–555. doi:10.1016/j.jaac.2016.04.017. https://linkinghub.elsevier.com/retrieve/pii/S089085671630171X. 
  90. ↑ Wiggins, Jillian Lee; Briggs-Gowan, Margaret J.; Brotman, Melissa A.; Leibenluft, Ellen; Wakschlag, Lauren S. (2021-03). "Toward a Developmental Nosology for Disruptive Mood Dysregulation Disorder in Early Childhood". Journal of the American Academy of Child & Adolescent Psychiatry 60 (3): 388–397. doi:10.1016/j.jaac.2020.04.015. PMID 32599006. PMC PMC7769590. https://linkinghub.elsevier.com/retrieve/pii/S0890856720303464. 
  91. ↑ Coie, John D.; Dodge, Kenneth A.; Terry, Robert; Wright, Virginia (1991-08). "The Role of Aggression in Peer Relations: An Analysis of Aggression Episodes in Boys' Play Groups". Child Development 62 (4): 812. doi:10.2307/1131179. https://www.jstor.org/stable/1131179?origin=crossref. 
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