Sage Journals: Discover world-class research

Abstract

Objective:

Irritability is an important theme in paediatric psychiatry considering its high frequency in developmental age, its association with negative outcomes and consequently significant public health impact. Present as main or associated feature of several psychiatric diagnoses, irritability represents a challenge for clinicians who try to understand its origin and role in developmental psychopathology. In this review we try to: (1) get an overview of this dimension and its relationship with each of the main neuropsychiatric disorders in paediatric population and (2) provide a summary of currently available instruments to assess irritability in children and adolescents.

Method:

In this narrative review, an overview of irritability in children and adolescents is proposed focusing on selected literature.

Results:

Irritability as feature of many paediatric psychiatric conditions has been evaluated by many authors and included in classifications of paediatric psychiatric diseases. Framework of irritability evolved over time and dimension of irritability has been investigated using different tools and methodologies, both qualitative and quantitative. Metrics of irritability as clinical dimension are important in the diagnostic process of paediatric diseases.

Conclusion:

Investigating the presence of irritability in all children with related disorders is mandatory if we consider the risk for functional impairment and affective and behavioural disorders associated with high levels of irritability. Using rigid threshold in developmental age to differentiate physiological from pathological irritability could lead many children having subthreshold levels of irritability to receive no diagnosis and, consequently, no treatment where instead a dimensional approach to irritability could allow to identify prodromal phase and prevent the evolution towards clinical pathological expressions.

Keywords

Irritability depression disruptive mood dysregulation disorder developmental psychopathology transdiagnostic

Introduction

Clinically significant irritability, intended as low frustration threshold and anger, which results in frequent, severe developmentally inappropriate temper outbursts, is one of the main reasons, if not the main one, for requesting consultation at child and adolescent mental health services (Mikita and Stringaris, 2013; Peterson et al., 1996; Roy et al., 2019).

Irritable mood and related behaviours are physiologically present during early childhood, a fundamental and unrepeatable period for the evolution of the individual, for the rapid development of the brain and the growing ability in emotion regulation. The increase of one’s motor, intellectual and cognitive abilities and the rising awareness of one’s own possibilities inevitably leads to clash with one’s own limits, generating frustration. As the child gets closer to school age, an increasingly important self-control of one’s actions, as well as of one’s feelings, is required, not always so easy. The modulation of irritability is therefore a capacity that presupposes the maturation, during preschool age, of cortical structures that mediate the emotional and behavioural regulation. Irritability, whims and emotional dyscontrol are frequently found in developmental age both in outpatient samples and in the general population, but with significant qualitative and quantitative differences (Carlson et al., 2016). Until the publication of the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5), there was no nosological condition characterized primarily and fundamentally by severe chronic irritability. However, irritability was present, and still is, as a requirement or associated feature of more than a dozen psychiatric diagnoses, many of which are frequently found in the child and adolescent population.

Irritability is, in fact, at a crossroads of both humoral and behavioural disorders of the developmental age. Studying the pathogenesis, pathophysiology and dimensionality of irritability in each of these disorders and over and above them, in an overall view, allows on one hand to better understand and characterize the individual disorders, and, on the other hand, to go beyond the boundaries of each diagnosis in order to have a unified definition of this dimension.

Here we will address, in a synthetic and focused way, the relationship between irritability and each of the main neuropsychiatric disorders, both internalizing and externalizing, related to it, and then try to get an overview.

Irritability and depression

The association between irritability and depression has a long history. The irritable dimension is strongly associated with contextual and subsequent problems of internalization and mood disorders, especially depression, as affirmed by several authors (Aebi et al., 2013, 2016; Althoff et al., 2014; Burke, 2012; Burke et al., 2010; Drabick and Gadow, 2012; Ezpeleta et al., 2012, 2016; Kolko and Pardini, 2010; Krieger and Stringaris, 2013; Kuny et al., 2013; Lavigne et al., 2014; Leadbeater and Homel, 2015; Leibenluft, 2011; Liu et al., 2019; Rowe et al., 2010; Savage et al., 2015; Stringaris and Goodman, 2009a, 2009b; Stringaris and Vidal-Ribas, 2019; Vidal-Ribas et al., 2016; Whelan et al., 2013); Diagnostic and Statistical Manual of Mental Disorders (DSM) itself considers irritable mood as a criterion for the diagnosis of depression in childhood.

According to Masi et al. (2003), irritability would be the most frequent symptom of depression in childhood, present in 82% of male children and 91% of female children with depression.

Moreover, it has been seen that the relationship between a maternal history of depression and the development of depression in adolescence is partly mediated by the presence of irritability in childhood (Whelan et al., 2015).

In particular, in a study conducted on twins, it has been hypothesized by (Stringaris et al., 2012b) that irritability and depression share the same genetic basis: they share the same ‘generalist genes’, i.e. genes with a general and not specific effect in a single disorder, which therefore exert very broad effects, giving rise to closely related phenotypes. This hypothesis on the sharing genes has been already advanced for anxiety and depression (Kendler, 1996). Shared generalist genes for irritability and depression could well explain the partial phenotypic overlap, but, while sharing the same genetic susceptibility, depression and irritability could differ in their phenotypic expressions due to unique environmental factors. In another study on twins (Savage et al., 2015), it has been shown that the impact of irritability on future internalizing symptoms is greater than that of internalizing symptoms on future irritability. In the authors’ opinion, these data support a causal role of irritability towards anxiety and depression.

It is therefore still questionable whether irritability is actually a determining factor for the future development of depression or rather whether irritability and depression are at different stages of the same longitudinal psychopathological path.

In both cases, it is legitimate to ask whether the depression preceded by irritability is to be considered as the depression diagnosed in the absence of irritable symptoms, contextual or previous, or whether it is a nosological category worthy of a specific classification and treatment.

Irritability and early bipolar disorder

For a long time, serious irritability has been considered the main symptom of bipolar disorder (BD) in children. This has been recognized as one of the major causes of increased diagnosis of BD in paediatric age in the period of transition from the old to the new millennium. Starting in the mid-1990s, in fact, there was a change in the early BD characterization: Wozniak et al. (1995) argued that bipolar children often lacked the typical episodicity present in adults and that the mania was presented, rather, in the form of a constant emotional dysregulation, accompanied by severe irritability, whether episodic or not.

This new conceptualization of early BD led to a drastic increase in its epidemiology (in the United States the diagnosis of BDs in childhood increased by 500%) (Blader and Carlson, 2007; Moreno et al., 2007) and to important problems in differential diagnosis, both with attention-deficit hyperactivity disorder (ADHD), whose symptoms were often in comorbidity, and with disruptive behaviour disorders (DBD), in particular with the oppositional defiant disorder (ODD), which better captured the phenotype of severe emotional dysregulation.

The result was a heated debate among those who were in favour of considering chronic and severe irritability as part of the expression of BD in developmental age and those who believed it is necessary to differentiate chronic emotional dysregulation and severe irritability without other typical symptoms of mania or hypomania from the typical BD; for those clinicians, BD in developmental age should maintain the same criteria of episodicity characteristic in adults.

In 2003, Leibenluft et al. (2003) proposed to differentiate mania in developmental age into three phenotypes:

the phenotype ‘narrow’, which reflected the adult pattern of episodicity and expanded mood;

the phenotype ‘intermediate’, which was atypical either for the presence of episodes of irritability, rather than euphoria, or for the duration of the episodes of euphoric excitement, shorter than the classic Manic Episode according to Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria;

the phenotype ‘broad’, which presented with a chronic or sub-continuous course and a mood characterized mainly by irritability and dysphoria. This phenotype was also described as ‘Severe Mood and Behavioral Dysregulation’.

In 2011, Leibenluft (2011) highlighted how children with severe mood dysregulation (SMD) showed clinical evolution, familiarity and pathophysiology different from children diagnosed with BD. In particular, SMD was found to be predictive of future depression, and, to a lesser extent, of anxiety disorders. Therefore, it was necessary to differentiate nosologically this particular phenotype of children, so in the drafting of the fifth edition of the DSM (American Psychiatric Association, 2013) a new diagnosis was introduced within the chapter of depressive disorders: disruptive mood dysregulation disorder (DMDD).

However, if the definition of SMD was based on three fundamental characteristics (temper outbursts, negative mood and hyperactivity), there is no hyperactivity in DMDD criteria and there is not even the exclusion criterion of an IQ lower than 80. This obviously implies that the two diagnoses are not completely overlapping. Thus, the evidences from studies conducted on SMD are not valid for DMDD.

A first study (Copeland et al., 2013) retrospectively analysed the epidemiology of this new diagnosis: only 38.9% of the patients who were diagnosed with SMD met the criteria DMDD.

Irritability and DMDD

DMDD is the first nosological picture of DSM to have irritability as its main characteristic. This new diagnosis has been placed within the chapter of depressive disorders; however, the definition of DMDD consists of a dysregulation that is both humoral and behavioural. The DSM-5 criteria for DMDD recognize two components of irritability: a phasic irritability, which manifests itself with developmentally inappropriate temper outbursts, and a tonic irritability, which persists between outbursts and characterizes the patient’s daily mood.

According to several authors (Althoff et al., 2016; Tufan et al., 2016), criteria for DMDD have very high thresholds and leave many children with severe irritability without a diagnosis. Other authors (Raven and Parry, 2012) claim that lowering the thresholds could mean granting unjustified use of psychotropic drugs in children who do not need them. In addition, diagnostic criteria of DMDD exclude children under 6 years of age, believing that before that age it is difficult to differentiate physiologically irritability from behaviours expressing pathological irritability, i.e. unjustified and especially disproportionate to the child’s developmental level. However, various studies have shown that even at preschool age, the presence of high levels of irritability is associated with functional impairment of the child ( Dougherty et al., 2015; Egger and Angold, 2006; Wakschlag et al., 2015). Currently, the threshold of 6 years for DMDD means that, in children of lower age, a clinical picture characterized by severe irritability is often framed in the DBD, in which this threshold is absent. Furthermore, it is not clear whether tonic irritability and phasic irritability are two distinct concepts corresponding to different clinical developments, treatment responses, pathogenetic mechanisms and familiarity (Leibenluft et al., 2006).

Of course, the introduction of this new nosological category has led to inevitable questions about its conceptual foundations, as well as its reliability and validity. In addition to the already mentioned controversies regarding frequency and age thresholds, several authors have expressed their disagreement about this new diagnosis.

Children who were previously diagnosed as bipolar and treated with mood stabilizers and new generation antipsychotics may receive a more appropriate diagnosis with the introduction of this new diagnosis, but they remain orphans of an effective therapy, as highlighted by Parens and Johnston (2010) who have generally emphasized the absence of validated treatments and defined risk–benefit relationships for drugs used for serious temper outbursts, at the time of the introduction of DMDD diagnosis.

Finally, some authors, such as Axelson et al. (2011; Axelson, 2013), openly opposed the inclusion of this new diagnosis in the fifth edition of the DSM, arguing that there was not enough empirical and scientific basis to justify the definition of a new diagnostic category that would have included a large and heterogeneous group of young patients with evolutionary trajectories and responses to pharmacological and psychotherapeutic treatments completely different.

Over time, several studies, both retrospective (Axelson et al., 2012; Margulies et al., 2012) and prospective (Mayes et al., 2015), have been able to observe the poor longitudinal stability of the diagnosis of DMDD, thus contesting its usefulness, and highlight the very high rate of comorbidity, (Dougherty et al., 2014; Evans et al., 2017) especially with ADHD and ODD, which occur in about 70–100% of patients with DMDD. This last data suggests that there are few children who previously received no diagnosis and therefore treatment for a humoral or behavioural disorder.

The real issue is if it was useful to introduce a new diagnosis rather than add a more specific definition of existing diagnoses in which chronic irritability is frequently present.

As regards the possibility of comorbidity, DSM states that DMDD cannot be diagnosed in comorbidity with BD, with intermittent explosive disorder (in which the outbursts of anger are present, but the irritable mood is missing) and with ODD, while diagnoses of ADHD, conduct disorder, substance abuse disorder and major depressive disorder may coexist.

As for the differential diagnosis between DMDD and ODD, if the same patient has symptoms that meet the criteria for both disorders, priority must be given to the diagnosis of DMDD, in which the intensity and frequency of symptoms shared with ODD is greater. This choice has been criticized (Evans et al., 2017), since, as will be discussed later, often the two diagnoses in question overlap and the hierarchy imposed by the DSM leads to omit many ODD diagnoses, leading the clinician to consider only the humoral disorder where there is also a behavioural disorder. This could lead to a lower use of behavioural interventions in the therapy of these young patients, leaning rather towards the use of psychotropic drugs such as antidepressants, antipsychotics and mood stabilizers, in the absence of enough evidence to support their use.

The placement of DMDD within depressive disorders has also been much discussed. The main reason for this placement was to emphasize the important component of irritable mood, the main feature of the diagnosis, for treatment purposes (Leibenluft, 2011). However, highlighting the mood disorder leaving aside the behavioural one may lead clinicians to underestimate the patient’s exteriorizing problems. The other critique moved against the decision of such a placement was instead more conceptual, contesting the inclusion of a disorder by definition chronic among the humoral disorders, characteristically episodic (Evans et al., 2017).

Finally, DMDD diagnosis is not present in the International Classification of Diseases, 11th Revision (ICD-11; World Health Organization, 2018). As will be discussed later, the World Health Organization has preferred to include chronic irritability as a new Specifier of ODD, rather than following the decision taken by the American Psychiatric Association to include a new diagnosis within depressive disorders.

Irritability and ADHD

Another disorder, this time of neurodevelopment, in which irritability plays an important role is ADHD. This is confirmed by the high number of comorbidities with DMDD: about 4–24% of children diagnosed with ADHD meet the criteria for DMDD (Ambrosini et al., 2013; Copeland et al., 2013; Mulraney et al., 2016).

These children, compared to the group of ADHD without comorbidity with DMDD, have less self-control (Mulraney et al., 2016), and higher levels of compromise, particularly in the social sphere (Eyre et al., 2017). In addition, it was found that comorbidity between these two disorders was more frequent in younger children (Eyre et al., 2017). This latter finding is reflected in a recent study (Riglin et al., 2019) founding that children with early-onset irritability – between 7 and 10 years – have a higher risk of developing ADHD than children with later-onset irritability. The authors stated the need for an evolutionary approach to irritability that takes into account the developmental trajectories of this dimension. Such an approach has already demonstrated its usefulness in the past, as for example in a study on antisocial behaviour (Moffitt, 1993). Evolutionary approach has allowed to distinguish different types of irritability: an early-onset irritability, associated with an ADHD-like phenotype with male predominance, and an adolescent-onset irritability, more common in girls and associated with mood disorders.

As in other disorders in which irritability is frequently present, in ADHD children with higher levels of irritability have worse outcomes (Karalunas et al., 2019), with a higher risk of developing another psychiatric disorder (Karalunas et al., 2014) – especially emotional disorders (Ambrosini et al., 2013). In these children irritability remains stable over time, going to outline a specific profile of ADHD, with a particularly risky evolution (Karalunas et al., 2014).

Several authors (Shaw et al., 2014; Sjöwall et al., 2013) are in favour of the theory that neural dysfunctions associated with ADHD, responsible for performance and cognitive flexibility deficits, hinder the child’s ability to regulate their emotions, leading to a picture of emotional dysregulation and irritability. Emotional lability has a strong genetic association with all three core characteristics of ADHD – hyperactivity, impulsiveness and inattention (Merwood et al., 2014) – and is considered by some authors to be the most responsible for functional impairment in patients with ADHD (Barkley and Fischer, 2010).

A recent study (Maire et al., 2020) stated that although in children with ADHD irritability and emotional lability are strongly correlated, they are longitudinally associated with different symptoms: while irritability predicts opposition and severe anxiety symptoms, emotional lability is associated with higher hyperactivity symptoms.

However, differentiating the items related to emotional lability from those related to irritability is rather difficult: depending on the scale used, a particular behaviour can be referred to irritability or emotional lability, for example the same item ‘temper outbursts’ is referred to emotional lability in CGI (Conners’ global index) and irritability in MAP-DB (Multidimensional Assessment of Preschool Disruptive Behavior) and CL-ARI (Clinician Affective Reactivity Index).

The considerations made so far have important clinical implications, highlighting the need to investigate the presence of irritability in all subjects diagnosed with ADHD, allowing to recognize a population particularly at risk of functional impairment and affective disorders. In these subjects, treatment with psychostimulants seems to reduce the symptoms of irritability, as well as emotional lability (Fernández de la Cruz et al., 2015; Winters et al., 2018).

Irritability and DBD

Since by irritability we mean a tendency to get easily impatient and a decreased threshold of response to provocation, we can easily understand how irritability can manifest with increased aggressivity, whims, temper outbursts, all elements that lead us back to DBD.

Aggressivity and irritability are dimensions both associated with disruptive behaviour in developmental age (Bolhuis et al., 2017), but distinct from it. This association is particularly evident for reactive aggression, which manifests itself as an impulsive and sudden response to a perceived threat. In children, reactive aggression is often preceded by negative emotionality (Vitaro et al., 2006) and low tolerance for frustration (Xu et al., 2009). Aggressivity is also associated with high levels of depression, low levels of emotional awareness (Rieffe et al., 2016) in children and adolescents, and, particularly in adolescents, with higher levels of anger and increased variability of fear levels throughout the day (Moore et al., 2019) as well as anxiety and substance abuse in adulthood (Raine et al., 2004).

Within the DBD, irritability is particularly expressed in the ODD, characterized by a frequent and persistent pattern of angry, irritable, polemic-provocative and vindictive behaviours. The diagnostic criteria of the ODD include three different types of symptoms: angry/irritable mood (expressed by frequently going angry and resentful, by being touchy and easily annoyed and by losing often temper), argumentative/defiant behaviour (expressed by rule violations and challenging and annoying behaviour towards others, especially those who represent authority) and vindictiveness. The presence and the severity of these different symptoms delineate two different phenotypes of ODD: the irritable phenotype and the defiant vindictive phenotype. This distinction has proven to have an important clinical and epidemiological value; it has been seen that, within the ODD, these dimensions correlate differently to subsequent developments and different comorbidities (Burke et al., 2014; Stringaris and Goodman, 2009b; Whelan et al., 2013).

In particular, the irritable dimension related importantly to emotional problems, whereas the hurtful subdimension related more strongly to callousness and the headstrong/opposition subdimension was found to be prospectively associated with conduct problems and hyperactivity (Stringaris and Goodman, 2009a).

Other authors have highlighted, in children with ODD, how irritable mood is associated with increased severity of internalizing symptoms and conduct problems (Aebi et al., 2016; Drabick and Gadow, 2012), as well as increased risk of suicide and self-harm (Aebi et al., 2016; Muratori et al., 2017).

Mikolajewski et al. (2017) in a study that investigates the outcome and the psychopathological evolution of the two profiles of the ODD, the irritable and the headstrong/hurtful, have shown how the association between irritable symptoms in childhood and overall internalizing problems in late adolescence was influenced by common genetic basis, whereas headstrong/hurtful symptoms share the same genetic influences of substance use disorder.

Previously, the group of (Stringaris et al., 2012b) had already demonstrated the presence of a genetic link between irritability and internalizing disorders, emphasizing that this correlation was stronger than the one existing between irritability and delinquency, which instead was found to be genetically associated with polemic/provocative behaviour. The author has therefore hypothesized that the proven association between ODD and depressive symptoms (Copeland et al., 2009) is mediated by irritability, which on one hand is the basis of oppositional symptoms and on the other hand is associated longitudinally to depressive disorders.

Other evidence in support of the strong link between ODD and irritability emerges from the review on irritability in developmental age published by Evans et al. on the occasion of the drafting of the ICD-11 (Evans et al., 2017). The article shows that the vast majority of studies conducted so far on patients with DMDD show a very high comorbidity with the ODD. In particular, in all studies, except one, limited by a very small sample size (n = 21 with DMDD) and the absence of any type of comparison group, the ODD was present in comorbidity in more than half of children with DMDD. On the basis of this finding in the ICD-11, rather than introducing the new diagnosis of DMDD whose validity is still very doubtful, it was preferred to differentiate a new subtype of ODD, characterized by persistent anger and irritable mood, which can be present regardless of any apparent provocation. Such placement as a subclass of ODD had been suggested some time earlier, in 2011, by Axelson et al. in the aforementioned article that opposed the introduction of DMDD as a new diagnosis within mood disorders in DSM-5 (Axelson et al., 2011).

Irritability and suicidality

Aebi et al. (2016) in a study of adolescent male offenders found that the irritable dimension predicted suicidality, as well as anxiety disorders, mood disorders and violent reoffending. The published literature is still poor in studies that examine the relationship between the presence of irritability in developmental age and the risk of suicide. Among the few studies present is the one of Orri et al. (2019). Children with rising irritability trajectories were at greater risk of suicide than those with persistently low irritability and this risk was largely due to a direct association, regardless of other psychiatric symptoms, that explained only 22.8% of the association between increasing irritability and suicide. Even children with persistently high irritability had a higher risk of suicide than those with persistently low irritability, but, in this case, 73.4% of the association was attributable to the presence of psychiatric symptoms, especially depressive ones, at the age of 13 years, which in itself increases the risk of subsequent suicide, regardless of the presence of irritability. Therefore, while persistent irritability is predictive of subsequent depression and therefore of an increased risk of suicide, irritability that appears or increases during preadolescence has an association with suicide even when no symptoms of depression are present.

Also Pickles et al. (2010) have found that the presence of irritability in adolescence (14–15 years) is a risk factor for suicide in adulthood (44–45 years), regardless of the presence of other psychiatric symptoms in adolescence. Conner et al. (2004) have instead investigated the presence of impulsivity and irritability in young boys of 15–20 years – elements considered expression of reactive aggression – and have shown that these are strongly associated with suicidal ideation.

Frazier et al. (2016) in a study conducted on adolescent psychiatric inpatients have shown how adolescent report of irritability is related to suicidal ideation independently of the several diagnoses commonly related with an increased risk for suicidal ideation in this age. Surprisingly, the irritability reported by parents differed from that reported by the patient and only the latter was found to be related to suicidal ideation. According to the authors, it is possible that the parents report only the externalized aspects of irritability, while those internalized, such as feelings and moods related to suicide, emerge only from the intimate experience of the adolescent.

Therefore, to evaluate suicidal ideation and suicide risk, for the clinician it is more important to assess irritability with the adolescent itself than with parents.

Irritability measures

Over the last 70 years, various instruments have been proposed to measure irritability in paediatric and adolescent population, in chronological order:

BDHI (Buss–Durkee Hostility Inventory) irritability subscale, developed by Buss and Durkee in 1957 as part of an instrument for measuring personality traits related to aggression (Buss and Durkee, 1957);

Irritability Scale–Youth Version, developed by Caprara et al. in 1985 on the basis of BDHI subscale irritability and addressed to the general adolescent population (Caprara et al., 1985);

Irritability, Depression, and Anxiety Scale, conceived for the adult population with psychopathologies by Snaith and Taylor in 1985, it consists of two subscales to detect manifest and non-manifest irritability (Snaith and Taylor, 1985);

Children’s Hostility Inventory irritability subscale, also based on the BDHI subscale irritability, developed by Kazdin, Rodgers, Colbus, and Siegel in 1987 and addressed to the paediatric population with a positive history for psychopathologies, in particular for conduct problems (Kazdin et al., 1987);

DB-DOS (Disruptive Behavior Diagnostic Observation Schedule), an evaluation based on the child’s performance during the examiner’s observation, designed by Wakschlag et al. in 2008 to investigate the ability of preschool children to regulate their behaviour to varying demands and social contexts (Wakschlag et al., 2008a, 2008b);

Affective Reactivity Index, a brief scale developed by Stringaris et al. in 2012, that assesses irritability in children, focusing on mood rather than hostility or aggressive behaviour; it consists of both parental and self-declared scales (Stringaris et al., 2012a);

The Multidimensional Assessment of Preschool Disruptive Behavior (MAP-DB), first elaborated by Wakschlag et al. in 2010; the version currently proposed by the authors refers to an update of 2012 (Wakschlag et al., 2012), it is a questionnaire used to assess four dimensions in children: Temper Loss, Noncompliance, Aggression and Low Concern for Others;

The CL-ARI, a semi-structured interview conceived by Haller et al. in 2020 in which parents and children are asked to describe the frequency, duration and severity of outbursts of anger and irritable moods (Haller et al., 2020);

The Early Childhood Irritability-Related Impairment Interview (E-CRI), recently developed by Wakschlag et al., the task of this semi-structured interview is to assess impairment associated with irritable mood and tantrums in preschool children across several contexts (Wakschlag et al., 2020);

The Clinical Evaluation of Emotional Regulation-9 (CEER-9), a nine-item scale recently proposed by Pylypow et al. to assess emotional disregulation and irritability (Pylypow et al., 2020).

The value of quantitative instruments, such as MAP-DB, DB-DOS and CL-ARI, is to assess the dimensionality of irritability, trying to differentiate the physiological irritable behaviour, present especially in early childhood, from an emerging psychopathological disorder. This is possible by evaluating the frequency and contexts in which irritable behaviour occurs, as well as the intensity, quality, stability and organization of this irritability.

Tools that allow to quantitatively highlight the various nuances of irritability are very useful if we consider that the boundary between physiological and pathological irritable behaviour is blurred and clinically significant irritability is not an ‘all or nothing’ phenomenon.

Wakschlag et al. (2015) found that the level of irritability in preschoolers is very unstable: in about a third of children it changes over the course of a year. In addition, even children within the normal range are subject to clinically significant developments over time: children with scores of 1 standard deviation above average develop clinically evident symptoms in 67% of cases (those with scores of 2 standard deviations above average, and therefore outside the normal range, in 83% of cases). For this reason, it is preferable to investigate irritability using tools that allow to identify not only children with clinically evident problems, but also children at risk or on the borderline between normality and abnormality.

Conclusion and clinical reflections

The fact that irritability is present transversally in several psychiatric diagnoses has often led to analyse it in a segmental way, as a specifier of each individual diagnosis, it is rare instead an overall view of irritability that crosses the various diagnoses and focuses on its dimensionality. Such a vision could lead to new etiopathogenetic hypotheses of some neuropsychiatric diseases of the developmental age, highlighting common aetiological pathways at the basis of different diagnoses that share an irritable dimension.

The dimensional approach to clinical phenomenology has long been a milestone in developmental psychopathology (Achenbach, 1997). DSM-5 diagnostic criteria provide a clinical description of an all-or-nothing pattern, detecting the clinically problematic behaviours of the child, rather than focusing on the entire behavioural spectrum. A dimensional approach is indispensable in the developmental age. The assumption of such an approach is that the presence or absence of a clinical element cannot be defined by crossing a specific threshold, but is rather expressed along a probabilistic risk spectrum (Markon et al., 2005). This is particularly important during the developmental age: partly because the rapid maturation and the specific developmental chronology of each child often do not allow to identify fixed thresholds between normality and pathology and the boundary is very thin, partly because identifying the prodromal phase of the disorders allows to prevent the evolution towards clinical pathological expressions and to better assist the delicate developmental path of the child in the developmental age.

To conclude, we think a dimensional approach to irritability could be useful also in non-psychiatric population. Some studies have already gone in this direction: Pickles et al. (2010) have highlighted the prevalence of significant irritability in adolescents with no psychiatric symptoms and the linkage with later suicidality, and Carlson et al. (2016) have underlined the differences in irritability between community and clinical sample. Basically, as some authors have suggested (Bell and Malhi, 2020), irritability may serve as a warning signal both in healthy individuals and in psychiatric patients. However, new studies are needed to focus on irritability in community children and adolescents and on his linkage with impairment, physical illness and reduced quality of life.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Maria Breda

References

Achenbach

(1997) What is normal? What is abnormal? Developmental perspectives on behavioral and emotional problems. In: Luthar

Burack

Cicchetti

, et al. (eds) Developmental Psychopathology: Perspectives on Adjustment, Risk, and Disorder. Cambridge: Cambridge University Press, pp. 93–114.

Aebi

Barra

Bessler

, et al. (2016) Oppositional defiant disorder dimensions and subtypes among detained male adolescent offenders. Journal of Child Psychology and Psychiatry and Allied Disciplines 57: 729–736.

Aebi

Plattner

Metzke

, et al. (2013) Parent- and self-reported dimensions of oppositionality in youth: Construct validity, concurrent validity, and the prediction of criminal outcomes in adulthood. Journal of Child Psychology and Psychiatry 54: 941–949.

Althoff

Kuny-Slock

Verhulst

, et al. (2014) Classes of oppositional-defiant behavior: Concurrent and predictive validity. Journal of Child Psychology and Psychiatry and Allied Disciplines 55: 1162–1171.

Althoff

Crehan

J-P

, et al. (2016) Disruptive mood dysregulation disorder at ages 13-18: Results from the national comorbidity survey – Adolescent supplement. Journal of Child and Adolescent Psychopharmacology 26: 107–113.

Ambrosini

Bennett

Elia

(2013) Attention deficit hyperactivity disorder characteristics: II. Clinical correlates of irritable mood. Journal of Affective Disorders 145: 70–76.

American Psychiatric Association (2013) American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. Arlington, VA: American Psychiatric Association.

Axelson

(2013) Taking disruptive mood dysregulation disorder out for a test drive. American Journal of Psychiatry 170: 136–139.

Axelson

Findling

Fristad

, et al. (2012) Examining the proposed disruptive mood dysregulation disorder diagnosis in children in the Longitudinal Assessment of Manic Symptoms study. Journal of Clinical Psychiatry 73: 1342–1350.

10.

Axelson

Birmaher

Findling

, et al. (2011) Concerns regarding the inclusion of temper dysregulation disorder with dysphoria in the DSM-5. Journal of Clinical Psychiatry 72: 1257–1262.

11.

Barkley

Fischer

(2010) The unique contribution of emotional impulsiveness to impairment in major life activities in hyperactive children as adults. Journal of the American Academy of Child and Adolescent Psychiatry 49: 503–513.

12.

Bell

Malhi

(2020) Irritability: An inability, or an ability? Australian and New Zealand Journal of Psychiatry 54: 1232–1233.

13.

Blader

Carlson

(2007) Increased rates of bipolar disorder diagnoses among U.S. child, adolescent, and adult inpatients, 1996-2004. Biological Psychiatry 62: 107–114.

14.

Bolhuis

Lubke

van der Ende

, et al. (2017) Disentangling heterogeneity of childhood disruptive behavior problems into dimensions and subgroups. Journal of the American Academy of Child and Adolescent Psychiatry 56: 678–686.

15.

Burke

(2012) An affective dimension within oppositional defiant disorder symptoms among boys: Personality and psychopathology outcomes into early adulthood. Journal of Child Psychology and Psychiatry 53: 1176–1183.

16.

Burke

Hipwell

Loeber

(2010) Dimensions of oppositional defiant disorder as predictors of depression and conduct disorder in preadolescent girls. Journal of the American Academy of Child and Adolescent Psychiatry 49: 484–492.

17.

Burke

Rowe

Boylan

(2014) Functional outcomes of child and adolescent oppositional defiant disorder symptoms in young adult men. Journal of Child Psychology and Psychiatry and Allied Disciplines 55: 264–272.

18.

Buss

Durkee

(1957) An inventory for assessing different kinds of hostility. Journal of Consulting Psychology 21: 343–349.

19.

Caprara

Cinanni

D’Imperio

, et al. (1985) Indicators of impulsive aggression: Present status of research on irritability and emotional susceptibility scales. Personality and Individual Differences 6: 665–674.

20.

Carlson

Danzig

Dougherty

, et al. (2016) Loss of temper and irritability: The relationship to tantrums in a community and clinical sample. Journal of Child and Adolescent Psychopharmacology 26: 114–122.

21.

Conner

Meldrum

Wieczorek

, et al. (2004) The association of irritability and impulsivity with suicidal ideation among 15- to 20-year-old males. Suicide and Life-Threatening Behavior 34: 363–373.

22.

Copeland

Shanahan

Costello

, et al. (2009) Childhood and adolescent psychiatric disorders as predictors of young adult disorders. Archives of General Psychiatry 66: 764–772.

23.

Copeland

Angold

Costello

, et al. (2013) Prevalence, comorbidity, and correlates of DSM-5 proposed disruptive mood dysregulation disorder. American Journal of Psychiatry 170: 173–179.

24.

Dougherty

Smith

Bufferd

, et al. (2014) DSM-5 disruptive mood dysregulation disorder: Correlates and predictors in young children. Psychological Medicine 44: 2339–2350.

25.

Dougherty

Smith

Bufferd

, et al. (2015) Preschool irritability predicts child psychopathology, functional impairment, and service use at age nine. Journal of Child Psychology and Psychiatry 56: 999–1007.

26.

Drabick

DAG

Gadow

(2012) Deconstructing oppositional defiant disorder: Clinic-based evidence for an anger/irritability phenotype. Journal of the American Academy of Child and Adolescent Psychiatry 51: 384–393.

27.

Egger

Angold

(2006) Common emotional and behavioral disorders in preschool children: Presentation, nosology, and epidemiology. Journal of Child Psychology and Psychiatry and Allied Disciplines 7: 313–337.

28.

Evans

Burke

Roberts

, et al. (2017) Irritability in child and adolescent psychopathology: An integrative review for ICD-11. Clinical Psychology Review 53: 29–45.

29.

Eyre

Langley

Stringaris

, et al. (2017) Irritability in ADHD: Associations with depression liability. Journal of Affective Disorders 215: 281–287.

30.

Ezpeleta

Granero

de la Osa

, et al. (2012) Dimensions of oppositional defiant disorder in 3-year-old preschoolers. Journal of Child Psychology and Psychiatry and Allied Disciplines 44: 115–128.

31.

Ezpeleta

Granero

de la Osa

, et al. (2016) Trajectories of oppositional defiant disorder irritability symptoms in preschool children. Journal of Abnormal Child Psychology 44: 115–128.

32.

Fernández de la Cruz

Simonoff

McGough

, et al. (2015) Treatment of children with attention-deficit/hyperactivity disorder (ADHD) and irritability: Results from the multimodal treatment study of children with ADHD (MTA). Journal of the American Academy of Child and Adolescent Psychiatry 54: 62–70.

33.

Frazier

Liu

Massing-Schaffer

, et al. (2016) Adolescent but not parent report of irritability is related to suicidal ideation in psychiatrically hospitalized adolescents. Archives of Suicide Research 20: 280–289.

34.

Haller

Kircanski

Stringaris

, et al. (2020) The clinician affective reactivity index: Validity and reliability of a clinician-rated assessment of irritability. Behavior Therapy. Association for Behavioral and Cognitive Therapies 51: 283–293.

35.

Karalunas

Fair

Musser

, et al. (2014) Subtyping attention-deficit/hyperactivity disorder using temperament dimensions: Toward biologically based nosologic criteria. JAMA Psychiatry 71: 1015–1024.

36.

Karalunas

Gustafsson

Fair

, et al. (2019) Do we need an irritable subtype of ADHD? Replication and extension of a promising temperament profile approach to ADHD subtyping. Psychological Assessment 31: 236–247.

37.

Kazdin

Rodgers

Colbus

, et al. (1987) Children’s hostility inventory: Measurement of aggression and hostility in psychiatric inpatient children. Journal of Clinical Child Psychology 16: 320–328.

38.

Kendler

(1996) Major depression and generalised anxiety disorder. British Journal of Psychiatry 168: 68–75.

39.

Kolko

Pardini

(2010) ODD dimensions, ADHD, and callous-unemotional traits as predictors of treatment response in children with disruptive behavior disorders. Journal of Abnormal Psychology 119: 713–725.

40.

Krieger

Stringaris

(2013) Bipolar disorder and disruptive mood dysregulation in children and adolescents: Assessment, diagnosis and treatment. Evidence-Based Mental Health 16: 93–94.

41.

Kuny

Althoff

Copeland

, et al. (2013) Separating the domains of oppositional behavior: Comparing latent models of the Conners’ oppositional subscale. Journal of the American Academy of Child and Adolescent Psychiatry 52: 172–183.

42.

Lavigne

Gouze

Bryant

, et al. (2014) Dimensions of oppositional defiant disorder in young children: Heterotypic continuity with anxiety and depression. Journal of Abnormal Child Psychology 42: 937–951.

43.

Leadbeater

Homel

(2015) Irritable and defiant sub-dimensions of ODD: Their stability and prediction of internalizing symptoms and conduct problems from adolescence to young adulthood. Journal of Abnormal Child Psychology 43: 407–421.

44.

Leibenluft

(2011) Severe mood dysregulation, irritability, and the diagnostic boundaries of bipolar disorder in youths. American Journal of Psychiatry 168: 129–142.

45.

Leibenluft

Charney

Towbin

, et al. (2003) Defining clinical phenotypes of juvenile mania. American Journal of Psychiatry 160: 430–437.

46.

Leibenluft

Cohen

Gorrindo

, et al. (2006) Chronic versus episodic irritability in youth: A community-based, longitudinal study of clinical and diagnostic associations. Journal of Child and Adolescent Psychopharmacology 16: 456–466.

47.

Liu

Chen

Vitoratou

, et al. (2019) Is emotional lability distinct from ‘angry/irritable mood’, ‘negative affect’, or other subdimensions of oppositional defiant disorder in children with ADHD? Journal of Attention Disorders 23: 859–868.

48.

Maire

Galera

Bioulac

, et al. (2020) Emotional lability and irritability have specific associations with symptomatology in children with attention deficit hyperactivity disorder. Psychiatry Research 285: 112789.

49.

Margulies

Weintraub

Basile

, et al. (2012) Will disruptive mood dysregulation disorder reduce false diagnosis of bipolar disorder in children? Bipolar Disorder 14: 488–496.

50.

Markon

Krueger

Watson

(2005) Delineating the structure of normal and abnormal personality: An integrative hierarchical approach. Journal of Personality and Social Psychology 88: 139–157.

51.

Masi

Millepiedi

Mucci

, et al. (2003) Phenomenology and comorbidity of dysthymic disorder in 100 consecutively referred children and adolescents: Beyond DSM-IV. Canadian Journal of Psychiatry 48: 99–105.

52.

Mayes

Mathiowetz

Kokotovich

, et al. (2015) Stability of disruptive mood dysregulation disorder symptoms (irritable-angry mood and temper outbursts) throughout childhood and adolescence in a general population sample. Journal of Abnormal Child Psychology 43: 1543–1549.

53.

Merwood

Chen

Rijsdijk

, et al. (2014) Genetic associations between the symptoms of attention-deficit/ hyperactivity disorder and emotional lability in child and adolescent twins. Journal of the American Academy of Child and Adolescent Psychiatry 53: 209.e4–220.e4.

54.

Mikita

Stringaris

(2013) Mood dysregulation. European Child and Adolescent Psychiatry 22: S11–S16.

55.

Mikolajewski

Taylor

Iacono

(2017) Oppositional defiant disorder dimensions: Genetic influences and risk for later psychopathology. Journal of Child Psychology and Psychiatry and Allied Disciplines 58: 702–710.

56.

Moffitt

(1993) Adolescence-limited and life-course-persistent antisocial behavior: A developmental taxonomy. Psychological Review 100: 674–701.

57.

Moore

Hubbard

Bookhout

, et al. (2019) Relations between reactive and proactive aggression and daily emotions in adolescents. Journal of Abnormal Child Psychology 47: 1495–1507.

58.

Moreno

Laje

Blanco

, et al. (2007) National trends in the outpatient diagnosis and treatment of bipolar disorder in youth. Archives of General Psychiatry 64: 1032–1039.

59.

Mulraney

Schilpzand

Hazell

, et al. (2016) Comorbidity and correlates of disruptive mood dysregulation disorder in 6–8-year-old children with ADHD. European Child and Adolescent Psychiatry 25: 321–330.

60.

Muratori

Pisano

Milone

, et al. (2017) Is emotional dysregulation a risk indicator for auto-aggression behaviors in adolescents with oppositional defiant disorder? Journal of Affective Disorders 208: 110–112.

61.

Orri

Galera

Turecki

, et al. (2019) Pathways of association between childhood irritability and adolescent suicidality. Journal of the American Academy of Child and Adolescent Psychiatry 58: 99–107.

62.

Parens

Johnston

(2010) Controversies concerning the diagnosis and treatment of bipolar disorder in children. Child and Adolescent Psychiatry and Mental Health 4: 9.

63.

Peterson

Zhang

Santa Lucia

, et al. (1996) Risk factors for presenting problems in child psychiatric emergencies. Journal of the American Academy of Child and Adolescent Psychiatry 35: 1162–1173.

64.

Pickles

Aglan

Collishaw

, et al. (2010) Predictors of suicidality across the life span: The Isle of Wight study. Psychological Medicine 40: 1453–1466.

65.

Pylypow

Quinn

Duncan

, et al. (2020) A measure of emotional regulation and irritability in children and adolescents: The clinical evaluation of emotional regulation–9. Journal of Attention Disorders 24: 2002–2011.

66.

Raine

Ishikawa

Arce

, et al. (2004) Hippocampal structural asymmetry in unsuccessful psychopaths. Biological Psychiatry 55: 185–191.

67.

Raven

Parry

(2012) Psychotropic marketing practices and problems: Implications for DSM-5. Journal of Nervous and Mental Disease 200: 512–516.

68.

Rieffe

Broekhof

Kouwenberg

, et al. (2016) Disentangling proactive and reactive aggression in children using self-report. European Journal of Developmental Psychology 13: 439–451.

69.

Riglin

Eyre

Thapar

, et al. (2019) Identifying novel types of irritability using a developmental genetic approach. American Journal of Psychiatry 176: 635–642.

70.

Rowe

Costello

Angold

, et al. (2010) Developmental pathways in oppositional defiant disorder and conduct disorder. Journal of Abnormal Psychology 119: 726–738.

71.

Roy

Brotman

Leibenluft

(2019) Introduction. In: Roy

Brotman

Leibenluft

(eds) Irritability in Pediatric Psychopathology. Oxford: Oxford University Press, pp. 1–10.

72.

Savage

Verhulst

Copeland

, et al. (2015) A genetically informed study of the longitudinal relation between irritability and anxious/depressed symptoms. Journal of the American Academy of Child and Adolescent Psychiatry 54: 377–384.

73.

Shaw

Stringaris

Nigg

, et al. (2014) Emotion dysregulation in attention deficit hyperactivity disorder. American Journal of Psychiatry 171: 276–293.

74.

Sjöwall

Roth

Lindqvist

, et al. (2013) Multiple deficits in ADHD: Executive dysfunction, delay aversion, reaction time variability, and emotional deficits. Journal of Child Psychology and Psychiatry and Allied Disciplines 54: 619–627.

75.

Snaith

Taylor

(1985) Irritability definition, assessment and associated factors. British Journal of Psychiatry 147: 127–136.

76.

Stringaris

Goodman

(2009a) Longitudinal outcome of youth oppositionality: Irritable, headstrong, and hurtful behaviors have distinctive predictions. Journal of the American Academy of Child and Adolescent Psychiatry 48: 404–412.

77.

Stringaris

Goodman

(2009b) Three dimensions of oppositionality in youth. Journal of Child Psychology and Psychiatry and Allied Disciplines 50: 216–223.

78.

Stringaris

Vidal-Ribas

(2019) Probing the irritability – Suicidality nexus. Journal of the American Academy of Child and Adolescent Psychiatry 58: 18–19.

79.

Stringaris

Goodman

Ferdinando

, et al. (2012a) The Affective Reactivity Index: A concise irritability scale for clinical and research settings. Journal of Child Psychology and Psychiatry and Allied Disciplines 53: 1109–1117.

80.

Stringaris

Zavos

Leibenluft

, et al. (2012b) Adolescent irritability: Phenotypic associations and genetic links with depressed mood. American Journal of Psychiatry 169: 47–54.

81.

Tufan

Topal

Demir

, et al. (2016) Sociodemographic and clinical features of disruptive mood dysregulation disorder: A chart review. Journal of Child and Adolescent Psychopharmacology 26: 94–100.

82.

Vidal-Ribas

Brotman

Valdivieso

, et al. (2016) The status of irritability in psychiatry: A conceptual and quantitative review. Journal of the American Academy of Child and Adolescent Psychiatry 55: 556–570.

83.

Vitaro

Barker

Boivin

, et al. (2006) Do early difficult temperament and harsh parenting differentially predict reactive and proactive aggression? Journal of Abnormal Child Psychology 34: 685–695.

84.

Wakschlag

Briggs-Gowan

Hill

, et al. (2008a) Observational assessment of preschool disruptive behavior, part II: Validity of the disruptive behavior diagnostic observation schedule (DB-DOS). Journal of the American Academy of Child and Adolescent Psychiatry 47: 632–641.

85.

Wakschlag

Choi

Carter

, et al. (2012) Defining the developmental parameters of temper loss in early childhood: Implications for developmental psychopathology. Journal of Child Psychology and Psychiatry and Allied Disciplines 53: 1099–1108.

86.

Wakschlag

Estabrook

Petitclerc

, et al. (2015) Clinical implications of a dimensional approach: The normal:abnormal spectrum of early irritability. Journal of the American Academy of Child and Adolescent Psychiatry 54: 626–634.

87.

Wakschlag

Hill

Carter

, et al. (2008b) Observational assessment of preschool disruptive behavior, part I: Reliability of the disruptive behavior diagnostic observation schedule (DB-DOS). Journal of the American Academy of Child and Adolescent Psychiatry 47: 622–631.

88.

Wakschlag

Krogh-Jespersen

Estabrook

, et al. (2020) The early childhood irritability-related impairment interview (E-CRI): A novel method for assessing young children’s developmentally impairing irritability. Behavior Therapy 51: 670–673.

89.

Whelan

Leibenluft

Stringaris

, et al. (2015) Pathways from maternal depressive symptoms to adolescent depressive symptoms: The unique contribution of irritability symptoms. Journal of Child Psychology and Psychiatry and Allied Disciplines 56: 1092–1100.

90.

Whelan

Stringaris

Maughan

, et al. (2013) Developmental continuity of oppositional defiant disorder subdimensions at ages 8, 10, and 13 years and their distinct psychiatric outcomes at age 16 years. Journal of the American Academy of Child and Adolescent Psychiatry 52: 961–969.

91.

Winters

Fukui

Leibenluft

, et al. (2018) Improvements in irritability with open-label methylphenidate treatment in youth with comorbid attention deficit/hyperactivity disorder and disruptive mood dysregulation disorder. Journal of Child and Adolescent Psychopharmacology 28: 298–305.

92.

World Health Organization (2018) International classification of diseases for mortality and morbidity statistics (11th Revision). Available at: https://icd.who.int/browse11/l-m/en

93.

Wozniak

Biederman

Kiely

, et al. (1995) Mania-like symptoms suggestive of childhood-onset bipolar disorder in clinically referred children. Journal of the American Academy of Child and Adolescent Psychiatry 34: 867–876.

94.

Farver

JAM

Zhang

(2009) Temperament, harsh and indulgent parenting, and Chinese children’s proactive and reactive aggression. Child Development 80: 244–258.

Irritability in developmental age: A narrative review of a dimension crossing paediatric psychopathology

Abstract

Objective:

Method:

Results:

Conclusion:

Keywords

Introduction

Irritability and depression

Irritability and early bipolar disorder

Irritability and DMDD

Irritability and ADHD

Irritability and DBD

Irritability and suicidality

Irritability measures

Conclusion and clinical reflections

Footnotes

Declaration of Conflicting Interests

Funding

ORCID iD

References