Differential Effects of Disruptive Mood Dysregulation Disorder Comorbidity in Attention Deficit Hyperactivity Disorder on Social Cognition and Empathy

Abstract

Objective:

This study aimed to investigate social cognition and empathy properties in children among Disruptive Mood Dysregulation Disorder (DMDD) + Attention and Hyperactivity Disorder(ADHD); ADHD and healthy controls from Türkiye.

Methods:

Twenty-two children with DMDD were compared to matched 30 children with ADHD and 60 healthy controls. We administered Affective Reactivity Index (ARI), KaSi Empathy Scale, Kiddie-SADS, and Reading Mind in the Eyes Test (RMET) to evaluate Theory of Mind skills to all study participants.

Results:

DMDD + ADHD group had lower performance in ToM skills and empathy than in two groups. The ARI scores were found to be statistically significantly higher in the DMDD group than in two groups. It was also found that ARI, empathy, and ToM scores were significantly related in children with DMDD + ADHD.

Conclusion:

These results might be important to understand the difficulties in social functioning and interpersonal relationship in children with DMDD and ADHD. Children with DMDD may attend specific therapeutic programs which include specific techniques in social cognition, emotion regulation, and irritability.

Keywords

disruptive mood dysregulation disorder affective empathy cognitive empathy irritability social cognition theory of mind

Introduction

Disruptive mood dysregulation disorder (DMDD) listed among depressive disorders in DSM-5 and 5-TR is characterized by persistently irritable/angry mood present most of the time and observable by others upon which severe, recurrent temper outbursts inconsistent with developmental level are superimposed. The outbursts should be grossly out of proportion in intensity/duration to the triggers and on average should occur at least three times a week. DSM-5 and 5-TR stipulate a duration of ≥12 months with a symptom free period of ≤3 months, presence of symptoms in at least two different settings (e.g., home, school, peers) with severe symptoms in one leading to impairment (American Psychiatric Association, 2013, 2022). The diagnosis should not be made initially among children aged <6 or those >18 years, the onset should be <10 years by history/observation. Manic/hypomanic episodes ≥1 day should not be present and symptoms should not be limited to a major depressive episode, nor should they be better explained by another disorder, the effects of a substance or a general medical condition. Comorbidity with oppositional defiant disorder (ODD), intermittent explosive disorder, and bipolar disorder are not allowed (American Psychiatric Association, 2013, 2022). DMDD was included first in DSM-5 (American Psychiatric Association, 2013) primarily to address concerns about overdiagnosis and overtreatment of bipolar disorder in children and adolescents although it has its detractors (Evans et al., 2021; Gupta & Gupta, 2022). Accordingly, ICD-11 suggests the diagnosis of ODD with chronic irritability/anger instead of DMDD (Evans et al., 2021). DMDD is reported to be common among clinically referred children although prevalence in the community is unclear. There may be a male preponderance in clinically referred samples although no consistent gender differences emerged in the community. Comorbidity with ADHD, disruptive behaviors, mood, anxiety, autism spectrum symptoms, and diagnoses may be elevated among children with DMDD (American Psychiatric Association, 2022).

Attention deficit hyperactivity disorder (ADHD) is one of the most frequent neurodevelopmental disorders in childhood characterized by developmentally inappropriate, pervasive, and impairing symptoms of inattention, hyperactivity, and impulsivity (American Psychiatric Association, 2013, 2022). Global prevalence among children was reported as 7.2% although cross-national prevalences vary widely from 0.1% to 10.2% of children and adolescents (American Psychiatric Association, 2022). Beyond core symptoms, youth with ADHD may also experience problems in social cognition and relationships and those problems may benefit from treatment of ADHD (Fantozzi et al., 2021a; Figueiredo et al., 2022). Additionally, almost one third of youth with ADHD may experience emotion dysregulation and irritability (Breaux et al., 2022; Colonna et al., 2022). Social-cognitive constructs such as mentalization, Theory of Mind (ToM), and empathy may be important in the etiology of these difficulties both in ADHD and DMDD.

Social cognition is important to understand others’ behaviors and to form and maintain interpersonal relationships. It consists of codification, representation, and interpretation of social cues and includes (1) recognizing others’ affects from face and prosody perception (i.e., emotion recognition), (2) making inferences regarding others’ mental states (i.e., theory of mind, ToM), and (3) sharing and understanding the emotional perspective of others (i.e., empathy) (Fantozzi et al., 2021a; Schurz et al., 2021).

The theory of mind (ToM), which can be defined as the capability of accurately attributing an individual’s mental state, beliefs, intentions, and desires, is important in adequate social and interpersonal functioning (Greenberg et al., 2023). Empathy refers to the reactions of one individual to the observed experiences of another and may require adequate social perception as well as the capacity to comprehend complex mental states (Arioli et al., 2021; Fantozzi et al., 2021a; Greenberg et al., 2023; Schurz et al., 2021). Empathy may also be subdivided as cognitive and affective. The cognitive part, also referred to as mentalizing, is the ability to comprehend the mental state of another whereas affective empathy denotes an emotional experience arising in response to an emotion experienced by another. Those domains are related but different (Arioli et al., 2021; Fantozzi et al., 2021b; Zaki 2020). The ToM is related to the concept of cognitive empathy, and most authors use the terms interchangeably. Also, previous studies showed that ToM ability was closely associated with the ability of empathizing (Arioli et al., 2021; Greenberg et al., 2023; Zaki, 2020). Both empathy and ToM require adequate attention modulation and cognitive appraisal although there are controversies on the underlying processes (Arioli et al., 2021; Colonna et al., 2022; Greenberg et al., 2023; McDonald et al., 2022; Schurz et al., 2021; Zaki, 2020).

Various correlates of DMDD and ADHD comorbidity have been studied previously (Brænden et al., 2023; Haller et al., 2022; Mulraney et al., 2016; Pagliaccio et al., 2017; Tufan et al., 2016; Uran & Kılıç, 2020). However, the literature on DMDD comorbid with ADHD and its effects on ToM and empathy are limited (Whitney et al., 2013). Due to increased rates of comorbidity between those constructs (American Psychiatric Association 2022; Mulraney et al., 2021) as well as the need to discern the clinical characteristics of the DMDD construct (Cardinale et al., 2021; Evans et al., 2021; Gupta & Gupta, 2022) we aimed to investigate,

a) the empathy and ToM skills in children with DMDD and comorbid ADHD,

b) to compare these skills with children diagnosed with ADHD only and healthy controls.

Methods

Study Center, Sampling, and Ethics

Participants consisted of consecutively admitted patients between the ages of 8 and 12 years who were diagnosed with DMDD (DSM-5 296.99, ICD-10 F34.8) between September 2019 and September 2021 in the Child and Adolescent Psychiatry Department of the study center. The diagnosis of DMDD was made in accordance with the DSM-5 criteria (American Psychiatric Association, 2013). Exclusion criteria of the case group of the study were presence of chronic medical disorders, a clinical diagnosis of autism spectrum disorder or mental retardation/intellectual disability (according to developmental/academic history and clinical examination), past or current epilepsy, brain injury and cerebral palsy, use of medications interfering with normal development (e.g., cortisol, any stimulant treatment, mood stabilizers). Since all children with DMDD within the study period received comorbid diagnoses, only those children diagnosed with DMDD comorbid with ADHD were included in the present study. Children diagnosed with ADHD were free of psychiatric comorbidity. The control group was determined after the enrollment of children with DMDD + ADHD and those with ADHD between September and December 2021. Age and gender-matched children applying to the pediatric outpatient clinics of the same hospital with minor physical symptoms (e.g., common cold, rhinitis) without any chronic medical conditions and free of lifetime psychopathology were included to the control group.

The participants were evaluated with the Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version (K-SADS-PL) implemented by blinded professionals (Ünal et al., 2019). All participants completed a battery of tests that assess their ToM abilities, emotional intelligence, emotion regulation skills, and clinical psychopathology levels in fixed order.

IRB approval of the study was obtained from Clinical Trials Ethics Committee. Verbal and written assent of children and written informed consents of the mothers who participated in the study were received prior to enrollment. All of the study procedures were in accordance with the Declaration of Helsinki and local laws and regulations.

Measurements

Socio-demographic data form

This form was prepared by the researchers to collect information about socio-demographic characteristics of children and parents. Participant children’s ages, genders, socioeconomic levels, academic conditions, peer relationships and their parents’ ages, educational, marital and vocational statuses, were entered in the form by the clinicians.

DuPaul Attention Deficit Hyperactivity Disorder Rating Scale (DuPaul ADHD-RS-IV Inventory)

DuPaul ADHD Inventory is a scale with 18 items evaluating symptoms of inattention, hyperactivity, and impulsivity to aid in diagnosis of ADHD. This inventory was developed by Du Paul and colleagues, completed by the clinician, evaluates severity of symptoms within the last week and was used previously among studies in Turkey (DuPaul, 1998; Özyurt et al., 2018)

Reading the mind in The Eyes Test (RMET)

The RMET evaluates one’s ability to understand mental states and emotions by looking at eye expressions. It was initially developed by Baron-Cohen et al. in 1997 and was later revised in 2001 (Baron-Cohen et al., 1997, 2001). RMET was frequently used in studies investigating the relationship between social cognition and psychopathology. The Turkish reliability study of the test was conducted in 2011 by Yıldırım and colleagues while psychometric properties (Yıldırım et al., 2011).

Affective Reactivity Index-Child and Parent Form

The Affective Reactivity Index (ARI) is a scale developed for the evaluation and monitoring of irritability according to children’s and parents’ reports. Stringaris and colleagues created it as a dimensional measure of irritability (Stringaris et al., 2012). Evaluating the symptoms of irritability for the last 6 months, this questionnaire involves six items for symptoms while the seventh item assesses the impairment in functioning. Ratings are given based on a three-point scale (i.e., “0 = not true,” “1 = sometimes true,” “2 = definitely true”). The reliability and validity of the ARI in typically developing children has been reported previously (Mulraney et al., 2014; Stringaris et al., 2012). The Turkish validity and reliability study was carried out by Kocael and colleagues (Kocael, 2015). The total ARI score ranges from 0 to 12 as the sum of the first six items. ARI-Parent report form was used in the current study.

KA-SI Empathic Tendency Scale for Children and Adolescents

This is an assessment instrument specific to Turkish culture that was developed to measure empathic tendencies of children and adolescents according to self-report (Kaya & Siyez, 2010). A two-factor structure (cognitive and affective empathy) was determined to be appropriate for both child and adolescent form according to explanatory and confirmatory factor analysis with greater scores reflecting higher empathy. KA-SI empathic tendency scale for children and adolescents was previously used among both community and clinical samples and was found to be valid and reliable (Özyurt et al., 2017).

Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version (K-SADS-PL)

The K-SADS-PL is a semi-structured diagnostic interview evaluating current and lifetime psychopathology among children and adolescents which was updated to reflect DSM-5 criteria (Kaufman et al., 1997, 2016). The Turkish version of the K-SADS-PL was found to be valid and reliable previously (Ünal et al., 2019). Blinded, trained child, and adolescent psychiatrists applied the interview to study participants.

Statistical Analysis

Statistical analysis was conducted by using the Statistical Package for the Social Sciences (IBM Corporation, Armonk, NY), version 22 for Windows^TM. Variables were controlled for the assumptions of the normal distribution by using the Shapiro–Wilk test. Continuous variables were summarized as means and standard deviations or medians and interquartile ranges (IQR) according to assumptions of normality and presence of outliers. Categorical variables were summarized as counts and frequencies. The chi-square test was implemented to compare categorical variables between study groups. Psychometric measures were compared across groups with multivariate analysis of variance (MANOVA). p was set at .05. Effect sizes for significant findings were also reported.

Results

Within the study period 30 patients with ADHD (n = 19, 63.3% male), 22 with ADHD + DMDD (n = 15, 68.2% male) and 60 controls (n = 34, 56.7% male) were enrolled. The groups did not significantly differ according to gender (χ² [2] = 1.0, p = .603). The median ages of children according to groups were 9.5 (IQR = 3.0), 9.0 (IQR = 4.0), and 10.0 (IQR = 2.0) years; respectively with no significant difference (Kruskal–Wallis test, χ² [2] = 2.3, p = .319). Family status, maternal features, and academic/peer functioning of participants are reported in Table 1.

Table 1.

Family Status, Maternal Features, and Functioning of Children With Attention Deficit Hyperactivity Disorder (ADHD), ADHD Comorbid With Disruptive Mood Dysregulation Disorder (ADHD + DMDD) and Control Children.

N (%)	ADHD (n = 30)	ADHD + DMDD (n = 22)	Controls (n = 60)	χ²/dF	p	E.S.*
Family status
Nuclear	22 (73.3)	16 (72.7)	48 (80.0)	6.6/4	.156	–
Extended	8 (26.7)	3 (13.6)	7 (11.7)
Separate/divorced/widowed	0 (0.0)	3 (13.6)	5 (8.3)
Maternal education
Primary school or lower	22 (73.3)	16 (72.7)	45 (75.0)	4.9/4	.302	–
High school	8 (26.7)	5 (22.7)	9 (15.0)
University or above	0 (0.0)	1 (4.5)	6 (10.0)
Maternal vocation
Housewife	21(70.0)	17 (77.3)	30 (50.0)	6.5/2	.039	0.24
Other	9 (30.0)	5 (22.7)	30 (50.0)	6.5/2	.039	0.24
Academic** achievement
High	9 (30.0)	2 (9.1)	48 (80.0)	54.7/4	.000	0.49
Moderate	11 (36.7)	6 (27.3)	12 (20.0)
Low	10 (33.3)	14 (63.6)	0 (0.0)
Peer relations**
Good	15 (50.0)	9 (40.9)	58 (96.7)	36.8/2	.000	0.57
Problematic	15 (50.0)	13 (59.1)	2 (3.3)	36.8/2	.000	0.57
Family history of medical disorders	6 (20.0)	3 (13.6)	6 (10.0)	1.7/2	.422	–
Family history of psychopathology	17 (56.7)	14 (63.6)	16 (26.7)	12.7/2	.002	0.34

Cramer’s V.

parent/self-reported.

Mothers were significantly more likely to be housewives among children with ADHD and ADHD + DMDD compared to controls. Similarly, family history of psychopathology, lower academic achievement, and problematic peer relationships were significantly more frequent in both groups compared to controls although ADHD and ADHD + DMDD groups did not differ between themselves (Bonferroni corrected). Maternal education, family status, and family history of medical disorders did not differ significantly between groups.

RMET, ARI parent form, KA-SI empathic tendency, and Du Paul ADHD total scores were compared across groups with MANOVA. Box’s test for homogeneity of covariance matrices (χ² [20] = 38.7, p = .007) as well as Shapiro–Wilk test of multivariate normality (W = 0.96, p < .001) were significant. Error variances were equal except total ADHD scores (Levene’s test, F [2, 109] = 4.6, p = .012). Therefore, Pillai’s trace criterion was used. According to analysis, group significantly affected test results (Pillai’s trace = 1.7, F [8, 214] = 129.0, p < .001, partial η² = 0.83). Results of univariate tests are illustrated in Table 2. The model could correctly explain 88.1% of the variance in ARI-parent form, 32.9% in RMET performance, 77.5% in empathy, and 94.1% in ADHD symptoms (adjusted R²s). According to pair-wise comparisons (Bonferroni corrected), all three groups differed significantly from each other in terms of parent rated affective irritability with controls being lowest and ADHD + DMDD group being highest. The reverse was true in terms of total empathy (i.e., controls were highest while children with ADHD + DMDD were lowest with all three groups differing significantly from each other). In RMET performance of children with ADHD and control children were similar and significantly elevated compared to those with ADHD + DMDD. Lastly, total ADHD symptom severity of children with ADHD and those with ADHD + DMDD were similar and were significantly elevated compared to control children.

Table 2.

Empathy, Theory of Mind, Affective Irritability, and ADHD Symptom Scores of Turkish Children with ADHD, ADHD and Disruptive Mood Dysregulation Disorder (DMDD) and Control Children.

	ADHD (n = 30)mean (SD)	ADHD + DMDD (n = 22)mean (SD)	Controls (n = 60)mean (SD)	F/dF	p	Partial η²
RMET	22.0 (1.5)	19.8 (1.2)	22.5 (1.5)	28.2/2	<.001	0.34
ARI-parent form	4.3 (1.2)	9.6 (0.9)	2.3 (1.0)	411.0/2	<.001	0.88
KA-SI empathic tendency scale—cognitive empathy	12.2 (1.4)	10.7 (1.2)	15.2 (1.3)	114.2/2	<.001	0.68
KA-SI empathic tendency scale affective empathy	16.2 (2.2)	13.8 (2.0)	21.2 (1.3)	184.9/2	<.001	0.77
KA-SI empathic tendency scale—total score	28.4 (3.4)	24.6 (3.0)	36.5 (2.1)	192.3/2	<.001	0.78
Du Paul-inattentive score	18.9 (2.0)	19.1 (3.5)	3.4 (1.8)	657.2/2	<.001	0.92
Du Paul-hyperactive/impulsive score	18.4 (2.3)	20.4 (2.8)	4.3 (1.8)	672.9/2	<.001	0.93
Du Paul total ADHD score	37.3 (3.3)	39.6 (5.1)	7.6 (3.6)	891.5/2	<.001	0.94

Note. SD = standard deviation; RMET = reading the mind in the eyes test; ARI = affective reactivity index.

An additional MANOVA analysis was conducted to differentiate the effects of group on cognitive/affective empathy and inattentive versus hyperactive/impulsive ADHD symptoms. Covariance matrices were not homogeneous (Box’s M, χ² [42] = 229.7, p < .001) and assumptions of multivariate normality were not met (Shapiro–Wilk test, p < .001). Error variances were equal except affective empathy (F[2, 109] = 3.3, p = .041) and inattentive symptoms (F[2, 109] = 14.4, p = .000). Therefore, Pillai’s trace was used in analyses. According to analysis, group significantly affected test results (Pillai’s trace = 1.7, F[12, 210] = 86.4, p < .001, partial η² = 0.83). Results of univariate tests are illustrated in Table 2.

The model could correctly explain 88.1% of the variance in ARI-parent form, 32.9% in RMET performance, 67.1% in cognitive empathy, 76.8% in affective empathy, 92.2% in inattentive, and 92.4% in hyperactive/impulsive symptoms (adjusted R²s). According to pair-wise comparisons (Bonferroni corrected), control children had the highest cognitive/affective empathy levels, followed by children with ADHD while those with ADHD + DMDD had the lowest level. All three groups differed significantly from each other. ADHD and ADHD + DMDD groups had similar levels of inattentive symptoms which significantly differed from controls. Lastly, ADHD + DMDD group had the highest levels of hyperactive/impulsive symptoms followed by those with ADHD while controls had the lowest levels with all three groups differing significantly from each other.

In correlation analyses of the whole sample ARI scores correlated negatively and significantly with RMET and cognitive/affective empathy while they were correlated positively and significantly with Du Paul inattentive and hyperactive/impulsive symptoms. RMET correlated positively with cognitive/affective empathy and negatively with Du Paul inattentive and hyperactive/impulsive symptoms. Cognitive and affective empathy were positively correlated while they correlated negatively with inattentive and hyperactive/impulsive symptoms. Lastly, inattentive, and hyperactive/impulsive symptoms were positively correlated (Figure 1). Among children with ADHD cognitive and affective empathy correlated positively and significantly. This positive correlation was weaker among children with ADHD + DMDD and inattentive symptoms correlated negatively and significantly with affective empathy. Finally, among control children inattentive and hyperactive/impulsive symptoms and cognitive/affective empathy were significantly and positively correlated (Figure 2).

Figure 1.

Heatmap of correlations between affective reactivity scores, theory of mind abilities, empathy dimensions, and inattentive versus hyperactive/impulsive symptoms in the whole sample (n = 112).

Figure 2.

Heatmap of correlations between affective reactivity scores, theory of mind abilities, empathy dimensions, and inattentive versus hyperactive/impulsive symptoms according to diagnosis.

A GLM mediation model was set up with ARI as dependent variable, inattentive, and hyperactive/impulsive symptoms as mediators, clinical diagnosis (ADHD ± DMDD or control) as factor and RMET along with cognitive and affective empathy as covariates. The effect of clinical diagnosis on ARI was mediated by inattentive symptoms (β = .4, 95% CI = 0.3–4.2, p = .027) as well as hyperactive/impulsive symptoms (β = −.8, 95% CI = −6.7 to −2.7, p < .001) while effects of RMET on ARI via inattentive (p = .736) and hyperactive/impulsive (p = .225) symptoms were not significant. Effects of cognitive and affective empathy domains mediated by inattentive (p = .136 and .089; respectively) and hyperactive/impulsive symptoms (p = .359 and .751; respectively) were also not significant. Direct effects of clinical diagnosis (p = .282) and of cognitive empathy (p = .792) on ARI were not significant. However, RMET score (β = −0.3, 95% CI = −0.6 to −0.2, p < .001) and affective empathy (β = −.6, 95% CI = −0.7 to −0.3, p < .001) affected ARI directly and significantly (Figure 3).

Figure 3.

GLM mediation model of cognitive/affective empathy, ToM, clinical diagnosis, inattentive, and hyperactive/impulsive symptoms on affective reactivity.

Discussion

In this single-center, cross-sectional, case-control study we evaluated the empathy and ToM skills in children with DMDD and comorbid ADHD and compared those skills with children diagnosed with ADHD only and healthy controls matched for age and gender. We found that control children had the greatest levels of self-reported empathy followed by those with DMDD + ADHD and those with ADHD, respectively. These findings were similar for both cognitive and affective empathy. On the other hand, irritability was highest in those with DMDD + ADHD, followed by those with ADHD and lowest among controls. Although total ADHD symptom severity and inattentive symptoms were similar in children with ADHD and those with ADHD + DMDD and elevated compared to controls, DMDD comorbidity significantly elevated hyperactive/impulsive symptom severity compared to children with ADHD.

RMET performance of children with ADHD was similar to control children and were significantly greater than those with DMDD + ADHD. Inattentive symptoms were significantly and negatively correlated with affective empathy in those with DMDD + ADHD and the correlation between cognitive and affective empathy was reduced. In mediation analyses, the effect of clinical diagnosis on affective reactivity was mediated by inattentive and hyperactive/impulsive symptoms while RMET score, and affective empathy affected ARI scores directly.

Recent studies showed difficulties in the skills of ToM and empathy in children diagnosed with neurodevelopmental disorders, especially autism spectrum disorder (ASD) (Bird & Viding, 2014; Peterson, 2014). Oppositional Defiant Disorder and Conduct Disorder with limited prosocial emotions (i.e., callous–unemotional traits, Golubchik & Weizman, 2017; Pijper et al., 2016) are also among the most frequently investigated disorders in terms of ToM and empathy. ToM and empathy deficits have been shown in children with ADHD (Fantozzi et al., 2021b; Figueiredo et al., 2022; Levy et al., 2022; Ozbaran et al., 2022; Özyurt et al., 2017; Singh et al., 2021) previously.

Additionally recent studies examining characteristics of empathy in cases of ADHD comorbid ODD and CD, empathy skills of children with ADHD having comorbid ODD or CD were found to be lower compared to children diagnosed with ADHD without comorbidity (Golubchik et al., 2017; Özyurt et al., 2017) The correlation between disruptive behavior problems and empathy deficiency was shown in previous studies (Frick et al., 2014; Golubchik et al., 2017). According to our results DMDD may act similar to other comorbidities accompanying ADHD to accentuate underlying difficulties in ToM and empathy. This effect may be explained, at least in part, hyperactive/impulsive and inattentive symptoms which may be linked to dysfunctions of the fronto-striatal brain networks, functionally related to empathic processing and executive functioning. Those hypotheses should be tested by future studies employing various imaging modalities (Arioli et al., 2021; Brænden et al., 2023).

As an important finding of the current study, children who were diagnosed with ADHD and DMDD had more difficulties in empathy and empathy difficulties, especially in the affective domain were directly related with irritability scores. Core “empathic” processes involve: (i) the inhibition of aggression in response to distress cues; (ii) the learning of the negative value of actions such as aggression that are associated with others’ distress; and (iii) reasoning about actions that are associated with others’ distress (Blair,2018). The greater the degree to which these empathic processes are compromised, as seen in ADHD or DMDD; the greater the likelihood that an individual will engage in in irritability as dysregulated anger. As such, individuals with ADHD and/or DMDD will be less influenced by the negative valence typically associated with actions that involve harm to others and thus more likely to choose those actions to achieve their goals. Similar to our results, Fantozzi et al. (2021b) found that treatment with methylphenidate improved affective empathy among children with ADHD and that this effect was achieved by reduction in inattentive symptoms. DMDD accompanying ADHD seem to reduce correlations between cognitive and affective empathy domains according to our results and future studies are needed to replicate this finding.

Emotion dysregulation problems were previously shown in children with ADHD, those with DMDD and others with both DMDD + ADHD. Empathy, especially cognitive empathy may be characterized by elaborated conscious forms of emotion regulation. All these conscious regulatory processes tend to be costly in terms of the investment of effort and may depend on the maturation of cortico-limbic connections. In a neuroimaging study it was found that youth who experienced elevated levels of irritability showed a relatively weak coupling between neural regions implicated in effective emotion regulation (Banks et al. 2007). Similarly, other studies found that that decreased neural regulation in the context of aberrant attentional processing may increase maladaptive irritability with impaired connectivity between the amygdala and subcortical regions (Uddin et al., 2017; Zhou et al., 2016). In accordance with those results, future studies may evaluate emotion regulation skills of children with ADHD and those with ADHD + DMDD by means of various paradigms (i.e., self-reports, emotional Stroop paradigms) and denote their relationships with inattentive and hyperactive/impulsive symptoms, empathy, and strengths of connectivity between cortical and subcortical regions (Arioli et al., 2021; Carver & Harmon-Jones, 2009; Greenberg et al., 2023, McDonald et al., 2022, Schurz et al., 2021, Zaki, 2020).

Irritability (i.e., dysregulated anger) may be related with elevated responsiveness of the amygdala and periaqueductal gray area in response to threat and social provocations (Carré et al., 2012). This relationship may be moderated by empathy levels (Carré et al., 2012; Cowan et al. 2014). The latter may depend on various complex and inter-related abilities such as emotion recognition, emotion regulation, ToM, vicarious learning, social problem solving, etc. (Blair, 2018). According to our results affective empathy and ToM may directly affect parent-reported irritability while the effects of diagnosis (i.e., DMDD and ADHD) on irritability may depend on inattentive and hyperactive/impulsive symptoms. Future studies may evaluate the effects of finer distinctions within the impulsivity construct on irritability, such as cognitive impulsivity and urgency (Cyders & Smith 2008; Kahle et al., 2021), bidirectional relationships, effects of gender and developmental stages. Also, the syndrome of DMDD as per DSM-5 and DSM-5TR may consist of a heterogenous sample of patients differing in terms of tonic and phasic irritability, context dependence, threat bias to angry faces, autonomic nervous system reactivity, and similar constructs (Naim et al., 2022; Vidal-Ribas et al., 2016). Future studies may employ more homogeneous subsamples of children with DMDD classified according to the abovementioned constructs and evaluate whether the relationships between ToM, empathy, inattentive/hyperactive-impulsive symptoms, and levels of irritability differ by subsamples.

Our results should be evaluated within their limitations. First, our results are valid for children with ADHD and ADHD + DMDD evaluated at the study center within the study duration and they may not be valid for children diagnosed at other study centers and those in the community. Second, we strived to enroll patients with ADHD free of comorbidity and it is known that ADHD in children is frequently comorbid with other neurodevelopmental/psychiatric disorders. As such, presence of internalizing/externalizing and other comorbid diagnoses may affect our results for ADHD. Third, we enrolled patients aged between 8 and 12 years and our results may not be valid for adolescents. Fourth, we only used RMET to evaluate ToM skills and our results may be enriched had we evaluated ToM skills with other, more dynamic paradigms (Dziobek et al., 2006). Fifth, we depended on parent reports for measuring irritability and future studies may use clinician evaluations, teacher reports, and electrophysiological measures to better characterize irritability levels among children (Ezpeleta et al., 2020; Hofman et al., 2013; Turan et al., 2022). Sixth, although consisting of factors for cognitive and affective empathy, the KaSi Empathic Tendency Scale for Children and Adolescents involves reading and reflecting on questions for empathic social interactions and it may predominantly tap cognitive, explicit and verbalized subdomains of empathy. Also, the results of this scale may be affected by reporting bias. Therefore, future studies on the relationships between ToM and empathy among children with ADHD and those with ADHD + DMDD may use implicit measures of empathy (Kim et al., 2021). Regardless of those limitations our results may suggest that DMDD comorbid with ADHD may further reduce empathy and ToM levels, weaken the correlations between cognitive and affective empathy domains and accentuate irritability levels. Inattentive symptoms and impaired affective empathy levels may especially contribute to irritability. Children with DMDD + ADHD may benefit from interventions reducing inattentive/hyperactive-impulsive symptoms and consequent to those interventions therapeutic interventions may explicitly target emotion recognition and regulation, empathy, and ToM skills.

Footnotes

Author Contributions

Gonca Özyurt: Conceptualization, Methodology, Writing Yusuf Öztürk.: Data curation, Writing—Original draft preparation. Ali Evren Tufan : Writing—Reviewing and Editing Aynur Akay: Visualization, Investigation. Neslihan Inal: Supervision.

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 iDs

Gonca Özyurt

Yusuf Öztürk

Author Biographies

Gonca Özyurt, MD is a member of the executive committee of the Turkish Association of Child and Adolescent Psychiatry (TACAP) and she has published extensively in international and national peer reviewed journals. She is interested in neuroscience, mood disorders, neurodevelopmental disorders and parent training programs.

Yusuf Öztürk, MD is a member of the TACAP and has published in international and national peer reviewed journals. He is interested in neurodevelopmental disorders, psychotherapeutic approaches and parent training programs.

Ali Evren Tufan, MD is a member of the executive committee of the TACAP and has published extensively in international and national peer reviewed journals. He was selected Donald J Cohen Fellow (2010) and Early Career Psychiatrist Fellow (2011). He is interested in epidemiology, psychopharmacology, neural sciences, and neurodevelopmental disorders.

Aynur Akay, MD is a member of the TACAP and has published in international and national peer reviewed journals She has received many national and international awards She is interested in neurodevelopmental disorders especially ADHD, consultation liaison psychiatry and eating disorders.

Neslihan İnal, MD is the head of TACAP and has published extensively in international and national peer reviewed journals. She was selected to AACAP Ülkü Ülgür, MD, International Scholar Award (2023). She is interested in mood disorders, psychopharmacology, neuroscience, and neurodevelopmental disorders

References

American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). American Psychiatric Association.

American Psychiatric Association. (2022). Diagnostic and statistical manual of mental disorders (5th ed.). American Psychiatric Association.

Arioli

Cattaneo

Ricciardi

Canessa

(2021). Overlapping and specific neural correlates for empathizing, affective mentalizing, and cognitive mentalizing: A coordinate-based meta-analytic study. Human Brain Mapping, 42(14), 4777–4804.

Banks

S. J.

Eddy

K. T.

Angstadt

Nathan

P. J.

Phan

K. L.

(2007). Amygdala–frontal connectivity during emotion regulation. Social Cognitive and Affective Neuroscience, 2(4), 303–312.

Baron-Cohen

Jolliffe

Mortimore

Robertson

(1997). Another advanced test of theory of mind: Evidence from very high functioning adults with autism or Asperger syndrome. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 38(7), 813–822.

Baron-Cohen

Wheelwright

Hill

Raste

Plumb

(2001). The ‘reading the mind in the eyes’ test revised version: A study with normal adults, and adults with Asperger syndrome or high-functioning autism. Journal of Child Psychology and Psychiatry, 42(2), 241–251.

Bird

Viding

(2014). The self to other model of empathy: Providing a new framework for understanding empathy impairments in psychopathy, autism, and alexithymia. Neuroscience & Biobehavioral Reviews, 47, 520–532.

Blair

R. J. R.

(2018). Traits of empathy and anger: Implications for psychopathy and other disorders associated with aggression. Philosophical Transactions of the Royal Society B, 373, 20170155. http://doi.org/10.1098/rstb.2017.0155

Brænden

Coldevin

Zeiner

Stubberud

Melinder

(2023). Executive function in children with disruptive mood dysregulation disorder compared to attention-deficit/hyperactivity disorder and oppositional defiant disorder, and in children with different irritability levels. European Child & Adolescent Psychiatry. Advance online publication. https://doi.org/10.1007/s00787-023-02143-6

10.

Breaux

Eadeh

H. M.

Swanson

C. S.

McQuade

J. D.

(2022). Adolescent emotionality and emotion regulation in the context of parent emotion socialization among adolescents with neurodevelopmental disorders: A call to action with pilot data. Research on Child and Adolescent Psychopathology, 50(1), 77–88.

11.

Cardinale

E. M.

Freitag

G. F.

Brotman

M. A.

Pine

D. S.

Leibenluft

Kircanski

(2021). Phasic versus tonic irritability: differential associations with attention-deficit/hyperactivity disorder symptoms. Journal of the American Academy of Child & Adolescent Psychiatry, 60(12), 1513–1523.

12.

Carré

J. M.

Fisher

P. M.

Manuck

S. B.

Hariri

A. R.

(2012). Interaction between trait anxiety and trait anger predict amygdala reactivity to angry facial expressions in men but not women. Social Cognitive and Affective Neuroscience, 7(2), 213–221. https://doi.org/10.1093/scan/nsq101

13.

Carver

C. S.

Harmon-Jones

(2009). Anger is an approach-related affect: Evidence and implications. Psychological Bulletin, 135(2), 183.

14.

Colonna

Eyre

Agha

S. S.

Thapar

van Goozen

Langley

(2022). Investigating the associations between irritability and hot and cool executive functioning in those with ADHD. BMC Psychiatry, 22(1), 166.

15.

Cowan

Saults

J. S.

Blume

C. L.

(2014). Central and peripheral components of working memory storage. Journal of Experimental Psychology: General, 143(5), 1806.

16.

Cyders

M. A.

Smith

G. T.

(2008). Emotion-based dispositions to rash action: Positive and negative urgency. Psychological Bulletin, 134(6), 807.

17.

DuPaul

G. J.

Power

T. J.

Anastopoulos

A. D.

Reid

(1998). ADHD rating scale—IV: Checklists, norms, and clinical interpretation. Guilford Press.

18.

Dziobek

Fleck

Kalbe

Rogers

Hassenstab

Brand

Kessler

Woike

J. K.

Wolf

O. T.

Convit

(2006). Introducing MASC: A movie for the assessment of social cognition. Journal of Autism and Developmental Disorders, 36, 623–636. https://doi.org/10.1007/s10803-006-0107-0

19.

Evans

S. C.

Roberts

M. C.

Keeley

J. W.

Rebello

T. J.

de la Peña

Lochman

J. E.

Burke

J. D.

Fite

P. J.

Ezpeleta

Matthys

Youngstrom

E. A.

Matsumoto

Andrews

H. F.

Elena Medina-Mora

Ayuso-Mateos

J. L.

Khoury

Kulygina

Robles

Sharan

. . . Reed

G. M.

(2021). 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, and Allied Disciplines, 62(3), 303–312. https://doi.org/10.1111/jcpp.13244

20.

Ezpeleta

Penelo

de la Osa

Navarro

J. B.

Trepat

(2020). How the affective reactivity index (ARI) works for teachers as informants. Journal of Affective Disorders, 261, 40–48. https://doi.org/10.1016/j.jad.2019.09.080

21.

Fantozzi

Muratori

Caponi

M. C.

Levantini

Nardoni

Pfanner

Ricci

Sesso

Tacchi

Milone

Masi

(2021). Treatment with methylphenidate improves affective but not cognitive empathy in youths with attention-deficit/hyperactivity disorder. Children, 8(7), 596.

22.

Fantozzi

Sesso

Muratori

Milone

Masi

(2021). Biological bases of empathy and social cognition in patients with attention-deficit/hyperactivity disorder: A focus on treatment with psychostimulants. Brain Sciences, 11(11), 1399.

23.

Figueiredo

Sudo

Serra-Pinheiro

M. A.

Tripp

Mattos

(2022). Interpersonal negotiation skills in ADHD. Social Neuroscience, 17(1), 86–93.

24.

Frick

P. J.

Ray

J. V.

Thornton

L. C.

Kahn

R. E.

(2014). Can callous-unemotional traits enhance the understanding, diagnosis, and treatment of serious conduct problems in children and adolescents? A comprehensive review. Psychological Bulletin, 140(1), 1.

25.

Golubchik

Weizman

(2017). The possible effect of methylphenidate treatment on empathy in children diagnosed with attention-deficit/hyperactivity disorder, both with and without comorbid oppositional defiant disorder. Journal of Child and Adolescent Psychopharmacology, 27(5), 429–432.

26.

Greenberg

D. M.

Warrier

Abu-Akel

Allison

Gajos

K. Z.

Reinecke

Rentfrow

P. J.

Radecki

M. A.

Baron-Cohen

(2023). Sex and age differences in “theory of mind” across 57 countries using the English version of the “Reading the Mind in the Eyes” test. Proceedings of the National Academy of Sciences of the United States of America, 120(1), e2022385119. https://doi.org/10.1073/pnas.2022385119

27.

Gupta

(2022). Disruptive mood dysregulation disorder: Does variance in treatment responses also add to the conundrum? The widening gap in the evidence is a signal needing attention. CNS Spectrums, 27(6), 659–661.

28.

Haller

S. P.

Stoddard

Botz-Zapp

Clayton

MacGillivray

Perhamus

Stiles

Kircanski

Penton-Voak

I. S.

Bar-Haim

Munafò

Towbin

K. E.

Brotman

M. A.

(2022). A randomized controlled trial of computerized interpretation bias training for disruptive mood dysregulation disorder: A fast-fail study. Journal of the American Academy of Child and Adolescent Psychiatry, 61(1), 37–45. https://doi.org/10.1016/j.jaac.2021.05.022

29.

Hofman

Terburg

van Wielink

Schutter

D. J.

(2013). Coalescence of dominance motivation and responses to facial anger in resting-state and event-related electrophysiology. NeuroImage, 79, 138–144. https://doi.org/10.1016/j.neuroimage.2013.04.088

30.

Kahle

Mukherjee

Dixon

J. F.

Leibenluft

Hinshaw

S. P.

Schweitzer

J. B.

(2021). Irritability predicts hyperactive/impulsive symptoms across adolescence for females. Research on Child and Adolescent Psychopathology, 49(2), 185–196. https://doi.org/10.1007/s10802-020-00723-7

31.

Kaufman

Birmaher

Axelson

Perepletchikova

Brent

Ryan

(2016). K-SADS-PL DSM-5. Western Psychiatric Institute and Clinic.

32.

Kaufman

Birmaher

Brent

Rao

U. M. A.

Flynn

Moreci

Williamson

Ryan

(1997). Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): Initial reliability and validity data. Journal of the American Academy of Child & Adolescent Psychiatry, 36(7), 980–988.

33.

Kaya

Siyez

D. M.

(2010). KA-Sİ çocuk ve ergenler için empatik eğilim ölçeği: Geliştirilmesi geçerlik ve güvenirlik çalışması. Eğitim ve Bilim, 35(156), 110–125.

34.

Kim

S. A.

Hamann

Kim

S. H.

(2021). Neurocognitive mechanisms underlying improvement of prosocial responses by a novel implicit compassion promotion task. NeuroImage, 240, 118333. https://doi.org/10.1016/j.neuroimage.2021.118333

35.

Kocael

. (2015). Irritability in children and adolescents: Turkish validity and reliability study of the affective reactivity index [Unpublished Medicine thesis, Bursa, Uludag University]. Faculty of Medicine.

36.

Levy

Peskin

Kohn

Sheinhorn

Schoen

Weizman

Golubchik

(2022). Callous-unemotional traits and face-emotion recognition as mediators in conduct problems of children with ADHD. Clinical Child Psychology and Psychiatry, 27(4), 978–990.

37.

McDonald

Böckler

Kanske

(2022). Soundtrack to the social world: Emotional music enhances empathy, compassion, and prosocial decisions but not theory of mind. Emotion, 22(1), 19.

38.

Mulraney

M. A.

Melvin

G. A.

Tonge

B. J.

(2014). Psychometric properties of the affective reactivity index in Australian adults and adolescents. Psychological Assessment, 26(1), 148.

39.

Mulraney

Coghill

Bishop

Mehmed

Sciberras

Sawyer

Efron

Hiscock

(2021). A systematic review of the persistence of childhood mental health problems into adulthood. Neuroscience & Biobehavioral Reviews, 129, 182–205.

40.

Mulraney

Schilpzand

E. J.

Hazell

Nicholson

J. M.

Anderson

Efron

Silk

T. J.

Sciberras

(2016). Comorbidity and correlates of disruptive mood dysregulation disorder in 6-8-year-old children with ADHD. European Child & Adolescent Psychiatry, 25(3), 321–330. https://doi.org/10.1007/s00787-015-0738-9

41.

Naim

Haller

S.P.

Linke

J.O.

Jaffe

Stoddard

Jones

Harrewijn

Kircanski

Bar-Haim

Brotman

M. A.

(2022). Context-dependent amygdala–prefrontal connectivity during the dot-probe task varies by irritability and attention bias to angry faces. Neuropsychopharmacology, 47, 2283–2291. https://doi.org/10.1038/s41386-022-01307-3

42.

Ozbaran

N. B.

Ozyasar

S. C.

Dogan

Kafali

H. Y.

Isik

Satar

Kose

Atik

Cogulu

(2022). Evaluation of social cognition, autistic traits, and dysmorphology in comorbid specific learning disorder and attention-deficit/hyperactivity disorder. Clinical Child Psychology and Psychiatry, 27(4), 991–1005.

43.

Özyurt

Öztürk

Akay

(2017). Relation of emotion regulation and empathy skills with maternal emotion regulation and attachment in children diagnosed with ADHD. Anatolian Journal of Psychiatry/Anadolu Psikiyatri Dergisi, 18(6), 611–620.

44.

Özyurt

Öztürk

Appak

Y. Ç.

Arslan

F. D.

Baran

Karakoyun

İ.

Tufan

A. E.

Pekcanlar

A. A.

(2018). Increased zonulin is associated with hyperactivity and social dysfunctions in children with attention deficit hyperactivity disorder. Comprehensive Psychiatry, 87, 138–142.

45.

Pagliaccio

Wiggins

J. L.

Adleman

N. E.

Curhan

Zhang

Towbin

K. E.

Brotman

M. A.

Pine

D. S.

Leibenluft

(2017). Behavioral and neural sustained attention deficits in disruptive mood dysregulation disorder and attention-deficit/hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 56(5), 426–435. https://doi.org/10.1016/j.jaac.2017.02.008

46.

Peterson

(2014). Theory of mind understanding and empathic behavior in children with autism spectrum disorders. International Journal of Developmental Neuroscience, 39, 16–21.

47.

Pijper

de Wied

van Rijn

van Goozen

Swaab

Meeus

(2016). Callous unemotional traits, autism spectrum disorder symptoms and empathy in boys with oppositional defiant disorder or conduct disorder. Psychiatry Research, 245, 340–345.

48.

Schurz

Radua

Tholen

M. G.

Maliske

Margulies

D. S.

Mars

R. B.

Sallet

Kanske

(2021). Toward a hierarchical model of social cognition: A neuroimaging meta-analysis and integrative review of empathy and theory of mind. Psychological Bulletin, 147(3), 293.

49.

Singh

Arun

Bajaj

M. K.

(2021). Theory of mind and executive functions in children with attention deficit hyperactivity disorder and specific learning disorder. Indian Journal of Psychological Medicine, 43(5), 392–398.

50.

Stringaris

Goodman

Ferdinando

Razdan

Muhrer

Leibenluft

Brotman

M. A.

(2012). The affective reactivity index: A concise irritability scale for clinical and research settings. Journal of Child Psychology and Psychiatry, 53(11), 1109–1117.

51.

Tufan

Topal

Demir

Taskiran

Savci

Cansiz

M. A.

Semerci

(2016). Sociodemographic and clinical features of disruptive mood dysregulation disorder: A chart review. Journal of Child and Adolescent Psychopharmacology, 26(2), 94–100.

52.

Turan

Ermiş

Ç.

Eray

Ş.

Yavuz

B. E.

Uzman

Ozbek

M. M.

Tunçtürk

Çıray

R. O.

İnal

(2022). Psychometric properties of the clinician affective reactivity index for assessment of irritability in a clinical sample of Turkish children and adolescents. Scandinavian Journal of Child and Adolescent Psychiatry and Psychology, 10(1), 24–32. https://doi.org/10.2478/sjcapp-2022-0002

53.

Uddin

L. Q.

Nomi

J. S.

Hébert-Seropian

Ghaziri

Boucher

(2017). Structure and function of the human insula. Journal of Clinical Neurophysiology: Official Publication of the American Electroencephalographic Society, 34(4), 300.

54.

Ünal

Öktem

Çetin Çuhadaroğlu

Çengel Kültür

S. E.

Akdemir

Foto Özdemir

Çak

H. T.

Ünal

Tıraş

Aslan

Kalaycı

B. M.

Aydos

B. S.

Kütük

Taşyürek

Karaokur

Karabucak

Karakök

Karaer

Artık

(2019). Reliability and validity of the schedule for affective disorders and schizophrenia for school-age children-present and lifetime version, DSM-5 November 2016-Turkish adaptation (K-SADS-PL-DSM-5-T). Turkish Journal of Psychiatry, 30(1), 42–50.

55.

Uran

Kılıç

B. G.

(2020). Family functioning, comorbidities, and behavioral profiles of children with ADHD and disruptive mood dysregulation disorder. Journal of Attention Disorders, 24(9), 1285–1294.

56.

Vidal-Ribas

Brotman

M. A.

Valdivieso

Leibenluft

Stringaris

(2016). The status of irritability in psychiatry: A conceptual and quantitative review. Journal of the American Academy of Child and Adolescent Psychiatry, 55(7), 556–570. https://doi.org/10.1016/j.jaac.2016.04.014

57.

Whitney

Howe

Shoemaker

Sanders

E. M.

Dijamco

Acquaye

Phillips

Singh

Chang

(2013). Socio-emotional processing and functioning of youth at high risk for bipolar disorder. Journal of Affective Disorders, 148(1), 112–117

58.

Yıldırım

E. A.

Kaşar

Güdük

Ateş

Küçükparlak

Ozalmete

E. O.

(2011). Investigation of the reliability of the “reading the mind in the eyes test” in a Turkish population. Turk Psikiyatri Dergisi = Turkish Journal of Psychiatry, 22(3), 177–186.

59.

Zaki

(2020). Integrating empathy and interpersonal emotion regulation. Annual Review of Psychology, 71, 517–540.

60.

Zhou

Schafer

R. J.

Desimone

(2016). Pulvinar-cortex interactions in vision and attention. Neuron, 89(1), 209–220.