Adolescent substance use outcomes in response to social consequences of use: the role of empathy.

Evidence suggests empathy deficits have a temporal relationship with substance use severity by late adolescence theorized to decrease use via recognition of social consequences. However, this has yet to be tested empirically along with differences in cognitive and affective empathy. Adolescents admitted to substance use treatment (n= 3,382) were followed through treatment and 12 months after treatment. Variable trajectories were fit using growth curve models; and cross-lagged effects of cognitive and affective empathy on response to social consequences of use were tested along with how response to social consequences affected the mean trajectory of substance use. Results indicate higher cognitive empathy predicted greater response to social consequences of use and response to these consequences at the end of treatment predicted a steeper decrease in substance use. This evidence highlights the importance of cognitive empathy for responding to social consequences of use for motivating less substance use in adolescents.

Associations between forms of aggression and peer victimization: Does prosocial behavior matter?

Relatively little is known regarding factors that may mitigate the strength of the associations between forms of aggressive behavior and peer victimization. The goal of the current study was to investigate prosocial behavior as a moderator of these links over a 2-year period during middle childhood. Participants included 410 third-grade students (53% boys) and their homeroom teachers. Results indicated that prosocial behavior was associated with lower initial levels of victimization, whereas relational aggression was associated with higher initial levels of victimization. Physical aggression predicted more stable patterns of victimization over time, and prosocial behavior moderated the prospective link from relational aggression to peer victimization; specifically, relational aggression predicted decreases in victimization at higher levels of prosocial behavior and more stable patterns over time when levels of prosocial behavior were low. Further, gender differences were observed in the moderating effect of prosocial behavior on the prospective link from physical aggression to peer victimization, such that it served as a risk factor for boys and a protective factor for girls.

Executive function and underlying brain network distinctions for callous-unemotional traits and conduct problems in adolescents.

The complexity of executive function (EF) impairments in youth antisocial phenotypes of callous-unemotional (CU) traits and conduct problems (CP) challenge identifying phenotypic specific EF deficits. We can redress these challenges by (1) accounting for EF measurement error and (2) testing distinct functional brain properties accounting for differences in EF. Thus, we employed a latent modeling approach for EFs (inhibition, shifting, fluency, common EF) and extracted connection density from matching contemporary EF brain models with a sample of 112 adolescents (ages 13-17, 42% female). Path analysis indicated CU traits associated with lower inhibition. Inhibition network density positively associated with inhibition, but this association was strengthened by CU and attenuated by CP. Common EF associated with three-way interactions between density*CP by CU for the inhibition and shifting networks. This suggests those higher in CU require their brain to work harder for lower inhibition, whereas those higher in CP have difficulty engaging inhibitory brain responses. Additionally, those with CP interacting with CU show distinct brain patterns for a more general EF capacity. Importantly, modeling cross-network connection density in contemporary EF models to test EF involvement in core impairments in CU and CP may accelerate our understanding of EF in these phenotypes.

Cognitive Mechanisms Underlying Prosocial Decision Making in Callous-Unemotional Traits.

Callous-unemotional (CU) traits are characterized by a lack of prosocial emotions, which has been demonstrated with prosocial behavior paradigms. While shaping our understanding of prosocial behavior in youth with CU traits, most of this work relies on outcomes that don't reliably capture cognitive processes during prosocial behavior. Examining prosocial cognitive processes can cue researchers into cognitive mechanisms underlying core impairments of CU traits. Drift diffusion modeling is a valuable tool for elucidating more precise outcomes of latent cognitive processes during forced choice tasks such as drift rate (information accumulation toward a decision boundary) and threshold separation (amount of information considered) as well as metrics outside of the decision-making processing including bias (starting point in decision process) and non-decision time (cognitive processes outside of choice). In a sample of 87 adolescents (12-14, 49% female) we applied diffusion modeling to a prosocial behavior task in which participants either accepted or rejected trials where a real monetary value was given to them and taken away from a charity (self-serving trial) or money was given to a charity and taken from them (donation trial). Results revealed that CU traits associated with information accumulation toward accepting self-serving trials. Exploratory sex differences suggested males trended toward rejecting donation trials and females considered more information during self-serving trials. CU trait associations were independent of conduct problems. Results suggest a unique cognitive profile that are differentiated by sex at higher CU traits when making prosocial decisions involving knowledge accumulation toward self-serving decisions.

Connectome-based predictive modeling of empathy in adolescents with and without the low-prosocial emotion specifier.

Empathy impairments are an important part of a broader affective impairments defining the youth antisocial phenotype callous-unemotional (CU) traits and the DSM-5 low prosocial emotion (LPE) specifier. While functional connectivity underlying empathy and CU traits have been well studied, less is known about what functional connections underly differences in empathy amongst adolescents qualifying for the LPE specifier. Such information can provide mechanistic distinctions for this clinically relevant specifier. The present study uses connectome-based predictive modeling that uses whole-brain resting-state functional connectivity data to predict cognitive and affective empathy for those meeting the LPE specifier (n = 29) and those that do not (n = 57). Additionally, we tested if models of empathy generalized between groups as well as density differences for each model of empathy between groups. Results indicate the LPE group had lower cognitive and affective empathy as well as higher CU traits and conduct problems. Negative and positive models were identified for affective empathy for both groups, but only the negative model for the LPE and positive model for the normative group reliably predicted cognitive empathy. Models predicting empathy did not generalize between groups. Density differences within the default mode, salience, executive control, limbic, and cerebellar networks were found as well as between the executive control, salience, and default mode networks. And, importantly, connections between the executive control and default mode networks characterized empathy differences the LPE group such that more positive connections characterized cognitive differences and less negative connections characterized affective differences. These findings indicate neural differences in empathy for those meeting LPE criteria that may explain decrements in empathy amongst these youth. These findings support theoretical accounts of empathy decrements in the LPE clinical specifier and extend them to identify specific circuits accounting for variation in empathy impairments. The identified negative models help understand what connections inhibit empathy whereas the positive models reveal what brain patterns are being used to support empathy in those with the LPE specifier. LPE differences from the normative group and could be an appropriate biomarker for predicting CU trait severity. Replication and validation using other large datasets are important next steps.

Efficiency of Heterogenous Functional Connectomes Explains Variance in Callous-Unemotional Traits After Computational Lesioning of Cortical Midline and Salience Regions.

Introduction: Callous-unemotional (CU) traits are a youth antisocial phenotype hypothesized to be a result of differences in the integration of multiple brain systems. However, mechanistic insights into these brain systems are a continued challenge. Where prior work describes activation and connectivity, new mechanistic insights into the brain's functional connectome can be derived by removing nodes and quantifying changes in network properties (hereafter referred to as computational lesioning) to characterize connectome resilience and vulnerability. Methods: Here, we study the resilience of connectome integration in CU traits by estimating changes in efficiency after computationally lesioning individual-level connectomes. From resting-state data of 86 participants (48% female, age 14.52 ± 1.31) drawn from the Nathan Kline institute's Rockland study, individual-level connectomes were estimated using graphical lasso. Computational lesioning was conducted both sequentially and by targeting global and local hubs. Elastic net regression was applied to determine how these changes explained variance in CU traits. Follow-up analyses characterized modeled node hubs, examined moderation, determined impact of targeting, and decoded the brain mask by comparing regions to meta-analytic maps. Results: Elastic net regression revealed that computational lesioning of 23 nodes, network modularity, and Tanner stage explained variance in CU traits. Hub assignment of selected hubs differed at higher CU traits. No evidence for moderation between simulated lesioning and CU traits was found. Targeting global hubs increased efficiency and targeting local hubs had no effect at higher CU traits. Identified brain mask meta-analytically associated with more emotion and cognitive terms. Although reliable patterns were found across participants, adolescent brains were heterogeneous even for those with a similar CU traits score. Conclusion: Adolescent brain response to simulated lesioning revealed a pattern of connectome resiliency and vulnerability that explains variance in CU traits, which can aid prediction of youth at greater risk for higher CU traits.

Affective theory of mind impairments underlying callous-unemotional traits and the role of cognitive control.

Affective theory of mind (aToM) impairments associated with the youth antisocial phenotype callous-unemotional (CU) traits predict antisocial behaviour above CU traits alone. Importantly, CU traits associate with decrements in complex but not basic aToM. aToM is modulated by cognitive control and CU traits associate with cognitive control impairments; thus, cognitive control is a plausible mechanism underlying aToM impairments in CU traits. Because cognitive control is dependent on the availability of cognitive resources, youth with CU traits may have difficulty with allocating cognitive resources under greater demands that impact complex aToM. To test this, 81 participants (ages 12-14, Female = 51.8%, Male = 48.2%) were recruited to complete a behavioural paradigm that involved an initial aToM task with complex and basic emotions followed by placing additional demands on cognitive control and a final repeat of the same aToM task. Results indicate adolescents higher in CU traits had intact basic aToM but less accuracy in complex aToM that worsened after taxing cognitive control; and this load only required a short duration to account for ToM decrements (200 ms [range 150-1600 ms]). These results demonstrate CU traits association with cognitive control limitations that impact complex aToM. This may partially explain antisocial behaviour associated with CU traits.

A revised prosocial behavior game: Testing associations with psychopathic traits and the effects of moral elevation using a randomized clinical trial.

BACKGROUND: Prosocial behavior is negatively associated with psychopathic traits and paradigms which measure prosocial behavior in the laboratory may be useful in better understanding moderators of this association. METHODS: We revised a previously validated game of prosocial behavior by including a new trial type (i.e., trials where the participant will lose money and the charity will gain money). This version of the game was administered online and participants were randomized to group (exposed to a control stimulus video or a video used to elicit moral elevation, i.e. a positive response to witnessing another's act of kindness). We used repeated game administration to test whether a moral elevation stimulus affected game behavior and moderated the negative association between psychopathic traits and prosocial behavior. RESULTS: Prosocial behavior on the new trial types added in this revised game correlated strongly with prosocial behavior on the old trial type (i.e., trials where the participant will gain money and the charity will lose money; r = 0.71; p-value<0.001; n = 485). Graphing trial acceptance rates by trial characteristics demonstrated expected patterns of behavior. Number of prosocial choices on the game correlated with psychopathic trait score (Levenson Factor 1 score; r = -0.52; p-value<0.001). Game repetition with a control stimulus in between runs, supported high immediate test-retest reliability of overall game behavior. Exposure to the moral elevation stimulus in between runs did not affect game behavior nor moderate the association between psychopathic traits and prosocial behavior. CONCLUSIONS: Choices on this revised game of prosocial behavior, which can be administered online, are associated with psychopathic traits scores. The game appears to have high immediate test-retest reliability. Exposure to the moral elevation stimulus did not affect prosocial behavior or impact the relationship between psychopathic trait scores and prosocial behavior. Future research should continue to test potential moderators of this relationship. Limitations of the current study are discussed.

Resting-state connectivity underlying cognitive control's association with perspective taking in callous-unemotional traits.

Callous-Unemotional (CU) traits are often associated with impairments in perspective taking and cognitive control (regulating goal directed behavior); and adolescents with CU traits demonstrate aberrant brain activation/connectivity in areas underlying these processes. Together cognitive control and perspective taking are thought to link mechanistically to explain CU traits. Because increased cognitive control demands modulate perspective taking ability among both typically developing samples and individuals with elevated CU traits, understanding the neurophysiological substrates of these constructs could inform efforts to alleviate societal costs of antisocial behavior. The present study uses GIMME to examine the heterogenous functional brain properties (i.e., connection density, node centrality) underlying cognitive control's influence on perspective taking among adolescents on a CU trait continuum. Results reveal that cognitive control had a negative indirect association with CU traits via perspective taking; and brain connectivity indirectly associated with lower CU traits - specifically the social network via perspective taking and conflict network via cognitive control. Additionally, less negative connection density between the social and conflict networks was directly associated with higher CU traits. Our results support the growing literature on cognitive control's influence on socio-cognitive functioning in CU traits and extends that work by identifying underlying functional brain properties.

Cognitive and Affective Empathy as Indirect Paths Between Heterogeneous Depression Symptoms on Default Mode and Salience Network Connectivity in Adolescents.

Depression amongst adolescents is a prevalent disorder consisting of heterogeneous emotional and functional symptoms-often involving impairments in social domains such as empathy. Cognitive and affective components of empathy as well as their associated neural networks (default mode network for cognitive empathy and salience network for affective empathy) are affected by depression. Depression commonly onsets during adolescence, a critical period for brain development underlying empathy. However, the available research in this area conceptualizes depression as a homogenous construct, and thereby miss to represent the full spectrum of symptoms. The present study aims to extend previous literature by testing whether cognitive and affective empathy indirectly account for associations between brain network connectivity and heterogeneous depression symptoms in adolescents. Heterogeneous functional and emotional symptoms of depression were measured using the child depression inventory. Our results indicate that cognitive empathy mediates the association between default mode network functional connectivity and emotional symptoms of depression. More specifically, that adolescents with a stronger positive association between the default mode network and cognitive empathy show lower emotional depression symptoms. This finding highlights the importance of cognitive empathy in the relationship between brain function and depression symptoms, which may be an important consideration for existing models of depression in adolescents.

Adolescents in Treatment for Substance Use Disorders: Callous-Unemotional Traits Moderate Associations Between Transdiagnostic Symptoms and Adolescent Suicidality.

Suicide, a common cause of death in adolescents, is linked to internalizing and externalizing symptoms. These associations are pronounced amongst adolescents who use substances. But these relationships are complex. For example, sex differences are present in association with internalizing/externalizing symptoms as well as differences in suicidality. A rarely explored factor that may account for this complexity as a moderator is callous-unemotional traits. The present study examines associations of internalizing and externalizing in relation to suicidality in the context of callous-unemotional traits amongst adolescents in substance use treatment. Additionally, sex differences were explored. A sample of 317 adolescents (13-18; 16.05 ± 1.22) in treatment for substance use completed measures for internalizing, externalizing, and suicidal symptoms. The main result suggested the presence of callous-unemotional (CU) traits attenuated the positive association between internalizing and a latent suicidality factor. This novel result contextualizes the association between transdiagnostic symptoms and suicidality. Assessing CU traits in the presence of internalizing symptoms may be an important component of understanding suicide risk amongst adolescents in treatment for substance use.

Emotion Identification for Self and Other Associated with Callous-Unemotional Traits and Sex Differences in Early Adolescents.

Callous-unemotional traits (CU) associates with impairments in emotional responsivity. However, there is less evidence on associations with specific emotions and sex differences utilizing both self and other oriented emotional stimuli. Given that the nuance of associations with specific emotions (including sex effects) is critical for understanding core impairments of this antisocial phenotype, the current study employed a behavioral paradigm with both self and other emotional stimuli for specific emotions (happy, sad, anger, fear, neutral) with a sample of male and female early adolescents (females = 51%, age = 12.86 ± 0.75). We examined accuracy and reaction times on this task, along with moderating effects of sex, in relation to CU traits. Results indicate CU traits associated with overall self-emotions negatively and sex moderated CU traits negative association with recognizing others overall emotions. CU traits negatively associated with accurate identification of both self and other emotions (happy, sad, and fear). Sex moderated all other emotion identification but only sad emotions for self. No reaction time differences were found. These findings evidence important nuance in CU traits and sex effects with identifying self and other emotions. Results have important implications for clinical understanding of sex differences in CU traits that require further consideration.

Associated functional network connectivity between callous-unemotionality and cognitive and affective empathy.

BACKGROUND: Low empathy is one component of affective impairments defining the antisocial youth phenotype callous-unemotional (CU) traits. Research suggests CU traits may be negatively associated with neural networks that are positively associated with cognitive and affective empathy - specifically the default mode (DMN), frontoparietal (FPN), and salience (SAL) networks. Determining which functional network connections are shared between CU traits and empathy could elucidate the extent to which CU traits shares neural substrates with cognitive versus affective empathy. The present study tested whether CU traits and both cognitive and affective empathy share network connections within and between the DMN, FPN, and SAL. METHODS: Participants (n = 112, aged 13-17, 43 % female) completed resting-state functional magnetic resonance imaging and self-reports for CU traits and empathy as part of a Nathan-Kline Institute study. RESULTS: Analyses revealed inverse associations with shared network connections between CU traits and both cognitive and affective empathy. Specifically, within-DMN connectivity negatively associated with CU traits, but positively associated with cognitive empathy; and between DMN-SAL connectivity positively associated with CU traits, but negatively associated with both cognitive and affective empathy. However, joint models revealed little variance explained by CU traits and empathy overlapped. LIMITATIONS: The sample was cross-sectional collection with limited participants (n = 112) from the community that may not generalize to incarcerated adolescents. CONCLUSIONS: Results demonstrate CU traits inversely associated with similar connectivity patterns as cognitive and affective empathy though prediction among constructs did not significantly overlap. Further investigation of these connections can inform a mechanistic understanding of empathy impairments in CU traits.

Callous-unemotional traits in adolescents moderate neural network associations with empathy.

Callous-unemotional (CU) traits in adolescents are a dimensional construct involving a symptom subset of empathy impairments amongst broader affective deficits. Higher CU trait scores associate with less cognitive and affective empathy; and brain regions linked with cognitive and affective empathy show aberrant function in those with CU traits. How CU traits impact the relationship between brain function and both cognitive and affective empathy in adolescents is less clear. Here we examine how functional properties of networks that support cognitive and affective empathy is moderated by CU traits. Eighty-four adolescents underwent resting-state fMRI scanning and completed self-reports for empathy (Interpersonal Reactivity Index) and CU traits (Inventory of Callous-Unemotional Traits). Analysis revealed that CU traits moderate the association between affective empathy and connectivity between the default mode-frontoparietal networks. Weaker between default mode-frontoparietal anticorrelation negatively associated with affective empathy at low to moderate CU traits. Those highest in CU traits had the lowest affective empathy; and negative associations for those highest in CU traits were insignificant as default mode-frontoparietal anticorrelation weakened. Our results indicate that functional properties of networks that support affective empathy is different at varying levels of CU traits. This novel finding demonstrates that CU traits presence changes the relationship between the brain and empathy.

Resting-state network topology characterizing callous-unemotional traits in adolescence.

BACKGROUND: Callous-unemotional (CU) traits, a youth antisocial phenotype, are hypothesized to associate with aberrant connectivity (dis-integration) across the salience (SAL), default mode (DMN), and frontoparietal (FPN) networks. However, CU traits have a heterogeneous presentation and previous research has not modeled individual heterogeneity in resting-state connectivity amongst adolescents with CU traits. The present study models individual-specific network maps and examines topological features of individual and subgroup maps in relation to CU traits. METHODS: Participants aged 13-17 (n = 84, male = 55%, female = 45%) completed resting-state functional connectivity and the inventory of callous-unemotional traits as part of the Nathan Klein Rockland study. A sparse network approach (GIMME) was used to derive individual-level and subgroup maps of all participants. We then examined heterogeneous network features, including positive and negative connection density, associated with CU traits. RESULTS: Higher rates of CU traits increased probability of inclusion in one subgroup, which had the highest mean level of CU traits. Analysis of network features reveals less density (positive and negative) within the FPN and greater density between DMN-FPN associated with CU traits. DISCUSSION: Findings indicate heterogeneous person-specific connections and some subgroup connections amongst adolescents associate with CU traits. Higher CU traits associate with lower density in the FPN, which has been associated with attention and inhibition, and higher density between the DMN-FPN, which have been linked with cognitive control, social working memory, and empathy. Our findings suggest less efficiency in FPN function which, when considered mechanistically, could result in difficulty suppressing DMN when task positive networks are engaged. This is an area for further exploration but could explain cognitive and socio-affective impairments in CU traits.

Network functional connectivity underlying dissociable cognitive and affective components of empathy in adolescence.

Empathy, the capacity to understand and share others' emotions, can occur through cognitive and affective components. These components are different conceptually, behaviorally, and in the brain. Neuroimaging task-based research in adolescents and adults document that cognitive empathy associates with the default mode and frontoparietal networks, whereas regions of the salience network underlie affective empathy. However, cognitive empathy is slower to mature than affective empathy and the extant literature reveals considerable developmental differences between adolescent and adult brains within and between these three networks. We extend previous work by examining empathy's association with functional connectivity within and between these networks in adolescents. Participants (n = 84, aged 13-17; 46.4% female) underwent resting state fMRI and completed self-report measures (Interpersonal Reactivity Index) for empathy as part of a larger Nathan-Kline Institute study. Regression analyses revealed adolescents reporting higher cognitive empathy had higher within DMN connectivity. Post hoc analysis revealed cognitive empathy's association within DMN connectivity is independent of affective empathy or empathy in general; and this association is driven by positive pairwise connections between the bilateral angular gyri and medial prefrontal cortex. These results suggest introspective cognitive processes related to the DMN are specifically important for cognitive empathy in adolescence.

Systematic review and meta-analysis of socio-cognitive and socio-affective processes association with adolescent substance use.

BACKGROUND: Social impairments are important features of a substance use disorder diagnosis; and recent models suggest early impairments in socio-cognitive and -affective processes may predict future use. However, no systematic reviews are available on this topic. METHODS: We conducted a systematic review and meta-analyses exploring the association between social-cognitive and -affective processes (empathy, callous-unemotional (CU) traits, theory of mind, and social cognition) and substance use frequency (alcohol, cannabis, general drug use). We examined moderating effects of study design, gender, age, and weather conduct problems were controlled for. We also review brain studies related to social cognition and substance use disorder (SUD) risk. RESULTS: Systematic review suggested a negative association for positively valenced constructs with substance use but mixed results on the negatively valenced construct CU traits. Meta-analyses revealed moderate positive association between CU traits with alcohol and general drug use but no significance with cannabis use. Moderate effect sizes were found for CU traits in youth predicting severity of substance use by late adolescence and significantly accounted for variance independently of conduct problems. Significant moderators included gender proportions, sample type, and age. Neuroimaging meta-analysis indicated 10 coordinates that were different in youth at a high risk/with SUD compared to controls. Three of these coordinates associate with theory of mind and social cognition. CONCLUSION: Socio-cognitive and -affective constructs demonstrate an association with current and future substance use, and neural differences are present when performing social cognitive tasks in regions with strongest associations with theory of mind and social cognition.

Longitudinal Effects of Cognitive and Affective Empathy on Adolescent Substance Use.

Background: A deficit in either socio-cognitive or socio-affective components of empathy is associated with the severity of substance use by late adolescence. What remains unknown is how longitudinal changes in these components of empathy predict adolescent substance using behavior. Methods: This secondary data analysis used data that followed adolescents in outpatient treatment for substance use (n = 826) during treatment and at 6 months post-treatment. To examine cross-lagged effects of empathy on substance use over time, we used a latent basis growth curve model. Results: Increases in affective empathy predicted reduced substance use over time. However, cognitive empathy did not predict substance use after controlling for other covariates. Conclusions: Lower levels of affective empathy may indicate a developmental vulnerability for substance using behavior. Modifying affective empathy may be a viable treatment target for reducing adolescent substance use.

Concrete services usage on child placement stability: Propensity score matched effects.

BACKGROUND: Experiencing poverty and financial difficulties are significant barriers to outcomes of permanency and placement stability. This is particularly true for children who are in out of home placements. The provision of concrete services is intended to meet concrete needs of families to address this barrier. However, little is known about how concrete services meet the needs of families in need of these services or if the use of concrete services is a viable treatment for children who are in out of home placements. METHODS: The present study examined differences between those who received and those who did not receive concrete services on factors of stability, child and caregiver traumatic stress, number of placements, and current out of home placement. Regression analysis examined the association between amount of concrete service spending and permanency. Then to test concrete services as an intervention for children in a current out of home placement, we used propensity score matching to match participants on characteristics that predicted whether they would receive concrete services. We then ran a hierarchical regression to test the treatment condition of concrete services with children who are in a current out of home placement. RESULTS: Participants who received concrete services were at a much higher level of need with significantly higher levels of traumatic stress and number of placements and lower levels of placement stability. The amount of money spent on concrete services was associated with increases in placement stability. And, children in a current out of home placement had an increase in placement stability when they received concrete services. CONCLUSIONS: The present study is the first to evidence concrete service as a treatment for placement stability for children in current out of home placements. Spending on concrete services in addition to child welfare services improves a child's current placement stability. This is an important finding with implications for improving child welfare services' approach to those in their care with financial burdens.

Improvements in Irritability with Open-Label Methylphenidate Treatment in Youth with Comorbid Attention Deficit/Hyperactivity Disorder and Disruptive Mood Dysregulation Disorder.

OBJECTIVE: The purpose of this open-label study was to examine the effects of long-acting methylphenidate (MPH) treatment on irritability and related emotional symptoms associated with disruptive mood dysregulation disorder (DMDD) in youth with comorbid attention-deficit/hyperactivity disorder (ADHD). METHODS: The sample included 22 medication-free male and female subjects (ages 9-15) who met criteria for both DMDD and ADHD. Participants underwent a 4-week trial of long-acting MPH treatment (Concerta®), with weekly dosing increases until a therapeutic dose was reached. Repeated measures t-tests were used to compare pre- and posttreatment ratings of primary and secondary measures. The primary outcome was self-report irritability. Secondary outcomes included parent and child ratings of emotional frequency, emotional lability, and negative affect (NA). Multiple regression was used to examine the impact baseline hyperactivity, age, gender, race, socioeconomic status, or comorbid diagnosis had on treatment outcomes. RESULTS: Significant improvements (medium to large effect sizes) in child-rated irritability as well as parent and child ratings of emotional lability, NA, and anger were found. As anticipated, ADHD symptoms also improved. While a majority of the sample saw improvement in child-rated irritability (71%), symptoms worsened a small proportion (19%), and an even smaller portion experienced no change (10%). No demographics, psychiatric comorbidities, or severity of ADHD symptoms influenced treatment outcomes. CONCLUSIONS: Study findings suggest that MPH treatment significantly improved mood and emotional symptoms associated with DMDD comorbid with ADHD. These findings, coupled with good tolerability in this open-label pilot study supports further research into the use of MPH as a first-line treatment for DMDD. Future work examining MPH treatment of youth with DMDD with and without comorbid ADHD is needed.