What I see, what you say: How cross-method variation sharpens characterization of irritability in early childhood.

OBJECTIVES: Identification of clinically significant irritability in preschool age is important to implement effective interventions. However, varying informant and measurement methods display distinct patterns. These patterns are associated with concurrent and future mental health concerns. Patterns across multi-informant methods in early-childhood irritability may have clinical utility, identifying risk for impaired psychosocial functioning. METHODS: Using data from the Multidimensional Assessment of Preschoolers Study (N = 425), latent profile analysis identified irritability patterns through the parent-reported Multidimensional Assessment Profile Scales-Temper Loss (MAPS-TL), parent-reported interviewer-rated Preschool Age Psychiatric Assessment (PAPA), and observer-rated Disruptive Behavior Diagnostic Observation Schedule (DB-DOS). These profiles were characterized on protective factors, global functioning, and mental health syndromes, concurrently and at early school age and preadolescent follow-up. RESULTS: Fit indices favored a five-class model: Low All, High Observation with Examiner (high DB-DOS Examiner Context), High All, High Parent Report (high MAPS-TL/PAPA), and Very High Parent Report (very high MAPS-TL/PAPA). Whereas Low All and High Observation with Examiner exhibited strong psychosocial functioning, remaining profiles showed impaired psychosocial functioning, with the Very High Parent Report group showing higher impairment at follow-ups, ds = 0.37-1.25. CONCLUSIONS: Multi-informant measurements of irritability may have utility for clinical prediction, and future studies should test utility for diagnostic precision.

Developmental Trajectories of Irritability across the Transition to Toddlerhood: Associations with Effortful Control and Psychopathology.

Preschool-age irritability is a transdiagnostic marker of internalizing and externalizing problems. However, researchers have generally been reluctant to examine irritability within a clinically salient framework at younger ages due to some instability during the "terrible twos" period. Developmentally sensitive and dense measurements to capture intra- and inter-individual variability, as well as exploration of developmental processes that predict change, are needed. This study aimed to examine (1) the trajectories of irritability at the transition to toddlerhood (12-24 months of age) using repeated measures, (2) whether effortful control was associated with individual differences in level and growth rate of irritability, and (3) whether individual differences in the irritability trajectories were associated with later psychopathology. Families were recruited when the child was 12-18 months old (N = 333, 45.65% female). Mothers reported on their toddler's irritability at baseline and every two months until a follow-up laboratory assessment approximately one year later. Effortful control was measured at baseline. Clinical internalizing/externalizing symptoms were measured at the follow-up assessment. Hierarchical linear models revealed an increase in irritability over time, yet there was relatively little within-person variability. Effortful control was only associated with the level of irritability and not growth rate. Level of irritability was associated with internalizing, externalizing, and combined symptoms, but growth rate was not. Findings suggest intraindividual stability in irritability at the transition to toddlerhood and the possibility that screening for elevated irritability at toddler age is meaningful.

Characterizing the spectrum of irritability in preadolescence: Dimensional and pragmatic applications.

OBJECTIVES: Characterize the dimensional spectrum of preadolescent (PA) irritability, a robust transdiagnostic vulnerability marker, using the youth version of the Multidimensional Assessment Profiles Temper Loss (MAPS-TL-Youth) scale including common and with developmentally specific items. Based on this, derive and validate a clinically optimized irritability screener to flag psychopathology risk in preadolescents. METHODS: The normal:abnormal irritability spectrum was modeled using MAPS-TL-Youth data from the Multidimensional Assessment of Preschoolers Study (MAPS) Study PA wave (n = 340) via item response theory. Both cross-cutting core items from the MAPS scales and developmentally specific items were used to generate this dimension. Stepwise logistic regression was then used to optimize MAPS-TL-Youth irritability items in relation to Kiddie Schedule of Affective Disorders and Schizophrenia impairment to generate a clinically optimized irritability screener. Receiver operator characteristic analysis identified the irritability threshold for the screener. For the first time, youth self-report of their own irritability on the MAPS-TL was also modeled via the MAPS-TL-Youth-Self-Report (MAPS-TL-Youth-SR). RESULTS: Irritability was unidimensional and ranged from mild and common to severe and rare behaviors. Developmentally specific items allowed detection of more severe irritability. Items for the screener were identified in relation to concurrent impairment. These included low frustration tolerance and pathognomonic severe behaviors. The clinically optimized screener demonstrated very good sensitively (87%) and specificity (81%) in regard to concurrent irritability-related DSM disorders. Modeling of the MAPS-TL-Youth-SR yielded similar results. CONCLUSION: Characterizing the normal: abnormal spectrum of irritability in preadolescence advances application of Research Domain Criteria methods to this developmental period. This foundational work yielded two developmentally specified tools for irritability characterization in preadolescence: a nuanced dimensional scale to precisely characterize the full normal-abnormal irritability spectrum, and a pragmatic, clinically optimized screener suitable for real world use. Future application in mechanistic and clinical studies will be important for establishing validity and incremental utility.

MAPping affective dimensions of behavior: Methodologic and pragmatic advancement of the Multidimensional Assessment Profiles scales.

Rigorous validation of the full developmentally sensitive normal:abnormal spectrum, including evaluating the incremental value of age-specific behaviors, is necessary for nuanced characterization of dimensional features of psychopathology. To maximize the clinical utility of transdiagnostic approaches to risk identification, derivation of psychometrically sound, pragmatic versions with empirically derived cutoffs is also key. This special section has a central focus on rigorous, developmentally-based measurement of irritability as an exemplar of this theory- and pragmatically-based approach. Elevated irritability is a robust transdiagnostic predictor of the common psychopathologies of childhood. The Multidimensional Assessment Profiles Temper Loss (MAPS-TL) Scales are the only irritability tool specifically designed to capture the normal:abnormal dimensional spectrum. These have been extensively investigated in preschool age but lack rigorous modeling at older and younger ages. In this special issue, (with three independent-and one longitudinal-set of samples), we test and improve measurement of irritability as a transdiagnostic phenotype of psychopathology risk as it unfolds across development, expanding the MAPS-TL scale in three important ways: (1) extending irritability dimensional modeling and the developmental specification approach to older ages, (2) advancing science to practice translation by generating pragmatic irritability screening tools across ages, and (3) extending the dimensional, developmental specification approach to other dimensions of behavior, that is, internalizing. Collectively, the special issue operationalizes and advances application of a neurodevelopmental, dimensional and transdiagnostic approach to psychopathology.

A pragmatic, clinically optimized approach to characterizing adolescent irritability: Validation of parent- and adolescent reports on the Multidimensional Assessment Profile Scales-Temper Loss Scale.

OBJECTIVES: Heightened irritability in adolescence is an impairing symptom that can lead to negative outcomes in adulthood, but effective screening tools are lacking. This study aimed to derive clinically-optimized cutoff scores using the Multidimensional Assessment Profile Scales-Temper Loss (MAPS-TL) to pragmatically identify adolescents with impairing irritability. METHODS: A diverse sample of 79 adolescents and their parents completed the MAPS-TL-Youth version. Stepwise logistic regression analyses were used to determine the items associated with impairment, and receiver operator characteristic (ROC) analyses were conducted to derive optimal cutoff scores. RESULTS: Three parent-report items (become frustrated easily, angry/irritable/grouchy throughout the day, difficulty calming down when angry) and two youth-report items (hit/shove/kick when lost temper, difficulty calming down when angry) were strongly associated with impairment. Optimal cutoff scores garnered very good sensitivity (91%, 73%) and specificity (77%, 75%) for the parent- and youth-report versions respectively. Scores above these cutoffs were associated with increased internalizing and externalizing problems and lower overall quality of life. CONCLUSIONS: The MAPS-TL clinically optimized irritability scores show preliminary validity for implementation in practical settings to efficiently identify adolescents who need additional evaluation and/or intervention. Further research is important to validate these cutoff scores with larger population-based samples and real-world settings.

Prevalence, stability, and predictive utility of the Multidimensional Assessment of Preschoolers Scales clinically optimized irritability score: Pragmatic early assessment of mental disorder risk.

OBJECTIVES: Characterizing the scope and import of early childhood irritability is essential for real-world actualization of this reliable indicator of transdiagnostic mental health risk. Thus, we utilize pragmatic assessment to establish prevalence, stability, and predictive utility of clinically significant early childhood irritability. METHODS: Data included two independent, diverse community samples of preschool age children (N = 1857; N = 1490), with a subset enriched for risk (N = 425) assessed longitudinally from early childhood through preadolescence (∼4-9 years old). A validated, brief (2-item) scale pragmatically assessed clinically significant irritability. In the longitudinal subsample, clinical interviews assessed internalizing/externalizing disorders. RESULTS: One in five preschool-age children had clinically significant irritability, which was independently replicated. Irritability was highly stable through preadolescence. Children with versus without clinically significant early childhood irritability had greater odds of early onset, persistent internalizing/externalizing disorders. The pragmatic assessment effectively screened out low-risk children and identified 2/3 of children with early-onset, persistent psychopathology. CONCLUSIONS: Clinically significant early childhood irritability prevalence is akin to the pediatric obesity epidemic and may warrant similar universal screening/intervention. Also, irritability's stability demonstrates the common guidance "they'll grow out of it" to be false. Finally, pragmatic irritability assessment has transdiagnostic predictive power and addresses a need for feasible measures to flag risk.

Advancing earlier transdiagnostic identification of mental health risk: A pragmatic approach at the transition to toddlerhood.

OBJECTIVES: In light of the youth mental health crisis, as 1 in 5 children have a mental disorder diagnosis by age 3, identification of transdiagnostic behavioral vulnerability prior to impairing psychopathology must occur at an earlier phase of the clinical sequence. Here, we lay the groundwork for a pragmatic irritability measure to identify at-risk infant-toddlers. METHODS: Data comprised N = 350 diverse infant-toddlers and their mothers assessed at ∼14 months old for irritability (Multidimensional Assessment Profiles- Temper Loss-Infant/Toddler (MAPS-TL-IT) and impairment (Early Childhood Irritability-Related Impairment Interview, E-CRI; and Family Life Impairment Scale (FLIS). Bimonthly follow-up surveys assessed impairment (FLIS) over the following year. RESULTS: Stepwise logistic regression indicated that 5 MAPS-TL-IT items were most informative for differentiating concurrent impairment on the FLIS: "frustrated about small things"; "hit, bite, or kick during tantrums"; "trouble cheering up when grumpy"; "grumpy during fun activities" and "tantrums in public". With this summed score, Receiver Operating Characteristics analysis differentiating concurrent impairment on the E-CRI indicated good classification accuracy for (Area under the curve = 0.755, p < 0.05), with a cutoff of 5 maximizing sensitivity (71.4%) and specificity (70.6%). Elevated irritability on this MAPS-TL-IT clinically optimized screener increased likelihood of persistently elevated FLIS impairment trajectories over the following year more than fourfold (OR = 4.37; Confidence intervals = 2.40-7.97, p < 0.001). CONCLUSIONS: Our findings represent the first step toward a pragmatic tool for screening for transdiagnostic mental health risk in toddlers, optimized for feasibility in clinical care. This has potential to strengthen resilience pathways via earlier identification of mental health risk and corollary prevention in toddlers.

Neural correlates of irritability symptom relief in adolescents pre- and post-trauma-focused cognitive behavioral therapy: A pilot study on reward processing.

Despite that Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) is a first-line, evidence-based treatment for youths experiencing trauma-related symptoms, treatment responses vary and it remains unclear for whom and how this treatment works. In this context, we examined pre-treatment neural reward processing and pre- vs. post-treatment changes in neural reward processing, in relation to irritability - a transdiagnostic and dimensional feature present in multiple trauma-related syndromes, following TF-CBT. Adolescents (N = 22) with childhood trauma history completed a child-friendly monetary incentive delay task during fMRI acquisition, prior to and after the treatment, and irritability symptoms were assessed at five time points over the course of the treatment. Individual irritability slopes (i.e., irritability change rate) and intercepts (i.e., initial irritability level), generated by linear growth curve modeling, were integrated with fMRI data. Repeated ANCOVAs demonstrated that both pre-treatment neural response to reward and pre- vs. post-treatment changes in neural reward processing correlated with irritability symptom relief, such that opposite baseline neural reward processing profiles and differential changing patterns were observed in individuals showing irritability symptom relief vs. not. Together, our findings provide proof of concept that integrating brain information with clinical information has the potential to identify predictors and mechanisms of symptom relief.

Irritability in early to middle childhood: Cross-sectional and longitudinal associations with resting state amygdala and ventral striatum connectivity.

BACKGROUND: Irritability is a common symptom that may affect children's brain development. This study aims to (1) characterize age-dependent and age-independent neural correlates of irritability in a sample of 4-8 year old children, and (2) examine early irritability as a predictor of change in brain connectivity over time. METHODS: Typically developing children, ages 4-8 years, with varying levels of irritability were included. Resting state fMRI and parent-rated irritability (via Child Behavior Checklist; CBCL) were collected at up to three time points, resulting in a cross-sectional sample at baseline (N = 176, M = 6.27, SD = 1.49), and two subsamples consisting of children who were either 4 or 6 years old at baseline that were followed longitudinally for two additional timepoints, one- and two-years post-baseline. That is, a "younger" cohort (age 4 at baseline, n = 34, M age = 4.44, SD = 0.25) and an "older" cohort (age 6 at baseline, n = 29, M age = 6.50, SD = 0.30). Across our exploratory analyses, we examined how irritability related to seed-based intrinsic connectivity via whole-brain connectivity ANCOVAs using the left and right amygdala, and left and right ventral striatum as seed regions. RESULTS: Cross-sectionally, higher levels of irritability were associated with greater amygdala connectivity with the posterior cingulate, controlling for child age. No age-dependent effects were observed in the cross-sectional analyses. Longitudinal analyses in the younger cohort revealed that early higher vs. lower levels of irritability, controlling for later irritability, were associated with decreases in amygdala and ventral striatum connectivity with multiple frontal and parietal regions over time. There were no significant findings in the older cohort. CONCLUSIONS: Findings suggest that irritability is related to altered neural connectivity during rest regardless of age in early to middle childhood and that early childhood irritability may be linked to altered changes in neural connectivity over time. Understanding how childhood irritability interacts with neural processes can inform pathophysiological models of pediatric irritability and the development of targeted mechanistic interventions.

Roads Diverged: Developmental Trajectories of Irritability From Toddlerhood Through Adolescence.

OBJECTIVE: Irritability is a dimensional trait that manifests from early life and is a robust transdiagnostic risk factor for psychopathology and impairment. A large, national dataset was leveraged to identify and broadly characterize trajectories from toddlerhood through adolescence, which is crucial for timely, targeted interventions. METHOD: Data on irritability and a broad array of potential factors affecting irritability development from 4,462 children assessed longitudinally at ages 3, 5, 9, and 15 were included. Latent class growth models identified groups of children based on their nonlinear irritability trajectories from toddlerhood to adolescence. LASSO regression then identified key characteristics differentiating trajectory groups. RESULTS: Five distinct irritability trajectories were identified, two of which were stable, maintaining medium or high irritability from age 3 to 15. Three trajectories showed undulating change over development, with an inflection point at the transition to adolescence (age 9): Most children had consistently low irritability. Two smaller groups started with high irritability at age 3 but diverged, sharply decreasing or increasing until a turning point at age 9. Developmental patterning of harsh/neglectful parenting and child internalizing symptoms most strongly differentiated trajectory groups. Sociodemographic characteristics, attachment style, neighborhood support, cognitive functioning, and genetic variation also differentiated trajectories. CONCLUSION: The results demonstrated the importance of the transition to adolescence as a critical inflection point for youths with fluctuating irritability trajectories. Identifying these patterns and multiple malleable factors associated with stably high or rising trajectories is an important step toward targeted interventions for the most vulnerable subgroups. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as living with a disability. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group.

White matter integrity in adolescent irritability: A preliminary study.

Irritability is a prevalent, impairing transdiagnostic symptom, especially during adolescence, yet little is known about irritability's neural mechanisms. A few studies examined the integrity of white matter tracts that facilitate neural communication in irritability, but only with extreme, disorder-related symptom presentations. In this preliminary study, we used a group connectometry approach to identify white matter tracts correlated with transdiagnostic irritability in a community/clinic-based sample of 35 adolescents (mean age = 14 years, SD = 2.0). We found positive and negative associations with irritability in local white matter tract bundles including sections of the longitudinal fasciculus; frontoparietal, parolfactory, and parahippocampal cingulum; corticostriatal and thalamocortical radiations; and vertical occipital fasciculus. Our findings support functional neuroimaging studies that implicate widespread neural pathways, particularly emotion and reward networks, in irritability. Our findings of positive and negative associations reveal a complex picture of what is "good" white matter connectivity. By characterizing irritability's neural underpinnings, targeted interventions may be developed.

Executive functioning moderates neural mechanisms of irritability during reward processing in youth.

Pediatric irritability is the most robust indicator of transdiagnostic psychopathology risk. It is associated with altered neural reward processing, including neural networks related to cognitive control, and better cognitive control has been hypothesized to mitigate irritability. We evaluated the relationship of executive functioning (EF) with irritability-related neural correlates of reward processing in youths with varying levels of irritability. Participants (N = 51, mean age=13.80 years, SD=1.94) completed a monetary incentive delay task during multiband fMRI acquisition. Irritability and EF were measured via the Affective Reactivity Index and the NIH Toolbox cognition battery, respectively. Whole-brain analyses, controlling for age, examined the moderating role of EF on irritability-related brain activation and connectivity (seeds: striatum, amygdala) during reward anticipation and performance feedback. Irritability-related neural patterns during reward processing depended on EF, in occipital areas during reward anticipation and limbic, frontal, and temporal networks during performance feedback. Higher irritability combined with higher EF was associated with neural patterns opposite to those observed for higher irritability with lower co-occurring EF. Although preliminary, findings suggest that EF may buffer irritability-related reward processing deficits. Additionally, individual differences in EF and their relation to irritability may be related to varied etiologic mechanisms of irritability with important implications for personalized prevention and intervention.

Bullying Perpetration and Victimization in Youth: Associations with Irritability and Anxiety.

Prior work on has demonstrated that irritability and anxiety are associated with bullying perpetration and victimization, respectively. Even though symptoms of irritability and anxiety often occur concurrently, few studies have tested their interactive effects on perpetration or victimization. The current study recruited 131 youths from a broader program of research that examines the pathophysiology and treatment of pediatric irritability and anxiety. Two moderation tests were performed to examine concurrent irritability and anxiety symptoms and their relation to perpetration and victimization of bullying. More severe anxiety was associated with greater victimization. However, more severe irritability was associated with, not just greater perpetration, but also greater victimization. An irritability-by-anxiety interaction demonstrated that youths with more severe irritability and lower levels of anxiety engaged in more perpetration. Our findings suggest a more nuanced approach to understanding how the commonly comorbid symptoms of irritability and anxiety interact in relation to peer-directed behavior in youths.

Contributions of childhood abuse and neglect to reward neural substrates in adolescence.

BACKGROUND: Childhood adverse experiences may come to bear particularly during adolescence, when neural reward systems are developing rapidly and psychopathology spikes. Despite prior work differentiating threat- (abuse) vs. deprivation- (neglect) related adversity, no research has yet identified their relative nor interactive contributions to reward neural substrates during adolescence. In the present study, we leveraged a diverse sample of adolescents with different childhood adversity profiles to examine neural responses to reward in relation to varying degrees of abuse vs. neglect. METHODS: Adolescents (N = 45; 23 females; mean age = 14.9 years, SD = 1.9) completed a child-friendly monetary incentive delay task during fMRI acquisition. The self-report Childhood Trauma Questionnaire assessed childhood abuse and neglect. Whole brain ANCOVA analyses evaluated reward anticipation (reward vs. no reward expected) and feedback (hitting vs. missing the target with a reward vs. no reward) in relation to abuse and neglect dimensions. RESULTS: Whole-brain analyses revealed that abuse, adjusted for neglect, is associated with greater differences between task conditions (reward vs. no reward, hit vs. miss) in regions associated with threat/emotion regulation (prefrontal and temporal cortices, as well as posterior regions including fusiform and posterior cingulate/precuneus). Additionally, level of neglect modulated neural response associated with abuse in prefrontal and temporoparietal regions, such that youths with high levels of both abuse and neglect showed qualitatively different, more exaggerated neural patterns compared to youths with elevated adversity in only one dimension. CONCLUSIONS: Our findings suggest that early experiences of abuse and neglect have a long developmental reach resulting in reward-related neural alterations in adolescence. Moreover, our results bolster theoretical conceptualizations of adversity along threat and deprivation dimensions and provide evidence that "adding up" adverse life events may not be sufficient to capture the qualitatively different neural profiles produced by differing combinations of types of adversity, which may in turn necessitate different treatment approaches.

Irritability-related neural responses to frustrative nonreward in adolescents with trauma histories: A preliminary investigation.

Irritability, conceptualized as a lowered frustration response threshold to blocked goal attainment (i.e., frustrative nonreward), is a common, detrimental symptom in adolescence. Yet, neural mechanisms of irritability are not well understood. This preliminary study aims to identify irritability-related neural patterns using a novel frustrative nonreward paradigm. Our study used a diverse sample of N = 31 non-White adolescent participants (mean age 14.53 years, SD = 1.74; 83.87% Hispanic/Latinx) to improve generalizability. During fMRI acquisition, participants performed a child-friendly monetary incentive delay task, modified to provide incorrect, negative feedback on performance. Irritability was associated with alterations in amygdala connectivity with basal ganglia, prefrontal, temporal, and parietal regions, and in activation of prefrontal and posterior cortical structures. Across clusters, youths with greater irritability showed activation/connectivity differences between reward blocked versus received conditions in the opposite direction compared to youths with lowered irritability. Alterations in amygdala-temporoparietal connectivity and lingual gyrus activation demonstrated an altered irritability-related recovery effect from the previous trial. These findings support the central role of frustrative nonreward as a key irritability pathway. Our work is one of the first to document neural correlates of difficult recovery from frustration characteristic of irritability and provides insight into novel treatment targets for irritability in diverse populations.

Reward-related neural correlates of early life stress in school-aged children.

OBJECTIVES: Early life stress likely contributes to dysfunction in neural reward processing systems. However, studies to date have focused almost exclusively on adolescents and adults, measured early life stress retrospectively, and have often failed to control for concurrent levels of stress. The current study examined the contribution of prospectively measured cumulative life stress in preschool-age children on reward-related neural activation and connectivity in school-age children. METHODS: Children (N = 46) and caregivers reported children's exposure to early life stress between birth and preschool age (mean = 4.8 years, SD = 0.80). At follow-up (mean age = 7.52 years, SD = .78), participants performed a child-friendly monetary incentive delay task during functional magnetic resonance imaging. RESULTS: Children with higher levels of cumulative early life stress, controlling for concurrent stressful life events, exhibited aberrant patterns of neural activation and connectivity in reward- and emotion-related regions (e.g., prefrontal cortex, temporal pole, culmen), depending on the presence of a potential reward and whether or not the target was hit or missed. CONCLUSIONS: Findings suggest that stress exposure during early childhood may impact neural reward processing systems earlier in development than has previously been demonstrated. Understanding how early life stress relates to alterations in reward processing could guide earlier, more mechanistic interventions.

Changes in neural reward processing following Amplification of Positivity treatment for depression and anxiety: Preliminary findings from a randomized waitlist controlled trial.

Positive valence system (PVS) deficits are increasingly recognized as important treatment targets for depression and anxiety. Emerging behavioral treatments designed to upregulate the PVS show initial promise; however, neural mechanisms underlying these approaches remain unknown. This study investigated neural reward-processing-related changes following Amplification of Positivity (AMP)-a treatment designed to enhance positive thinking, emotions and behaviors through positive activity interventions (Clinicaltrials.gov: NCT02330627). Individuals with depression and/or anxiety (N = 29) were randomized to 10 sessions of AMP (n = 16) or waitlist (WL; n = 13). Participants completed a monetary incentive delay task during fMRI at baseline and post-assessment. Hypothesis-driven region of interest (ventral striatum, insula, anterior cingulate) and exploratory whole-brain activation and connectivity analyses evaluated pre-to-post changes for AMP vs. WL when anticipating potential monetary gain or loss. No between-group brain activation changes emerged in regions of interest or whole-brain analyses. Increased neural connectivity from pre-to-post-treatment was observed in AMP vs. WL, including ventral striatum, anterior insula, and anterior cingulate connectivity with prefrontal, limbic, occipital and parietal regions-predominantly during loss anticipation. This preliminary study is the first to examine neural mechanisms of positive activity interventions in depression and anxiety and suggests that AMP may strengthen brain connectivity in reward processing, attention, and emotion regulation networks.

Reward-related neural correlates in adolescents with excess body weight.

The functional and connectivity reward processing in adults with excessive body weight is well documented, though is relatively less researched during adolescence. Given that reward and inhibition may be highly malleable during adolescence, it is unknown how impulsive behaviors, potentially stemming from impaired inhibitory control and heightened sensitivity to rewarding cues, relate to increases in body weight in adolescents. Adolescents (N = 76; mean age = 14.10 years, SD = 1.92) with varied body mass index (BMI) performed a child-friendly monetary incentive delay task during functional magnetic resonance imaging, to study reward processing during the anticipation of rewards (cue) and reactions to feedback about rewards (feedback). Our results show that adolescents with greater BMI z-score show neural activation and ventral striatum connectivity alterations in networks implicated in reward, salience detection, and inhibitory control. These bottom-up reward and top-down inhibitory control networks, as well as interactions between these networks were prevalent during the anticipation period (when the cue is presented) as well as when receiving feedback about whether one has received a reward. Specifically, our results were mainly driven by failure to receive a reward in the feedback period, and the anticipation of a potential reward in the anticipation period. Overall, we provide evidence for heightened reward salience as well as inhibitory control deficits that, in combination, may contribute to the impulsive behaviors that lead to higher BMI in adolescents.

Editorial: Defining the Clinical Boundary of Disruptive Mood Dysregulation Disorder Symptoms in Youth.

Disruptive mood dysregulation disorder (DMDD) is a novel diagnosis emerging from a continuing discourse on the best diagnostic home for children with severe, chronic irritability. DMDD emerged from a research diagnosis that was developed to test the hypothesis that severe, chronic irritability is a developmental phenotype of pediatric bipolar disorder.1 That is, such irritability is a phenomenon that emerges prior to a hypo/manic episode that defines bipolar disorder. For many, such irritability in conjunction with attention-deficit/hyperactivity disorder (ADHD) symptoms had been treated as a prodrome of bipolar disorder. Although this line of research did not establish a deterministic association between the DMDD syndrome and later bipolar disorder, it did provide guidance for assessing the risk of irritability for later bipolar disorder.2 Among the outcomes was the introduction of DMDD as a new diagnosis in DSM-5. It is defined by 2 core symptoms-temper outbursts and irritable/angry mood-the 2 major features of irritability. However, what qualifies as DMDD-level irritable mood and temper outbursts is unclear, and, unlike other mood disorders, no ancillary symptom criteria are available to establish a diagnosis of DMDD. Through the example of the relationship between DMDD and ODD, we will illustrate the clinical impact of this lack of clarity and describe the current efforts to establish a developmentally sensitive clinical nosology for irritability.