Transdiagnostic Symptom Research Articles

Anhedonia in adolescents at transdiagnostic familial risk for severe mental illness: Clustering by symptoms and mechanisms of association with behavior

BackgroundAnhedonia is a transdiagnostic symptom of severe mental illness (SMI) and emerges during adolescence. Possible subphenotypes and neural mechanisms of anhedonia in adolescents at risk for SMI are understudied. MethodsAdolescents at familial risk for SMI (N = 81) completed anhedonia (e.g., consummatory, anticipatory, social), demographic, and clinical measures and one year prior, a subsample (N = 46) completed fMRI scanning during a monetary reward task. Profiles were identified using k-means clustering of anhedonia type and differences in demographics, suicidal ideation, impulsivity, and emotional processes were examined. Moderation analyses were conducted to investigate whether levels of brain activation of reward regions moderated the relationships between anhedonia type and behaviors. ResultsTwo-clusters emerged: a high anhedonia profile (high-anhedonia), characterized by high levels of all types of anhedonia, (N = 32) and a low anhedonia profile (low-anhedonia), characterized by low levels of anhedonia types (N = 49). Adolescents in the high-anhedonia profile reported more suicidal ideation and negative affect, and less positive affect and desire for emotional closeness than low-anhedonia profile. Furthermore, more suicidal ideation, less positive affect, and less desire for emotional closeness differentiated the familial high-risk, high-anhedonia profile adolescents from the familial high-risk, low-anhedonia profile adolescents. Across anhedonia profiles, moderation analyses revealed that adolescents with high dmPFC neural activation in response to reward had positive relationships between social, anticipatory, and consummatory anhedonia and suicidal ideation. LimitationsSmall subsample with fMRI data. ConclusionProfiles of anhedonia emerge transdiagnostically and vary on clinical features. Anhedonia severity and activation in frontostriatal reward areas have value for clinically important outcomes such as suicidal ideation.

Transdiagnostic cognitive biases in psychiatric disorders: A systematic review and network meta-analysis

Psychiatric disorders are characterized by cognitive deficits, which have been proposed as a transdiagnostic feature of psychopathology (“C” factor). Similarly, cognitive biases (e.g., in attention, memory, and interpretation) represent common tendencies in information processing that are often associated with psychiatric symptoms. However, the question remains whether cognitive biases are also transdiagnostic or are specific to certain psychiatric disorders/symptoms. The current systematic review sought to address whether the proposed “C” factor of transdiagnostic cognitive dysfunction in psychopathology can be extended to cognitive biases. Overall, 31 studies comprising 4401 participants (2536 patients, 1865 non-clinical controls) met inclusion criteria, assessing 19 cognitive biases across 20 diagnostic categories, with most studies focusing on interpretation (k = 22) and attention (k = 11) biases and only 2 assessing memory biases. Traditional meta-analyses found a moderate effect size (g = 0.32) for more severe cognitive biases in all patients relative to non-clinical controls, as well as small but significant associations between interpretation biases and transdiagnostic symptom categories (general psychopathology: r = 0.20, emotion dysfunction: r = 0.17, psychotic symptoms: r = 0.25). Network meta-analyses revealed significant patient versus non-clinical control differences on attention and interpretation biases across diagnoses, as well as significant differences between diagnoses, with highest severity in panic disorder for attention biases and obsessive-compulsive disorder for interpretation biases. The current findings extend the big “C” interpretation of transdiagnostic cognitive dysfunction in psychiatric disorders to cognitive biases and transdiagnostic symptom dimensions. Results also suggest that while the presence of cognitive biases is transdiagnostic, bias severity differs across diagnoses, as in traditional neurocognitive deficits.

Interval Timing as a Computational Pathway From Early Life Adversity to Affective Disorders.

Adverse early life experiences can have remarkably enduring negative consequences on mental health, with numerous, varied psychiatric conditions sharing this developmental origin. Yet, the mechanisms linking adverse experiences to these conditions remain poorly understood. Here, we draw on a principled model of interval timing to propose that statistically optimal adaptation of temporal representations to an unpredictable early life environment can produce key characteristics of anhedonia, a transdiagnostic symptom associated with affective disorders like depression and anxiety. The core observation is that early temporal unpredictability produces broader, more imprecise temporal expectations. As a result, reward anticipation is diminished, and associative learning is slowed. When agents with such representations are later introduced to more stable environments, they demonstrate a negativity bias, responding more to the omission of reward than its receipt. Increased encoding of negative events has been proposed to contribute to disorders with anhedonia as a symptom. We then examined how unpredictability interacts with another form of adversity, low reward availability. We found that unpredictability's effect was most strongly felt in richer environments, potentially leading to categorically different phenotypic expressions. In sum, our formalization suggests a single mechanism can help to link early life adversity to a range of behaviors associated with anhedonia, and offers novel insights into the interactive impacts of multipleadversities.

Psychometric properties of the Global Psychotrauma Screen in the United States

ABSTRACT Background Prior research assessing the psychometric properties of the Global Psychotrauma Screen provided support for its internal consistency reliability, construct validity, convergent validity, and divergent validity in several international samples, but not specifically in a U.S. subsample. Objective The purpose of this study was to assess psychometric properties of the GPS in the U.S. Method This observational study included a convenience sample of individually recruited participants (N = 231) who completed an initial study with 126-item online questionnaire and a two-week follow-up study with GPS alone through the weblinks provided by the research team. Data analyzes included measuring internal consistency and test–retest reliability, exploratory and confirmatory factor analyzes (EFA and CFA), convergent and divergent validity, sensitivity, specificity, and severity of the GPS symptom items. Additional CFA was conducted with data (N = 947) from the GPS multinational research project, U.S. subsample. Results The results showed acceptable internal consistency and test–retest reliability, convergent validity, and divergent validity of the GPS. The construct validity results supported a three-factor structure of the GPS symptoms. The GPS domains showed acceptable sensitivity and specificity with the cut-off scores of 3 for PTSD and 5 for CPTSD domains; and the scores of 1 for the anxiety, depression, and insomnia domains respectively. The GPS risk factors predicted the GPS symptom severity. Conclusions This study provides new and additional evidence on the psychometric properties of the GPS which may help health care providers with the selection of an appropriate screening instrument for trauma-related transdiagnostic symptoms. The study limitations should be addressed in future research through the replication of EFA and CFA internationally with larger samples, and the inclusion of a reference standard for dissociation.

Gender differences in transdiagnostic domains and function of adults measured by DSM-5 assessment scales at the first clinical visit: a cohort study

BackgroundMeasurement-based care has been called for as best practice in psychiatric care and learning health systems and use of transdiagnostic measures was suggested as part of the DSM-5. Our objective is to examine gender differences in first visit socioeconomic, transdiagnostic, and functional characteristics of a dynamic, real-world measurement-based care cohort.MethodsTransdiagnostic, functional, and clinical measures were collected from 3,556 patients at first visit in an ambulatory psychiatric clinic. All patients were evaluated at the first visit by board-certified psychiatrists or licensed clinical psychologists. Demographic variables and clinical diagnoses were collected from the Electronic Medical Record. Self-report measures were collected that assessed transdiagnostic symptoms (DSM-5 Level 1 Cross-cutting Measure and Level 2 symptom scales), disability, alcohol use, attention deficit hyperactivity disorder (ADHD) symptoms, depression, anxiety, mania, suicidal thoughts and behaviors, and trauma exposure.ResultsMen and women did not differ in age, BMI, household income, high school graduation rate, race, or ethnicity, but women were more likely to be formerly married and less likely to have commercial insurance. Compared to men, women reported significantly higher overall psychopathology on the transdiagnostic Level 1 Cross-cutting measure and had higher depression, anxiety, sleep, anger, ADHD combined presentation, and suicidality severity. Women also had higher disability scores than men. However, men reported higher alcohol, tobacco and substance use, and more risky behavior than women. Trauma exposure differed significantly by gender; men reported more exposure to accidents, war-related trauma, serious accidents, and major disasters and women reported more unwanted sexual contact.ConclusionsThis cross-sectional study of a transdiagnostic, ecologically-valid real-word measurement-based care cohort demonstrates gender differences in socioeconomic factors, trauma exposure, transdiagnostic symptoms, and functioning.

Headache and psychological variables as predictors of disability in individuals with primary headache disorders.

To examine the relative contribution of headache symptoms and psychological factors to headache-related disability. Both headache symptoms and comorbid psychological factors (psychiatric symptoms and transdiagnostic constructs) negatively impact functioning among individuals with migraine and tension-type headache, but few studies have explored their relative contribution to headache-related disability. We hypothesized that psychiatric symptoms and transdiagnostic variables would afford incremental contribution to disability beyond headache symptoms, and we investigated the moderating role of headache diagnosis on these relationships. This cross-sectional study examined data from a southern U.S. university online sample of 1818 young adults (mean [SD] age 19.0 [5.1] years; 74.6% female) who met the International Classification of Headache Disorders, third edition criteria for primary headache disorders (46.6% episodic migraine, 11.6% chronic migraine, 38.3% episodic tension-type headache, 3.5% chronic tension-type headache) and completed measures assessing psychological factors and headache-related disability. Headache, psychiatric symptoms, and transdiagnostic factors were examined in relation to headache-related disability, after controlling for sex. Moderation analyses examined the conditional effect of diagnosis on disability. As predicted, both psychiatric and transdiagnostic symptoms accounted for unique variance in headache-related disability beyond headache symptoms (R2 changes of 2.7% and 2.3%, respectively). Significant three-way interactions revealed the relationship between psychiatric symptoms and disability (b = -3.16, p = 0.002), and between transdiagnostic variables and disability (b = -2.37, p = 0.034). Tests of simple slopes showed greater psychiatric symptoms and transdiagnostic variables were associated with higher levels of disability. However, the associations of these variables with disability were strongest among individuals with chronic tension-type headache (B = 3.93 for psychiatric symptoms and B = 4.62 for transdiagnostic symptoms, both p < 0.001). Psychiatric and transdiagnostic factors contribute uniquely to headache-related functional impairment, which may be important for expanding targeted assessment and behavioral interventions.

Is Sexual Aversion a Distinct Disorder or a Trans-Diagnostic Symptom across Sexual Dysfunctions? A Latent Class Analysis

Sexual aversion disorder (SAD) is a chronic condition that impacts sexual and psychological well-being. However, the relevance of SAD as a discrete disorder remains highly debated. This study aimed to clarify the status of SAD as either a distinct disorder or a trans-diagnostic symptom shared among sexual dysfunctions. This cross-sectional study used a latent class analysis approach among a Canadian community sample (n = 1,363) to identify how patterns of SAD symptoms (i.e., sexual fear, disgust, and avoidance) emerge across different spheres of sexual functioning (i.e., desire and arousal, erection or lubrication, genito-pelvic pain, and orgasm) and examine sociodemographic and psychosexual correlates of the identified classes. Examination of fit indices suggested four classes: Sexually functional, Impaired desire and responsiveness, Sexual aversion, and Comorbid sexual dysfunctions. Sexual aversion class members were more likely to be single, had experienced sexual assault in adulthood, and report lower levels of sexual satisfaction and psychological well-being, compared to Sexually functional class members. Results suggest that SAD is a distinct clinical syndrome, while its symptoms may co-occur with other sexual dysfunctions. To ensure that the needs of people with SAD are met with tailored treatment options, future nosography might consider reclassifying SAD as a specific disorder.

Enhanced Skills Training in Affective and Interpersonal Regulation (ESTAIR): A New Modular Treatment for ICD-11 Complex Posttraumatic Stress Disorder (CPTSD).

ICD-11 Complex Posttraumatic Stress Disorder (CPTSD) is a relatively new condition; therefore, there is limited available evidence for its treatment. Prior to the recognition of CPTSD as a separate trauma condition, people who met criteria were often diagnosed with multiple co-morbid conditions such as PTSD, anxiety, depression, and emotional dysregulation difficulties. In the absence of a coherent evidence base, treatment tended to involve multiple treatments for these multiple conditions or lengthy phase-based interventions, often delivered in an integrative fashion, which was not standardized. In this paper, we present Enhanced Skills Training in Affective and Interpersonal Regulation (ESTAIR), a new flexible multi-modular approach for the treatment of CPTSD and its transdiagnostic symptoms. ESTAIR is consistent with trauma-informed and patient-centered care, which highlights the importance of patient choice in identification and sequencing in targeting CPTSD symptoms. Directions for future research are discussed.

Treatment of worry and comorbid symptoms within depression, anxiety, and insomnia with a group-based rumination-focused cognitive-behaviour therapy in a primary health care setting: a randomised controlled trial.

Repetitive negative thinking (RNT) has been described as a maintaining transdiagnostic factor for psychopathology within the areas of depression, anxiety and insomnia. We investigated the effects of rumination-focused cognitive-behaviour therapy (RF-CBT) in a group format at a primary health care centre on symptoms of depression, anxiety, insomnia, RNT, and quality of life. The participants presented clinical symptom levels of worry and at least two disorders among anxiety disorders, major depressive disorder, and insomnia disorder. A randomised controlled superiority parallel arm trial was used. 73 participants were included and randomised in pairs to either group-administered RF-CBT or a waiting list condition. The primary outcomes were self-rated worry and transdiagnostic symptoms (depression, anxiety, and insomnia). Intention-to-treat analyses of group differences were conducted using linear mixed models. Adverse side effects and incidents were presented descriptively. Group RF-CBT significantly reduced self-reported insomnia at post-treatment and self-reported insomnia and depression at the 2 month-follow-up, relative to the wait-list control group. There was no significant difference in change in RNT, anxiety, or quality of life. The current study suggests that group-administered RF-CBT may be effective for insomnia and potentially effective for depression symptomatology. However, the study was underpowered to detect small and moderate effects and the results should therefore be interpreted with caution.

Refining the study of decision-making in animals: differential effects of d-amphetamine and haloperidol in a novel touchscreen-automated Rearing-Effort Discounting (RED) task and the Fixed-Ratio Effort Discounting (FRED) task

Effort-based decision-making is impaired in multiple psychopathologies leading to significant impacts on the daily life of patients. Preclinical studies of this important transdiagnostic symptom in rodents are hampered, however, by limitations present in currently available decision-making tests, including the presence of delayed reinforcement and off-target cognitive demands. Such possible confounding factors can complicate the interpretation of results in terms of decision-making per se. In this study we addressed this problem using a novel touchscreen Rearing-Effort Discounting (RED) task in which mice choose between two single-touch responses: rearing up to touch an increasingly higher positioned stimulus to obtain a High Reward (HR) or touching a lower stimulus to obtain a Low Reward (LR). To explore the putative advantages of this new approach, RED was compared with a touchscreen version of the well-studied Fixed Ratio-based Effort Discounting (FRED) task, in which multiple touches are required to obtain an HR, and a single response is required to obtain an LR. Results from dopaminergic (haloperidol and d-amphetamine), behavioral (changes in the order of effort demand; fixed-ratio schedule in FRED or response height in RED), and dietary manipulations (reward devaluation by pre-feeding) were consistent with the presence of variables that may complicate interpretation of conventional decision-making tasks, and demonstrate how RED appears to minimize such variables.

The next stages of treatment-oriented research: Commentary on Wade et al. (2023).

Treatments for eating disorders have established benefits; yet, current psychotherapies focus specifically on the cognitions and behaviors of the eating disorder. Wade et al. (2023) propose that the myriad symptoms and disorders that occur together with eating disorders merit specific attention in treatment research protocols. We seek to amplify the authors' call to take a fresh look at the characterization of eating disorders, and the need for treatment research to consider both the role of symptoms that occur as part and parcel of an eating disorder (such as mood, anxiety, and obsessionality) and the role of co-occurring disorders (such as obsessive-compulsive disorder and substance use disorders). We discuss additional aspects in the care of patients with eating disorders that were beyond the scope of Wade et al., such as the impact of systems of care, and consideration of medication trials. We propose that current research priorities (mechanism-based treatment development, transdiagnostic symptoms, and patient perspectives) can be leveraged to advance treatment research and develop a systematic approach to evaluation and treatment planning.

Developmental Trajectories of Internalizing and Externalizing Symptoms in Youth and Associated Gender Differences: A Directed Network Perspective.

Psychopathology in youth is highly prevalent and associated with psychopathology in adulthood. However, the developmental trajectories of psychopathology symptoms, including potential gender differences, are markedly underspecified. The present study employed a directed network approach to investigate longitudinal relationships and gender differences among eight transdiagnostic symptom domains across three years, in a homogenous age sample of youth participants (n = 6,414; mean baseline age = 10.0years; 78.6% White; Adolescent Brain Cognitive Development study). Anxious/depressed problems and aggressive behaviors were central symptoms and most predictive of increases in other symptom clusters at later timepoints. Rule-breaking behaviors, aggressive behaviors, and withdrawn/depressed problems emerged as bridge symptoms between externalizing and internalizing problems. Results supported cascade models in which externalizing problems predicted future internalizing problems, but internalizing problems also significantly predicted future externalizing problems, which is contrary to cascade models. Network structure, symptom centrality, and patterns of bridge symptoms differed between female and male participants, suggesting gender differences in the developmental trajectories of youth psychopathology. Results provide new insights into symptom trajectories and associated gender differences that may provide promising pathways for understanding disorder (dis)continuity and co-occurrence. The central and bridge symptoms identified here may have important implications for screening and early intervention for youth psychopathology.

Tackling Costly Fearful Avoidance Using Pavlovian Counterconditioning

Avoidance behavior constitutes a major transdiagnostic symptom that exacerbates anxiety. It hampers fear extinction and predicts poor therapy-outcome. Pavlovian counterconditioning with a reward could alleviate avoidance better than traditional extinction by reducing negative valence of the feared situation. However, previous studies are scarce and did not consider that pathological avoidance is often costly and typically evolves from an approach-avoidance conflict. Therefore, we used an approach-avoidance conflict paradigm to model effects of counterconditioning on costly avoidance (i.e., avoidance that leads to missing out on rewards). Results from our preregistered Bayesian Mixed Model analyses in 51 healthy participants (43 females) indicated that counterconditioning was more effective in reducing negative valuation and decreasing costly avoidance than traditional extinction. This study supports application of a simple counterconditioning technique, shows that its efficacy transfers to more complex avoidance situations, and suggests treatment may benefit from increasing reward drive in combination with extinction to overcome avoidance. Application in a clinical sample is a necessary next step to assess clinical utility of counterconditioning.

Effects of olanzapine on anhedonia in schizophrenia: mediated by complement factor H.

Anhedonia is a trans-diagnostic symptom in schizophrenia and MDD. Our recent work indicated that increased plasma level of complement factor H (CFH) is associated with anhedonia in major depressive disorder. This study hypothesized that CFH is likely to be a biomarker of anhedonia in schizophrenia. A 12-week prospective study is performed to observe the effects of olanzapine on anhedonia and CFH. We used the Chinese version of Snaith-Hamilton Pleasure Scale (SHAPS) to evaluate anhedonic phenotype in patients with schizophrenia. Plasma levels of C-reactive protein (CRP), C3, C4 and CFH were measured. Of the recruited 152 samples, patients with anhedonia were found in 99/152 (65.13%). Patients with anhedonia had notably higher PANSS negative subscores, SHAPS total score and higher level of plasma CFH than those without anhedonia (Ps<0.05). Stepwise multivariate linear regression analysis showed that increasing level of plasma CFH was a risk factor for SHAPS total score (β = 0.18, p = 0.03). Of the 99 patients with anhedonia, 74 completed the 12-week follow-up. We observed significantly reduced scores of PANSS, SHAPS and decreased plasma CFH level, when the patients completed this study. The change of SHAPS total score is positively correlated with the level of CFH decrease (p = 0.02). Our results implied that plasma CFH levels may be a biomarker for anhedonia in schizophrenia, and the effect of olanzapine on treating anhedonia is through decreasing plasma CFH levels.

Brain structure and function link to variation in biobehavioral dimensions across the psychopathological continuum.

In line with the Research Domain Criteria (RDoC), we set out to investigate the brain basis of psychopathology within a transdiagnostic, dimensional framework. We performed an integrative structural-functional linked independent component analysis, to study the relationship between brain measures and a broad set of biobehavioral measures in a sample (n = 295) with both mentally healthy participants and patients with diverse non-psychotic psychiatric disorders (i.e. mood, anxiety, addiction, and neurodevelopmental disorders). To get a more complete understanding of the underlying brain mechanisms, we used gray and white matter measures for brain structure and both resting-state and stress scans for brain function. The results emphasize the importance of the executive control network (ECN) during the functional scans, for the understanding of transdiagnostic symptom dimensions. The connectivity between the ECN and the frontoparietal network in the aftermath of stress, was correlated with symptom dimensions across both the cognitive and negative valence domains, and also with various other health related biological and behavioral measures. Finally, we identified a multimodal component that was specifically associated with the diagnosis of autism spectrum disorder (ASD). The involvement of the default mode network, precentral gyrus and thalamus across the different modalities of this component, may reflect the broad functional domains that may be affected in ASD, like theory of mind, motor problems and sensitivity to sensory stimuli respectively. Taken together, the findings from our extentensive, exploratory analyses emphasize the importance of a dimensional and more integrative approach for getting a better understanding of the brain basis of psychopathology.

The curse and opportunity of heterogeneity in the pursuit of psychiatric biomarkers.

The curse and opportunity of heterogeneity in the pursuit of psychiatric biomarkers.

A comparison of DSM-5 and ICD-11 models of PTSD: Measurement invariance and psychometric validation in Filipino trauma samples

This study examined and compared the factor structure of DSM-5 and ICD-11 PTSD models and their relationships with transdiagnostic symptoms (i.e., anxiety, depression, negative affect, and somatic symptoms) in eight trauma samples: (1) natural disaster relocatees; (2) Typhoon Haiyan survivors; (3) indigenous people exposed to armed conflict; (4) internally displaced persons due to armed conflict; (5) soldiers regularly involved in armed conflict; (6) police exposed to work-related traumatic events; (7) abused women; and (8) college students with diverse trauma experiences. Results showed that while the ICD-11 PTSD has better model fit than that of DSM-5, the DSM-5 PTSD model has stronger relationships with all transdiagnostic symptoms in almost all of the samples. The study highlights that in choosing which PTSD nomenclature to use, both the factor structure and comorbidity with other symptoms must be considered.

A bottom-up approach to developing a unified trauma-minority stress model for transgender and gender diverse people.

Transgender and gender diverse (TGD) people are at heightened risk of both Criterion A trauma exposure and other bias-related minority stressors (e.g., discrimination, rejection). In the absence of a unified trauma-minority stress theory, it remains unclear how to best conceptualize psychopathology for people who experience both trauma and minority stress. Using a participant-driven q-sort methodology and network analytic approach, we analyzed card sort data from 18 TGD people and 16 providers with expertise in TGD care to derive thematic networks of trauma and minority stress experiences, as they connected to transdiagnostic symptoms (e.g., hyperarousal, avoidance). The TGD participants' resulting network illustrates conceptualizations of identity- and nonidentity-based Criterion A traumas as similar and only related to psychiatric symptoms via the shared connection through other minority stressors. The provider network was more granular, although the general pattern was consistent with TGD participants, demonstrating similar perceptions of how these experiences are associated. Evidence of inextricable links between trauma and psychiatric symptoms through the conduit of minority stressors lays the groundwork for novel, integrated models of trauma, minority stress, and their transdiagnostic symptom sequelae. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Transdiagnostic Symptoms in Children with Neurodevelopmental Disabilities and Perceived Parent-Child Relationship Quality: A Pilot Study

This pilot study examined associations between transdiagnostic symptoms and parent-perceived parent-child relationship quality in treatment-seeking families of children with neurodevelopmental disabilities, and interactions among clinical symptoms and cognitive functioning. Sixty-three children between 8 to 13 years of age and their caregivers were assessed at baseline while seeking cognitive behaviour therapy for emotion regulation and mental health difficulties. Diagnoses included autism, ADHD, cerebral palsy, and learning disability, with 52% of children having multiple diagnoses. Parent-perceived parent-child relationship quality was assessed by the Positive Affect Index, autism symptoms (e.g., social communication, repetitive behaviours) by the Social Responsiveness Scale, Second Edition, mental health (i.e., internalizing problems, externalizing problems, behavioural symptoms) by the Behaviour Assessment Scale for Children, Third Edition, and IQ by the Weschler Abbreviated Scale of Intelligence, Second Edition. Results revealed that higher IQ scores and greater social communication challenges, externalizing problems, and behavioural symptoms, were associated with lower parent-child relationship quality. Interaction effects were found between IQ and social communication challenges, reflecting significantly stronger relationships between social communication challenges and lower parent-child relationship quality in the context of higher IQ. Understanding the interactions between cognitive functioning and social communication challenges can help to inform individualized supports, and advocate for a transdiagnostic approach to intervention.

Irritability and rejection-elicited aggression in adolescents and young adults.

Violence exacts staggering personal and financial costs - a burden disproportionally born by adolescents and young adults. This may be partially due to an increased sensitivity to social rejection during this critical phase of development. Irritability, a transdiagnostic symptom, is often elicited by social interactions. Yet, little is known about age differences in social rejection-elicited aggression and irritability. Progress toward testing such relations has been hindered by a lack of ecologically-valid tasks that enable the measurement of in-the-moment social rejection-elicited aggression. In this paper, we describe an initial study of young adults (n = 55) that demonstrates the efficacy of a novel Virtual School and Aggression Paradigm (VS-AP). Next, we replicate these results in a second study of adolescents and young adults (ages 11-25 years; n = 173) and examine relations between social rejection-elicited aggression, irritability, and age. We found that aggressive behavior in the VS-AP differed for accepting, rejecting, and unpredictable peer types (Study 1: F(2, 108) = 20.57, p < .001, ε2 = .28; Study 2: F(2, 344) = 152.13, p < .001, ε2 = .47), demonstrating that the VS-AP successfully models social rejection-elicited aggression. In Study 2, age was negatively correlated with aggressive behavior (r = -.29, p < .001) and irritability (r = -.28, p < .001), while irritability was positively correlated with aggressive behavior (r = .28, p < .001). Age moderated the relation between social rejection-elicited aggression and irritability. Specifically, irritability was more predictive of aggression in young adults than in adolescents (F(3, 167) = 7.07, p < .001). Data suggest mechanisms promoting rejection-elicited aggression may differ across development and vary for those with and without high levels of irritability. The VS-AP is a promising tool for probing neurocognitive, developmental, and clinically relevant mechanisms underlying social rejection-elicited aggression.