Irritability in young people with copy number variants associated with neurodevelopmental disorders (ND-CNVs).

A range of rare mutations involving micro-deletion or -duplication of genetic material (copy number variants (CNVs)) have been associated with high neurodevelopmental and psychiatric risk (ND-CNVs). Irritability is frequently observed in childhood neurodevelopmental conditions, yet its aetiology is largely unknown. Genetic variation may play a role, but there is a sparsity of studies investigating the presentation of irritability in young people with ND-CNVs. This study aimed to investigate whether there is a difference in irritability in young people with rare ND-CNVs compared to those without ND-CNVs, and to what extent irritability is associated with psychiatric diagnoses and cognitive ability (IQ). Irritability and broader psychopathology were assessed in 485 young people with ND-CNVs and 164 sibling controls, using the child and adolescent psychiatric assessment. Autism was assessed using the social communication questionnaire, and intelligence quotient (IQ) by the Wechsler abbreviated scale of intelligence. Fifty four percent of young people with ND-CNVs met the threshold for irritability; significantly more than controls (OR = 3.77, CI = 3.07-7.90, p = 5.31 × 10-11). When controlling for the presence of other psychiatric comorbidities, ND-CNV status was still associated with irritability. There was no evidence for a relationship between irritability and IQ. Irritability is an important aspect of the clinical picture in young people with ND-CNVs. This work shows that genetic variation is associated with irritability in young people with ND-CNVs, independent of psychiatric comorbidities or IQ impairment. Clinicians should be aware of this increased risk to inform management and interventions.

Prevalence and risk factors associated with circadian syndrome in community-dwelling middle-aged to older adults: Based on health ecology model.

OBJECTIVES: To explore the prevalence and risk factors associated with circadian syndrome (CricS) in community-dwelling middle-aged to older adults. METHOD: We performed a cross-sectional analysis of 13,516 participants from the China Health and Retirement Longitudinal Study (CHARLS). We used logistic regression to compute the odds ratios (OR) and 95 % confidence intervals (Cls), using covariates derived through the health ecology model. RESULTS: The overall prevalence of CricS was 31.5 % (25.0 % males and 37.1 % females). With controlling all covariates, social isolation (OR 1.164, 95%CI 1.033-1.310), irritable mood (OR 1.689, 95%CI 1.488-1.917), fear responses (OR 1.546, 95%CI 1.262-1.894), chronic disease (OR 1.577, 95%CI 1.392-1.788), and financial debt (OR 0.806, 95%CI 0.657-0.990) were significantly correlated with increased CricS risk in males, whereas CricS syndrome was significantly associated with age (OR 1.285, 95%CI 1.214-1.361), married (OR 1.258, 95%CI 1.089-1.452), current drinkers (OR 0.835, 95%CI 0.716-0.974), social isolation (OR 1.175, 95%CI 1.065-1.296), irritable mood (OR 1.346, 95%CI 1.210-1.497), fear responses (OR 1.202, 95%CI 1.047-1.378), chronic disease (OR 1.363, 95%CI 1.225-1.517), chronic pain (OR 1.177, 95%CI 1.058-1.309), and universal basic income (OR 0.742, 95%CI 0.611-0.900) in females. CONCLUSION: CricS is common in middle-aged to older adults, and health behavior factors have an important impact on CricS. The potential predictors identified for CricS should be further studied to prevent the occurrence of adverse health events in the presenium stage.

Future Directions: The Phenomenology of Irritable Mood and Outbursts: Hang Together or Hang Separately1.

Recognition of the importance of irritable mood and outbursts has been increasing over the past several decades. This "Future Directions" aims to develop a set of recommendations for future research emphasizing that irritable mood and outbursts "hang together," but have important distinctions and thus also need to "hang separately." Outbursts that are the outcome of irritable mood may be quite different from outbursts that are the trigger or driving force that make youth and his/her environment miserable. What, then, is the relation between irritable mood and outbursts? As the field currently stands, we not only cannot answer this question, but we may also lack the tools to effectively do so. Here, we will propose recommendations for understanding the phenomenology of irritable mood and outbursts so that more directed and clinically useful assessment tools can be designed. We discuss the transdiagnostic and treatment implications that relate to improvements in measurement. We describe the need to do more than repurpose our current assessment tools, specifically interviews and rating scales, which were designed for different purposes. The future directions of the study and treatment of irritable mood and outbursts will require, among others, using universally accepted nomenclature, supporting the development of tools to measure the characteristics of each irritable mood and outbursts, understanding the effects of question order, informant, development and longitudinal course, and studying the ways in which outbursts and irritable mood respond to treatment.

The utility of the irritability scale in Huntington's disease patients with evidence of irritability or aggression.

INTRODUCTION: Irritability, a common neuropsychiatric symptom in Huntington's disease (HD), lacks a standardized measurement. The Irritability Scale (IS), tailored for HD, has patient and informant versions, but variable interrater agreement has been reported frequently in previous studies. To enhance the clinical utility of the IS, this study aimed to identify the most reliable components estimating the underlying construct and develop a shortened version for time-limited contexts. METHODS: Participant and informant/observer concordance and the relationship of individual items to the complete IS scale were assessed. The short-form (SF) items were selected based on interrater agreement, exploratory factor analysis (EFA), and Item Response Theory (IRT) analysis results. Pair-wise correlation and covariance models were used to examine how SF predicted total IS score in 106 participants from the STAIR (Safety, Tolerability, and Activity of SRX246 in Irritable Subjects with Huntington's Disease) trial. Item Response Theory (IRT) analysis was used to evaluate the range and function of the selected items. RESULTS: IS interrater agreement was statistically significant (r = 0.33, p = .001). In combination with EFA factors and IRT analyses, five items were identified that showed good reliability and performance in differentiating levels of irritability. CONCLUSION: The proposed 5-item SF IS provided a reliable measure of the full scale and may be less burdensome for use in a clinical setting.

Making it "EASI" for pediatricians to determine when toddler tantrums are "more than the terrible twos": Proof-of-concept for primary care screening with the Multidimensional Assessment Profiles-Early Assessment Screener for Irritability (MAPS-EASI).

BACKGROUND: Up to 20% of youth have impairing mental health problems as early as age 3. Early identification and intervention of mental health risks in pediatric primary care could mitigate this crisis via prevention prior to disease onset. The purpose of this study was to establish the feasibility and acceptability of implementing a brief transdiagnostic screening instrument in pediatric primary care for irritability and corollary impairment. METHOD: Five pediatric clinicians in a Midwest clinic implemented the Multidimensional Assessment Profiles-Early Assessment Screener of Irritability (MAPS-EASI) for toddlers (24-30 months) and their families. MAPS-EASI (psychometrically derived from the well-validated MAPS-Scales) includes six items (scored 0-5) about symptoms (e.g., tantrums, grumpy mood), context, and frequency and two items (scored 0-3) assessed impairment. Positive screens (MAPS-EASI ≥ 5 plus impairment ≥ 2) were referred to an evidence-based parenting intervention. We assessed reach and outcomes of MAPS-EASI screening. Follow-up interviews with clinicians assessed perspectives on irritability screening and MAPS-EASI implementation. RESULTS: Of 201 eligible families, 100 (49.8%) completed the screener for a 24- or 30-month well-child visit. Mean MAPS-EASI scores were 5.8 (SD = 3.2), mean impairment scores were 0.9 (SD = 0.9), and 24 (24.0%) screened positive. Clinicians indicated that irritability screening for toddlers was aligned with their prevention-oriented, developmentally based practice. MAPS-EASI had face validity and increased clinician decision-making confidence. Finally, clinicians identified barriers and facilitators to large-scale implementation. CONCLUSIONS: MAPS-EASI proved to be feasible and acceptable in pediatric primary care. Further tailoring will be needed as the MAPS-EASI processes are scaled out to new contexts and populations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Can period-related symptoms predict menstrual manipulation among Australian female cyclists?

This study explored the extent of menstrual manipulation and its associated impact on period-related symptoms and training disruptions in Australian Female Cyclists. 205 female cyclists, from recreational to elite level, participated in an online "Female Cyclist Questionnaire (FCQ)". The FCQ utilised a series of validated questionnaires to obtain demographic information and menstrual function of the respondents, and to investigate their menstrual manipulation habits and perceptions on how their period-related symptoms affected their well-being, mood, energy and training tolerance. More than 80% of the cyclists reported that their period-related symptoms impacted upon training and 41% made training adjustments based on these symptoms. Two-thirds of respondents thought their training should be phase-controlled yet only half discussed their hormonal cycles with their coaches. Menstrual manipulation was predicted by reduced "workout tolerance" in these cyclists (odds ratio = 0.632). Half of the respondents reported compromised ability to tolerate high-intensity interval training with period-related symptoms. Period pain, increased irritability, lower energy levels and more sugar cravings were commonly reported but did not predict menstrual manipulation. The data indicated that period-related symptoms are present in Australian female cyclists across all levels of participation. However, the perceived impact to training and subsequent behavioural changes varied among individuals.

Comparing Symptoms of Major Depression in Youth with Confirmed Versus Suspected Bipolar Disorder.

Background: While numerous studies have compared symptoms of major depressive episodes (MDEs) associated with bipolar disorder (BD; i.e., bipolar depression) versus major depressive disorder (MDD; i.e., unipolar depression), little is known about this topic in youth. We compared MDE symptoms in youth with BD with youth with suspected BD who have similar clinical and familial characteristics aside from having BD. Methods: MDE symptoms based on Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children (K-SADS) Depression Rating Scale items for the most severe past episode were compared in youth, ages 13-21 years, with BD (n = 208) versus suspected BD (n = 165). Diagnoses were confirmed via semistructured interviews. Symptoms with between-group differences (p < 0.05) in univariate analyses were evaluated in a multivariate forward stepwise regression. All analyses controlled for age and sex. Results: Youth with BD had significantly higher (more severe) ratings on depressed mood (p = 0.001, η2 = 0.05), irritability (p = 0.037, η2 = 0.02), anhedonia (p = 0.004, η2 = 0.04), negative self-image (p < 0.001, η2 = 0.07), hopelessness (p = 0.04, η2 = 0.02), fatigue (p = 0.001, η2 = 0.05), hypersomnia (p = 0.001, η2 = 0.05), suicidal ideation (p = 0.04, η2 = 0.02), and recurrent thoughts of death (p < 0.001, η2 = 0.05). In regression analyses, the only symptom that remained significant in the BD group was depressed mood (p = 0.002). Conclusions: These findings demonstrate greater severity of depressive symptoms in youth with BD versus MDD across mood, and cognitive and neurovegetative symptom domains. These differences are especially noteworthy given that the MDD group was highly similar to the BD group, aside from BD diagnosis. Present findings emphasize the need for novel treatment approaches to bipolar depression in youth, and for studies examining potential mechanisms underlying the increased severity of bipolar depression.

Effects of cariprazine on reducing symptoms of irritability, hostility, and agitation in patients with manic or mixed episodes of bipolar I disorder.

BACKGROUND: Hostility, irritability, and agitation are common in patients with bipolar I disorder. Post hoc analyses evaluated the effect of cariprazine on these symptoms in patients with bipolar I mania. METHODS: Data were pooled from three randomized, double-blind, placebo-controlled phase 3 cariprazine trials in adults with bipolar I manic/mixed episodes (NCT00488618, NCT01058096, NCT01058668); pooled cariprazine doses (3-12 mg/d) were analyzed. Patients were categorized into hostility/irritability and agitation subgroups by baseline scores: Young Mania Rating Scale (YMRS) irritability and disruptive-aggressive behavior items score ≥ 2; Positive and Negative Syndrome Scale (PANSS) hostility item ≥ 2; PANSS-Excited Component (PANSS-EC) total score ≥ 14 and score ≥ 4 on ≥ 1 individual item. Changes from baseline to week 3 in hostility/irritability- and agitation-related outcomes were evaluated. Adjustments were made for the presence of other manic symptoms, sedation, and akathisia. RESULTS: Most patients met subgroup inclusion criteria (YMRS hostility = 930; PANSS hostility = 841, PANSS-EC agitation = 486). In the YMRS subgroup, least squares mean differences in change from baseline were statistically significant for cariprazine versus placebo on YMRS hostility/irritability-related items (irritability [-0.93], disruptive-aggressive behavior [-0.79], combined [-1.75]; P ≤ 0.001 each), YMRS total score (-5.92, P ≤ 0.0001), and all individual YMRS items (-0.25 to -0.93, P ≤ 0.0001); differences remained significant after adjustment for other manic symptoms, sedation, and akathisia. Differences in PANSS hostility and PANSS-EC subgroups were significant for cariprazine versus placebo (P ≤ 0.001). LIMITATIONS: Post hoc analysis. CONCLUSION: Cariprazine demonstrated specific antihostility/irritability and anti-agitation effects in patients with manic/mixed episodes of bipolar I disorder and baseline hostility, irritability, or agitation.

Art therapy masks reflect emotional changes in military personnel with PTSS.

Among disabling post-traumatic stress symptoms (PTSS) are irritability, aggressive behavior, distressing memories and general impaired cognition and negative mood. Art therapy interventions, including mask-making, can potentially alleviate these symptoms. We tested the hypothesis that art conveys emotions and predicted that blinded viewers would be able to perceive changes in theoretically derived emotional profiles expressed in art made by military personnel with PTSS from the onset to the end of therapy. Five service members and veterans exhibiting PTSS were enrolled in an 8-session art therapy protocol, during which they artistically transformed papier-mâché masks at the beginning and end of the protocol. We found that blinded viewers without knowledge of the masks' creation stage (onset or end of therapy) read initial masks as conveying more negative emotions (e.g., angry, upset, and challenged) and later masks as conveying more positive emotions (calm and pleasure). Based on the assessments from the blinded evaluators, we infer the emotional transition experienced by the participants was expressed in the masks. In an exploratory arm of the study, we also found that viewers were better able to empathize with the negative emotions experienced by participants with PTSS when asked to explicitly take their perspective.

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.

Dysphoria as trans-diagnostic mood symptom and as lived experience. Lessons from prose, poetry and philosophy.

This paper attempts to provide a characterisation of it from a first-person perspective of dysphoria, answering the question 'how it feels like to be dysphoric?'. Starting with a definition of emotions as embodied phenomena that provide the person with a felt motivation to move, a rich characterisation of dysphoria is provided centred on the coenesthetic and kinesthetic feelings inherent to this emotion. To fulfil this task, a selected choice of literary, poetic, theatrical and philosophical texts is used to compensate for the quasi-ineffability of the contrasting feelings inherent to dysphoria. Current definitions of dysphoria only highlight the 'negative' side of dysphoria, including irritability, discontent, surrender and interpersonal resentment. A more accurate characterisation necessitates the recognition of the 'positive' side of dysphoria and the ambiguities and contradictions inherent in this emotion. Dysphoric persons feel burdened by a weight that prevents them from moving and simultaneously incites movement. The inertia that accompanies dysphoria is inextricably tied in with a vital urge, however disordered and purposeless. Dysphoria is experienced both as a deadly stagnation and as a chaotic, wild impulse that brings with it an inane aspiration to explore the darkest parts of one's self in search of a glimmer of meaning and authenticity. This characterisation of dysphoria can help to differentiate it from other emotions such as sadness, anger, anxiety and anguish, and thus to identify it more precisely within the spectrum of mood disorders.

Substance use disorders in adults with attention-deficit/hyperactivity disorder: The role of affective temperament.

OBJECTIVE: Substance Use Disorders (SUD) are common in adults with Attention-Deficit/Hyperactivity Disorder (ADHD). Although predictors of SUD in this population are relevant for prevention and treatment, they need further clarification. Affective temperaments potentially associated with SUD in adult ADHD patients were explored. METHODS: ADHD patients with and without SUD were compared for sociodemographic, clinical, and psychological characteristics through: Adult ADHD Self-Report Scale; Wender Utah Rating Scale; Temperament Evaluation Memphis for Pisa, Paris, and San Diego-Autoquestionnaire. Logistic regression investigated factors associated with SUD. RESULTS: We included one-hundred and thirty-six ADHD patients with (n = 51, 37.5 %) and without SUD (n = 85, 62.5 %). The presence of SUD was associated with irritable temperament (p = 0.009), as well as more frequent school failure (p = 0.038), legal problems (p = 0.039), and lifetime suicide attempts (p = 0.014). LIMITATIONS: The cross-sectional design, the relatively small sample size, and the use of self-administered questionnaires. CONCLUSIONS: This study confirms the greater overall severity of adult ADHD-SUD compared with ADHD-only patients and suggests the potential role of irritable temperament as a predictor of substance-related problems.

Irritability across adolescence: Examining longitudinal trajectory, stability, and associations with psychopathology and functioning at age 18.

BACKGROUND: Irritability, marked by diminished frustration tolerance, holds significant implications for youth mental health treatment. Despite prior research on irritability trajectories, understanding of individual differences during adolescence remains limited. This study examines the stability and trajectory of irritability across ages 12-18, investigating associations with psychopathology and functioning at age 18. METHODS: A community sample of families with 3-year-old children (N = 518) was recruited via commercial mailing lists. Irritability was assessed at ages 12, 15, and 18 using the Affective Reactivity Index. Psychopathology at age 18 was evaluated with the Kiddie Schedule for Affective Disorders and Schizophrenia, and functioning was assessed through the UCLA Life Stress Interview. Measurement invariance analyses and latent growth curve modeling were conducted within a structural equation modeling (SEM) framework. RESULTS: Configural, metric, and scalar invariance models were supported. Elevated irritability at age 12 predicted adverse outcomes at age 18, including increased psychotropic medication use, mental health treatment, suicidal ideation, self-injury, and psychiatric disorders. Importantly, these associations persisted even after accounting for corresponding variables at age 12. The trajectory of irritability during early adolescence significantly predicted heightened risks for various outcomes at age 18, including suicidal ideation, depression, anxiety, disruptive behavior disorders, and impaired interpersonal functioning. DISCUSSION: Limitations include using only youth-reported data at age 18, limited generalizability from a mostly White, middle-class sample, and insufficient exploration of the broader developmental trajectory of irritability. Nevertheless, the findings emphasize the crucial role of irritability's trajectory in influencing various psychopathological and functional outcomes in late adolescence.

How are irritability and anhedonia symptoms linked? A network approach.

BACKGROUND: Anhedonia and irritability are two prevalent symptoms of major depressive disorder (MDD) that predict greater depression severity and poor outcomes, including suicidality. Although both symptoms have been proposed to result from paradoxical reward processing dysfunctions, the interactions between these symptoms remain unclear. Anhedonia is a multifaceted symptom reflecting impairments in multiple dimensions of reward processing (e.g., pleasure, desire, motivation, and effort) across distinct reward types (e.g., food, sensory experiences, social activities, hobbies) that may differentially interact with irritability. This study investigated the complex associations between anhedonia and irritability using network analysis. METHOD: Participants (N = 448, Mage = 33.29, SD = 14.58) reported their symptoms of irritability on the Brief Irritability Test (Holtzman et al., 2015) and anhedonia (i.e., pleasure, desire, motivation, and effort dimensions across four reward types) on the Dimensional Anhedonia Rating Scale (Rizvi et al., 2015). A regularized Gaussian Graphical Model was built to estimate the network structure between items. RESULTS: Irritability was negatively related to willingness to expand effort to obtain food/drinks (estimate = -0.18), social activities (-0.13), and hobbies (-0.12) rewards. Irritability was positively associated with a desire for food/drinks (0.12). LIMITATIONS: Only a small proportion (5.8%) of our sample was clinical and the study design was cross-sectional. CONCLUSION: A specific link between irritability and the effort dimension of the hedonic response across three reward types was identified. Investigating effort expenditure deficits with experimental paradigms may help us understand the mechanisms underlying the comorbidity between irritability and anhedonia in the context of MDD.

Key psychosocial issues in medical care.

OBJECTIVE: The aim of this review is to illustrate an innovative framework for assessing the psychosocial aspects of medical disorders within the biopsychosocial model. It is based on clinimetrics, the science of clinical measurements. It may overcome the limitations of DSM-5 in identifying highly individualized responses at the experiential, behavioral, and interpersonal levels. METHOD: A critical review of the clinimetric formulations of the biopsychosocial model in the setting of medical disease was performed. References were identified through searches from PubMed for English articles on human subjects published from January 1982 to October 2023. RESULTS: Clinimetric methods of classification have been found to deserve special attention in four major areas: allostatic load (the cumulative cost of fluctuating and heightened neural or neuroendocrine responses to environmental stressors); health attitudes and behavior; persistent somatization; demoralization and irritable mood. This type of assessment, integrated with traditional psychiatric nosography, may disclose pathophysiological links and provide clinical characterizations that demarcate major prognostic and therapeutic differences among patients who otherwise seem deceptively similar because they have the same medical diagnosis. It may be of value in a number of medical situations, such as: high level of disability or compromised quality of life in relation to what is expected by disease status; delayed or partial recovery; insufficient participation in self-management and/or rehabilitation; failure to resume healthy role after convalescence; unhealthy lifestyle; high attendance of medical facilities disproportionate to detectable disease; lack of treatment adherence; illness denial. CONCLUSIONS: The clinimetric approach to the assessment of key psychosocial variables may lead to unique individual profiles, that take into account both biology and biography. It may offer new opportunities for integrating psychosocial and medical perspectives.

Irritability in Youths: A Critical Integrative Review.

Irritability, defined as proneness to anger that may impair an individual's functioning, is common in youths. There has been a recent upsurge in relevant research. The authors combine systematic and narrative review approaches to integrate the latest clinical and translational findings and provide suggestions for addressing research gaps. Clinicians and researchers should assess irritability routinely, and specific assessment tools are now available. Informant effects are prominent, are stable, and vary by age and gender. The prevalence of irritability is particularly high among individuals with attention deficit hyperactivity disorder, autism spectrum disorder, and mood and anxiety disorders. Irritability is associated with impairment and suicidality risk independent of co-occurring diagnoses. Developmental trajectories of irritability (which may begin early in life) have been identified and are differentially associated with clinical outcomes. Youth irritability is associated with increased risk of anxiety, depression, behavioral problems, and suicidality later in life. Irritability is moderately heritable, and genetic associations differ based on age and comorbid illnesses. Parent management training is effective for treating psychological problems related to irritability, but its efficacy in treating irritability should be tested rigorously, as should novel mechanism-informed interventions (e.g., those targeting exposure to frustration). Associations between irritability and suicidality and the impact of cultural context are important, underresearched topics. Analyses of large, diverse longitudinal samples that extend into adulthood are needed. Data from both animal and human research indicate that aberrant responses to frustration and threat are central to the pathophysiology of irritability, revealing important translational opportunities.

Study Preregistration: Understanding the Etiology of Externalizing Problems in Young Children: The Roles of Callous-Unemotional Traits and Irritability.

Externalizing behavioral problems in young children are associated with later delinquency and crime,1 which can cause burdens at both personal and socialeconomic levels. The heterogeneity of externalizing problems emphasizes the importance of examining the etiological mechanisms that underlie externalizing problems and related behaviors. The present study focuses on 2 risk factors for externalizing behavioral problems in early childhood: callous-unemotional traits (CU), characterized as a lack of guilt and empathy,2 and irritability, a tendency to show anger and frustration.3 Behavioral genetic studies find that externalizing problems, CU, and irritability are heritable,4,5 raising the possibility of common genetic effects linking the 3 behaviors, but this has not been previously explored. Neurological evidence suggests distinct pathways from CU and irritability to externalizing problems,6 implying that the genetic and environmental factors linking externalizing problems and CU may differ from those linking externalizing problems and irritability. We predict that there will be common genetic influences operating across externalizing problems, CU, and irritability; but we also predict unique genetic and environmental influences representing distinctive risks shared between externalizing problems and CU, and between externalizing problems and irritability, respectively.

Psychopharmacology Management in Autism Spectrum Disorder.

Persons with autism spectrum disorder (ASD) may have other psychiatric conditions that warrant treatment. Symptoms may not be easy to discern from rigidity or irritability that are sometimes considered to be constituent parts of ASD. Pathophysiology that involves hyperexcitable neurons and anomalous connectivity may provide justification for using psychopharmacologic agents, although nonmedical strategies may also be effective. Hyperactivity, irritability, and tantrums with or without aggression may be rational targets for psychopharmacological intervention. The best-studied drug class to date has been the second-generation antipsychotics targeting irritability.

Neural Responses to Intranasal Oxytocin in Youths With Severe Irritability.

OBJECTIVE: The authors investigated the neural impact of intranasal oxytocin on emotion processing areas in youths with severe irritability in the context of disruptive mood and behavior disorders. METHODS: Fifty-two participants with severe irritability, as measured by a score ≥4 on the Affective Reactivity Index (ARI), with diagnoses of disruptive behavior disorders (DBDs) and/or disruptive mood dysregulation disorder (DMDD) were randomly assigned to treatment with intranasal oxytocin or placebo daily for 3 weeks. Assessments were conducted at baseline and at the end of the trial; the primary outcomes were measures of irritability on the ARI and ratings on the Clinical Global Impressions severity scale (CGI-S) focusing on DBD and DMDD symptoms, and secondary outcomes included the CGI improvement scale (CGI-I) and ratings of proactive and reactive aggressive behavior on the Reactive-Proactive Aggression Questionnaire. Forty-three participants (22 in the oxytocin group and 21 in the placebo group) completed pre- and posttreatment functional MRI (fMRI) scans with the affective Stroop task. RESULTS: Youths who received oxytocin showed significant improvement in CGI-S and CGI-I ratings compared with those who received placebo. In the fMRI data, blood-oxygen-level-dependent (BOLD) responses to emotional stimuli in the dorsomedial prefrontal cortex and posterior cingulate cortex were significantly reduced after oxytocin compared with placebo. These BOLD response changes were correlated with improvement in clinical severity. CONCLUSIONS: This study provides initial and preliminary evidence that intranasal oxytocin may induce neural-level changes in emotion processing in youths with irritability in the context of DBDs and DMDD. This may lead to symptom and severity changes in irritability.